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1. Prevention of Peritonitis in Peritoneal Dialysis (PEPS)

Author: Odense University Hospital, Rigshospitalet, Denmark, Central Hospital HF, Lillehammer, Norway (dr Dag Paulsen), Tampere University Hospital, Pauls Stradins Clinical University Hospital, Tartu University Hospital, Tartu, Estonia (dr Mai Rosenberg), Karolinska Institutet, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Sheffield Teaching Hospitals NHS Foundation Trust, and Susanne Ljungman, professor
Published: 2019

2. Priorities for collaborative research using very preterm birth cohorts

Author: Jo Lebeer, Jennifer Zeitlin, Heili Varendi, Elizabeth S Draper, Andrei S. Morgan, Henrique Barros, Rolf F. Maier, Mikael Norman, Pierre-Yves Ancel, Marina Cuttini, Mariane Sentenac, Samantha Johnson, Instituto de Saúde Pública da Universidade do Porto, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Epidemiology Research Unit [Porto, Portugal] (EPIUnit), Instituto de Saúde Pública [Porto, Portugal], Universidade do Porto-Universidade do Porto, Clinical Care and Management Innovation Research Area [Roma, Lazio, Italy], Children's Hospital Bambino Gesù IRCCS [Rome], Department of Health Sciences [Leicester], University of Leicester, Department of Primary & Interdisciplinary Care, Disability Studies [Antwerpen, Belgium] (Faculty of Medicine), University of Antwerp (UA), Philipps University of Marburg, Department of Clinical Science, Intervention and Technology [Stockholm, Sweden], Karolinska Institutet [Stockholm], Department of Neonatal Medicine [Stockholm, Sweden], Karolinska University Hospital [Stockholm], University of Tartu, Tartu University Hospital [Tartu, Estonia], This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 733280., RECAP Preterm child cohort research group : Ådén U, Benhammou V, Bilsteen JF, Boerch K, Halvorsen T, Kajantie E, Kallen K, Lehtonen L, Pierrat V, Sarrechia I, Reempts PV, Walz JM, Wolke D, Ylijoki M., European Project: 733280,RECAP preterm, Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade do Porto = University of Porto-Universidade do Porto = University of Porto, Philipps Universität Marburg = Philipps University of Marburg, Sentenac, Mariane, RECAP preterm: Research on European Children and Adults born Preterm - RECAP preterm - 0000-00-00 - 0000-00-00 - 733280 - VALID, Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade do Porto [Porto]-Universidade do Porto [Porto], and European Project: 0733280(2007)
Subjects: Male, Parents, medicine.medical_specialty, Delphi Technique, Emotions, education, Nutritional Status, neonatology, 03 medical and health sciences, Child Development, 0302 clinical medicine, 030225 pediatrics, Epidemiology, medicine, Humans, Very Preterm Birth, 030212 general & internal medicine, Neonatology, Cooperative Behavior, Original Research, neurodevelopment, Socioemotional selectivity theory, business.industry, Research, Extremely preterm, Infant, Newborn, Stakeholder, Obstetrics and Gynecology, General Medicine, patient perspective, 3. Good health, Very preterm, Mental Health, Socioeconomic Factors, Ranking, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Infant, Extremely Premature, Family medicine, Pediatrics, Perinatology and Child Health, Female, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, business, Stress, Psychological
Abstract: ObjectivesTo develop research priorities on the consequences of very preterm (VPT) birth for the RECAP Preterm platform which brings together data from 23 European VPT birth cohorts.Design and settingThis study used a two-round modified Delphi consensus process. Round 1 was based on 28 research themes related to childhood outcomes (ResultsOf 71 individuals contacted, 64 (90%) participated as panel members comprising obstetricians, neonatologists, nurses, general and specialist paediatricians, psychologists, physiotherapists, parents, adults born preterm, policy makers and epidemiologists from 17 countries. All 28 initial themes were ranked in the top 10 by at least six panel members. Highest ranking themes were: education (73% of panel members' top 10 choices); care and outcomes of extremely preterm births, including ethical decisions (63%); growth and nutrition (60%); emotional well-being and social inclusion (55%); parental stress (55%) and impact of social circumstances on outcomes (52%). Highest ranking themes were robust across panel members classified by background. 15 new themes had at least 6 top 10 endorsements in round 2.ConclusionsThis study elicited a broad range of research priorities on the consequences of VPT birth, with good consensus on highest ranks between stakeholder groups. Several highly ranked themes focused on the socioemotional needs of children and parents, which have been less studied.
Published: 2020

3. European Headache Federation (EHF) consensus on the definition of effective treatment of a migraine attack and of triptan failure

Author: Simona Sacco, Christian Lampl, Faisal Mohammad Amin, Mark Braschinsky, Christina Deligianni, Derya Uludüz, Jan Versijpt, Anne Ducros, Raquel Gil-Gouveia, Zaza Katsarava, Paolo Martelletti, Raffaele Ornello, Bianca Raffaelli, Deirdre M. Boucherie, Patricia Pozo-Rosich, Margarita Sanchez-del-Rio, Alexandra Sinclair, Antoinette Maassen van den Brink, Uwe Reuter, Veritati - Repositório Institucional da Universidade Católica Portuguesa, Institut Català de la Salut, [Sacco S] Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio 1, L’Aquila, Italy. [Lampl C] Department of Neurology, Headache Medical Center at the Konventhospital BHB Linz, Linz, Austria. [Amin FM] Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, University of Copenhagen, Copenhagen, Denmark. Department of Neurorehabilitation/Traumatic Brain Injury, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. [Braschinsky M] Department of Neurology, Institute of Clinical Medicine, University of Tartu, Headache Clinic, Department of Neurology, Tartu University Hospital, Tartu, Estonia. [Deligianni C] Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, University of Copenhagen, Copenhagen, Denmark. [Uludüz D] Department of Neurology Istanbul Cerrahpasa Medical Faculty, Istanbul, Turkey. [Pozo-Rosich P] Unitat de Cefalea, Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Cefalea i Dolor Neurològic, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Brussels Heritage Lab, Clinical sciences, Neuroprotection & Neuromodulation, and Neurology
Subjects: Consensus, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::trastornos con cefaleas::cefaleas primarias::trastornos migrañosos [ENFERMEDADES], NSAIDs, Neuroscience(all), Migraine Disorders, Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Neurotransmitter [CHEMICALS AND DRUGS], aminoácidos, péptidos y proteínas::proteínas::proteínas de membranas::receptores de superficie celular::receptores de neurotransmisores [COMPUESTOS QUÍMICOS Y DROGAS], Medizin, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Migranya - Tractament, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Neurotransmissors - Receptors, Humans, Tryptamines/pharmacology, Serotonin 5-HT1 Receptor Agonists/therapeutic use, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Headache Disorders::Headache Disorders, Primary::Migraine Disorders [DISEASES], Migraine, Headache/drug therapy, Headache, Presa de decisions, General Medicine, Attack, Serotonin 5-HT1 Receptor Agonists, Psychological Phenomena::Mental Processes::Thinking::Decision Making::Consensus [PSYCHIATRY AND PSYCHOLOGY], Tryptamines, Ditan, Migraine Disorders/diagnosis, Triptan, Anesthesiology and Pain Medicine, Neurology (clinical), fenómenos psicológicos::procesos mentales::pensamiento::toma de decisión::consenso [PSIQUIATRÍA Y PSICOLOGÍA], Transcription Factors/therapeutic use, Gepant, Transcription Factors
Abstract: BackgroundTriptans are migraine-specific acute treatments. A well-accepted definition of triptan failure is needed in clinical practice and for research. The primary aim of the present Consensus was to provide a definition of triptan failure. To develop this definition, we deemed necessary to develop as first a consensus definition of effective treatment of an acute migraine attack and of triptan-responder.Main bodyThe Consensus process included a preliminary literature review, a Delphi round and a subsequent open discussion. According to the Consensus Panel, effective treatment of a migraine attack is to be defined on patient well-being featured by a) improvement of headache, b) relief of non-pain symptoms and c) absence of adverse events. An attack is considered effectively treated if patient’s well-being, as defined above, is restored within 2 hours and for at least 24 hours. An individual with migraine is considered as triptan-responder when the given triptan leads to effective acute attack treatment in at least three out of four migraine attacks. On the other hand, an individual with migraine is considered triptan non-responder in the presence of failure of a single triptan (not matching the definition of triptan-responder). The Consensus Panel defined an individual with migraine as triptan-resistant in the presence of failure of at least 2 triptans; triptan refractory, in the presence of failure to at least 3 triptans, including subcutaneous formulation; triptan ineligibile in the presence of an acknowledged contraindication to triptan use, as specified in the summary of product characteristics.ConclusionsThe novel definitions can be useful in clinical practice for the assessment of acute attack treatments patients with migraine. They may be helpful in identifying people not responding to triptans and in need for novel acute migraine treatments. The definitions will also be of help in standardizing research on migraine acute care. Background: Triptans are migraine-specific acute treatments. A well-accepted definition of triptan failure is needed in clinical practice and for research. The primary aim of the present Consensus was to provide a definition of triptan failure. To develop this definition, we deemed necessary to develop as first a consensus definition of effective treatment of an acute migraine attack and of triptan-responder. Main body: The Consensus process included a preliminary literature review, a Delphi round and a subsequent open discussion. According to the Consensus Panel, effective treatment of a migraine attack is to be defined on patient well-being featured by a) improvement of headache, b) relief of non-pain symptoms and c) absence of adverse events. An attack is considered effectively treated if patient’s well-being, as defined above, is restored within 2 hours and for at least 24 hours. An individual with migraine is considered as triptan-responder when the given triptan leads to effective acute attack treatment in at least three out of four migraine attacks. On the other hand, an individual with migraine is considered triptan non-responder in the presence of failure of a single triptan (not matching the definition of triptan-responder). The Consensus Panel defined an individual with migraine as triptan-resistant in the presence of failure of at least 2 triptans; triptan refractory, in the presence of failure to at least 3 triptans, including subcutaneous formulation; triptan ineligibile in the presence of an acknowledged contraindication to triptan use, as specified in the summary of product characteristics. Conclusions: The novel definitions can be useful in clinical practice for the assessment of acute attack treatments patients with migraine. They may be helpful in identifying people not responding to triptans and in need for novel acute migraine treatments. The definitions will also be of help in standardizing research on migraine acute care.
Published: 2022

4. ESO guideline for the management of extracranial and intracranial artery dissection

Author: Stéphanie Debette, Alessandro Pezzini, Stefan T. Engelter, Mikael Mazighi, Isabella Canavero, Julien Haemmerli, Anna Bersano, Philippe Bijlenga, Avtar Lal, Marcel Arnold, David J. Seiffge, Kaori Miwa, Masatoshi Koga, Hugh S. Markus, Sabrina Schilling, Piotr Tekiela, Janika Kõrv, Jennifer J. Majersik, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), FHU NeuroVasc [Site Sainte-Anne, Paris] (GHU-PPN), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Faculté de médecine [Genève], University of Brescia, National Cerebral and Cardiovascular Center (NCCC - OSAKA), Osaka University [Osaka], Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Tartu, Tartu University Hospital [Tartu, Estonia], University of Utah, University of Bern, University of Cambridge [UK] (CAM), and University of Basel (Unibas)
Subjects: medicine.medical_specialty, Subarachnoid hemorrhage, medicine.medical_treatment, Population, 030204 cardiovascular system & hematology, Guidelines, Extracranial artery dissection, Cervical artery dissection, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Endovascular treatment, cardiovascular diseases, Intensive care medicine, education, Stroke, education.field_of_study, Aspirin, business.industry, Anticoagulants, Thrombolysis, Guideline, medicine.disease, 3. Good health, Clinical trial, Intracranial artery dissection, Observational study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Cardiology and Cardiovascular Medicine, business, Mechanical thrombectomy, 030217 neurology & neurosurgery
Abstract: International audience; The aim of the present European Stroke Organisation guideline is to provide clinically useful evidence-based recommendations on the management of extracranial artery dissection (EAD) and intracranial artery dissection (IAD). EAD and IAD represent leading causes of stroke in the young, but are uncommon in the general population, thus making it challenging to conduct clinical trials and large observational studies. The guidelines were prepared following the Standard Operational Procedure for European Stroke Organisation guidelines and according to GRADE methodology. Our four recommendations result from a thorough analysis of the literature comprising two randomized clinical trials (RCTs) comparing anticoagulants to anti-platelets in the acute phase of ischemic stroke and twenty-six comparative observational studies. In EAD patients with acute ischemic stroke we recommend using intravenous thrombolysis (IVT) with alteplase within 4.5 hours of onset if standard inclusion/exclusion criteria are met, and mechanical thrombectomy in patients with large vessel occlusion of the anterior circulation. We further recommend early endovascular or surgical intervention for IAD patients with subarachnoid hemorrhage (SAH). Based on evidence from two phase 2 RCTs that have shown no difference between the benefits and risks of anticoagulants versus anti-platelets in the acute phase of symptomatic EAD, we strongly recommend that clinicians can prescribe either option. In post-acute EAD patients with residual stenosis or dissecting aneurysms and in symptomatic IAD patients with an intracranial dissecting aneurysm and isolated headache, there is insufficient data to provide a recommendation on the benefits and risks of endovascular/surgical treatment. Finally, nine expert consensus statements, adopted by 8 to 11 of the 11 experts involved, propose guidance for clinicians when the quality of evidence was too low to provide recommendations. Some of these pertain to the management of IAD (use of IVT, endovascular treatment, and antiplatelets versus anticoagulation in IAD with ischemic stroke and use of endovascular or surgical interventions for IAD with headache only). Other expert consensus statements address the use of direct anticoagulants and dual antiplatelet therapy in EAD-related cerebral ischemia, endovascular treatment of the EAD/IAD lesion and multidisciplinary assessment of the best therapeutic approaches in specific situations.
Published: 2021

5. ARIA‐EAACI care pathways for allergen immunotherapy in respiratory allergy

Author: Bousquet, Jean, Pfaar, Oliver, Agache, Ioana, Bedbrook, Anna, Akdis, Cezmi A, Canonica, Giorgio Walter, Chivato, Tomas, Al-Ahmad, Mona, Rasib, A. H. Abdul, Ansotegui, Ignacio J, Bachert, Claus, Soto-Martinez, Manuel, Laune, Daniel, Casale, Tomas, Levin, Michael, Larenas-Linnemann, Désirée, Samolinski, Boleslaw, Lodrup Carlsen, Karin C, O'Mahony, Liam, Lombardi, Carlo, Riggioni, Carmen, Hossny, Elham, Barata, Luís Taborda, Lourenço, Olga, Devillier, Philippe, Mahboub, Bassam, Malling, Hans-Jørgen, Sheikh, Aziz, Manning, Patrick, Passalacqua, Giovanni, Marshall, Gailen D, Sanchez-Borges, Mario, Toppila-Salmi, Sanna, Melén, Erik, Fokkens, Wytske J, Meltzer, Eli O, Miculinic, Neven, Soto-Quiros, Manuel, Milenkovic, Branislava, Roberts, Graham, Ohta, Ken, Scichilone, Nicola, Moin, Mostafa, Odemyr, Mikaëla, Montefort, Stephen, Almeida, Mário Morais, Bom, Ana Todo, Mortz, Charlotte G, Serpa, Faradiba S, Patella, Vincenzo, Sova, Milan, Mösges, Ralph, Mullol, Joaquim, Namazova Baranova, Leyla, Tsiligianni, Ioanna, Neffen, Hugo, Bjermer, Leif, Rodriguez-Gonzales, Monica, Torres, Maria J, Okamoto, Yoshitaka, Okubo, Kimi, Pajno, Giovanni B, Baharuddin, Abdullah, Cecchi, Lorenzo, Sastre, Joaquin, Untersmayr, Eva, Pawankar, Ruby, Pham-Thi, Nhân, Plavec, Davor, Cardona, Victoria, Dokic, Dejan, Sisul, Juan Carlos, Rosario, Nelson, Rottem, Menachem, Rouadi, Philip W, Del Giacco, Stefano, Fonseca, Joao A, Schwarze, Jürgen, Scadding, Glenis K, Shamji, Mohamed H, Schmid-Grendelmeier, Peter, Niedoszytko, Marek, Valentin-Rostan, Marylin, Sofiev, Mikhail, Solé, Dirceu, Sooronbaev, Talant, Palkonen, Susanna, Urrutia-Pereira, Marilyn, Skypala, Isabel, Suppli-Ulrik, Charlotte, Bonini, Matteo, Popov, Todor A, Tomazic, Peter-Valentin, Valero, Antonio, Cepeda Sarabia, Alfonso M, Ryan, Dermot, Bosnic-Anticevich, Sinthia, Valiulis, Arunas, Durham, Stephen L, Schünemann, Holger, Kalayci, Omer, Valovirta, Erkka, Panzner, Petr, Vandenplas, Olivier, Ventura, Maria Teresa, Gotua, Maia, Vichyanond, Pakit, Chkhartishvili, Ekaterine, Wagenmann, Martin, Fontaine, Jean-François, Kull, Inger, Wallace, Dana, Recto, Marysia, Walusiak-Skorupa, Jolanta, Wang, De Yun, Hrubiško, Martin, Waserman, Susan, Ebisawa, Motohiro, Bosse, Isabelle, Grisle, Ineta, Wong, Gary Wk, Bindslev-Jensen, Carsten, Yorgancioglu, Arzu, Yusuf, Osman M, Khaitov, Musa, Zernotti, Mario, Gawlik, Radoslaw, Chu, Derek K, Irani, Carla, Zhang, Luo, Zidarn, Mihaela, Zuberbier, Torsten, Kuna, Piotr, Jutel, Marek, Guzmán, Maria Antonieta, El-Gamal, Yehia, Klimek, Ludger, Brough, Helen A, Brussino, Luisa, Calderon, Moises A, Caraballo, Luis, O'Hehir, Robyn E, Gelincik, Asli, Kvedariene, Violeta, Cirule, Ieva, Cruz, Alvaro A, Czarlewski, Wienczyslawa, Nekam, Kristof, Papadopoulos, Nikolaos G., Haahtela, Tari, Emuzyte, Regina, Gamkrelidze, Amiran, Fauquert, Jean Luc, Palomares, Oscar, Regateiro, Frederico S, Ivancevich, Juan Carlos, Gemicioglu, Bilun, Gereda, Jose E, Gerth van Wijk, Roy, Bergmann, Karl-Christian, Knol, Edward, Halken, Susanne, Heffler, Enrico, Hoffmann-Sommergruber, Karin, Martins, Pedro Carreiro, Kritikos, Vicky, Ispayeva, Zhanat, Julge, Kaja, Kaidashev, Igor, Demoly, Pascal, Kowalski, Marek, Kraxner, Helga, Ollert, Markus, Fiocchi, Alessandro, Lauerma, Antti, Lau, Susanne, Park, Hae-Sim, Gomez, R Maximiliano, Comprehensive Health Research Centre (CHRC) - pólo NMS, Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), uBibliorum, Bousquet J., Pfaar O., Agache I., Bedbrook A., Akdis C.A., Canonica G.W., Chivato T., Al-Ahmad M., Abdul Latiff A.H., Ansotegui I.J., Bachert C., Baharuddin A., Bergmann K.-C., Bindslev-Jensen C., Bjermer L., Bonini M., Bosnic-Anticevich S., Bosse I., Brough H.A., Brussino L., Calderon M.A., Caraballo L., Cardona V., Carreiro-Martins P., Casale T., Cecchi L., Cepeda Sarabia A.M., Chkhartishvili E., Chu D.K., Cirule I., Cruz A.A., Czarlewski W., del Giacco S., Demoly P., Devillier P., Dokic D., Durham S.L., Ebisawa M., El-Gamal✝ Y., Emuzyte R., Gamkrelidze A., Fauquert J.L., Fiocchi A., Fokkens W.J., Fonseca J.A., Fontaine J.-F., Gawlik R., Gelincik A., Gemicioglu B., Gereda J.E., Gerth van Wijk R., Gomez R.M., Gotua M., Grisle I., Guzman M.-A., Haahtela T., Halken S., Heffler E., Hoffmann-Sommergruber K., Hossny E., Hrubisko M., Irani C., Ivancevich J.C., Ispayeva Z., Julge K., Kaidashev I., Kalayci O., Khaitov M., Klimek L., Knol E., Kowalski M.L., Kraxner H., Kull I., Kuna P., Kvedariene V., Kritikos V., Lauerma A., Lau S., Laune D., Levin M., Larenas-Linnemann D.E., Lodrup Carlsen K.C., Lombardi C., Lourenco O.M., Mahboub B., Malling H.-J., Manning P., Marshall G.D., Melen E., Meltzer E.O., Miculinic N., Milenkovic B., Moin M., Montefort S., Morais-Almeida M., Mortz C.G., Mosges R., Mullol J., Namazova Baranova L., Neffen H., Nekam K., Niedoszytko M., Odemyr M., O'Hehir R.E., Ollert M., O'Mahony L., Ohta K., Okamoto Y., Okubo K., Pajno G.B., Palomares O., Palkonen S., Panzner P., G Papadopoulos N., Park H.-S., Passalacqua G., Patella V., Pawankar R., Pham-Thi N., Plavec D., Popov T.A., Recto M., Regateiro F.S., Riggioni C., Roberts G., Rodriguez-Gonzales M., Rosario N., Rottem M., Rouadi P.W., Ryan D., Samolinski B., Sanchez-Borges✝ M., Serpa F.S., Sastre J., Scadding G.K., Shamji M.H., Schmid-Grendelmeier P., Schunemann H.J., Sheikh A., Scichilone N., Sisul J.C., Sofiev M., Sole D., Sooronbaev T., Soto-Martinez M., Soto-Quiros M., Sova M., Schwarze J., Skypala I., Suppli-Ulrik C., Taborda-Barata L., Todo-Bom A., Torres M.J., Valentin-Rostan M., Tomazic P.-V., Valero A., Toppila-Salmi S., Tsiligianni I., Untersmayr E., Urrutia-Pereira M., Valiulis A., Valovirta E., Vandenplas O., Ventura M.T., Vichyanond P., Wagenmann M., Wallace D., Walusiak-Skorupa J., Wang D.Y., Waserman S., Wong G.W.K., Yorgancioglu A., Yusuf O.M., Zernotti M., Zhang L., Zidarn M., Zuberbier T., Jutel M., HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, University of Helsinki, Department of Pathology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Philipps Universität Marburg = Philipps University of Marburg, Transilvania University of Brasov, Universität Zürich [Zürich] = University of Zurich (UZH), Humanitas University [Milan] (Hunimed), Universidad San Pablo CEU, Kuwait University, Al-Rashed Allergy Center [Kuwait City], Pantai Hospital [Kuala Lumpur], Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Sun Yat-Sen University [Guangzhou] (SYSU), Universiti Sains Malaysia (USM), Humboldt University Of Berlin, Berlin Institute of Health (BIH), Odense University Hospital (OUH), Skane University Hospital [Lund], Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Woolcock Institute of Medical Research [Sydney], The University of Sydney, Guy's and St Thomas' Hospital [London], King‘s College London, Università degli studi di Torino = University of Turin (UNITO), University of Cartagena, Vall d'Hebron University Hospital [Barcelona], Centro Hospitalar de Lisboa Central E.P.E, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA)-Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), University of South Florida [Tampa] (USF), Azienda Usl Toscana centro [Firenze], Universidad Simon Bolivar (USB), David Tvildiani Medical University (DTMU), McMaster University [Hamilton, Ontario], Children's Clinical University Hospital [Riga, Latvia] (CCUH), Universidade Federal da Bahia (UFBA), Università degli Studi di Cagliari = University of Cagliari (UniCa), Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Foch [Suresnes], Sagamihara National Hospital [Kanagawa, Japan], Université Ain Shams, Vilnius University [Vilnius], CHU Clermont-Ferrand, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Universidade do Porto = University of Porto, Silesian Medical University, Katowice, Poland, Cerrahpasa Faculty of Medicine, Istanbul University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universidad de Chile = University of Chile [Santiago] (UCHILE), Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Medizinische Universität Wien = Medical University of Vienna, Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), Tartu University Hospital [Tartu, Estonia], Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Hacettepe University = Hacettepe Üniversitesi, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Siriraj Hospital, Mahidol University, Mahidol University [Bangkok], Nova Southeastern University (NSU), Nofer Institute of Occupational Medicine (NIOM), National University of Singapore (NUS), Yong Loo Lin School of Medicine [Singapore], The Chinese University of Hong Kong [Hong Kong], Manisa Celal Bayar University, Universidad Nacional de Villa María, Universidad Católica de Córdoba, Beijing Tongren Hospital, Herrada, Anthony, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, and UCL - (MGD) Service de pneumologie
Subjects: Pulmonary and Respiratory Medicine, precision medicine, education, Immunology, Review, Settore MED/10 - Malattie Dell'Apparato Respiratorio, immune system diseases, HDE ALER, allergic rhinitis, asthma, immunotherapy, Medicine and Health Sciences, Immunology and Allergy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, ComputingMilieux_MISCELLANEOUS, Rhinitis, RC581-607, respiratory tract diseases, 3121 General medicine, internal medicine and other clinical medicine, Immunologic diseases. Allergy, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, allergic rhinitis, asthma, immunotherapy, precision medicine
Abstract: Funding Information: BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. Funding Information: NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. Funding Information: CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith‐Kline, advisory role in scibase. Funding Information: MJTreports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. Funding Information: LK reports grants and personal fees from Allergopharma, MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quintiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. Funding Information: DPreports grants and personal fees from GlaxoSmithKline, personal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, personal fees and non‐financial support from Boehringer Ingelheim, non‐financial support from Philips. Funding Information: OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Pohl‐Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. publishersversion published
Published: 2021

6. Bronchodilator response and lung function decline:Associations with exhaled nitric oxide with regard to sex and smoking status

Author: Thorainn Gislasson, Angelo Corsico, Simone Accordini, Dennis Nowak, Joost Weyler, Rune Nielsen, Össur Ingi Emilsson, Isabelle Pin, Deborah Jarvis, Vivi Schlunnsen, Elisabet Nerpin, Francisco Gómez Real, Christer Janson, José Antonio Gullón, Diogenes S. Ferreira, Giulia Squillacioti, Andrei Malinovschi, Joachim Heinrich, Rain Jõgi, Ane Johannessen, Anna-Carin Olin, Bertil Forsberg, Chantal Raherison Semjen, Antonio Pereira-Vega, Alessandro Marcon, Pascal Demoly, Isabel Urrutia, Judith Garcia-Aymerich, Mario Olivieri, Commission of the European Communities, Uppsala University, Dalarna University, School of Public Health and Preventive Medicine [Melbourne, Australia], Universidade Federal do Parana [Curitiba] (UFPR), Universidade Federal do Paraná (UFPR), University of Antwerp (UA), Aarhus University [Aarhus], Tartu University Hospital [Tartu, Estonia], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Université de Montpellier (UM), Epidemiology of Allergic and Respiratory Diseases Department [Paris] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ludwig-Maximilians University [Munich] (LMU), German Research Center for Environmental Health - Helmholtz Center München (GmbH), University of Melbourne, German Center for Lung Research, Foundation IRCCS Policlinico San Matteo, University of Pavia, University of Verona (UNIVR), University of Turin, Haukeland University Hospital, University of Bergen (UiB), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Galdakao Hospital, Hospital Juan Ramón Jiménez, University of Gothenburg (GU), Umeå University, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Imperial College London
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.drug_class, Bronchodilatation, Epidemiology, FeNO, Lung function, Respiratory Medicine and Allergy, Immunology, Article, 03 medical and health sciences, FEV1/FVC ratio, 0302 clinical medicine, Bronchodilator, Internal medicine, medicine, Immunology and Allergy, 030223 otorhinolaryngology, Respiratory health, Asthma, Lungmedicin och allergi, business.industry, 1103 Clinical Sciences, RC581-607, respiratory system, medicine.disease, 3. Good health, respiratory tract diseases, 030228 respiratory system, Feno, Lung Function, Exhaled nitric oxide, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Smoking status, Human medicine, Immunologic diseases. Allergy, business
Abstract: Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients.The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. Results: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p¼0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p ¼ 0.001) and females (p ¼ 0.001) in stratified analyses. Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. Conclusions: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects. The coordination of ECRHS III was supported by the Medical Research Council (Grant Number 92091).We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.
Published: 2021

7. Cumulative Occupational Exposures and Lung Function Decline in Two Large General Population Cohorts

Author: Josep M. Antó, Deborah Jarvis, Roberto Bono, Simona Villani, Dennis Nowak, Hayat Bentouhami, Jan Paul Zock, Bénédicte Leynaert, Theodore Lytras, Kjell Torén, Isabel Urrutia, Joachim Heinrich, Bertil Forsberg, Isabelle Pin, Joost Weyler, Chantal Raherison Semjen, Jesús Martínez-Moratalla, Vivi Schlünssen, Giulia Squillacioti, Dirk Keidel, Nicole Probst-Hensch, Øistein Svanes, Torben Sigsgaard, Rain Jõgi, Pascal Demoly, Mathias Holm, Paul D. Blanc, Antonio Pereira Vega, John Watkins, Mario Olivieri, Amar Mehta, Anne-Elie Carsin, Anna Beckmeyer-Borowko, David Vernez, Thorarinn Gislason, Dan Norbäck, Roel Vermeulen, José Antonio Gullón, Manolis Kogevinas, Geza Benke, A. Sonia Buist, Hans Kromhout, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Utrecht University [Utrecht], University of Antwerp (UA), Klinikum der Universitat Munchen, Ludwig-Maximilians-Universität München (LMU), German Center for Lung Research, Galdakao Hospital, Complejo Hospitalario Universitario de Albacete, Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Hospital Juan Ramón Jiménez, Cancer environnement (EPICENE ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine aiguë spécialisée, CHU Grenoble-Hôpital Michallon, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Università degli Studi di Pavia = University of Pavia (UNIPV), Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], University of Bergen (UiB), Sahlgrenska University Hospital [Gothenburg], Umeå University, Uppsala University, University of Copenhagen = Københavns Universitet (UCPH), Université de Lausanne = University of Lausanne (UNIL), Monash University [Melbourne], Tartu University Hospital [Tartu, Estonia], Sahlgrenska Academy at University of Gothenburg [Göteborg], Aarhus University [Aarhus], Università degli studi di Verona = University of Verona (UNIVR), University of California [San Francisco] (UC San Francisco), University of California (UC), Cardiff University, Università degli studi di Torino = University of Turin (UNITO), Oregon Health and Science University [Portland] (OHSU), Imperial College London, and Herrada, Anthony
Subjects: longitudinal studies, lung function, occupational disease, occupational exposure, spirometry, Vital Capacity, Spirometry, Lung function, Occupational Exposure, Occupational Disease, Longitudinal studies, VENTILATORY FUNCTION, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Occupational Exposure, Cohort Studies, 0302 clinical medicine, Forced Expiratory Volume, Medicine, 030212 general & internal medicine, Lung, MESH: Cohort Studies, Original Research, RISK, education.field_of_study, medicine.diagnostic_test, WORKERS, Occupational Diseases, SWISS, Occupational exposure, BURDEN, Adult, MESH: Occupational Diseases, Pulmonary and Respiratory Medicine, MESH: Bayes Theorem, Population, AMERICAN THORACIC SOCIETY, Occupational disease, MEDLINE, MESH: Forced Expiratory Volume, OBSTRUCTIVE PULMONARY-DISEASE, 03 medical and health sciences, Environmental health, Humans, COPD, MESH: Lung, education, MESH: Humans, business.industry, Bayes Theorem, MESH: Adult, AIR-POLLUTION, MESH: Vital Capacity, medicine.disease, respiratory tract diseases, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Human medicine, business, FOLLOW-UP
Abstract: International audience; Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.
Published: 2021

8. Regulatory landscape of providing information on newborn screening to parents across Europe

Author: Franková, Věra, Driscoll, Riona O., Jansen, Marleen E., Loeber, J. Gerard, Kožich, Viktor, Bonham, James, Borde, Patricia, Brincat, Ian, Cheillan, David, Dekkers, Eugenie, Fingerhut, Ralph, Kuš, Iva Bilandžija, Girginoudis, Panagiotis, Groselj, Urh, Hougaard, David, Knapková, Mária, la Marca, Giancarlo, Malniece, Ieva, Nanu, Michaela Iuliana, Nennstiel, Uta, Olkhovych, Nataliia, Oltarzewski, Mariusz, Pettersen, Rolf D., Racz, Gabor, Reinson, Karit, Salimbayeva, Damilya, Songailiene, Jurgita, Vilarinho, Laura, Vogazianos, Marios, Zetterström, Rolf H., Zeyda, Maximilian, Members of the European Society of Human Genetics (ESHG)-EuroGentest Quality Sub-Committee, CarMeN, laboratoire, First Faculty of Medicine Charles University [Prague], National Institute for Public Health and the Environment [Bilthoven] (RIVM), International Society for Neonatal Screening Office [Bilthoven, The Netherlands] (ISNSO), Sheffield Children's NHS Foundation Trust, Mater Dei Hospital [Malta], Hospices Civils de Lyon (HCL), University Children’s Hospital Zurich, University Hospital Centre Zagreb, Partenaires INRAE, Institute of Child Health [Athens, Greece], University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Statens Serum Institute [Copenhagen], Matej Bel University (UMB), Children's University Hospital [Banska Bystrica, Slovakia] (CUH-BB), Azienda Ospedaliero Universitaria A. Meyer [Firenze, Italy], Children's Clinical University Hospital [Riga, Latvia] (CCUH), National Institute for Mother & Child Health [Bucharest, Romania] (NIMCH), Bavarian Health and Food Safety Authority [Oberschleißheim, Germany], National Children's Specialized Hospital 'Okhmatdyt' [Kiev, Ukraine] (NCSHO), National Research Institute of Mother and Child [Warsaw, Poland], Oslo University Hospital [Oslo], University of Szeged [Szeged], Tartu University Hospital [Tartu, Estonia], Scientific centre of Gynaecology, Obstetrics and Perinatology [Almaty, Kazakhstan] (SGOP), International Science and Technology Center [Almaty, Kazakhstan] ( ISTC), Vilnius University [Vilnius], Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Limassol General Hospital, Karolinska University Hospital [Solna, Sweden] (KUH), Medizinische Universität Wien = Medical University of Vienna, Human genetics, and APH - Quality of Care
Subjects: Male, Parents, European level, Best practice, [SDV]Life Sciences [q-bio], MEDLINE, Disclosure, Guidelines, Article, Public healthcare, 03 medical and health sciences, Neonatal Screening, 0302 clinical medicine, Surveys and Questionnaires, 030225 pediatrics, Genetics, Humans, European Union, Genetic Testing, 030212 general & internal medicine, Genetics (clinical), Medical education, Newborn screening, Infant, Newborn, food and beverages, Organizational Policy, 3. Good health, Doenças Genéticas, Europe, [SDV] Life Sciences [q-bio], Practice Guidelines as Topic, embryonic structures, Female, Sample collection, Business, Newborn Screening
Abstract: Newborn screening (NBS) is an important part of public healthcare systems in many countries. The provision of information to parents about NBS is now recognised as an integral part of the screening process. Informing parents on all aspects of screening helps to achieve the benefits, promote trust and foster support for NBS. Therefore, policies and guidelines should exist to govern how the information about NBS is provided to parents, taking into account evidence-based best practices. The purpose of our survey was to explore whether any legally binding provisions, guidelines or recommendations existed pertaining to the provision of information about NBS to parents across Europe. Questions were designed to determine the regulatory process of when, by whom and how parents should be informed about screening. Twenty-seven countries participated in the survey. The results indicated that most countries had some sort of legal framework or guidelines for the provision of information to parents. However, only 37% indicated that the provision of information was required prenatally. The majority of countries were verbally informing parents with the aid of written materials postnatally, just prior to sample collection. Information was provided by a neonatologist, midwife or nurse. A website dedicated to NBS was available for 67% of countries and 89% had written materials about NBS for parents. The survey showed that there is a lack of harmonisation among European countries in the provision of information about NBS and emphasised the need for more comprehensive guidelines at the European level. Institutional support was provided by projects LM2018132 from the Large Infrastructure Projects of the Czech Ministry of Education, PROGRES Q26 from Charles University and RVO VFN 64165 from the Ministry of Health, Czech Republic. Several authors of this publication are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN)—Project ID No. 739543. info:eu-repo/semantics/publishedVersion
Published: 2021

9. Cohort profile : effective Perinatal Intensive Care in Europe (EPICE) very preterm birth cohort

Author: Zeitlin, J, Maier, RF, Cuttini, M, Aden, U, Boerch, K, Gadzinowski, J, Jarreau, P-H, Lebeer, J, Norman, M, Pedersen, P, Petrou, S, Pfeil, JM, Toome, L, van Heijst, A, van Reempts, P, Varendi, H, Barros, H, Groups, EPICE and SHIPS Research, Sarrechia, Iemke, EPICE Reseach Group, SHIPS Research Group, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DHU Risques Et Grossesse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Philipps Universität Marburg = Philipps University of Marburg, IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Department of Women's and Children's Health [Stockholm, Sweden], Karolinska University Hospital [Stockholm], Copenhagen University Hospital Hvidovre [Hvidovre, Danemark], University of Copenhagen = Københavns Universitet (UCPH), Poznan University of Medical Sciences [Poland] (PUMS), Department of Primary & Interdisciplinary Care, Disability Studies [Antwerpen, Belgium] (Faculty of Medicine), University of Antwerp (UA), Department of Clinical Science, Intervention and Technology [Stockholm, Sweden], Karolinska Institutet [Stockholm], Aalborg University [Denmark] (AAU), Warwick Medical School, University of Warwick [Coventry], Nuffield Department of Primary Care Health Sciences, University of Oxford, University of Oxford, European Foundation for the Care of Newborn Infants [Munich, Germany] (EFCNI), Tallinn Children's Hospital [Tallinn, Estonia], University of Tartu, Radboud University Medical Center [Nijmegen], Antwerp University Hospital [Edegem] (UZA), Study Centre for Perinatal Epidemiology [Brussels, Belgium] (SCPE), Tartu University Hospital [Tartu, Estonia], Instituto de Saúde Pública da Universidade do Porto [Porto, Portugal] (ISPUP), Universidade do Porto = University of Porto, University of Leicester, EPICE and SHIPS Research Group: J Lebeer, P Van Reempts, E Bruneel, E Cloet, A Oostra, E Ortibus, I Sarrechia, K Boerch, L Huusom, P Pedersen, T Weber, L Toome, H Varendi, M Männamaa, P Y Ancel, A Burguet, P H Jarreau, V Pierrat, P Truffert, R F Maier, M Zemlin, B Misselwitz, S Schmidt, L Wohlers, M Cuttini, D Di Lallo, G Ancora, D Baronciani, V Carnielli, I Croci, G Faldella, F Ferrari, F Franco, G Gargano, A van Heijst, C Koopman-Esseboom, J Gadzinowski, J Mazela, A Montgomery, T Pikuła, H Barros, R Costa, L Mendes Graça, M do Céu Machado, C Rodrigues, T Rodrigues, U Aden, A K Edstedt Bonamy, M Norman, E S Draper, E M Boyle, A Fenton, S J Johnson, B N Manktelow, D W A Milligan, S Mader, N Thiele, J M Walz, S Petrou, J Zeitlin, M Bonet, C Bonnet, R El Raffei, A Piedvache, A V Seppanen, PHILIBERT, Marianne, Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Philipps University of Marburg, University of Copenhagen = Københavns Universitet (KU), University of Oxford [Oxford], and Universidade do Porto
Subjects: Critical Care, [SDV]Life Sciences [q-bio], Infant, Newborn, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Cohort Studies, Europe, [SDV] Life Sciences [q-bio], Perinatal Care, Treatment Outcome, Pregnancy, Infant, Extremely Premature, Humans, Premature Birth, Female, Human medicine, Cohort Profiles, ComputingMilieux_MISCELLANEOUS
Abstract: Contains fulltext : 220753.pdf (Publisher’s version ) (Open Access)
Published: 2020

10. International severe asthma registry (ISAR): protocol for a global registry

Author: Eileen Wang, Trung N. Tran, Marianna Alacqua, Todor A. Popov, Ruth Murray, George Christoff, Lauri Lehtimäki, Chris A. Price, Mohsen Sadatsafavi, James Zangrilli, Naeimeh Hosseini, Andrew Menzies-Gow, John Busby, Luis Perez-de-Llano, Mariko Siyue Koh, Unnur S. Bjornsdottir, Guy Brusselle, Paul E Pfeffer, Vibeke Backer, Michael E. Wechsler, Mark Hew, Anke H. Maitland-van der Zee, Peter G. Gibson, Alan Altraja, Lakmini Bulathsinhala, Dora Ludviksdottir, Celeste Porsbjerg, Liam G Heaney, Richard W. Costello, Enrico Heffler, Rupert Jones, Leif Bjermer, Yuji Tohda, Borja G. Cosío, Nikolaos G. Papadopoulos, J. Mark FitzGerald, Giorgio Walter Canonica, Chin Kook Rhee, Victoria Carter, Neva Eleangovan, Takashi Iwanaga, Isha Chaudhry, You Sook Cho, Arnaud Bourdin, Matthew J. Peters, David Price, Thao Le, David A. Jackson, Epidemiology, Pulmonary Medicine, The Lung Centre Vancouver General Hospital, UBC Institute for Heart and Lung Health, Vancouver, BC, AstraZeneca, Gaithersburg, MD, USA, AstraZeneca, Luton, United Kingdom of Great Britain and Northern Ireland., Department of Pulmonary Medicine, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia, Center of Physical Activity Research, Rigshospitalet and Copenhagen University, Copenhagen, Denmark., Department of Respiratory Medicine & Allergology, Skåne University Hospital, Lund, Sweden, Faculty of Medicine, University of Iceland, Reykjavik, Iceland, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ghent University Hospital, Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Queen's University [Belfast] (QUB), Dipartimento di Scienze Mediche, Università degli studi di Torino (UNITO), Department of Electrical and Computer Engineering [Houston], University of Houston, Royal Brompton Hospital, Lung Division, London, United Kingdom of Great Britain and Northern Ireland., MedScript Ltd, UPC Research Laboratories, Allergy Department, Institute for Nuclear Research and Nuclear Energy (INRNE), Académie des sciences de Bulgarie, Aberystwyth University, Division of Infection and Immunity, School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff], Tampere University, Department of Respiratory medicine, Dermatology and Allergology, Clinical Medicine, Pulmonology, Paediatric Pulmonology, AII - Inflammatory diseases, APH - Personalized Medicine, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, and University of Iceland
Subjects: Severe asthma, Epidemiology, [SDV]Life Sciences [q-bio], Delphi method, Health informatics, 0302 clinical medicine, DESIGN, Health care, Medicine and Health Sciences, Protocol, Registries, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, lcsh:R5-920, OUTCOMES, education.field_of_study, 030503 health policy & services, Pharmacoepidemiology, Astmi, 3142 Public health care science, environmental and occupational health, 3. Good health, SAFETY, Medical emergency, lcsh:Medicine (General), 0305 other medical science, Research Article, Adult, Adolescent, Population, PHENOTYPES, Health Informatics, 03 medical and health sciences, Disease registry, Skráning gagna, Pharmacovigilance, medicine, Humans, education, Disease burden, TO-TREAT ASTHMA, MEPOLIZUMAB, business.industry, medicine.disease, Asthma, EXACERBATIONS, DEFINITION, Real-world, HEALTH-CARE, business, COSTS
Abstract: Publisher's version (útgefin grein), Background: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour. Methods: ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC; comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (=18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR's collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics and Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders. Conclusions: ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally., The International Severe Asthma Registry is conducted by Optimum Patient Care Global Limited, and co-funded by Optimum Patient Care Global Limited and AstraZeneca. ISAR is supported by grants from AstraZeneca and Optimum Patient Care (OPC) Global (a not-for-profit social enterprise). The ISAR steering committee (ISC) was involved in the development of the protocol and is responsible for approving research proposals via a democratic voting process. In addition to 47 clinicians and researchers with an interest and experience in severe asthma, the ISC also includes members of OPC and four medical experts from AstraZeneca. AstraZeneca reviewed the draft before submission; however, decision to submit was made by the authors. Medical writing support was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3).
Published: 2020

11. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19

Author: Bastard, P., Rosen, L. B., Zhang, Q., Michailidis, E., Hoffmann, H. -H., Zhang, Y., Dorgham, K., Philippot, Q., Rosain, J., Beziat, V., Manry, J., Shaw, E., Haljasmagi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A. A., Belot, A., Kallaste, A., Catherinot, E., Tandjaoui-Lambiotte, Y., Le Pen, J., Kerner, G., Bigio, B., Seeleuthner, Y., Yang, R., Bolze, A., Spaan, A. N., Delmonte, O. M., Abers, M. S., Aiuti, A., Casari, G., Lampasona, V., Piemonti, L., Ciceri, F., Bilguvar, K., Lifton, R. P., Vasse, M., Smadja, D. M., Migaud, M., Hadjadj, J., Terrier, B., Duffy, D., Quintana-Murci, L., van de Beek, D., Roussel, L., Vinh, D. C., Tangye, S. G., Haerynck, F., Dalmau, D., Martinez-Picado, J., Brodin, P., Nussenzweig, M. C., Boisson-Dupuis, S., Rodriguez-Gallego, C., Vogt, G., Mogensen, T. H., Oler, A. J., Gu, J., Burbelo, P. D., Cohen, J. I., Biondi, A., Bettini, L. R., Dangio, M., Bonfanti, P., Rossignol, P., Mayaux, J., Rieux-Laucat, F., Husebye, E. S., Fusco, F., Ursini, M. V., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Castagnoli, R., Montagna, D., Licari, A., Marseglia, G. L., Duval, X., Ghosn, J., Tsang, J. S., Goldbach-Mansky, R., Kisand, K., Lionakis, M. S., Puel, A., Zhang, S. -Y., Holland, S. M., Gorochov, G., Jouanguy, E., Rice, C. M., Cobat, A., Notarangelo, L. D., Abel, L., H. C., Su, Casanova, J. -L., Arias, A. A., Boisson, B., Boucherit, S., Bustamante, J., Chbihi, M., Chen, J., Chrabieh, M., Kochetkov, T., Le Voyer, T., Liu, D., Nemirovskaya, Y., Ogishi, M., Papandrea, D., Patissier, C., Rapaport, F., Roynard, M., Vladikine, N., Woollett, M., Zhang, P., Kashyap, A., Ding, L., Bosticardo, M., Wang, Q., Ochoa, S., Liu, H., Chauvin, S. D., Stack, M., Koroleva, G., Bansal, N., Dalgard, C. L., Snow, A. L., Abad, J., Aguilera-Albesa, S., Akcan, O. M., Darazam, I. A., Aldave, J. C., Ramos, M. A., Nadji, S. A., Alkan, G., Allardet-Servent, J., Allende, L. M., Alsina, L., Alyanakian, M. -A., Amador-Borrero, B., Amoura, Z., Antoli, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H. B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinieres, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, M., Borie, R., Bousfiha, A. A., Bouvattier, C., Boyarchuk, O., Bueno, M. R. P., Agra, J. J. C., Calimli, S., Capra, R., Carrabba, M., Casasnovas, C., Caseris, M., Castelle, M., Castelli, F., de Vera, M. C., Castro, M. V., Chalumeau, M., Charbit, B., Cheng, M. P., Clave, P., Clotet, B., Codina, A., Colkesen, F., Colobran, R., Comarmond, C., Corsico, A. G., Darley, D. R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Di Sabatino, A., Diehl, J. -L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M. H., Emiroglu, M., Erdeniz, E. H., Aytekin, S. E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M. F., Flores, C., Francois, B., Fumado, V., Solis, B. G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M. G., Girona-Alarcon, M., Goffard, J. -C., Gok, F., Gonzalez-Montelongo, R., Guerder, A., Gul, Y., Guner, S. N., Gut, M., Halwani, R., Hammarstrom, L., Hatipoglu, N., Hernandez-Brito, E., Holanda-Pena, M. S., Horcajada, J. P., Hraiech, S., Humbert, L., Iglesias, A. D., Inigo-Campos, A., Jamme, M., Arranz, M. J., Jordan, I., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K. K., Keles, S., Demirkol, Y. K., Klocperk, A., Krol, Z. J., Kuentz, P., Kwan, Y. W. M., Lagier, J. -C., Lau, Y. -L., Le Bourgeois, F., Leo, Y. -S., Lopez, R. L., Leung, D., Levin, M., Levy, M., Levy, R., Li, Z., Linglart, A., Lorenzo-Salazar, J. M., Louapre, C., Lubetzki, C., Luyt, C. -E., Lye, D. C., Mansouri, D., Marjani, M., Pereira, J. M., Martin, A., Pueyo, D. M., Marzana, I., Mathian, A., Matos, L. R. B., Matthews, G. V., Mege, J. -L., Melki, I., Meritet, J. -F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melian, A. M., Martinez, A. M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Munoz-Barrera, A., Nafati, C., Neves, J. F., L. F. P., Ng, Medina, Y. N., Cuadros, E. N., Gonzalo Ocejo-Vinyals, J., Orbak, Z., Oualha, M., Ozcelik, T., Hammarstrom, Q. P., Parizot, C., Pascreau, T., Paz-Artal, E., de Diego, R. P., Philippe, A., Philippota, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A. -S., Reisli, I., Ricart, P., Richard, J. -C., Rivet, N., Riviere, J. G., Blanch, G. R., Rodrigo, C., Rodriguez-Palmero, A., Romero, C. S., Rothenbuhler, A., Rozenberg, F., del Prado, M. Y. R., Riera, J. S., Sanchez, O., Sanchez-Ramon, S., Schluter, A., Schmidt, M., Schweitzer, C. E., Scolari, F., Sediva, A., Seijo, L. M., Sene, D., Senoglu, S., Seppanen, M. R. J., Ilovich, A. S., Shahrooei, M., Smadja, D., Sobh, A., Moreno, X. S., Sole-Violan, J., Soler, C., Soler-Palacin, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiottea, Y., Taupin, J. -L., Tavernier, S. J., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J. T., Trouillet-Assanta, S., Troya, J., Tucci, A., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., van Den Rym, A. M., Vandernoot, I., Vatansev, H., Velez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M. E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B. E., Yucel, F., Zannad, F., Zatz, M., Belota, A., Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M. G., Cazzaniga, M., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abela, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'Ortenzio, E., da Silveira, C., Debray, M. -P., Deplanque, D., Descamps, D., Desvallees, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Eloy, P., Enouf, V. V. E., Esperou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouenan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F. -X., Levy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J. C., Malvy, D., Mambert, M., Mentre, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puechal, O., Rosa-Calatrava, M., Rossignol, B., Roy, C., Schneider, M., Semaille, C., Mohammed, N. S., Tagherset, L., Tardivon, C., Tellier, M. -C., Teoule, F., Terrier, O., Timsit, J. -F., Treoux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Abelc, L., Alcover, A., Aschard, H., Astrom, K., Bousso, P., Bruhns, P., Cumano, A., Demangel, C., Deriano, L., Santo, J. D., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Gomperts-Boneca, I., Hasan, M., Hercberg, S., Lantz, O., Patin, E., Pellegrini, S., Pol, S., Rausell, A., Rogge, L., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M. -N., Albert, M. L., Alavoine, L., Amat, K. K. A., Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J. -L., Enouf, V., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Lucet, J. -C., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A. G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H. J., Bomers, M., Bos, L., Botta, M., de Brabander, J., Bree, G., Brouwer, M. C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M. P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S. M., Heunks, L., Hollmann, M. W., Horn, J., Hovius, J. W., de Jong, M. D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J. M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M. J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C. S., Stilma, W., Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, A. P. J., de Vries, H., van Vugt, M., Joost Wiersinga, W., Wouters, D., Zwinderman, A. H., Abelb, L., Muhsen, S. A., Al-Mulla, F., Anderson, M. S., Bogunovic, D., Bondarenko, A., Bryceson, Y., Bustamante, C. D., Butte, M., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M. A., Derisi, J. L., Desai, M., Drolet, B. A., Espinosa, S., Franco, J. L., Gregersen, P. K., Hagin, D., Heath, J., Henrickson, S. E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisanda, K., C. -L., Ku, Ling, Y., Lucas, C. L., Maniatis, T., Marodi, L., Milner, J. D., Mironska, K., Morio, T., Notarangeloa, L. D., Novelli, G., Novelli, A., O'Farrelly, C., Okada, S., Planas, A. M., Prando, C., Pujol, A., Renia, L., Renieri, A., Sancho-Shimizu, V., Sankaran, V., Barrett, K. S., Snow, A., Tangye, S., Turvey, S., Uddin, F., Uddin, M. J., Vazquez, S. E., von Bernuth, H., Washington, N., Zawadzki, P., Sua, H. C., Casanovaa, J. -L., Bastard, Paul, Rosen, Lindsey B, Zhang, Qian, Michailidis, Eleftherio, Hoffmann, Hans-Heinrich, Zhang, Yu, Dorgham, Karim, Philippot, Quentin, Rosain, Jérémie, Béziat, Vivien, Manry, Jérémy, Shaw, Elana, Haljasmägi, Lii, Peterson, Pärt, Lorenzo, Lazaro, Bizien, Lucy, Trouillet-Assant, Sophie, Dobbs, Kerry, de Jesus, Adriana Almeida, Belot, Alexandre, Kallaste, Anne, Catherinot, Emilie, Tandjaoui-Lambiotte, Yacine, Le Pen, Jeremie, Kerner, Gaspard, Bigio, Benedetta, Seeleuthner, Yoann, Yang, Rui, Bolze, Alexandre, Spaan, András N, Delmonte, Ottavia M, Abers, Michael S, Aiuti, Alessandro, Casari, Giorgio, Lampasona, Vito, Piemonti, Lorenzo, Ciceri, Fabio, Bilguvar, Kaya, Lifton, Richard P, Vasse, Marc, Smadja, David M, Migaud, Mélanie, Hadjadj, Jérome, Terrier, Benjamin, Duffy, Darragh, Quintana-Murci, Llui, van de Beek, Diederik, Roussel, Lucie, Vinh, Donald C, Tangye, Stuart G, Haerynck, Filomeen, Dalmau, David, Martinez-Picado, Javier, Brodin, Petter, 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Leo, Y, Lopez, R, Leung, D, Levin, M, Levy, M, Levy, R, Li, Z, Linglart, A, Lorenzo-Salazar, J, Louapre, C, Lubetzki, C, Luyt, C, Lye, D, Mansouri, D, Marjani, M, Pereira, J, Martin, A, Pueyo, D, Marzana, I, Mathian, A, Matos, L, Matthews, G, Mege, J, Melki, I, Meritet, J, Metin, O, Meyts, I, Mezidi, M, Migeotte, I, Millereux, M, Mirault, T, Mircher, C, Mirsaeidi, M, Melian, A, Martinez, A, Morange, P, Mordacq, C, Morelle, G, Mouly, S, Munoz-Barrera, A, Nafati, C, Neves, J, Ng, L, Medina, Y, Cuadros, E, Gonzalo Ocejo-Vinyals, J, Orbak, Z, Oualha, M, Ozcelik, T, Hammarstrom, Q, Parizot, C, Pascreau, T, Paz-Artal, E, de Diego, R, Philippe, A, Philippota, Q, Planas-Serra, L, Ploin, D, Poissy, J, Poncelet, G, Pouletty, M, Quentric, P, Raoult, D, Rebillat, A, Reisli, I, Ricart, P, Richard, J, Rivet, N, Riviere, J, Blanch, G, Rodrigo, C, Rodriguez-Palmero, A, Romero, C, Rothenbuhler, A, Rozenberg, F, del Prado, M, Riera, J, Sanchez, O, Sanchez-Ramon, S, Schluter, A, Schmidt, M, Schweitzer, C, Scolari, F, Sediva, A, Seijo, L, Sene, D, Senoglu, S, Seppanen, M, Ilovich, A, Shahrooei, M, Sobh, A, Moreno, X, Sole-Violan, J, Soler, C, Soler-Palacin, P, Stepanovskiy, Y, Stoclin, A, Taccone, F, Tandjaoui-Lambiottea, Y, Taupin, J, Tavernier, S, Thumerelle, C, Tomasoni, G, Toubiana, J, Alvarez, J, Trouillet-Assanta, S, Troya, J, Tucci, A, Uzunhan, Y, Vabres, P, Valencia-Ramos, J, van Den Rym, A, Vandernoot, I, Vatansev, H, Velez-Santamaria, V, Viel, S, Vilain, C, Vilaire, M, Vincent, A, Voiriot, G, Vuotto, F, Yosunkaya, A, Young, B, Yucel, F, Zannad, F, Zatz, M, Belota, A, Foti, G, Bellani, G, Citerio, G, Contro, E, Pesci, A, Valsecchi, M, Cazzaniga, M, Bole-Feysot, C, Lyonnet, S, Masson, C, Nitschke, P, Pouliet, A, Schmitt, Y, Tores, F, Zarhrate, M, Abela, L, Andrejak, C, Angoulvant, F, Bachelet, D, Basmaci, R, Behillil, S, Beluze, M, Benkerrou, D, Bhavsar, K, Bompart, F, Bouadma, L, Bouscambert, M, Caralp, M, Cervantes-Gonzalez, M, Chair, A, Coelho, A, Couffignal, C, Couffin-Cadiergues, S, D'Ortenzio, E, da Silveira, C, Debray, M, Deplanque, D, Descamps, D, Desvallees, M, Diallo, A, Diouf, A, Dorival, C, Dubos, F, Eloy, P, Enouf, V, Esperou, H, Esposito-Farese, M, Etienne, M, Ettalhaoui, N, Gault, N, Gaymard, A, Gigante, T, Gorenne, I, Guedj, J, Hoctin, A, Hoffmann, I, Jaafoura, S, Kafif, O, Kaguelidou, F, Kali, S, Khalil, A, Khan, C, Laouenan, C, Laribi, S, Le, M, Le Hingrat, Q, Le Mestre, S, Le Nagard, H, Lescure, F, Levy, Y, Levy-Marchal, C, Lina, B, Lingas, G, Lucet, J, Malvy, D, Mambert, M, Mentre, F, Mercier, N, Meziane, A, Mouquet, H, Mullaert, J, Neant, N, Noret, M, Pages, J, Papadopoulos, A, Paul, C, Peiffer-Smadja, N, Petrov-Sanchez, V, Peytavin, G, Picone, O, Puechal, O, Rosa-Calatrava, M, Rossignol, B, Roy, C, Schneider, M, Semaille, C, Mohammed, N, Tagherset, L, Tardivon, C, Tellier, M, Teoule, F, Terrier, O, Timsit, J, Treoux, T, Tual, C, Tubiana, S, van der Werf, S, Vanel, N, Veislinger, A, Visseaux, B, Wiedemann, A, Yazdanpanah, Y, Abelc, L, Alcover, A, Aschard, H, Astrom, K, Bousso, P, Bruhns, P, Cumano, A, Demangel, C, Deriano, L, Santo, J, Dromer, F, Eberl, G, Enninga, J, Fellay, J, Gomperts-Boneca, I, Hasan, M, Hercberg, S, Lantz, O, Patin, E, Pellegrini, S, Pol, S, Rausell, A, Rogge, L, Sakuntabhai, A, Schwartz, O, Schwikowski, B, Shorte, S, Tangy, F, Toubert, A, Touvier, M, Ungeheuer, M, Albert, M, Alavoine, L, Amat, K, Bielicki, J, Bruijning, P, Burdet, C, Caumes, E, Charpentier, C, Coignard, B, Costa, Y, Damond, F, Dechanet, A, Delmas, C, Ecobichon, J, Frezouls, W, Houhou, N, Ilic-Habensus, E, Kikoine, J, Lebeaux, D, Leclercq, A, Lehacaut, J, Letrou, S, Manchon, P, Mandic, M, Meghadecha, M, Motiejunaite, J, Nouroudine, M, Piquard, V, Postolache, A, Quintin, C, Rexach, J, Roufai, L, Terzian, Z, Thy, M, Vignali, V, van Agtmael, M, Algera, A, van Baarle, F, Bax, D, Beudel, M, Bogaard, H, Bomers, M, Bos, L, Botta, M, de Brabander, J, Bree, G, Brouwer, M, de Bruin, S, Bugiani, M, Bulle, E, Chouchane, O, Cloherty, A, Elbers, P, Fleuren, L, Geerlings, S, Geerts, B, Geijtenbeek, T, Girbes, A, Goorhuis, B, Grobusch, M, Hafkamp, F, Hagens, L, Hamann, J, Harris, V, Hemke, R, Hermans, S, Heunks, L, Hollmann, M, Horn, J, Hovius, J, de Jong, M, Koning, R, van Mourik, N, Nellen, J, Paulus, F, Peters, E, van der Poll, T, Preckel, B, Prins, J, Raasveld, J, Reijnders, T, Schinkel, M, Schultz, M, Schuurman, A, Sigaloff, K, Smit, M, Stijnis, C, Stilma, W, Teunissen, C, Thoral, P, Tsonas, A, van der Valk, M, Veelo, D, Vlaar, A, de Vries, H, van Vugt, M, Joost Wiersinga, W, Wouters, D, Zwinderman, A, Abelb, L, Iuti, F, Muhsen, S, Al-Mulla, F, Anderson, M, Bogunovic, D, Bondarenko, A, Bryceson, Y, Bustamante, C, Butte, M, Chakravorty, S, Christodoulou, J, Cirulli, E, Condino-Neto, A, Cooper, M, Derisi, J, Desai, M, Drolet, B, Espinosa, S, Franco, J, Gregersen, P, Hagin, D, Heath, J, Henrickson, S, Hsieh, E, Imai, K, Itan, Y, Karamitros, T, Kisanda, K, Ku, C, Ling, Y, Lucas, C, Maniatis, T, Marodi, L, Milner, J, Mironska, K, Morio, T, Notarangeloa, L, Novelli, G, Novelli, A, O'Farrelly, C, Okada, S, Planas, A, Prando, C, Pujol, A, Renia, L, Renieri, A, Sancho-Shimizu, V, Sankaran, V, Barrett, K, Turvey, S, Uddin, F, Uddin, M, Vazquez, S, von Bernuth, H, Washington, N, Zawadzki, P, Sua, H, Casanovaa, J, Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Rockefeller University [New York], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Tartu, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Lyon Immunopathology Federation (LIFe), Tartu University Hospital [Tartu, Estonia], Hôpital Foch [Suresnes], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Helix [San Mateo, CA], University Medical Center [Utrecht], IRCCS Ospedale San Raffaele [Milan, Italy], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Yale University School of Medicine, Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université de Paris (UP), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Chaire Génomique humaine et évolution, Collège de France (CdF (institution)), Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], McGill University Health Center [Montreal] (MUHC), Garvan Institute of Medical Research [Darlinghurst, Australia], University of New South Wales [Sydney] (UNSW), Ghent University Hospital, Hospital Universitario Mutua de Terrassa, Universitat de Barcelona (UB), Institut d’Investigació Germans Trias i Pujol = Germans Trias i Pujol Research Institute (IGTP), Universitat de Vic-Universitat Central de Catalunya, España, Institució Catalana de Recerca i Estudis Avançats (ICREA), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Hospital Universitario de Gran Canaria Dr Negrin, University Fernando Pessoa - UFP, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Aarhus University Hospital, Aarhus University [Aarhus], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Fondazione MBBM-Ospedale [Monza, Italie], San Gerardo Hospital, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bergen (UiB), Haukeland University Hospital, Consiglio Nazionale delle Ricerche [Napoli] (CNR), Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], Università degli Studi di Brescia [Brescia], Università degli Studi di Pavia, Fondazione IRCCS Policlinico San Matteo, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Université de Paris - UFR Médecine Paris Nord [Santé] (UP Médecine Paris Nord), Service d'Immunologie [CHU Pitié-Salpétrière], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), UM1 HG006504/HG/NHGRI NIH HHS/United States, P01 AI138938/AI/NIAID NIH HHS/United States, U19 AI111825/AI/NIAID NIH HHS/United States, U24 HG008956/HG/NHGRI NIH HHS/United States, MR/S032304/1/MRC_/Medical Research Council/United Kingdom, UKRI Future Leader's Fellowship, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, The Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, the Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the Investments for the Future program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project (ANRS-COV05), the Square Foundation, Grandir – Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, the Institut Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Paris. Samples from San Raffaele Hospital were obtained through the Covid-BioB project and by healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical laboratory and clinical research unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort Study Group was sponsored by INSERM and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The Milieu Intérieur Consortium was supported by the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence Milieu Intérieur grant (ANR-10-LABX-69-01) (primary investigators: L.Q.-M. and D.Du.). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant 'DIGITAL COVID' (primary investigator: G.G.). S.G.T. is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia and a COVID19 Rapid Response Grant awarded by UNSW Sydney. C.R.-G. and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation RTC-2017-6471-1, AEI/FEDER, UE) and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). S.T.-A. and A.B. were supported by ANR-20-COVI-0064 (primary investigator: A.Be.). This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013,' by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and by a public grant overseen by the French National Research Agency (ANR) as part of the second Investissements d’Avenir program FIGHT-HF (reference no. ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d’Excellence' (reference no. ANR-15-IDEX-04-LUE) (45), and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology, by a grant from the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to F.R.-L.), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants from the Amsterdam Corona Research Fund, the Dr. C.J. Vaillant Fund, and the Netherlands Organization for Health Research and Development [ZonMw, NWO-Vici-Grant (grant no. 918·19·627 to D.v.d.B.)]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e comorbidita'). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. J.H. holds an Institut Imagine M.D.-Ph.D. fellowship from the Fondation Bettencourt Schueller. J.R. is supported by the INSERM Ph.D. program ('poste d’accueil Inserm'). P.Ba. was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the M.D.-Ph.D. program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association 'Turner et vous' for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K.K. was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (contract no. HHSN316201300006W/HHSN27200002 to MSC, Inc.), the Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data, and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support. Biomedical Advanced Research and Development Authority was supported under contract no. HHSO10201600031C (to J.H.). Financial support was provided by the National Institute of Allergy and Infectious Diseases (NIAID) K08AI135091, the Burroughs Wellcome Fund CAMS, the Clinical Immunology Society, and the American Academy of Allergy, Asthma, and Immunology, We thank the patients, their families, and healthy donors for placing their trust in us. We thank the French Incontinentia pigmenti association for their help and support. We thank Y. Nemirovskaya, D. Papandrea, M. Woollett, D. Liu, C. Rivalain, and C. Patissier for administrative assistance, D. Kapogiannis (National Institute on Aging) for providing healthy donor samples, and S. Xirasager, J. Barnett, X. Cheng, S. Weber, J. Danielson, B. Garabedian, and H. Matthews for their assistance in this study. We also thank R. Apps, B. Ryan, and Y. Belkaid of the CHI for their assistance. We thank the CRB-Institut Jérôme Lejeune, CRB-BioJeL, Paris, France, for their assistance. We thank M. C. García Guerrero, I. Erkizia, E. Grau, M. Massanella from IrsiCaixa AIDS Research Institute, Badalona, Spain, and J. Guitart from the Department of Clinical Genetics, University Hospital Germans Trias i Pujol, Badalona, Spain, for providing samples. We also thank J. Dalmau from IrsiCaixa for assistance, HGID Lab, NIAID-USUHS Immune Response to COVID Group, COVID Clinicians, COVID-STORM Clinicians, Imagine COVID Group, French COVID Cohort Study Group, The Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic, CoV-Contact Cohort: Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning, Charles Burdet, Eric Caumes, Charlotte Charpentier, Bruno Coignard, Yolande Costa, Sandrine Couffin-Cadiergues, Florence Damond, Aline Dechanet, Christelle Delmas, Diane Descamps, Xavier Duval, Jean-Luc Ecobichon, Vincent Enouf, Hélène Espérou, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, Ouifiya Kafif, John Kikoine, Quentin Le Hingrat, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Bruno Lina, Jean-Christophe Lucet, Denis Malvy, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejunaite, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, Layidé Roufai, Zaven Terzian, Michael Thy, Sarah Tubiana, Sylvie van der Werf, Valérie Vignali, Benoit Visseaux, Yazdan Yazdanpanah, COVID Human Genetic Effort: Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al-Mulla, Mark S. Anderson, Andrés Augusto Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth Cirulli, Antonio Condino-Neto, Megan A. Cooper, Clifton L. Dalgard, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, Jose Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani, Jim Heath, Sarah E. Henrickson, Elena Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davoud Mansouri, Laszlo Marodi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Antonio Novelli, Cliona O'Farrelly, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Alessandra Renieri, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Vijay Sankaran, Kelly Schiabor Barrett, Mohammed Shahrooei, Andrew Snow, Pere Soler-Palacín, András N. Spaan, Stuart Tangye, Stuart Turvey, Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova, Amsterdam UMC Covid-19 Biobank: Michiel van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Bart Geerts, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Jeaninne Nellen, Frederique Paulus, Edgar Peters, Tom van der Poll, Benedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurman, Kim Sigaloff, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa Tsonas, Marc van der Valk, Denise Veelo, Alexander P. J. Vlaar, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. (Koos) Zwinderman, Diederik van de Beek, HGID Lab: Andrés Augusto Arias, Bertrand Boisson, Soraya Boucherit, Jacinta Bustamante, Marwa Chbihi, Jie Chen, Maya Chrabieh, Tatiana Kochetkov, Tom Le Voyer, Dana Liu, Yelena Nemirovskaya, Masato Ogishi, Dominick Papandrea, Cécile Patissier, Franck Rapaport, Manon Roynard, Natasha Vladikine, Mark Woollett, Peng Zhang, NIAID-USUHS Immune Response to COVID Group: Anuj Kashyap, Li Ding, Marita Bosticardo, Qinlu Wang, Sebastian Ochoa, Hui Liu, Samuel D. Chauvin, Michael Stack, Galina Koroleva, Neha Bansal, Clifton L. Dalgard, Andrew L. Snow, COVID Clinicians: Jorge Abad, Sergio Aguilera-Albesa, Ozge Metin Akcan, Ilad Alavi Darazam, Juan C. Aldave, Miquel Alfonso Ramos, Seyed Alireza Nadji, Gulsum Alkan, Jerome Allardet-Servent, Luis M. Allende, Laia Alsina, Marie-Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Sevket Arslan, Sophie Assant, Terese Auguet, Axelle Azot, Fanny Bajolle, Aurélie Baldolli, Maite Ballester, Hagit Baris Feldman, Benoit Barrou, Alexandra Beurton, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blazquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Ahmed A. Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita P. Bueno, Jacinta Bustamante, Juan José Cáceres Agra, Semra Calimli, Ruggero Capra, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew P. Cheng, Père Clavé, Bonaventura Clotet, Anna Codina, Fatih Colkesen, Fatma Colkesen, Roger Colobran, Cloé Comarmond, Angelo G. Corsico, David Dalmau, David Ross Darley, Nicolas Dauby, Stéphane Dauger, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroglu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Carlos Flores, Bruno Francois, Victoria Fumadó, Francesca Fusco, Blanca Garcia Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Monica Girona Alarcon, Mónica Girona-Alarcón, Jean-Christophe Goffard, Funda Gok, Rafaela González-Montelongo, Antoine Guerder, Yahya Gul, Sukru Nail Guner, Marta Gut, Jérôme Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoglu, Elisa Hernandez-Brito, María Soledad Holanda-Peña, Juan Pablo Horcajada, Sami Hraiech, Linda Humbert, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Iolanda Jordan, Fikret Kanat, Hasan Kapakli, Iskender Kara, Adem Karbuz, Kadriye Kart Yasar, Sevgi Keles, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew J. Król, Paul Kuentz, Yat Wah M. Kwan, Jean-Christophe Lagier, Yu-Lung Lau, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Agnes Linglart, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles-Edouard Luyt, David C. Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martin, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail V. Matthews, Julien Mayaux, Jean-Louis Mège, Isabelle Melki, Jean-François Meritet, Ozge Metin, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martinez, Pierre Morange, Clémence Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz-Barrera, Cyril Nafati, João Farela Neves, Lisa F. P. Ng Yeray Novoa Medina, Esmeralda Nuñez Cuadros, J. Gonzalo Ocejo-Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Özçelik, Qiang Pan Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz-Artal, Rebeca Pérez de Diego, Aurélien Philippe, Quentin Philippot, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne-Sophie Rebillat, Ismail Reisli, Pilar Ricart, Jean-Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodriguez-Gallego, Agustí Rodríguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Flore Rozenberg, Maria Yolanda Ruiz del Prado, Joan Sabater Riera, Oliver Sanchez, Silvia Sánchez-Ramón, Agatha Schluter, Matthieu Schmidt, Cyril E. Schweitzer, Francesco Scolari, Anna Sediva, Luis M. Seijo, Damien Sene, Sevtap Senoglu, Mikko R. J. Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, David Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi Solé-Violán, Catherine Soler, Pere Soler-Palacín, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Yacine Tandjaoui-Lambiotte, Jean-Luc Taupin, Simon J. Tavernier, Benjamin Terrier, Caroline Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, Jesús Troya, Alessandra Tucci, Matilde Valeria Ursini‬, Yurdagul Uzunhan, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Hulya Vatansev, Valentina Vélez-Santamaria, Sébastien Viel, Cédric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby E. Young, Fatih Yucel, Faiez Zannad, Mayana Zatz, Alexandre Belot, COVID-STORM Clinicians: Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga, Imagine COVID Group: Christine Bole-Feysot, Stanislas Lyonnet, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate, French COVID Cohort Study Group: Laurent Abel, Claire Andrejak, François Angoulvant, Delphine Bachelet, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, François Bompart, Lila Bouadma, Maude Bouscambert, Mireille Caralp, Minerva Cervantes-Gonzalez, Anissa Chair, Alexandra Coelho, Camille Couffignal, Sandrine Couffin-Cadiergues, Eric D’ortenzio, Charlene Da Silveira, Marie-Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent V. E. Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Yves Lévy, Claire Levy-Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France Mentré, Noémie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Marion Noret, Justine Pages, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadj, Ventzislava Petrov-Sanchez, Gilles Peytavin, Olivier Picone, Oriane Puéchal, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Théo Treoux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanan, The Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L. Albert, Darragh Duffy, Lluis Quintana-Murci, ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0003,GENCOVID,Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé(2020), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-20-COVI-0064,IFN-COVID19,Etude de la régulation de la réponse interferon de type I dans le control de l'infection par SARS-Cov2 et sa pathogènese(2020), ANR-15-RHUS-0004,FIGHT-HF,Combattre l'insuffisance cardiaque(2015), ANR-15-IDEX-0004,LUE,Isite LUE(2015), ANR-20-COVI-0022,AIROCovid19,Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé(2020), Howard Hughes Medical Institute, Rockefeller University, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), George Mason University, National Human Genome Research Institute (US), Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Pershing Square Foundation, Institut National de la Santé et de la Recherche Médicale (France), Université de Paris, Fondazione Telethon, Ministère des Solidarités et de la Santé (France), European Commission, National Health and Medical Research Council (Australia), University of New South Wales (Australia), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Cabildo de Tenerife, Fondation Bettencourt Schueller, Estonian Research Council, Rosen, Lindsey B., Michailidis, Eleftherios, Haljasmägi, Liis, Spaan, András N., Quintana-Murci, Lluis, Beek, Diederik van der, Vinh, Donald C., Tangye, Stuart G., Martínez-Picado, Javier, Brodin, Peter, Nussenzweig, Michel C., Rodríguez-Gallego, Carlos, Mogensen, Trine, Oler, Andrew J., Burbelo, Peter D., Husebye, Eystein S., Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Infectious diseases, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, ACS - Microcirculation, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Yale School of Medicine [New Haven, Connecticut] (YSM), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génomique humaine et évolution, Garvan Institute of medical research, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), San Gerardo Hospital of Monza, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Pavia = University of Pavia (UNIPV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and J. Guitart from the Department of Clinical Genetics, University Hospital Germans Trias i Pujol, Badalona, Spain, for providing samples. We also thank J. Dalmau from IrsiCaixa for assistance HGID Lab, NIAID-USUHS Immune Response to COVID Group, COVID Clinicians, COVID-STORM Clinicians, Imagine COVID Group, French COVID Cohort Study Group, The Milieu Intérieur Consortium, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic CoV-Contact Cohort: Loubna Alavoine, Karine K. A. Amat, Sylvie Behillil, Julia Bielicki, Patricia Bruijning, Charles Burdet, Eric Caumes, Charlotte Charpentier, Bruno Coignard, Yolande Costa, Sandrine Couffin-Cadiergues, Florence Damond, Aline Dechanet, Christelle Delmas, Diane Descamps, Xavier Duval, Jean-Luc Ecobichon, Vincent Enouf, Hélène Espérou, Wahiba Frezouls, Nadhira Houhou, Emila Ilic-Habensus, Ouifiya Kafif, John Kikoine, Quentin Le Hingrat, David Lebeaux, Anne Leclercq, Jonathan Lehacaut, Sophie Letrou, Bruno Lina, Jean-Christophe Lucet, Denis Malvy, Pauline Manchon, Milica Mandic, Mohamed Meghadecha, Justina Motiejunaite, Mariama Nouroudine, Valentine Piquard, Andreea Postolache, Caroline Quintin, Jade Rexach, Layidé Roufai, Zaven Terzian, Michael Thy, Sarah Tubiana, Sylvie van der Werf, Valérie Vignali, Benoit Visseaux, Yazdan Yazdanpanah COVID Human Genetic Effort: Laurent Abel, Alessandro Aiuti, Saleh Al Muhsen, Fahd Al-Mulla, Mark S. Anderson, Andrés Augusto Arias, Hagit Baris Feldman, Dusan Bogunovic, Alexandre Bolze, Anastasiia Bondarenko, Ahmed A. Bousfiha, Petter Brodin, Yenan Bryceson, Carlos D. Bustamante, Manish Butte, Giorgio Casari, Samya Chakravorty, John Christodoulou, Elizabeth Cirulli, Antonio Condino-Neto, Megan A. Cooper, Clifton L. Dalgard, Joseph L. DeRisi, Murkesh Desai, Beth A. Drolet, Sara Espinosa, Jacques Fellay, Carlos Flores, Jose Luis Franco, Peter K. Gregersen, Filomeen Haerynck, David Hagin, Rabih Halwani, Jim Heath, Sarah E. Henrickson, Elena Hsieh, Kohsuke Imai, Yuval Itan, Timokratis Karamitros, Kai Kisand, Cheng-Lung Ku, Yu-Lung Lau, Yun Ling, Carrie L. Lucas, Tom Maniatis, Davoud Mansouri, Laszlo Marodi, Isabelle Meyts, Joshua D. Milner, Kristina Mironska, Trine Mogensen, Tomohiro Morio, Lisa F. P. Ng, Luigi D. Notarangelo, Giuseppe Novelli, Antonio Novelli, Cliona O'Farrelly, Satoshi Okada, Tayfun Ozcelik, Rebeca Perez de Diego, Anna M. Planas, Carolina Prando, Aurora Pujol, Lluis Quintana-Murci, Laurent Renia, Alessandra Renieri, Carlos Rodríguez-Gallego, Vanessa Sancho-Shimizu, Vijay Sankaran, Kelly Schiabor Barrett, Mohammed Shahrooei, Andrew Snow, Pere Soler-Palacín, András N. Spaan, Stuart Tangye, Stuart Turvey, Furkan Uddin, Mohammed J. Uddin, Diederik van de Beek, Sara E. Vazquez, Donald C. Vinh, Horst von Bernuth, Nicole Washington, Pawel Zawadzki, Helen C. Su, Jean-Laurent Casanova Amsterdam UMC Covid-19 Biobank: Michiel van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Lieuwe Bos, Michela Botta, Justin de Brabander, Godelieve Bree, Matthijs C. Brouwer, Sanne de Bruin, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas Fleuren, Suzanne Geerlings, Bart Geerts, Theo Geijtenbeek, Armand Girbes, Bram Goorhuis, Martin P. Grobusch, Florianne Hafkamp, Laura Hagens, Jorg Hamann, Vanessa Harris, Robert Hemke, Sabine M. Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Jeaninne Nellen, Frederique Paulus, Edgar Peters, Tom van der Poll, Benedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Reijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurman, Kim Sigaloff, Marry Smit, Cornelis S. Stijnis, Willemke Stilma, Charlotte Teunissen, Patrick Thoral, Anissa Tsonas, Marc van der Valk, Denise Veelo, Alexander P. J. Vlaar, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. (Koos) Zwinderman, Diederik van de Beek HGID Lab: Andrés Augusto Arias, Bertrand Boisson, Soraya Boucherit, Jacinta Bustamante, Marwa Chbihi, Jie Chen, Maya Chrabieh, Tatiana Kochetkov, Tom Le Voyer, Dana Liu, Yelena Nemirovskaya, Masato Ogishi, Dominick Papandrea, Cécile Patissier, Franck Rapaport, Manon Roynard, Natasha Vladikine, Mark Woollett, Peng Zhang NIAID-USUHS Immune Response to COVID Group: Anuj Kashyap, Li Ding, Marita Bosticardo, Qinlu Wang, Sebastian Ochoa, Hui Liu, Samuel D. Chauvin, Michael Stack, Galina Koroleva, Neha Bansal, Clifton L. Dalgard, Andrew L. Snow COVID Clinicians: Jorge Abad, Sergio Aguilera-Albesa, Ozge Metin Akcan, Ilad Alavi Darazam, Juan C. Aldave, Miquel Alfonso Ramos, Seyed Alireza Nadji, Gulsum Alkan, Jerome Allardet-Servent, Luis M. Allende, Laia Alsina, Marie-Alexandra Alyanakian, Blanca Amador-Borrero, Zahir Amoura, Arnau Antolí, Sevket Arslan, Sophie Assant, Terese Auguet, Axelle Azot, Fanny Bajolle, Aurélie Baldolli, Maite Ballester, Hagit Baris Feldman, Benoit Barrou, Alexandra Beurton, Agurtzane Bilbao, Geraldine Blanchard-Rohner, Ignacio Blanco, Adeline Blandinières, Daniel Blazquez-Gamero, Marketa Bloomfield, Mireia Bolivar-Prados, Raphael Borie, Ahmed A. Bousfiha, Claire Bouvattier, Oksana Boyarchuk, Maria Rita P. Bueno, Jacinta Bustamante, Juan José Cáceres Agra, Semra Calimli, Ruggero Capra, Maria Carrabba, Carlos Casasnovas, Marion Caseris, Martin Castelle, Francesco Castelli, Martín Castillo de Vera, Mateus V. Castro, Emilie Catherinot, Martin Chalumeau, Bruno Charbit, Matthew P. Cheng, Père Clavé, Bonaventura Clotet, Anna Codina, Fatih Colkesen, Fatma Colkesen, Roger Colobran, Cloé Comarmond, Angelo G. Corsico, David Dalmau, David Ross Darley, Nicolas Dauby, Stéphane Dauger, Loic de Pontual, Amin Dehban, Geoffroy Delplancq, Alexandre Demoule, Antonio Di Sabatino, Jean-Luc Diehl, Stephanie Dobbelaere, Sophie Durand, Waleed Eldars, Mohamed Elgamal, Marwa H. Elnagdy, Melike Emiroglu, Emine Hafize Erdeniz, Selma Erol Aytekin, Romain Euvrard, Recep Evcen, Giovanna Fabio, Laurence Faivre, Antonin Falck, Muriel Fartoukh, Morgane Faure, Miguel Fernandez Arquero, Carlos Flores, Bruno Francois, Victoria Fumadó, Francesca Fusco, Blanca Garcia Solis, Pascale Gaussem, Juana Gil-Herrera, Laurent Gilardin, Monica Girona Alarcon, Mónica Girona-Alarcón, Jean-Christophe Goffard, Funda Gok, Rafaela González-Montelongo, Antoine Guerder, Yahya Gul, Sukru Nail Guner, Marta Gut, Jérôme Hadjadj, Filomeen Haerynck, Rabih Halwani, Lennart Hammarström, Nevin Hatipoglu, Elisa Hernandez-Brito, María Soledad Holanda-Peña, Juan Pablo Horcajada, Sami Hraiech, Linda Humbert, Alejandro D. Iglesias, Antonio Íñigo-Campos, Matthieu Jamme, María Jesús Arranz, Iolanda Jordan, Fikret Kanat, Hasan Kapakli, Iskender Kara, Adem Karbuz, Kadriye Kart Yasar, Sevgi Keles, Yasemin Kendir Demirkol, Adam Klocperk, Zbigniew J. Król, Paul Kuentz, Yat Wah M. Kwan, Jean-Christophe Lagier, Yu-Lung Lau, Fleur Le Bourgeois, Yee-Sin Leo, Rafael Leon Lopez, Daniel Leung, Michael Levin, Michael Levy, Romain Lévy, Zhi Li, Agnes Linglart, José M. Lorenzo-Salazar, Céline Louapre, Catherine Lubetzki, Charles-Edouard Luyt, David C. Lye, Davood Mansouri, Majid Marjani, Jesus Marquez Pereira, Andrea Martin, David Martínez Pueyo, Javier Martinez-Picado, Iciar Marzana, Alexis Mathian, Larissa R. B. Matos, Gail V. Matthews, Julien Mayaux, Jean-Louis Mège, Isabelle Melki, Jean-François Meritet, Ozge Metin, Isabelle Meyts, Mehdi Mezidi, Isabelle Migeotte, Maude Millereux, Tristan Mirault, Clotilde Mircher, Mehdi Mirsaeidi, Abián Montesdeoca Melián, Antonio Morales Martinez, Pierre Morange, Clémence Mordacq, Guillaume Morelle, Stéphane Mouly, Adrián Muñoz-Barrera, Cyril Nafati, João Farela Neves, Lisa F. P. Ng Yeray Novoa Medina, Esmeralda Nuñez Cuadros, J. Gonzalo Ocejo-Vinyals, Zerrin Orbak, Mehdi Oualha, Tayfun Özçelik, Qiang Pan Hammarström, Christophe Parizot, Tiffany Pascreau, Estela Paz-Artal, Rebeca Pérez de Diego, Aurélien Philippe, Quentin Philippot, Laura Planas-Serra, Dominique Ploin, Julien Poissy, Géraldine Poncelet, Marie Pouletty, Paul Quentric, Didier Raoult, Anne-Sophie Rebillat, Ismail Reisli, Pilar Ricart, Jean-Christophe Richard, Nadia Rivet, Jacques G. Rivière, Gemma Rocamora Blanch, Carlos Rodrigo, Carlos Rodriguez-Gallego, Agustí Rodríguez-Palmero, Carolina Soledad Romero, Anya Rothenbuhler, Flore Rozenberg, Maria Yolanda Ruiz del Prado, Joan Sabater Riera, Oliver Sanchez, Silvia Sánchez-Ramón, Agatha Schluter, Matthieu Schmidt, Cyril E. Schweitzer, Francesco Scolari, Anna Sediva, Luis M. Seijo, Damien Sene, Sevtap Senoglu, Mikko R. J. Seppänen, Alex Serra Ilovich, Mohammad Shahrooei, David Smadja, Ali Sobh, Xavier Solanich Moreno, Jordi Solé-Violán, Catherine Soler, Pere Soler-Palacín, Yuri Stepanovskiy, Annabelle Stoclin, Fabio Taccone, Yacine Tandjaoui-Lambiotte, Jean-Luc Taupin, Simon J. Tavernier, Benjamin Terrier, Caroline Thumerelle, Gabriele Tomasoni, Julie Toubiana, Josep Trenado Alvarez, Sophie Trouillet-Assant, Jesús Troya, Alessandra Tucci, Matilde Valeria Ursini‬, Yurdagul Uzunhan, Pierre Vabres, Juan Valencia-Ramos, Ana Maria Van Den Rym, Isabelle Vandernoot, Hulya Vatansev, Valentina Vélez-Santamaria, Sébastien Viel, Cédric Vilain, Marie E. Vilaire, Audrey Vincent, Guillaume Voiriot, Fanny Vuotto, Alper Yosunkaya, Barnaby E. Young, Fatih Yucel, Faiez Zannad, Mayana Zatz, Alexandre Belot COVID-STORM Clinicians: Giuseppe Foti, Giacomo Bellani, Giuseppe Citerio, Ernesto Contro, Alberto Pesci, Maria Grazia Valsecchi, Marina Cazzaniga Imagine COVID Group: Christine Bole-Feysot, Stanislas Lyonnet, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate French COVID Cohort Study Group: Laurent Abel, Claire Andrejak, François Angoulvant, Delphine Bachelet, Romain Basmaci, Sylvie Behillil, Marine Beluze, Dehbia Benkerrou, Krishna Bhavsar, François Bompart, Lila Bouadma, Maude Bouscambert, Mireille Caralp, Minerva Cervantes-Gonzalez, Anissa Chair, Alexandra Coelho, Camille Couffignal, Sandrine Couffin-Cadiergues, Eric D’ortenzio, Charlene Da Silveira, Marie-Pierre Debray, Dominique Deplanque, Diane Descamps, Mathilde Desvallées, Alpha Diallo, Alphonsine Diouf, Céline Dorival, François Dubos, Xavier Duval, Philippine Eloy, Vincent V. E. Enouf, Hélène Esperou, Marina Esposito-Farese, Manuel Etienne, Nadia Ettalhaoui, Nathalie Gault, Alexandre Gaymard, Jade Ghosn, Tristan Gigante, Isabelle Gorenne, Jérémie Guedj, Alexandre Hoctin, Isabelle Hoffmann, Salma Jaafoura, Ouifiya Kafif, Florentia Kaguelidou, Sabina Kali, Antoine Khalil, Coralie Khan, Cédric Laouénan, Samira Laribi, Minh Le, Quentin Le Hingrat, Soizic Le Mestre, Hervé Le Nagard, François-Xavier Lescure, Yves Lévy, Claire Levy-Marchal, Bruno Lina, Guillaume Lingas, Jean Christophe Lucet, Denis Malvy, Marina Mambert, France Mentré, Noémie Mercier, Amina Meziane, Hugo Mouquet, Jimmy Mullaert, Nadège Neant, Marion Noret, Justine Pages, Aurélie Papadopoulos, Christelle Paul, Nathan Peiffer-Smadj, Ventzislava Petrov-Sanchez, Gilles Peytavin, Olivier Picone, Oriane Puéchal, Manuel Rosa-Calatrava, Bénédicte Rossignol, Patrick Rossignol, Carine Roy, Marion Schneider, Caroline Semaille, Nassima Si Mohammed, Lysa Tagherset, Coralie Tardivon, Marie-Capucine Tellier, François Téoulé, Olivier Terrier, Jean-François Timsit, Théo Treoux, Christelle Tual, Sarah Tubiana, Sylvie van der Werf, Noémie Vanel, Aurélie Veislinger, Benoit Visseaux, Aurélie Wiedemann, Yazdan Yazdanpanan The Milieu Intérieur Consortium: Laurent Abel, Andres Alcover, Hugues Aschard, Kalla Astrom, Philippe Bousso, Pierre Bruhns, Ana Cumano, Caroline Demangel, Ludovic Deriano, James Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Serge Hercberg, Olivier Lantz, Hugo Mouquet, Etienne Patin, Sandra Pellegrini, Stanislas Pol, Antonio Rausell, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Matthew L. Albert, Darragh Duffy, Lluis Quintana-Murci, Bastard, Paul [0000-0002-5926-8437], Rosen, Lindsey B. [0000-0001-5894-3878], Zhang, Qian [0000-0002-9040-3289], Michailidis, Eleftherios [0000-0002-9907-4346], Dorgham, Karim [0000-0001-9539-3203], Béziat, Vivien [0000-0002-4020-824X], Manry, Jérémy [0000-0001-5998-2051], Shaw, Elana [0000-0001-9265-8026], Haljasmägi, Liis [0000-0001-7162-9808], Peterson, Pärt [0000-0001-6755-791X], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Trouillet-Assant, Sophie [0000-0001-6439-4705], Dobbs, Kerry [0000-0002-3432-3137], Belot, Alexandre [0000-0003-4902-5332], Kallaste, Anne [0000-0002-7492-667X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], Le Pen, Jeremie [0000-0001-7025-9526], Kerner, Gaspard [0000-0003-0146-9428], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Bolze, Alexandre [0000-0001-7399-2766], Spaan, András N. [0000-0001-5981-7259], Aiuti, Alessandro [0000-0002-5398-1717], Lampasona, Vito [0000-0001-5162-8445], Piemonti, Lorenzo [0000-0002-2172-2198], Bilguvar, Kaya [0000-0002-7313-7652], Migaud, Mélanie [0000-0003-3062-1214], Hadjadj, Jérome [0000-0002-2520-3272], Terrier, Benjamin [0000-0001-6612-7336], Duffy, Darragh [0000-0002-8875-2308], Quintana-Murci, Lluis [0000-0003-2429-6320], Beek, Diederik van der [0000-0002-4571-044X], Roussel, Lucie [0000-0001-5355-702X], Vinh, Donald C. [0000-0003-1347-7767], Tangye, Stuart G. [0000-0002-5360-5180], Dalmau, David [0000-0003-1936-478X], Martínez-Picado, Javier [0000-0002-4916-2129], Brodin, Peter [0000-0002-8103-0046], Nussenzweig, Michel C. [0000-0003-0592-8564], Boisson-Dupuis, Stéphanie [0000-0002-7115-116X], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Mogensen, Trine [0000-0002-1853-9704], Oler, Andrew J. [0000-0002-6310-0434], Burbelo, Peter D. [0000-0003-1717-048X], Cohen, Jeffrey [0000-0003-0238-7176], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Rieux-Laucat, Frédéric [0000-0001-7858-7866], Husebye, Eystein S. [0000-0002-7886-2976], Castagnoli, Riccardo [0000-0003-0029-9383], Licari, Amelia [0000-0002-1773-6482], Vougny, Marie-Christine, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Laboratoires d'excellence - GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE - - MILIEU INTERIEUR2010 - ANR-10-LABX-0069 - LABX - VALID, ISITE - Isite LUE - - LUE2015 - ANR-15-IDEX-0004 - IDEX - VALID, Combattre l'insuffisance cardiaque - - FIGHT-HF2015 - ANR-15-RHUS-0004 - RHUS - VALID, Etude de la régulation de la réponse interferon de type I dans le control de l'infection par SARS-Cov2 et sa pathogènese - - IFN-COVID192020 - ANR-20-COVI-0064 - COVID-19 - VALID, Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé - - AIROCovid192020 - ANR-20-COVI-0022 - COVID-19 - VALID, Identification des défauts monogéniques de l'immunité responsables des formes sévères de COVID-19 chez les patients précédemment en bonne santé - - GENCOVID2020 - ANR-20-COVI-0003 - COVID-19 - VALID, Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anesthésiologie et soins intensifs [CHU Pitié-Salpêtrière], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Paris Diderot - Paris 7 - UFR Lettres, Arts, Langues, Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Service d'immunologie [CHU Pitié-Salpétrière], Funding: The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut Institut National de la Santé et de la Recherche Médicale (INSERM) and the University of Paris. Samples from San Raffaele Hospital were obtained within the Covid-BioB project and healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical lab and clinical research Unit, funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The 'Milieu Intérieur' cohort was supported by was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence 'Milieu Intérieur' Grant (ANR-10-LABX-69-01) (PI: L Quintana-Murci & D Duffy). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant 'DIGITAL COVID' (PI: G Gorochov). SGT is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney. CRG and colleagues were supported by Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation -RTC-2017-6471-1, AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19'). SA and AB were supported by ANR-20-COVI-0064 (PI: A Belot). This work is supported by the French Ministry of Health 'Programme Hospitalier de Recherche Clinique Inter regional 2013', by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second 'Investissements d’Avenir' program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project 'Lorraine Université d’Excellence', reference ANR-15-IDEX-04-LUE (45) and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology and by a grant from the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to FRL), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants of the Amsterdam Corona Research Fund, Dr. C.J. Vaillant Fund, and Netherlands Organization for Health Research and Development (ZonMw, NWO-Vici-Grant [grant number 918·19·627 to DvdB]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project 'Risposta immune in pazienti con COVID-19 e comorbidita'). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. JH holds an Institut Imagine MD-PhD fellowship from the Fondation Bettencourt Schueller. JR is supported by the Inserm PhD program ('poste d’accueil Inserm'). PB was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association 'Turner et vous' for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. DCV is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K. Kisand was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (Contract HHSN316201300006W/HHSN27200002 to MSC, Inc) and Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support., The Milieu Intérieur Consortium : Laurent Abel 1, Andres Alcover 2, Hugues Aschard 2, Kalla Astrom 3, Philippe Bousso 2, Pierre Bruhns 2, Ana Cumano 2, Caroline Demangel 2, Ludovic Deriano 2, James Di Santo 2, Françoise Dromer 2, Gérard Eberl 2, Jost Enninga 2, Jacques Fellay 4, Ivo Gomperts-Boneca 2, Milena Hasan 2, Serge Hercberg 5, Olivier Lantz 6, Hugo Mouquet 2, Etienne Patin 2, Sandra Pellegrini 2, Stanislas Pol 7, Antonio Rausell 8, Lars Rogge 2, Anavaj Sakuntabhai 2, Olivier Schwartz 2, Benno Schwikowski 2, Spencer Shorte 2, Frédéric Tangy 2, Antoine Toubert 9, Mathilde Touvier 10, Marie-Noëlle Ungeheuer 2, Matthew L. Albert 11*, Darragh Duffy 2*, Lluis Quintana-Murci 2* - 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2Pasteur Institute, Paris, France. 3Lund University, Lund, Sweden. 4EPFL, Lausanne, Switzerland. 5Université Paris 13, Paris, France. 6Curie Institute, Paris, France. 7Cochin Hospital, Paris, France. 8INSERM UMR 1163 – Institut Imagine, Paris, France. 9Hôpital Saint-Louis, Paris, France. 10Sorbonne Paris Nord University, Inserm U1153, Inrae U1125, Cnam, Nutritional Epidemiology Research Team (EREN), Bobigny, France. 11In Sitro, San Francisco, CA, USA. *Co-coordinators of The Milieu Intérieur Consortium. Additional information can be found at: www.milieuinterieur.fr/en., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC, Netherlands Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Deparment of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Joseph L. DeRisi21, Murkesh Desai22, Beth A. Drolet23, Sara Espinosa24, Jacques Fellay25, Carlos Flores26, Jose Luis Franco27, Peter K. Gregersen28, Filomeen Haerynck29, David Hagin30, Rabih Halwani31, Jim Heath32, Sarah E. Henrickson33, Elena Hsieh34, Kohsuke Imai35, Yuval Itan8, Timokratis Karamitros36, Kai Kisand37, Cheng-Lung Ku38, Yu-Lung Lau39, Yun Ling40, Carrie L. Lucas41, Tom Maniatis42, Davoud Mansouri43, Laszlo Marodi44, Isabelle Meyts45, Joshua D. Milner46, Kristina Mironska47, Trine Mogensen48, Tomohiro Morio49, Lisa F. P. Ng50, Luigi D. Notarangelo51, Giuseppe Novelli52, Antonio Novelli53, Cliona O'Farrelly54, Satoshi Okada55, Tayfun Ozcelik56, Rebeca Perez de Diego57, Anna M. Planas58, Carolina Prando59, Aurora Pujol60, Lluis Quintana-Murci61, Laurent Renia62, Alessandra Renieri63, Carlos Rodríguez-Gallego64, Vanessa Sancho-Shimizu65, Vijay Sankaran66, Kelly Schiabor Barrett9, Mohammed Shahrooei67, Andrew Snow68, Pere Soler-Palacín69, András N. Spaan70, Stuart Tangye71, Stuart Turvey72, Furkan Uddin73, Mohammed J. Uddin74, Diederik van de Beek75, Sara E. Vazquez76, Donald C. Vinh77, Horst von Bernuth78, Nicole Washington9, Pawel Zawadzki79, Helen C. Su51*, Jean-Laurent Casanova80* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Dasman Diabetes Institute, Department of Genetics and Bioinformatics, Dasman, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Department, Faculty of Medicine and Pharmacy, Averroes University Hospital, LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Department of Pediatrics and Children’s Healthcare of Atlanta, Emory University, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21University of California San Francisco, Chan Zuckerberg Biohub, San Francisco, CA, USA. 22Bai Jerbai Wadia Hospital for Children, Mumbai, India. 23 School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 24Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 25Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 26Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 27University of Antioquia, Medellín, Colombia. 28Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 29Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 30The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 31Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. 32Institute for Systems Biology, Seattle, WA, USA. 33Children's Hospital of Philadelphia, Philadelphia, PA, USA. 34Anschutz Medical Campus, Aurora, CO, USA. 35Riken, Tokyo, Japan. 36Hellenic Pasteur Institute, Athens, Greece. 37University of Tartu, Tartu, Estonia. 38Chang Gung University, Taoyuan County, Taiwan. 39The University of Hong Kong, Hong Kong, China. 40Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 41Yale School of Medicine, New Haven, CT, USA. 42New York Genome Center, New York, NY, USA. 43Shahid Beheshti University of Medical Sciences, Tehran, Iran. 44Semmelweis University Budapest, Budapest, Hungary. 45KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 46Columbia University Medical Center, New York, NY, USA. 47University Clinic for Children's Diseases, Skopje, North Macedonia. 48Aarhus University, Aarhus, Denmark. 49Tokyo Medical & Dental University Hospital, Tokyo, Japan. 50Singapore Immunology Network, Singapore. 51National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 52Department of Biomedicine and Prevention, University of Rome 'Tor Vergata,' Rome, Italy. 53Bambino Gesù Children's Hospital, Rome, Italy. 54Trinity College, Dublin, Ireland. 55Hiroshima University, Hiroshima, Japan. 56Bilkent University, Ankara, Turkey. 57Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 58IIBB-CSIC, IDIBAPS, Barcelona, Spain. 59Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 60Neurometabolic Diseases Laboratory, IDIBELL - Hospital Duran I Reynals, Catalan Institution for Research and Advanced Studies (ICREA), CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 61Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 62Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 63Medical Genetics, University of Siena, Italy, Genetica Medica, Azienda Ospedaliero-Universitaria Senese, GEN-COVID Multicenter Study, Italy. 64Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System, Canary Islands, Spain. 65Imperial College London, London, UK. 66Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 67Saeed Pathobiology and Genetic Laboratory, Tehran, Iran. 68Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, USA. 69Hospital Universitari Vall d'Hebron, Barcelona, Spain. 70University Medical Center Utrecht, Amsterdam, Netherlands. 71Garvan Institute of Medical Research, Sydney, Australia. 72The University of British Columbia, Vancouver, Canada. 73Holy Family Red Crescent Medical College, Centre for Precision Therapeutics, NeuroGen Children's Healthcare, Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 74Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, United Arab Emirates, The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 75Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, Netherlands. 76University of California, San Francisco, San Francisco, CA, USA. 77McGill University Health Centre, Montreal, Canada. 78Charité - Berlin University Hospital Center, Berlin, Germany. 79Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 80The Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., ANR-10-LABX-0062,IBEID,Biologie Intégrative des Maladies Infectieuses Emergentes(2011), ANR-10-LABX-0020,NUMEV,Digital and Hardware Solutions and Modeling for the Environement and Life Sciences(2010), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Pulmonary medicine, Medical Microbiology and Infection Prevention, Internal medicine, Intensive care medicine, APH - Quality of Care, and Özçelik, Tayfun
Subjects: Male, COVID19, Immunoglobulin G, DISEASE, MESH: Antibodies, Neutralizing, 0302 clinical medicine, MESH: Interferon alpha-2, 80 and over, Medicine, Asymptomatic Infections, MESH: Immunoglobulin G, Aged, 80 and over, 0303 health sciences, MESH: Middle Aged, COVID Clinicians, MESH: Case-Control Studies, 3. Good health, Settore MED/03, 030220 oncology & carcinogenesis, MESH: Critical Illness, Interferon Type I, Science & Technology - Other Topics, Viral disease, MESH: Pandemics, [SDV.IMM] Life Sciences [q-bio]/Immunology, Critical Illness, Immunology, Pneumonia, Viral, Interferon alpha-2, HGID Lab, 03 medical and health sciences, Betacoronavirus, Genetics, Humans, MESH: SARS-CoV-2, COVID Human Genetic Effort, Aged, Autoantibodies, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Science & Technology, CYTOKINES, MESH: Adult, Pneumonia, medicine.disease, Antibodies, Neutralizing, COVID-STORM Clinicians, MESH: Pneumonia, Viral, Case-Control Studies, NIAID-USUHS Immune Response to COVID Group, MESH: Female, MESH: Interferon Type I, MESH: Coronavirus Infections, CHRONIC MUCOCUTANEOUS CANDIDIASIS, [SDV.GEN] Life Sciences [q-bio]/Genetics, medicine.disease_cause, Autoimmunity, CoV-Contact Cohort, MESH: Aged, 80 and over, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Medicine and Health Sciences, MESH: Autoantibodies, MESH: COVID-19, Online, Viral, Chronic mucocutaneous candidiasis, Imagine COVID Group, Amsterdam UMC Covid-19 Biobank, Neutralizing, Research Articles, MESH: Aged, Multidisciplinary, biology, Middle Aged, Multidisciplinary Sciences, Milieu Intérieur Consortium, MESH: Betacoronavirus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Coronavirus Infections, Research Article, Sciences exactes et naturelles, Adult, INTERFERON, General Science & Technology, PROTEINS, French COVID Cohort Study Group, MESH: Asymptomatic Infections, COVID-19, Pandemics, SARS-CoV-2, Asymptomatic, Antibodies, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, Phenocopy, business.industry, R-Articles, Autoantibody, GAMMA, MESH: Male, 3121 General medicine, internal medicine and other clinical medicine, ANTIBODIES, biology.protein, 3111 Biomedicine, business
Abstract: HGID Lab Andrés Augusto Arias1,3, Bertrand Boisson1,2, Soraya Boucherit2, Jacinta Bustamante1,2, Marwa Chbihi2, Jie Chen1, Maya Chrabieh2, Tatiana Kochetkov1, Tom Le Voyer2, Dana Liu1, Yelena Nemirovskaya1, Masato Ogishi1, Dominick Papandrea1, Cécile Patissier2, Franck Rapaport1, Manon Roynard2, Natasha Vladikine2, Mark Woollett1, Peng Zhang1 1St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University. 2Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children. 3School of Microbiology and Group of Primary Immunodeficiencies, University of Antioquia UdeA, Medellin, Colombia., NIAID-USUHS Immune Response to COVID Group Anuj Kashyap1, Li Ding1, Marita Bosticardo1, Qinlu Wang2, Sebastian Ochoa1, Hui Liu1, Samuel D. Chauvin3, Michael Stack1, Galina Koroleva4, Neha Bansal5, Clifton L. Dalgard6,7, Andrew L. Snow8 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2Bioinformatics and Computational Biosciences Branch, NIAID Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 3Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 4NIH Center for Human Immunology, NIH, Bethesda, MD, USA. 5Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD, USA. 6PRIMER, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 7Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 8Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Ahmed A. Bousfiha33, Claire Bouvattier34, Oksana Boyarchuk35, Maria Rita P. Bueno36, Jacinta Bustamante20, Juan José Cáceres Agra37, Semra Camli38, Ruggero Capra39, Maria Carrabba40, Carlos Casasnovas41, Marion Caseris42, Martin Castelle43, Francesco Castelli44, Martín Castillo de Vera45, Mateus V. Castro36, Emilie Catherinot46, Martin Chalumeau47, Bruno Charbit48, Matthew P. Cheng49, Père Clavé31, Bonaventura Clotet50, Anna Codina51, Fatih Colkesen52, Fatma Colkesen53, Roger Colobran 54, Cloé Comarmond55, Angelo G. Corsico56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Antonio Di Sabatino65, Jean-Luc Diehl66, Stephanie Dobbelaere67, Sophie Durand68, Waleed Eldars69, Mohamed Elgamal70, Marwa H. Elnagdy71, Melike Emiroglu72, Emine Hafize Erdeniz73, Selma Erol Aytekin74, Romain Euvrard75, Recep Evcen76, Giovanna Fabio40, Laurence Faivre77, Antonin Falck42, Muriel Fartoukh78, Morgane Faure79, Miguel Fernandez Arquero80, Carlos Flores81, Bruno Francois82, Victoria Fumadó83, Francesca Fusco84, Blanca Garcia Solis85, Pascale Gaussem86, Juana Gil-Herrera87, Laurent Gilardin88, Monica Girona Alarcon89, Mónica Girona-Alarcón89, Jean-Christophe Goffard90, Funda Gok91, Rafaela González-Montelongo92, Antoine Guerder93, Yahya Gul94, Sukru Nail Guner94, Marta Gut95, Jérôme Hadjadj96, Filomeen Haerynck97, Rabih Halwani98, Lennart Hammarström99, Nevin Hatipoglu100, Elisa Hernandez-Brito101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Sami Hraiech104, Linda Humbert105, Alejandro D. Iglesias106, Antonio Íñigo-Campos92, Matthieu Jamme107, María Jesús Arranz108, Iolanda Jordan109, Fikret Kanat110, Hasan Kapakli111, Iskender Kara112, Adem Karbuz113, Kadriye Kart Yasar114, Sevgi Keles115, Yasemin Kendir Demirkol116, Adam Klocperk117, Zbigniew J. Król118, Paul Kuentz119, Yat Wah M. Kwan120, Jean-Christophe Lagier121, Yu-Lung Lau122, Fleur Le Bourgeois60, Yee-Sin Leo123, Rafael Leon Lopez124, Daniel Leung122, Michael Levin125, Michael Levy60, Romain Lévy20, Zhi Li48, Agnes Linglart126, José M. Lorenzo-Salazar92, Céline Louapre127, Catherine Lubetzki127, Charles-Edouard Luyt128, David C. Lye129, Davood Mansouri130, Majid Marjani131, Jesus Marquez Pereira132, Andrea Martin133, David Martínez Pueyo134, Javier Martinez-Picado135, Iciar Marzana136, Alexis Mathian14, Larissa R. B. Matos36, Gail V. Matthews137, Julien Mayaux138, Jean-Louis Mège139, Isabelle Melki140, Jean-François Meritet141, Ozge Metin142, Isabelle Meyts143, Mehdi Mezidi144, Isabelle Migeotte145, Maude Millereux146, Tristan Mirault147, Clotilde Mircher68, Mehdi Mirsaeidi148, Abián Montesdeoca Melián149, Antonio Morales Martinez150, Pierre Morange151, Demence Mordacq105, Guillaume Morelle152, Stéphane Mouly13, Adrián Muñoz-Barrera92, Cyril Nafati153, João Farela Neves154, Lisa F. P. Ng155, Yeray Novoa Medina156, Esmeralda Nuñez Cuadros157, J. Gonzalo Ocejo-Vinyals158, Zerrin Orbak159, Mehdi Oualha20, Tayfun Özçelik160, Qiang Pan Hammarström161, Christophe Parizot138, Tiffany Pascreau162, Estela Paz-Artal163, Sandra Pellegrini48, Rebeca Pérez de Diego85, Aurélien Philippe164, Quentin Philippot78, Laura Planas-Serra165, Dominique Ploin166, Julien Poissy167, Géraldine Poncelet42, Marie Pouletty168, Paul Quentric138, Didier Raoult139, Anne-Sophie Rebillat68, Ismail Reisli169, Pilar Ricart170, Jean-Christophe Richard171, Nadia Rivet28, Jacques G. Rivière172, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego173, Agustí Rodríguez-Palmero174, Carolina Soledad Romero175, Anya Rothenbuhler176, Flore Rozenberg177, Maria Yolanda Ruiz del Prado178, Joan Sabater Riera15, Oliver Sanchez179, Silvia Sánchez-Ramón180, Agatha Schluter165, Matthieu Schmidt181, Cyril E. Schweitzer182, Francesco Scolari183, Anna Sediva184, Luis M. Seijo185, Damien Sene13, Sevtap Senoglu114, Mikko Seppänen186, Alex Serra Ilovich187, Mohammad Shahrooei62, David Smadja188, Ali Sobh189, Xavier Solanich Moreno15, Jordi Solé-Violán190, Catherine Soler191, Pere Soler-Palacín133, Yuri Stepanovskiy192, Annabelle Stoclin193, Fabio Taccone145, Yacine Tandjaoui-Lambiotte194, Jean-Luc Taupin195, Simon J. Tavernier196, Benjamin Terrier197, Caroline Thumerelle105, Gabriele Tomasoni198, Julie Toubiana47, Josep Trenado Alvarez199, Sophie Trouillet-Assant200, Jesús Troya201, Alessandra Tucci202, Matilde Valeria Ursini‬84, Yurdagul Uzunhan203, Pierre Vabres204, Juan Valencia-Ramos205, Ana Maria Van Den Rym85, Isabelle Vandernoot206, Hulya Vatansev207, Valentina Vélez-Santamaria41, Sébastien Viel166, Cédric Vilain208, Marie E. Vilaire68, Audrey Vincent34, Guillaume Voiriot209, Fanny Vuotto105, Alper Yosunkaya91, Barnaby E. Young123, Fatih Yucel210, Faiez Zannad211, Mayana Zatz36, Alexandre Belot212* 1University Hospital and Research Institute “Germans Trias i Pujol”, Badalona, Spain. 2Navarra Health Service Hospital, Pamplona, Spain. 3Division of Pediatric Infectious Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 4Department of Infectious Diseases, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru. 6Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat Spain. 7Virology Research Center, National institutes of Tuberculosis and Lung diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8Division of Pediatric Infectious Diseases, Faculty of Medicine, Selcuk University, Konya, Turkey. 9Intensive care unit, Hôpital Européen, Marseille, France. 10Immunology Department, University Hospital 12 de Octubre. Research Institute imas12. Complutense University, Madrid, Spain. 11Hospital Sant Joan de Déu, Barcelona, Spain. 12Department of Biological Immunology, Necker Hospital for Sick Children, APHP and INEM, Paris, France. 13Internal medicine department, Hôpital Lariboisière, APHP; Université de Paris, Paris, France. 14Internal medicine department, Pitié-Salpétrière Hospital, Paris, France. 15Hospital Universitari de Bellvitge, Barcelona, Spain. 16Division of Clinical Immunology and Allergy, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 17Joint Research Unit, Hospices Civils de Lyon-bio Mérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 18Hospital U. de Tarragona Joan XXIII. Universitat Rovira i Virgili (URV). IISPV, Tarragona, Spain. 19Private practice, Paris, France. 20Necker Hospital for Sick Children, AP-HP, Paris, France. 21Department of Infectious Diseases, CHU de Caen, Caen, France. 22Consorcio Hospital General Universitario, Valencia, Spain. 23The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 24Dept Urology, Nephrology, Transplantation, APHP-SU, Sorbonne Université, INSERM U 1082, Paris, France. 25Service de Médecine Intensive–Réanimation et Pneumologie, APHP Hôpital Pitié–Salpêtrière, Paris, France. 26Cruces University Hospital, Bizkaia, Spain. 27Paediatric Immunology and Vaccinology Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. 28Hematology, Georges Pompidou Hospital, APHP, Paris, France. 29Pediatric Infectious Diseases Unit. Instituto de Investigación 12 de Octubre (imas12). Hospital Universitario 12 de Octubre, Madrid, Spain. 30Department of Immunology, Motol University Hospital, 2nd Faculty of Medicine, Charles University, Department of Pediatrics, Thomayer’s Hospital, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. 31Centro de Investigación Biomédica en Red de Enfermedades Hepàticas y Digestivas (Ciberehd). Hospital de Mataró, Consorci Sanitari del Maresme, Mataró, Spain. 32Service de Pneumologie, Hopital Bichat, APHP, Paris, France. 33Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University, Casablanca, Morocco. 34Endocrinology unit, APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 35Department of Children's Diseases and Pediatric Surgery, I.Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. 36Human Genome and stem-cell research center- University of São Paulo, São Paulo, Brazil. 37Hospital Insular, Las Palmas de Gran Canaria, Spain. 38Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Konya State Hospital, Konya, Turkey. 39MS Center, Spedali Civili, Brescia, Italy. 40Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 41Bellvitge University Hospital, L'Hospitalet de Llobregat, Barcelona, Spain. 42Hopital Robert Debré, Paris, France. 43Pediatric Immuno-hematology Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France. 44Department of Infectious and Tropical Diseases, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 45Doctoral Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 46Hôpital Foch, Suresnes, France. 47Necker Hospital for Sick Children, Paris University, AP-HP, Paris, France. 48Pasteur Institute, Paris, France. 49McGill University Health Centre, Montreal, Canada. 50University Hospital and Research Institute “Germans Trias i Pujol”, IrsiCaixa AIDS Research Institute, UVic-UCC, Badalona, Spain. 51Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Esplugues, Spain. 52Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 53Department of Infectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, Turkey. 54Hospital Universitari Vall d’Hebron, Barcelona, Spain. 55Pitié-Salpêtrière Hospital, Paris, France. 56Respiratory Diseases Division, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy. 57Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 58UNSW Medicine, St Vincent's Clinical School; Department of Thoracic Medicine, St Vincent's Hospital Darlinghurst, Sidney, Australia. 59CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium. 60Pediatric Intensive Care Unit, Robert-Debré University Hospital, APHP, Paris, France. 61Sorbonne Paris Nord, Hôpital Jean Verdier, APHP, Bondy, France. 62Specialized Immunology Laboratory of Dr. Shahrooei, Sina Medical Complex, Ahvaz, Iran. 63Centre de génétique humaine, CHU Besançon, Besançon, France. 64Sorbonne Université médecine and APHP Sorbonne université site Pitié-Salpêtrière, Paris, France. 65Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. 66Intensive Care unit, Georges Pompidou Hospital, APHP, Paris, France. 67Department of Pneumology, AZ Delta, Roeselare, Belgium. 68Institut Jérôme Lejeune, Paris, France. 69Department of Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 70Department of Chest, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 71Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 72Faculty of Medicine, Division of Pediatric Infectious Diseases, Selcuk University, Konya, Turkey. 73Division of Pediatric Infectious Diseases, Ondokuz Mayıs University, Samsun, Turkey. 74Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, Turkey. 75Centre Hospitalier Fleyriat, Bourg-en-Bresse, France. 76Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 77Centre de Génétique, CHU Dijon, Dijon, France. 78APHP Tenon Hospital, Paris, France. 79Sorbonne Universités, UPMC University of Paris, Paris, France. 80Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain. 81Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Research Unit, Hospital Universitario N.S. de Candelaria, Santa Cruz de Tenerife, Spain; Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, San Cristóbal de La Laguna, Spain. 82CHU Limoges and Inserm CIC 1435 & UMR 1092, Limoges, France. 83Infectious Diseases Unit, Department of Pediatrics, Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Sant Joan de Déu, Spain; Universitat de Barcelona (UB), Barcelona, Spain. 84Institute of Genetics and Biophysics ‘Adriano Buzzati-Traverso’, IGB-CNR, Naples, Italy. 85Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 86Hematology, APHP, Hopital Européen Georges Pompidou and Inserm UMR-S1140, Paris, France. 87Hospital General Universitario and Instituto de Investigación Sanitaria "Gregorio Marañón", Madrid, Spain. 88Bégin military Hospital, Bégin, France. 89Pediatric Intensive Care Unit, Hospital Sant Joan de Déu, Barcelona, Spain. 90Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 91Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 92Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain. 93Assistance Publique Hôpitaux de Paris, Paris, France. 94Division of Allergy and Immunology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 95CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST); Universitat Pompeu Fabra (UPF), Barcelona, Spain. 96Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Paris, France. 97Ghent University Hospital, Ghent, Belgium. 98Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 99Department of Biosciences and Nutrition, SE14183, Huddinge, Karolinska Institutet, Stockholm, Sweden. 100Pediatric Infectious Diseases Unit, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 101Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 102IntensivenCare Unit. Marqués de Valdecilla Hospital, Santander, Spain. 103Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. 104Intensive care unit, APHM, Marseille, France. 105CHU Lille, Lille, France. 106Department of Pediatrics, Columbia University, New York, NY, USA. 107Centre hospitalier intercommunal Poissy Saint Germain en Laye, Poissy, France. 108Division of Respiratory Diseases, Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain. 109Hospital Sant Joan de Déu, Kids Corona Platfform, Barcelona, Spain. 110Selcuk University, Faculty of Medicine, Chest Diseases Department, Konya, Turkey. 111Division of Allergy and Immunology, Balikesir Ataturk City Hospital, Balikesir, Turkey. 112Division of Critical Care Medicine, Selcuk University, Faculty of Medicine, Konya, Turkey. 113Division of Pediatric Infectious Diseases, Prof. Dr. Cemil Tascıoglu City Hospital, Istanbul, Turkey. 114Departments of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. 115Meram Medical Faculty, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 116Health Sciences University, Umraniye Education and Research Hospital, Istanbul, Turkey. 117Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic. 118Central Clinical Hospital of Ministry of the Interior and Administration in Warsaw, Warsaw, Poland. 119Oncobiologie Génétique Bioinformatique, PC Bio, CHU Besançon, Besançon, France. 120Paediatric Infectious Disease Unit, Hospital Authority Infectious Disease Center, Princess Margaret Hospital, Hong Kong (Special Administrative Region), China. 121Aix Marseille Univ, IRD, MEPHI, IHU Méditerranée Infection, Marseille, France. 122Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China. 123National Centre for Infectious Diseases, Singapore. 124Hospital Universitario Reina Sofía, Cordoba, Spain. 125Imperial College, London, England. 126Endocrinology and diabetes for children, AP-HP, Bicêtre Paris-Saclay hospital, Le Kremlin-Bicêtre, France. 127Neurology unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 128Intensive care unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. 129National Centre for Infectious Diseases; Tan Tock Seng Hospital; Yong Loo Lin School of Medicine; Lee Kong Chian School of Medicine, Singapore. 130Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 131Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 132Hospital Sant Joan de Déu and University of Barcelona, Barcelona, Spain. 133Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. 134Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona, Spain. 135IrsiCaixa AIDS Research Institute, ICREA, UVic-UCC, Research Institute “Germans Trias i Pujol”, Badalona, Spain. 136Department of Laboratory, Cruces University Hospital, Barakaldo, Bizkaia, Spain. 137University of New South Wales, Australia. 138APHP Pitié-Salpêtrière Hospital, Paris, France. 139Aix-Marseille University, APHM, Marseille, France. 140Robert Debré Hospital, Paris, France. 141APHP Cohin Hospital, Paris, France. 142Necmettin Erbakan University Meram Faculty of Medicine Department of Pediatric Infectious Diseases, Konya, Turkey. 143University Hospitals Leuven, Leuven, Belgium. 144Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France. 145Hôpital Erasme, Brussels, Belgium. 146CH Gonesse, Gonesse, France. 147Vascular Medicine, Georges Pompidou Hospital, APHP, Paris, France. 148Division of Pulmonary and Critical Care, University of Miami, Miami, USA. 149Guanarteme Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. 150Regional University Hospital of Malaga, Malaga, Spain. 151Aix-Marseille Université, Marseille, France. 152Department of General Paediatrics, Hôpital Bicêtre, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France. 153CHU de La Timone, Marseille, France. 154Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal. 155Infectious Diseases Horizontal Technlogy Centre, A*STAR; Singapore Immunology Network, A*STAR, Singapore. 156Department of Pediatrics, Complejo Hospitalario Universitario Insular-Materno Infantil, Canarian Health System, Las Palmas de Gran Canaria, Spain. 157Regional Universitary Hospital of Malaga, Málaga, Spain. 158Hospital Universitario Marqués de Valdecilla, Santander, Spain. 159Ataturk University Medical Faculty, Erzurum, Turkey. 160Bilkent University, Department of Molecular Biology and Genetics, Ankara, Turkey. 161Department of Laboratory Medicine, Karolinska Institutet, SE14186, Stockholm, Sweden. 162L'Hôpital Foch, Suresnes, France. 163Department of Immunology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. 164APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. 165Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona; CIBERER U759, ISCiii Madrid, Spain. 166Hospices Civils de Lyon, Lyon, France. 167Université de Lille, Inserm U1285, CHU Lille, Paris, France. 168Departement of General Pediatrics, University Hospital Robert Debré, APHP, Paris, France. 169Necmettin Erbakan University, Konya, Turkey. 170Germans Trias i Pujol Hospital, Badalona, Spain. 171Medical intensive care unit. Hopital de la Croix-Rousse. Hospices Civils de Lyon, Lyon, France. 172Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d'Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus., Barcelona, Spain. 173Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain, EU. University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. 174Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona, Spain. 175Consorcio Hospital General Universitario, Valencia, Spain. 176APHP Hôpitaux Universitaires Paris-Sud, Paris, France. 177Virology unit, Université de Paris, Cohin Hospital, APHP, Paris, France. 178Hospital San Pedro, Logroño, Spain. 179Respiratory medicine, Georges Pompidou Hospital, APHP, Paris, France. 180Dept. Immunology, Hospital Clínico San Carlos, Madrid, Spain. 181Service de Médecine Intensive Réanimation, Institut de Cardiologie, Hopital Pitié-Salpêtrière, Paris, France. 182CHRU de Nancy, Hôpital d'Enfants, Vandoeuvre, France. 183Chair of Nephrology, University of Brescia, Brescia, Italy. 184Department of Immunology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic. 185Clínica Universidad de Navarra, Madrid, Spain. 186HUS Helsinki University Hospital, Children and Adolescents, Rare Disease Center, and Inflammation Center, Adult Immunodeficiency Unit, Majakka, Helsinki, Finland. 187Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain. 188Hopital Européen Georges Pompidou, Paris, France. 189Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 190Critical Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. 191CHU de Saint Etienne, Saint-Priest-en-Jarez, France. 192Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 193Gustave Roussy Cancer Campus, Villejuif, France. 194Intensive Care Unit, Avicenne Hospital, APHP, Bobigny, France. 195Laboratory of Immunology and Histocompatibility, Saint-Louis Hospital, Paris University, Paris, France. 196Department of Internal Diseases and Pediatrics, Primary Immune Deficiency Research Lab, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium. 197Department of Internal Medicine, Université de Paris, INSERM, U970, PARCC, F-75015, Paris, France. 198First Division of Anesthesiology and Critical Care Medicine, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. 199Intensive Care Department, Hospital Universitari MutuaTerrassa, Universitat Barcelona, Terrassa, Spain. 200Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. 201Infanta Leonor University Hospital, Madrid, Spain. 202Hematology Department, ASST Spedali Civili di Brescia, Brescia, Italy. 203Pneumologie, Hôpital Avicenne, APHP, INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France. 204Dermatology unit, Laboratoire GAD, INSERM UMR1231 LNC, université de Bourgogne, Dijon, France. 205University Hospital of Burgos, Burgos, Spain. 206Center of Human Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 207Department of Chest Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. 208CHU de Caen, Caen, France. 209Sorbonne Université, Service de Médecine Intensive Réanimation, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. 210General Intensive Care Unit, Konya Training and Research Hospital, Konya, Turkey. 211CHU de Nancy, Nancy, France. 212University of Lyon, CIRI, INSERM U1111, National referee centre RAISE, Pediatric Rheumatology, HFME, Hospices Civils de Lyon, Lyon, France. *Leader of the COVID-clinicians group., COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT., Imagine COVID Group Christine Bole-Feysot1, Stanislas Lyonnet1*, Cécile Masson1, Patrick Nitschke1, Aurore Pouliet1, Yoann Schmitt1, Frederic Tores1, Mohammed Zarhrate1 1Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID group., French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cardiergues14, Eric D’ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent V. E. Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Treoux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22Rouen - SMIT, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d'Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28Bordeaux - SMIT, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Colombes - Louis Mourier - Gynécologie, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT; (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35hôpital la timone, Marseille, France. 36Paris - Bichat - SMIT, France., The Milieu Intérieur Consortium Laurent Abel1, Andres Alcover2, Hugues Aschard2, Kalla Astrom3, Philippe Bousso2, Pierre Bruhns2, Ana Cumano2, Caroline Demangel2, Ludovic Deriano2, James Di Santo2, Françoise Dromer2, Gérard Eberl2, Jost Enninga2, Jacques Fellay4, Ivo Gomperts-Boneca2, Milena Hasan2, Serge Hercberg5, Olivier Lantz6, Hugo Mouquet2, Etienne Patin2, Sandra Pellegrini2, Stanislas Pol7, Antonio Rausell8, Lars Rogge2, Anavaj Sakuntabhai2, Olivier Schwartz2, Benno Schwikowski2, Spencer Shorte2, Frédéric Tangy2, Antoine Toubert9, Mathilde Touvier10, Marie-Noëlle Ungeheuer2, Matthew L. Albert11*, Darragh Duffy2*, Lluis Quintana-Murci2* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2Pasteur Institute, Paris, France. 3Lund University, Lund, Sweden. 4EPFL, Lausanne, Switzerland. 5Université Paris 13, Paris, France. 6Curie Institute, Paris, France. 7Cochin Hospital, Paris, France. 8INSERM UMR 1163 – Institut Imagine. 9Hôpital Saint-Louis, Paris, France. 10Université Paris 13, Paris, France. 11In Sitro. *Co-coordinators of the Milieu Intérieur Consortium. Additional information can be found at: https://www.pasteur.fr/labex/milieu-interieur., CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cardièrgues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d'Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M'Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children’s Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University hospital Bichat Claude Bernard, Virology, F-75018 Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France . 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, BORDEAUX. 16Hôpital Hotel Dieu, APHP, Paris, France. 17ervice des explorations fonctionnelles, Hôpital Bichat- Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anne Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, O. Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno de Jong12, Rutger Koning4, Mourik van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Bennedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P. J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek18* 1Department of Infectious Diseases, Amsterdam UMC, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Netherlands. 3Experimental Immunology, Amsterdam UMC, Netherlands. 4Department of Neurology, Amsterdam UMC, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Netherlands. 7Department of Pathology, Amsterdam UMC, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Netherlands. 10Amsterdam UMC, THE NETHERLANDS Biobank Core Facility, Amsterdam UMC, Netherlands. 11Department of Radiology, Amsterdam UMC, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Netherlands. 15Deparment of Intensive Care, Amsterdam UMC, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Netherlands. 18Department of Neurology, Amsterdam UMC, Netherlands. *Leader of the AMC consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Joseph L. DeRisi21, Murkesh Desai22, Beth A. Drolet23, Sara Espinosa24, Jacques Fellay25, Carlos Flores26, Jose Luis Franco27, Peter K. Gregersen28, Filomeen Haerynck29, David Hagin30, Rabih Halwani31, Jim Heath32, Sarah E. Henrickson33, Elena Hsieh34, Kohsuke Imai35, Yuval Itan8, Timokratis Karamitros36, Kai Kisand37, Cheng-Lung Ku38, Yu-Lung Lau39, Yun Ling40, Carrie L. Lucas41, Tom Maniatis42, Davoud Mansouri43, Laszlo Marodi44, Isabelle Meyts45, Joshua Milner46, Kristina Mironska47, Trine Mogensen48, Tomohiro Morio49, Lisa P. Ng50, Luigi D. Notarangelo51, Giuseppe Novelli52, Antonio Novelli53, Cliona O'Farrelly54, Satoshi Okada55, Tayfun Ozcelik56, Rebeca Perez de Diego57, Anna M. Planas58, Carolina Prando59, Aurora Pujol60, Lluis Quintana-Murci61, Laurent Renia62, Alessandra Renieri63, Carlos Rodríguez-Gallego64, Vanessa Sancho-Shimizu65, Vijay Sankaran66, Kelly Schiabor Barrett9, Mohammed Shahrooei67, Andrew Snow68, Pere Soler-Palacín69, András N. Spaan70, Stuart Tangye71, Stuart Turvey72, Furkan Uddin73, Mohammed J. Uddin74, Diederik van de Beek75, Sara E. Vazquez76, Donald C. Vinh77, Horst von Bernuth78, Nicole Washington9, Pawel Zawadzki79, Helen C. Su51*, Jean-Laurent Casanova80* 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical immunology unit, pediatric infectious disease departement, Faculty of Medicine and Pharmacy, Averroes University Hospital. LICIA Laboratoire d'immunologie clinique, d'inflammation et d'allergie, Hassann Ii University., Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21University of California San Francisco; Chan Zuckerberg Biohub, San Francisco, CA, United States. 22Bai Jerbai Wadia Hospital for Children, Mumbai, India. 23 School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 24Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 25Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 26Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 27University of Antioquia, Medellín, Colombia. 28Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 29Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID research lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 30The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 31Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 32Institute for Systems Biology, Seattle, WA, USA. 33Children's Hospital of Philadelphia, Philadelphia, PA, USA. 34Anschutz Medical Campus, Aurora, CO, USA. 35Riken, Tokyo, Japan. 36Hellenic Pasteur Institute, Athens, Greece. 37University of Tartu, Tartu, Estonia. 38Chang Gung University, Taoyuan County, Taiwan. 39The University of Hong Kong, Hong Kong, China. 40Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 41Yale School of Medicine, New Haven, CT, USA. 42New York Genome Center, New York, NY, USA. 43Shahid Beheshti University of Medical Sciences, Tehran, Iran. 44Semmelweis University Budapest, Budapest, Hungary. 45KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 46Columbia University Medical Center, New York, NY, USA. 47University Clinic for Children's Diseases, Skopje, North Macedonia. 48Aarhus University, Aarhus, Denmark. 49Tokyo Medical & Dental University Hospital, Tokyo, Japan. 50Singapore Immunology Network, Singapore. 51National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 52Bambino Gesù Children's Hospital, Rome, Italy; Dept. Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy. 53Bambino Gesù Children's Hospital, Rome, Italy, Rome, Italy, Italy. 54Trinity College, Dublin, Ireland. 55Hiroshima University, Hiroshima, Japan. 56Bilkent University, Ankara, Turkey. 57Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid 28046, Spain, EU, Madrid, Spain, Spain. 58IIBB-CSIC, IDIBAPS, Barcelona, Spain. 59Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 60Neurometabolic Diseases Laboratory, IDIBELL- Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 61Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 62Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 63University of Siena, Siena, Italy. 64Hospital Universitario de Gran Canaria Dr Negrín, Canarian Health System, Canary Islands, Spain. 65Imperial College London, London, UK. 66Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 67Saeed Pathobiology and Genetic Lab, Tehran, Iran. 68Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, USA. 69Hospital Universitari Vall d'Hebron, Barcelona, Spain. 70University Medical Center Utrecht, Amsterdam, Netherlands. 71Garvan Institute of Medical Research, Sydney, Australia. 72The University of British Columbia, Vancouver, Canada. 73Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children's Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 74Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, Dhaka, Bangladesh. 75Amsterdam UMC, Amsterdam, Netherlands. 76University of California, San Francisco, San Francisco, CA, United States. 77McGill University Health Centre, Montreal, Canada. 78Charité - Berlin University Hospital Center, Berlin, Germany. 79Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 80Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62- IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut Institut National de la Santé et de la Recherche Médicale (INSERM) and the University of Paris. Samples from San Raffaele Hospital were obtained within the Covid-BioB project and healthcare personnel of San Raffaele Hospital, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET) clinical lab and clinical research Unit; funded by the Program Project COVID-19 OSR-UniSR and Fondazione Telethon. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). The Cov-Contact Cohort was supported by the REACTing consortium, the French Ministry of Health, and the European Commission (RECOVER WP 6). The “Milieu Intérieur” cohort was supported by was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence “Milieu Intérieur” Grant (ANR-10-LABX-69-01) (PI: L QuintanaMurci & D Duffy). The Simoa experiment was supported by the PHRC-20-0375 COVID-19 grant “DIGITAL COVID” (PI: G Gorochov). SGT is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia, and a COVID19 Rapid Response Grant awarded by UNSW Sydney. CRG and colleagues were supported by Instituto de Salud Carlos III (COV20_01333 and COV20_01334, Spanish Ministry of Science and Innovation -RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). SA and AB were supported by ANR-20-COVI-0064 (PI: A Belot). This work is supported by the French Ministry of Health “Programme Hospitalier de Recherche Clinique Inter regional 2013”, by the Contrat de Plan Etat-Lorraine and FEDER Lorraine, and a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project “Lorraine Université d’Excellence”, reference ANR15-IDEX-04-LUE (45) and biobanking is performed by the Biological Resource Center Lorrain BB-0033-00035. This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology and by a grant from the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to FRL), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. The Amsterdam UMC Covid-19 Biobank was supported by grants of the Amsterdam Corona Research Fund, Dr. C.J. Vaillant Fund, and Netherlands Organization for Health Research and Development (ZonMw; NWO-Vici-Grant [grant number 918·19·627 to DvdB]. This work was also supported by the Division of Intramural Research of the National Institute of Dental Craniofacial Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e comorbidita”). The opinions and assertions expressed herein are those of the author(s) and do not necessarily reflect the official policy or position of the Uniformed Services University or the Department of Defense. JH holds an Institut Imagine MD-PhD fellowship from the Fondation Bettencourt Schueller. JR is supported by the Inserm PhD program (“poste d’accueil Inserm”). PB was supported by the French Foundation for Medical Research (FRM, EA20170638020) and the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). We thank the Association “Turner et vous” for their help and support. Sample processing at IrsiCaixa was possible thanks to the crowdfunding initiative YoMeCorono. DCV is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. K. Kisand was supported by the Estonian Research Council grant PUT1367. We thank the GEN-COVID Multicenter Study (https://sites.google.com/dbm.unisi.it/gen-covid). We thank the NIAID Office of Cyber Infrastructure and Computational Biology, Bioinformatics and Computational Biosciences Branch (Contract HHSN316201300006W/HHSN27200002 to MSC, Inc) and Operations Engineering Branch for developing the HGRepo system to enable streamlined access to the data and the NCI Advanced Biomedical Computational Science (ABCS) for data transformation support.
Published: 2020

12. Restrictive spirometry pattern is associated with low physical activity levels. A population based international study

Author: Valeria Bellisario, Anne-Elie Carsin, Cecilie Svanes, Chantal Raherison, Bénédicte Leynaert, Elaine Fuertes, Stefano Guerra, José Luis Sánchez Ramos, Emmanuel Schaffner, Joachim Heinrich, Thorarinn Gislason, Nicole Probst-Hensch, Christer Janson, Medea Imboden, Isabelle Pin, Josep M. Antó, Pascal Demoly, Jesús Martínez-Moratalla, Kjell Torén, José Antonio Gullón, Isa Cerveri, Francisco Gómez Real, Bertil Forsberg, Joost Weyler, Anna Beckmeyer-Borowko, Silvia Pascual, Dirk Keidel, Rain Jõgi, Dennis Nowak, Margareta Emtner, Seraina Caviezel, Simone Accordini, Wasif Raza, Judith Garcia-Aymerich, Shyamali C. Dharmage, Deborah Jarvis, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, University Hospital Basel [Basel], Imperial College London, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Helmholtz Zentrum München = German Research Center for Environmental Health, German Centre for Lung Research, Partenaires INRAE, School of Medicine [University of Melbourne], University of Melbourne, Haukeland University Hospital, University of Bergen (UiB), Universiteit Antwerpen = University of Antwerpen [Antwerpen], Ludwig Maximilian University [Munich] (LMU), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Respiratory Department, Hospital Universitario San Agustín (HUSA), Universidad de Huelva, Swiss Tropical and Public Health Institute [Basel], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université (SU), IRCCS 'San Matteo' Hospital Foundation [Pavie, Italie], Università degli Studi di Pavia = University of Pavia (UNIPV), University Hospital of Verona, Landspitali National University Hospital of Iceland, Göteborgs Universitet (GU), Uppsala University Hospital, University of Tartu, Umeå University, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Galdakao Hospital, University of Arizona, Melbourne School of Population and Global Health [Melbourne], Universitat Pompeu Fabra [Barcelona] (UPF), Salvy-Córdoba, Nathalie, Helmholtz-Zentrum München (HZM), University of Turin, Universiteit Antwerpen [Antwerpen], Universidad de Castilla-La Mancha (UCLM), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), University of Pavia, Department of Pulmonary Medicine, University of Tartu and Lung Clinic, Tartu University Hospital, Tartu, Estonia, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Medical Research Council (MRC), and Commission of the European Communities
Subjects: Male, DISORDER, Cardiac & Cardiovascular Systems, Cross-sectional study, Epidemiology, Vital Capacity, Respiratory System, ACTIVITY QUESTIONNAIRE, Disease, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, DISEASE, 0302 clinical medicine, Forced Expiratory Volume, Prevalence, Prospective Studies, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Prospective cohort study, Lung, Body mass index, RISK, medicine.diagnostic_test, Middle Aged, IMPAIRMENT, Respiratory Function Tests, 3. Good health, Europe, LUNG-FUNCTION, medicine.anatomical_structure, Lung function, Physical activity, Restrictive spirometry pattern, Female, Life Sciences & Biomedicine, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, MESH: Exercise / physiology, Lung / physiopathology, Lung Diseases, Obstructive / physiopathology, Obesity / epidemiology, Spirometry / adverse effects, NATIONAL-HEALTH, Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, Restrictive Spirometry Pattern, Body Mass Index, Lung Function, Physical Activity, 1102 Cardiovascular Medicine And Haematology, EVENTS, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Internal medicine, medicine, Humans, Lung Diseases, Obstructive, Obesity, Exercise, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Science & Technology, business.industry, MORTALITY, 1103 Clinical Sciences, medicine.disease, Cross-Sectional Studies, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cardiovascular System & Cardiology, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, business
Abstract: Introduction: Restrictive spirometry pattern is an under-recognised disorder with a poor morbidity and mortality prognosis. We compared physical activity levels between adults with a restrictive spirometry pattern and with normal spirometry. Methods: Restrictive spirometry pattern was defined as a having post-bronchodilator FEV1/FVC ≥ Lower Limit of Normal and a FVC
Published: 2019

13. Pharmacological treatment of asthma in a cohort of adults during a 20-year period : results from the European Community Respiratory Health Survey I, II and III

Author: Christer Janson, Simone Accordini, Lucia Cazzoletti, Isa Cerveri, Sebastien Chanoine, Angelo Corsico, Diogenes Seraphim Ferreira, Judith Garcia-Aymerich, David Gislason, Rune Nielsen, Ane Johannessen, Rain Jogi, Andrei Malinovschi, Jesús Martinez-Moratalla Rovira, Alessandro Marcon, Isabelle Pin, Jennifer Quint, Valerie Siroux, Enrique Almar, Valeria Bellisario, Karl A. Franklin, José A. Gullón, Mathias Holm, Joachim Heinrich, Dennis Nowak, José Luis Sánchez-Ramos, Joost J. Weyler, Deborah Jarvis, The members of the ECRHS I scientific team., P. Burney, S. Chinn, C. Luczynska, D. Jarvis, E. Lai, P. Vermeire, H. Kesteloot, J. Bousquet, D. Nowak, J. Prichard, R. de Marco, B. Rijcken, J.M. Anto, J. Sunyer, J. Alves, G. Boman, N. Nielsen, P. Paoletti, M. Abramson, J. Kutin, F. van Bastelaer, R. Jõgi, A. Taytard, I. Pin, C. Pison, F. Neukirch, R. Liard, J. Knani, H-E. Wichmann, J. Heinrich, H. Magnussen, T. Gislason, D. Gislason, A. Marinoni, I. Cerveri, M. Bugiani, C. Bucca, C. Romano, L. Cascio, C. Campello, J. Droste, M. Kerkhof, A. Gulsvik, E. Omenaas, J. Martinez-Moratalla, E. Almar, A. Mateos, M. Arévalo, A. Sánchez, M. Vizcaya, X. Aguilar, A. Teixidó, J.M. Antó, M. Kogevinas, F. Burgos, J. Castellsagué, J. Roca, JB. Soriano, A. Tobías, N. Muiñozguren, J. Ramos González, A. Capelastegui, J. Maldonado Pérez, A. Pereira, J. Sánchez, J. Quiros, I. Huerta, F. Payo, N. Lindholm, P. Plaschke, C. Janson, E. Björnsson, L. Rosenhall, E. Norrman, B. Lundbäck, U. Ackermann-Liebrich, N. Küenzli, A. Perruchoud, M. Burr, J. Layzell, R. Hall, B. Harrison, The members of the ECRHS II scientific team., J. Knox, M. Wjst, N. Kuenzli, E.H. Walters, J. Raven, J. Weyler, M. van Sprundel, V. Nelen, A. Soon, C. Raherison, J. Ferran-Quentin, B. Leynaert, M. Zureik, P.J. Bousquet, C. Frye, I. Meyer, E. Bjornsson, K.B. Jörundsdóttir, S. Villani, M. Ponzio, F. Frigerio, M. Comelli, M. Grassi, A. Corsico, R. Bono, P. Piccioni, E. Caria, A. Carosso, E. Migliore, G. Castiglioni, G. Verlato, E. Zanolin, S. Accordini, A. Poli, V. Lo Cascio, M. Ferrari, I. Cazzoletti, C. Svanes, B. Laerum, J. Martinez-Moratalla Rovira, C. Boix, G. González, J.M. Ignacio García, J. Solera, J. Damián, J.P. Zock, X. Basagaña, A. Jaen, C. Acosta, N. Muñozguren, J. Ramos, I. Urrutia, U. Aguirre, J. Maldonado, J.L. Sanchez, A. de la Vega, L. Palenciano, J. Azofra, A. Cañada, K. Toren, L. Lillienberg, A.C. Olin, B. Balder, A. Pfeifer-Nilsson, R. Sundberg, D. Norback, G. Wieslander, M. Gunnbjornsdottir, M. Soderberg, K.A. Franklin, B. Lundback, B. Forsberg, L. Nystrom, B. Dibbert, M. Hazenkamp, M. Brutsche, D. Seaton, The members of the ECRHS III scientific team., M. Tumilty, J. Potts, T. Gislasson, T. Rochat, B. Leyneart, G. Benke, S. Dharmage, B. Thompson, S. Kaushik, M. Matheson, H. Bentouhami, H. Orru, P.O. Girodet, V. Siroux, J. Ferran, J.L. Cracowski, P. Demoly, A. Bourdin, I. Vachier, D. Soussan, D. Courbon, C. Neukirch, L. Alavoine, X. Duval, I. Poirier, E. Becker, G. Woelke, O. Manuwald, A-M. Kirsten, B. Benediktsdottir, E.S. Arnardottir, M. Clausen, G. Gudmundsson, L. Gudmundsdottir, H. Palsdottir, K. Olafsdottir, S. Sigmundsdottir, K. Bara-Jörundsdottir, A. Grosso, F. Albicini, E. Gini, E.M. Di Vincenzo, V. Ronzoni, F. Campanella, M. Gnesi, F. Manzoni, L. Rossi, O. Ferraro, R. Tassinari, V. Bellisario, G. Trucco, L. Calciano, L. Cazzoletti, A.M. Fratta Pasini, F. Locatelli, P. Marchetti, A. Marcon, E. Montoli, G. Nguyen, M. Olivieri, C. Papadopoulou, C. Posenato, G. Pesce, P. Vallerio, H.M. Boezen, A. Johannessen, T. Skorge, F. Gomez Real, S. García, A. Núñez, P. López, R. Sánchez, E. Mancebo, J-M. Antó, J. Garcia-Aymerich, A.E. Carsin, C. Sanjuas, S. Guerra, B. Jacquemin, P. Davdand Galdakao, S. Pascual, J. Antonio Maldonado, J.L. Sánchez, L. Palacios, N. Sánchez, M. Fernández, B. Robles, K. Torén, M. Holm, J-L. Kim, A-C. Olin, A. Dahlman-Höglund, L. Braback, L. Modig, B. Järvholm, K.A. Bertilsson, H. Franklin, C. Wahlgreen, B. Andersson, U. Spetz Nystrom, G.M. Bodinaa Lund, K. Nisser, N.M. Probst-Hensch, N. Künzli, D. Stolz, C. Schindler, J.M. Gaspoz, E. Zemp Stutz, M. Adam, C. Autenrieth, I. Curjuric, J. Dratva, A. Di Pasquale, R. Ducret-Stich, E. Fischer, L. Grize, A. Hensel, D. Keidel, A. Kumar, M. Imboden, N. Maire, A. Mehta, H. Phuleria, M. Ragettli, M. Ritter, E. Schaffner, G.A. Thun, A. Ineichen, T. Schikowski, M. Tarantino, M. Tsai, S. Kapur, R. Newson, N. Innes, A. Wilson, Uppsala University, National Heart and Lung Institute [London] (NHLI), Royal Brompton and Harefield NHS Foundation Trust-Imperial College London, University of Verona (UNIVR), University of Pavia, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Monash University [Melbourne], Universidade Federal do Parana [Curitiba] (UFPR), Universidade Federal do Paraná (UFPR), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Landspitali National University Hospital of Iceland, Haukeland University Hospital, University of Bergen (UiB), Tartu University Hospital [Tartu, Estonia], Complejo Hospitalario Universitario de Albacete, University of Castilla-La Mancha (UCLM), Service de chirurgie pédiatrique [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), Service of the Health Delegation of Albacete [Albacete, Spain], University of Turin, Umeå University, Universidad Nacional de San Agustín (UNSA), University of Gothenburg (GU), Ludwig Maximilian University [Munich] (LMU), Helmholtz-Zentrum München (HZM), Melbourne School of Population and Global Health [Melbourne], University of Melbourne, German Center for Lung Research - DZL [Munich, Germany], Universidad de Huelva, University of Antwerp (UA), Medical Research Council (MRC), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Università degli studi di Verona = University of Verona (UNIVR), Università degli Studi di Pavia = University of Pavia (UNIPV), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Università degli studi di Torino = University of Turin (UNITO), Helmholtz Zentrum München = German Research Center for Environmental Health, and Siroux, Valérie
Subjects: Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, European community, Period (gene), Respiratory Medicine and Allergy, MEDLINE, lcsh:Medicine, ECRHS, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Pharmacological treatment, 03 medical and health sciences, 0302 clinical medicine, Medicine, 030212 general & internal medicine, Respiratory health, Asthma, Lungmedicin och allergi, Asthma, treatment, ECRHS, treatment, business.industry, lcsh:R, Original Articles, medicine.disease, 3. Good health, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Cohort, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma., Despite increased ICS use, only 34% of subjects with persistent asthma take ICSs on a regular basis
Published: 2019

14. Associations of Cardiovascular Health Metrics in Childhood and Adolescence With Arterial Health Indicators in Adolescence: The PANIC Study.

Author: Kraav J, Zagura M, Viitasalo A, Soininen S, Veijalainen A, Kähönen M, Jürimäe J, Tillmann V, Haapala E, and Lakka T
Abstract: Background: Our aim was to assess the relationships of cardiovascular health metrics, cardiorespiratory fitness, lean mass, and fat percentage with arterial structure and function from childhood to adolescence., Methods and Results: Five hundred four children aged 6 to 9 years were examined in the PANIC (Physical Activity and Nutrition in Children) study at baseline, 2 and 8 years later. The associations of adjusted American Heart Association cardiovascular health metrics (smoking status, body mass index-SD score, moderate-to-vigorous physical activity, diet quality, plasma total cholesterol, systolic blood pressure, plasma glucose categorized into poor, intermediate, and ideal), the American Heart Association cardiovascular health score, cardiorespiratory fitness measured by maximal oxygen uptake in a bicycle exercise test, lean mass and fat percentage with carotid intima-media thickness (cIMT) and pulse wave velocity (PWV) were analyzed cross-sectionally and longitudinally in 277 participants at age 15 to 17 years. Higher American Heart Association cardiovascular health score at baseline was associated with lower PWV at 8-year follow-up (ß, -0.19 [95% CI, -0.32 to -0.05]). Higher body mass index-SD score and systolic blood pressure were associated with higher cIMT (ß, 0.18 [95% CI, 0.05-0.31]); and (ß, 0.13 [95% CI, 0.00-0.25]; respectively) and PWV (ß, 0.20 [95% CI, 0.07-0.34]) and (ß, 0.13 [95% CI, 0.00-0.26]; respectively) at 8-year follow-up. Higher moderate-to-vigorous physical activity was associated with higher cIMT (ß, 0.25 [95% CI, 0.07-0.43]); yet lower PWV (ß, -0.25 [95% CI, -0.44 to -0.06]) at 8-year follow-up. Better cardiorespiratory fitness (ß, 0.29 [95% CI, 0.08-0.51]) and higher lean mass (ß, 0.51 [95% CI, 0.03-0.98]) were associated with higher cIMT after accounting for American Heart Association cardiovascular health score at 8-year follow-up., Conclusions: While our results suggest that higher cardiometabolic risk factors in childhood may exert unfavorable effects on arterial health during adolescence, we demonstrated the complexity of relationships between cardiovascular health metrics and arterial health indicators in childhood and adolescence. We found different associations of cardiovascular health metrics with cIMT and PWV in childhood and adolescence, calling for caution when interpreting the results of various cardiovascular risk factors with measures of arterial health, particularly in youth., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01803776.
Published: 2024
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15. CILP-2 expression in the intervertebral discs of patients with lumbar radiculopathy.

Author: Kõiv K, Aunapuu M, Torga T, Rätsep T, Bakhoff K, and Arend A
Subjects: Humans, Middle Aged, Male, Female, Adult, Aged, Extracellular Matrix Proteins metabolism, Pain Measurement, Radiculopathy metabolism, Radiculopathy pathology, Radiculopathy surgery, Lumbar Vertebrae surgery, Lumbar Vertebrae pathology, Intervertebral Disc Degeneration metabolism, Intervertebral Disc Degeneration surgery, Intervertebral Disc Degeneration pathology, Intervertebral Disc pathology, Intervertebral Disc metabolism, Intervertebral Disc surgery
Abstract: Background: Intervertebral disc (IVD) degeneration (IVDD) is one of the main causes of low back pain. One of the most important features of IVDD is the loss of extracellular matrix (ECM) with its structural components. Cartilage intermediate layer proteins (CILPs), minor glycoproteins residing in ECM, have been found to be increased in IVD as degeneration and aging progresses. The aim of the present study was to evaluate the expression of CILP-2 in the IVD of patients with lumbar radiculopathy., Methods: The IVD samples were collected from 25 patients during spinal surgery (interlaminectomy, herniated disc removal). The control IVD samples were obtained from nine patients who underwent lateral corpectomies in the thoracic region. CILP-2 expression was detected by immunohistochemistry. The patients were divided into two groups - aged under or over 50 years. A standardized clinical examination with assessment of radicular signs and deficits was performed. Subjective disability and pain were assessed using the visual analogue scale and Oswestry Disability Index (ODI). The pre-operative MRI was graded for the degree of IVD degeneration by Pfirrmann grading system. IVD samples obtained during operations were subjected to the standardized histopathological analysis applying modified Boos classification. The data were analysed by t-test, Mann-Whitney U-test, and Spearman correlation test., Results: Both histopathology scores and Pfirrmann grades did not differ between patients' groups. Also, no correlations were found between histopathology and Pfirrmann grades, neither were any differences seen when correlating both grades to ODI, back pain or leg pain scores. CILP-2 staining was noted in all studied samples, notably strong staining was seen around large cell clusters. However, no differences in CILP-2 staining were seen between the age groups of patients. No correlations were found between CILP-2 staining and Pfirrmann grades. Grading of CILP-2 immunostaining in nine control patient samples resulted in significantly lower values. The difference is statistically significant (P = 0.002) compared to CILP-2 staining scores of all 25 patients' samples., Conclusion: In this study, we detected increased CILP-2 expression in the human IVD as compared to the control group patients. CILP-2 can be a possible IVDD marker; however, as knowledge about the role of CILP-2 is limited, further studies are required., (© 2024. The Author(s).)
Published: 2024
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16. Gastrointestinal ultrasound in the critically ill: A narrative review and a proposal for a protocol.

Author: Mihnovits V, Reintam Blaser A, Gualdi T, Forbes A, and Piton G
Subjects: Humans, Clinical Protocols, Critical Care methods, Critical Illness, Ultrasonography methods, Gastrointestinal Tract diagnostic imaging, Gastrointestinal Diseases diagnostic imaging, Enteral Nutrition methods, Intensive Care Units
Abstract: Critically ill patients are at risk of presenting with gastrointestinal dysfunction at intensive care unit admission or during their stay. However, identifying gastrointestinal dysfunction is difficult because clinical evaluation is frequently nonspecific and validated biomarkers are lacking. In this context, ultrasound of the digestive tract may help to identify gastrointestinal dysfunction. In this narrative review, we summarize available evidence and propose a protocol for assessment of the gastrointestinal tract with ultrasound. First, we report available evidence from use of four available protocols: the gastrointestinal and urinary tract sonography protocol, the acute gastrointestinal injury ultrasound score, the transabdominal gastrointestinal ultrasound protocol, and the Lai protocol, each addressing somewhat different aspects. Outputs from these protocols have been associated with clinical scores of gastrointestinal failure, feeding intolerance, and 28-day mortality. Second, we describe the potential pitfalls of using ultrasound in the critically ill, such as obesity, abdominal dressings, or the presence of intraluminal gas. Third, we suggest perspectives of ultrasound in monitoring the response to enteral nutrition and for early identification of nonocclusive mesenteric ischemia. Fourth, we propose a structured protocol for gastrointestinal ultrasound describing all the different structures that should be evaluated and provide detailed guidance for a clockwise abdominal examination. In conclusion, the use of a specific and structured protocol might help to identify patients presenting with gastrointestinal dysfunction, guide nutrition, and allow the proposal of pathophysiological hypotheses (complications of enteral nutrition, intra-abdominal infection, bowel ischemia, etc.). The benefit of using a structured protocol requires further investigation., (© 2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)
Published: 2024
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17. Genetic susceptibility to temporomandibular joint involvement in juvenile idiopathic arthritis.

Author: Niibo P, Nikopensius T, Jagomägi T, Voog Ü, Haller T, Tõnisson N, Metspalu A, Saag M, and Pruunsild C
Subjects: Humans, Female, Male, Child, Adolescent, Genotype, Polymorphism, Single Nucleotide, Case-Control Studies, Temporomandibular Joint physiopathology, Arthritis, Juvenile genetics, Arthritis, Juvenile physiopathology, Temporomandibular Joint Disorders genetics, Temporomandibular Joint Disorders physiopathology, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract: Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Temporomandibular joint (TMJ) is among the most commonly affected joints in JIA patients. When JIA involves the TMJ, it may affect condylar growth in the joint; therefore, JIA patients are at risk of unfavourable long-term outcomes from associated joint damage. If undetected, TMJ involvement can lead to various functional disabilities such as reduced mandibular mobility and disorders of the mastication muscles. Limitations in sagittal and vertical mandibular growth can result in micrognathia and anterior open bite with aesthetic and functional restrictions., Objective: Genetic factors may play a role in determining which individuals are more prone to develop TMJ disorders or in predicting the severity of the disease process. Therefore, we applied a GWAS approach to identify loci associated with TMJ involvement in a sample of Estonian patients with JIA. Our aim was to address the potential role of genetic susceptibility factors in TMJ-JIA, a condition not previously studied in this context., Methods: The case group consisted of 55 JIA patients with TMJ involvement and 208 patients without TMJ involvement comprised the control group. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. Imputation was performed using a nationwide reference panel obtained of 2240 individuals whose data were obtained from the Estonian Biobank., Results: We identified six loci as being associated with the risk of TMJ-JIA in Estonian JIA patients. The strongest associations were identified at CD6 rs3019551 (P = 3.80 × 10 -6 ), SLC26A8/MAPK14 rs9470191 (P = 6.15 × 10 -6 ), NLRP3 rs2056795 (P = 8.91 × 10 -6 ) and MAP2K4 rs7225328 (P = 1.64 × 10 -5 )., Conclusion: This study provides first insights into the risk-associated loci between JIA and its manifestation in the TMJ. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that render the TMJ susceptible to involvement by JIA in Estonian patients., (© 2024 John Wiley & Sons Ltd.)
Published: 2024
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18. Disease Burden and Access to Biologic Therapy in Patients with Severe Asthma, 2017-2022: An Analysis of the International Severe Asthma Registry.

Author: Le TT, Price DB, Erhard C, Cook B, Quinton A, Katial R, Christoff GC, Perez-de-Llano L, Altraja A, Bergeron C, Bourdin A, Koh MS, Lehtimäki L, Mahboub B, Papadopoulos NG, Pfeffer P, Rhee CK, Carter V, Martin N, and Tran TN
Abstract: Introduction: Patients with severe asthma may be prescribed biologic therapies to improve disease control. The EVEREST study aimed to characterize the global disease burden of patients with severe asthma without access to biologics and those who have access but do not receive biologics, as well as the remaining unmet need despite use of these therapies., Methods: This was a historical cohort study of patients with severe asthma (aged ≥18 years) in the International Severe Asthma Registry receiving Global Initiative for Asthma (GINA) 2018 step 5 treatment, or with uncontrolled disease at GINA step 4. Prospective data on patient clinical characteristics, healthcare resource utilization, and medication use over a 12-month period between December 2017 and May 2022 were assessed for the following five groups: biologics accessible (omalizumab, mepolizumab, reslizumab, benralizumab, or dupilumab); biologics inaccessible; biologics accessible but not received; biologics accessible and received; and biologic recipients whose asthma remained suboptimally controlled., Results: Overall, 9587 patients from 21 countries were included. Among patients in the biologics accessible (n=5073), biologics inaccessible (n=3041), and biologics accessible but not received (n=382) groups, 41.4%, 18.7%, and 49.6% experienced at least two exacerbations, 11.5%, 10.5%, and 6.2% required at least one hospitalization, 47.9%, 54.6%, and 71.2% had uncontrolled asthma, and 23.9%, 8.6%, and 11.0% received long-term oral corticosteroids (LTOCS), respectively. Following biologic therapy, among patients who received biologics overall (n=2666) and among those whose asthma remained suboptimally controlled (n=1780), 19.1% and 23.0% experienced at least two exacerbations, 2.7% and 2.9% required at least one hospitalization, and 16.7% and 22.0% received LTOCS, respectively., Conclusion: There is a substantial disease burden in both patients without access to biologics and those with access who do not receive these therapies, although specific outcomes may vary between these groups. There also remains a high unmet need among biologic recipients, many of whom have a suboptimal response to treatment., Competing Interests: Tham T. Le, Clement Erhard, Bill Cook, Anna Quinton, Neil Martin, and Trung N. Tran are employees of AstraZeneca and may own stock or stock options in AstraZeneca. David B Price has participated in advisory boards with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Thermo Fisher, and Viatris; has consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GSK, Medscape, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, Theravance, and Viatris; has received grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, the UK National Health Service, and Viatris; has received payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GSK, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, and Viatris; has received payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Circassia, Mundipharma, Novartis, Teva Pharmaceuticals, and Thermo Fisher; has received funding for patient enrollment or completion of research from Novartis; has stock or stock options with AKL Research and Development Ltd; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); owns 5% shareholding in Timestamp; is a peer reviewer for Health Technology Assessment and the grant committees of the UK Efficacy and Mechanism Evaluation Programme; and was an expert witness for GSK. Rohit Katial is a former employee of AstraZeneca and has been an advisory board participant and speaker for GSK and Sanofi/Regeneron. Luis Perez-de-Llano has received grants from AstraZeneca, Chiesi, and Teva Pharmaceuticals; personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, FAES, GEBRO, GSK, Mundipharma, Novartis, Sanofi, and Teva Pharmaceuticals; and nonfinancial support from Boehringer Ingelheim, Esteve, GSK, Menarini, Mundipharma, Novartis, and Teva Pharmaceuticals. Alan Altraja has received lecture fees from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, CSL Behring, GSK, MSD, Norameda, Novartis, Orion, Sanofi Regeneron, and Zentiva; sponsorships from AstraZeneca, Berlin-Chemie Menarini, Boehringer Ingelheim, CSL Behring, GSK, MSD, Norameda, Novartis, and Sanofi Regeneron; and has participated in advisory boards for AstraZeneca, Boehringer Ingelheim, CSL Behring, GSK, Novartis, Sanofi Regeneron, and Teva Pharmaceuticals. Celine Bergeron has participated in advisory boards for GSK, Sanofi-Regeneron, AstraZeneca, Amgen, Takeda, and Valeo Pharma; has received honoraria for presentations for AstraZeneca, Amgen, Grifols, GSK, Sanofi-Regeneron, and Valeo Pharma; and her institution has received grants from AstraZeneca, Biohaven, GSK, OPRI/ISAR, Novartis, Sanofi-Regeneron and Teva. Arnaud Bourdin has received industry-sponsored grants from AstraZeneca, Boehringer Ingelheim, Cephalon/Teva, GSK, Novartis, and Sanofi-Regeneron; and been a consultant for Actelion, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, MedinCell, Merck, Novartis, Regeneron-Sanofi, and Roche. Mariko Siyue Koh has received grants from AstraZeneca; and honoraria for lectures and advisory board meetings paid to her hospital (Singapore General Hospital) from GSK, AstraZeneca, Boehringer Ingelheim, Novartis, Roche, and Sanofi. Lauri Lehtimäki has received personal fees from ALK, AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis, Orion Pharma, and Sanofi. Nikolaos G Papadopoulos has been a speaker and/or advisory board member for Abbott, AbbVie, ALK, Asit Biotech, AstraZeneca, Biomay, Boehringer Ingelheim, GSK, HAL, Faes Farma, Medscape, Menarini, MSD, Mylan, Novartis, Nutricia, OM Pharma, Regeneron, Sanofi, Takeda, and Viatris. Paul Pfeffer has attended advisory boards for AstraZeneca, GSK, and Sanofi; has given lectures at meetings supported by AstraZeneca and GSK; has taken part in clinical trials sponsored by AstraZeneca, GSK, Novartis, and Sanofi, for which his institution received remuneration; has received speaker fee from Chiesi for an educational webinar and has a current research grant funded by GSK. Chin Kook Rhee received consulting/lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, GSK, MSD, Mundipharma, Novartis, Sanofi, Takeda, and Teva. Victoria Carter is an employee of Optimum Patient Care, a co-funder of ISAR. The authors report no other conflicts of interest in this work., (© 2024 Le et al.)
Published: 2024
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19. Integration of genetic and chromatin modification data pinpoints autoimmune-specific remodeling of enhancer landscape in CD4 + T cells.

Author: Daga N, Servaas NH, Kisand K, Moonen D, Arnold C, Reyes-Palomares A, Kaleviste E, Kingo K, Kuuse R, Ulst K, Steinmetz L, Peterson P, Nakic N, and Zaugg JB
Subjects: Humans, Polymorphism, Single Nucleotide, Autoimmune Diseases genetics, Autoimmune Diseases immunology, Autoimmune Diseases pathology, Gene Regulatory Networks, Chromatin Assembly and Disassembly, Autoimmunity genetics, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Enhancer Elements, Genetic genetics, Chromatin metabolism
Abstract: CD4 + T cells play a crucial role in adaptive immune responses and have been implicated in the pathogenesis of autoimmune diseases (ADs). Despite numerous studies, the molecular mechanisms underlying T cell dysregulation in ADs remain incompletely understood. Here, we used chromatin immunoprecipitation (ChIP)-sequencing of active chromatin and transcriptomic data from CD4 + T cells of healthy donors and patients with systemic lupus erythematosus (SLE), psoriasis, juvenile idiopathic arthritis (JIA), and Graves' disease to investigate the role of enhancers in AD pathogenesis. By generating enhancer-based gene regulatory networks (eGRNs), we identified disease-specific dysregulated pathways and potential downstream target genes of enhancers harboring AD-associated single-nucleotide polymorphisms (SNPs), which we also validated using chromatin-capture (HiC) data and CRISPR interference (CRISPRi) in primary CD4 + T cells. Our results suggest that alterations in the regulatory landscapes of CD4 + T cells, including enhancers, contribute to the development of ADs and provide a basis for developing new therapeutic approaches., Competing Interests: Declaration of interests The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2024
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20. Harmonizing neuropathic pain research: outcomes of the London consensus meeting on peripheral tissue studies.

Author: Villa S, Aasvang EK, Attal N, Baron R, Bourinet E, Calvo M, Finnerup NB, Galosi E, Hockley JRF, Karlsson P, Kemp H, Körner J, Kutafina E, Lampert A, Mürk M, Nochi Z, Price TJ, Rice ASC, Sommer C, Taba P, Themistocleous AC, Treede RD, Truini A, Üçeyler N, Bennett DL, Schmid AB, and Denk F
Abstract: Abstract: Neuropathic pain remains difficult to treat, with drug development hampered by an incomplete understanding of the pathogenesis of the condition, as well as a lack of biomarkers. The problem is compounded by the scarcity of relevant human peripheral tissues, including skin, nerves, and dorsal root ganglia. Efforts to obtain such samples are accelerating, increasing the need for standardisation across laboratories. In this white paper, we report on a consensus meeting attended by neuropathic pain experts, designed to accelerate protocol alignment and harmonization of studies involving relevant peripheral tissues. The meeting was held in London in March 2024 and attended by 28 networking partners, including industry and patient representatives. We achieved consensus on minimal recommended phenotyping, harmonised wet laboratory protocols, statistical design, reporting, and data sharing. Here, we also share a variety of relevant standard operating procedures as supplementary protocols. We envision that our recommendations will help unify human tissue research in the field and accelerate our understanding of how abnormal interactions between sensory neurons and their local peripheral environment contribute towards neuropathic pain., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)
Published: 2024
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21. Gender- and personality-specific differences in academic qualifications, research motivation, and attractiveness of leadership positions: a survey among radiologists from Germany.

Author: Molwitz I, Kemper C, Stahlmann K, Yamamura J, Adam G, Langenbach MC, Reim M, Wegner F, Bannas P, Lotz J, Can E, Zagrosek-Regitz V, Hamm B, and Keller-Yamamura S
Abstract: This study investigated gender- and personality-specific differences in academic qualifications, research motivation, and options to increase the attractiveness of leadership positions in radiology.A validated questionnaire with 66 questions was distributed via the German Roentgen Society and individually sent to 4,500 radiologists in Germany. Participants were asked about their gender. Personality dimensions were assessed using the OCEAN (Big Five) model. Multivariable regression analyses were employed.Of 510 included participants (women 237 (46.5%)), men were four times more likely to have acquired an associated professorship (AP, Habilitation Privatdozent) ((odds ratio (OR) 4.39 (2.22-8.67)). Also, they planned to achieve an AP more frequently (OR 2.87 (1.47-5.61)). The only gender-specific motivator for an AP was the option to become eligible for the position of chief physician (men OR 2.56 (1.07-6.15)). Mentors increased the probability of acquiring an AP (OR 2.07 (1.13-3.80)) or striving for an AP (4.82 (2.39-9.73)). Female mentees were likelier to have female mentors (OR 4.62 (1.68-12.73)). To increase the attractiveness of leadership positions, female radiologists perceived gender balance at the management level (OR 3.32 (2.28-4.82)), top sharing (OR 2.22 (1.48-3.32)), and better work-life balance (OR 2.02 (1.19-3.43)) as more relevant than male radiologists. More pronounced openness (OR 1.62 (1.10-2.38)) and extroversion (OR 1.45 (1.07-1.97)) were positively associated with planning an AP. More pronounced agreeableness (OR 0.67 (0.50-0.91)) was negatively associated.Research motivation is mainly independent of gender. Academic qualification varies with gender and personality dimensions. Mentoring, female role models, top sharing, and better work-family compatibility could motivate women to pursue academic leadership. · Male radiologists are more frequently motivated to pursue an associated professorship by the option of becoming a chief physician.. · Openness and extroversion make pursuing an associated professorship more likely.. · Role models at the management level, top sharing, and flexible work time are more important for female radiologists.. · Molwitz I, Kemper C, Stahlmann K et al. Gender- and personality-specific differences in academic qualifications, research motivation, and attractiveness of leadership positions: a survey among radiologists from Germany. Fortschr Röntgenstr 2024; DOI 10.1055/a-2415-7337., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)
Published: 2024
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22. Pituitary gland duplication syndrome - An international imaging analysis.

Author: Löbel U, Catala M, D'Arco F, Lequin MH, Pasquariello R, Ilves P, Loorits D, Tähepõld A, Pezzetti G, Craven I, Severino M, and Rossi A
Abstract: Background and Purpose: Duplication of the pituitary gland is a rare developmental anomaly. Multiple associated craniofacial malformations have previously been reported with the largest series to date consisting of five patients. In this multi-institutional series of ten patients, we present a detailed review of the imaging features and discuss a possible overarching pathogenesis that would explain most of the detected malformations., Materials and Methods: Inclusion criteria for this retrospective imaging review were the presence of a pituitary stalk and gland duplication and the characteristic appearance of the hypothalamic ventral midline. In addition to the clinical presentation, we recorded the imaging findings of ten patients (9 female) through onsite and online reviews. Genetic analysis was available for six patients., Results: The duplicated pituitary stalk and gland showed normal imaging appearances in all patients. Mammillary bodies were clearly identified lateral to the characteristic prominence of the hypothalamic ventral midline. Strands of tissue extending to the anterior dura ("limited ventral myeloschisis") were noted at the medulla oblongata in 10, and at the cervical spinal cord in 7 patients. The medulla oblongata showed a "butterfly" appearance on axial images in 9 patients. Ten patients had cervical segmentation anomalies ("zipper"-like), 9 anterior-posterior brainstem patterning defects (small pons, elongated medulla), and corpus callosum measurements were abnormal in all patients. Three patients each presented with diencephalic-mesencephalic junction abnormalities and 4 with an anterior mesencephalic "cap". An oropharyngeal teratoma was present in four patients. Genetics was normal in three of the six patients studied; the remainder were found to have mutations in EFNB1 and a gene variant of GIT1 , two copies of 7. And 8. exon of SMN1 gene, and 2.126 megabase duplication at bands q11.1 and q11.2 of one chromosome 15, respectively., Conclusions: Duplication of the pituitary gland presents as well-defined craniofacial and cervical spine malformation phenotype. Axial mesoderm duplication generating an excess of Sonic Hedgehog may be the primary embryological driver leading to this condition., Abbreviations: CFNS＝ Craniofrontonasal Syndrome; DPG＝ Duplication of the Pituitary Gland; SHH＝ Sonic Hedgehog., Competing Interests: The authors have no conflicts of interest to disclose regarding the subject of this article., (© 2024 by American Journal of Neuroradiology.)
Published: 2024
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23. Insights from triggers and prodromal symptoms on how migraine attacks start: The threshold hypothesis.

Author: Sebastianelli G, Atalar AÇ, Cetta I, Farham F, Fitzek M, Karatas-Kursun H, Kholodova M, Kukumägi KH, Montisano DA, Onan D, Pantovic A, Skarlet J, Sotnikov D, Caronna E, and Pozo-Rosich P
Subjects: Humans, Brain physiopathology, Brain diagnostic imaging, Prodromal Symptoms, Migraine Disorders physiopathology, Migraine Disorders diagnosis
Abstract: Background: The prodrome or premonitory phase is the initial phase of a migraine attack, and it is considered as a symptomatic phase in which prodromal symptoms may occur. There is evidence that attacks start 24-48 hours before the headache phase. Individuals with migraine also report several potential triggers for their attacks, which may be mistaken for premonitory symptoms and hinder migraine research., Methods: This review aims to summarize published studies that describe contributions to understanding the fine difference between prodromal/premonitory symptoms and triggers, give insights for research, and propose a way forward to study these phenomena. We finally aim to formulate a theory to unify migraine triggers and prodromal symptoms. For this purpose, a comprehensive narrative review of the published literature on clinical, neurophysiological and imaging evidence on migraine prodromal symptoms and triggers was conducted using the PubMed database., Results: Brain activity and network connectivity changes occur during the prodromal phase. These changes give rise to prodromal/premonitory symptoms in some individuals, which may be falsely interpreted as triggers at the same time as representing the early manifestation of the beginning of the attack. By contrast, certain migraine triggers, such as stress, hormone changes or sleep deprivation, acting as a catalyst in reducing the migraine threshold, might facilitate these changes and increase the chances of a migraine attack. Migraine triggers and prodromal/premonitory symptoms can be confused and have an intertwined relationship with the hypothalamus as the central hub for integrating external and internal body signals., Conclusions: Differentiating migraine triggers and prodromal symptoms is crucial for shedding light on migraine pathophysiology and improve migraine management., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GS received personal fees from AbbVie. KHK received travel grant from AbbVie and honoraria for participation in advisory board from Medison Pharma. MF received personal fees from Novartis and Teva. AÇA, IC, FF, HK, MK, DO, DAM, AP, DS and JS declared no conflict of interest. EC has received honoraria from Novartis, Chiesi, Lundbeck, TEVA, Lilly, Medscape. PPR reports that within the prior 36 months, having received honoraria as a consultant and speaker for: AbbVie, Amgen, Biohaven, Chiesi, Eli Lilly, Lundbeck, Medscape, Novartis, Pfizer and Teva. Her research group has received research grants from Novartis, Teva, AbbVie, EraNET Neuron, RIS3CAT FEDER, AGAUR, ISCIII and International Headache Society, and has received funding for clinical trials from Alder, Amgen, Biohaven, Eli Lilly, Lundbeck, Novartis and Teva. She is the Honorary Secretary of the International Headache Society. She is a member of the Clinical Trials Guideline Committee of the International Headache Society. She serves as an associate editor for Cephalalgia, Headache, The Journal of Headache and Pain, Neurologia and Revista de Neurologia. She is the founder of www.midolordecabeza.org. PP-R does not own stocks from any pharmaceutical company.
Published: 2024
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24. Landiolol for heart rate control in patients with septic shock and persistent tachycardia. A multicenter randomized clinical trial (Landi-SEP).

Author: Rehberg S, Frank S, Černý V, Cihlář R, Borgstedt R, Biancofiore G, Guarracino F, Schober A, Trimmel H, Pernerstorfer T, Siebers C, Dostál P, Morelli A, Joannidis M, Pretsch I, Fuchs C, Rahmel T, Podbregar M, Duliczki É, Tamme K, Unger M, Sus J, Klade C, Krejcy K, Kirchbaumer-Baroian N, Krumpl G, and Duška F
Subjects: Humans, Male, Female, Middle Aged, Aged, Europe, Shock, Septic drug therapy, Shock, Septic complications, Shock, Septic physiopathology, Urea analogs & derivatives, Urea therapeutic use, Urea pharmacology, Tachycardia drug therapy, Tachycardia physiopathology, Tachycardia complications, Heart Rate drug effects, Morpholines therapeutic use, Morpholines pharmacology
Abstract: Purpose: Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting β1-blocker landiolol., Methods: This randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80-94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events., Results: Out of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4-28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events., Conclusion: The ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control., (© 2024. The Author(s).)
Published: 2024
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25. Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

Author: Denton E, Hew M, Peters MJ, Upham JW, Bulathsinhala L, Tran TN, Martin N, Bergeron C, Al-Ahmad M, Altraja A, Larenas-Linnemann D, Murray R, Celis-Preciado CA, Al-Lehebi R, Belhassen M, Bhutani M, Bosnic-Anticevich SZ, Bourdin A, Brusselle GG, Busby J, Canonica GW, Heffler E, Chapman KR, Charriot J, Christoff GC, Chung LP, Cosio BG, Côté A, Costello RW, Cushen B, Fingleton J, Fonseca JA, Gibson PG, Heaney LG, Huang EW, Iwanaga T, Jackson DJ, Koh MS, Lehtimäki L, Máspero J, Mahboub B, Menzies-Gow AN, Mitchell PD, Papadopoulos NG, Papaioannou AI, Perez-de-Llano L, Perng DW, Pfeffer PE, Popov TA, Porsbjerg CM, Rhee CK, Roche N, Sadatsafavi M, Salvi S, Schmid JM, Sheu CC, Sirena C, Torres-Duque CA, Salameh L, Patel PH, Ulrik CS, Wang E, Wechsler ME, and Price DB
Subjects: Humans, Male, Female, Middle Aged, Treatment Outcome, Adult, Cohort Studies, Aged, Asthma drug therapy, Registries, Biological Products therapeutic use, Anti-Asthmatic Agents therapeutic use, Severity of Illness Index
Abstract: Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma., Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV 1 ) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV 1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day., Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV 1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria., Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Published: 2024
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26. How Real-World Data Can Facilitate the Development of Precision Medicine Treatment in Psychiatry.

Author: Koch E, Pardiñas AF, O'Connell KS, Selvaggi P, Camacho Collados J, Babic A, Marshall SE, Van der Eycken E, Angulo C, Lu Y, Sullivan PF, Dale AM, Molden E, Posthuma D, White N, Schubert A, Djurovic S, Heimer H, Stefánsson H, Stefánsson K, Werge T, Sønderby I, O'Donovan MC, Walters JTR, Milani L, and Andreassen OA
Subjects: Humans, Electronic Health Records, Artificial Intelligence, Algorithms, Precision Medicine methods, Mental Disorders therapy, Mental Disorders genetics, Psychiatry methods
Abstract: Precision medicine has the ambition to improve treatment response and clinical outcomes through patient stratification and holds great potential for the treatment of mental disorders. However, several important factors are needed to transform current practice into a precision psychiatry framework. Most important are 1) the generation of accessible large real-world training and test data including genomic data integrated from multiple sources, 2) the development and validation of advanced analytical tools for stratification and prediction, and 3) the development of clinically useful management platforms for patient monitoring that can be integrated into health care systems in real-life settings. This narrative review summarizes strategies for obtaining the key elements-well-powered samples from large biobanks integrated with electronic health records and health registry data using novel artificial intelligence algorithms-to predict outcomes in severe mental disorders and translate these models into clinical management and treatment approaches. Key elements are massive mental health data and novel artificial intelligence algorithms. For the clinical translation of these strategies, we discuss a precision medicine platform for improved management of mental disorders. We use cases to illustrate how precision medicine interventions could be brought into psychiatry to improve the clinical outcomes of mental disorders., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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27. Adapting the early recognition inventory ERIraos to Estonian: A validation study.

Author: Sirts K, Anni K, Balõtšev R, Jakobsoo S, Jaanson KL, and Haring L
Subjects: Humans, Adolescent, Female, Estonia, Male, Adult, Young Adult, Reproducibility of Results, Early Diagnosis, Risk Assessment, Prospective Studies, Psychiatric Status Rating Scales, Checklist, Psychotic Disorders diagnosis, Psychotic Disorders psychology, Prodromal Symptoms
Abstract: Aim: Validated assessment tools are needed to identify clinically high risk for psychosis. This study aimed to validate the early recognition inventory ERIraos, which consists of the ERIraos Checklist for risk screening and the ERIraos Symptom List for a more thorough risk assessment in the Estonian language to detect psychotic prodromal symptoms., Methods: A prospective cohort study provided an opportunity to evaluate the characteristics of the ERIraos instrument in predicting the increased risk of a psychotic disorder in the future. The 177 study participants, aged 13-42 years old, were divided into groups without an increased risk and three risk groups with different risk severity levels based on the ERIraos Symptom List assessment., Results: The results indicated excellent inter-rater reliability for the ERIraos Symptom List total score. The ability of the ERIraos checklist to screen persons with an elevated psychosis risk was very good (ROC-AUC = 0.86). The capability of the ERIraos Symptom List scores to predict the probability of transitioning to psychosis within 2 years was very good (ROC-AUC = 0.83). Brief limited intermittent psychotic symptoms and observable behavioural and affective symptoms were statistically significant predictors of transition to psychosis. There were strong and statistically significant correlations between the ERIraos Symptom List scores and other clinical measures assessing functioning and psychopathology., Conclusions: The results of this study demonstrate the reliability and validity of the Estonian version of the ERIraos instrument and support the usability of ERIraos as a two-step tool for the early recognition of psychosis risk., (© 2024 John Wiley & Sons Australia, Ltd.)
Published: 2024
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28. Exploring Definitions and Predictors of Severe Asthma Clinical Remission after Biologic Treatment in Adults.

Author: Perez-de-Llano L, Scelo G, Tran TN, Le TT, Fagerås M, Cosio BG, Peters M, Pfeffer PE, Al-Ahmad M, Al-Lehebi RO, Altraja A, Bergeron C, Bjermer LH, Bjerrum AS, Bulathsinhala L, Busby J, Cano Rosales DJ, Canonica GW, Carter VA, Charriot J, Christoff GC, Denton EJ, Dorscheid DR, Fernandez Sanchez MJ, Fonseca JA, Gibson PG, Goh CYY, Heaney LG, Heffler E, Hew M, Iwanaga T, Katial R, Koh MS, Kuna P, Larenas-Linnemann DES, Lehtimäki L, Mahboub B, Martin N, Matsumoto H, Menzies-Gow AN, Papadopoulos NG, Popov TA, Porsbjerg CM, Patel P, Rhee CK, Sadatsafavi M, Taillé C, Torres-Duque CA, Tsai MJ, Ulrik CS, Upham JW, von Bülow A, Wang E, Wechsler ME, and Price DB
Subjects: Humans, Male, Female, Adult, Middle Aged, Longitudinal Studies, Severity of Illness Index, Anti-Asthmatic Agents therapeutic use, Cohort Studies, Treatment Outcome, Registries, Biological Products therapeutic use, Aged, Asthma drug therapy, Asthma physiopathology, Remission Induction
Abstract: Rationale: There is no consensus on criteria to include in an asthma remission definition in real life. Factors associated with achieving remission after biologic initiation remain poorly understood. Objectives: To quantify the proportion of adults with severe asthma achieving multidomain-defined remission after biologic initiation and identify prebiologic characteristics associated with achieving remission that may be used to predict it. Methods: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1 year before and after biologic initiation. A priori- defined remission cutoffs were: 0 exacerbations/yr, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted FEV 1 ⩾ 80%. Remission was defined using two (exacerbations + LTOCS), three (+control or +lung function), and four of these domains. The association between prebiologic characteristics and postbiologic remission was assessed by multivariable analysis. Measurements and Main Results: A total of 50.2%, 33.5%, 25.8%, and 20.3% of patients met criteria for two-, three- (+control), three- (+lung function), and four-domain remission, respectively. The odds of achieving four-domain remission decreased by 15% for every additional 10 years of asthma duration (odds ratio, 0.85; 95% confidence interval, 0.73-1.00). The odds of remission increased in those with fewer exacerbations per year, lower LTOCS daily dose, better control, and better lung function before biologic initiation. Conclusions: One in five patients achieved four-domain remission within 1 year of biologic initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission after biologic treatment, indicating that biologic treatment should not be delayed if remission is the goal.
Published: 2024
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29. Impact of self-perceived oral health and socio-economic factors on oral health-related behavior in Estonian adults.

Author: Sinijärv M, Olak J, Murakas R, and Runnel R
Subjects: Humans, Estonia, Adult, Female, Male, Middle Aged, Aged, Surveys and Questionnaires, Self Concept, Oral Health, Socioeconomic Factors, Health Behavior
Abstract: Objective: To identify which socioeconomic factors are affecting oral health-related behavior and to provide suggestions for improving the population's oral health. Materials and methods: The survey includes population groups from age 35 and older from all 15 Estonian counties and major cities (n = 2,376). The study is based on data from a nationwide Estonian Adult Oral Health Survey questionnaire. In addition to analyzing eight aspects of oral health-related behavior and self-perceived oral health variables, the survey also includes participants' socio-economic and demographic characteristics. The study utilizes frequency tables (including cumulative distributions), means, correlations, and regression analysis as its methods., Results: The mean number of beneficial behaviors reported by the participant was 4.2 (SD 1.6). The value of the oral health-related behavior index (OHBI, the number of reported behaviors from the eight) is initially determined by the optimal timing between meals, abstinence from smoking, and the choice of drinking water or refraining from any intake between meals. Participants with higher OHBI tended to rate their self-perceived oral health better. Adherence to beneficial dental health-related behavior in Estonian adults is primarily influenced by gender, educational level, type of settlement, and household income level., Conclusions: In order to significantly improve oral health and related behaviors, it is imperative to integrate dental services into universal health coverage and deliver ongoing oral health education for adults.
Published: 2024
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30. Corrigendum: Genome-wide association study identifying variants related to performance and injury in high-performance athletes.

Author: Ebert JR, Magi A, Unt E, Prans E, Wood DJ, and Koks S
Abstract: [This corrects the article DOI: 10.1177/15353702231198068.]., (Copyright © 2024 Ebert, Magi, Unt, Prans, Wood and Koks.)
Published: 2024
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31. Reduced Intensity transplantation vs chemotherapy in CR1. A prospective, pseudorandomized study in 50-70 year old AML patients.

Author: Brune M, Kiss T, Anderson H, Nicklasson M, Delage R, Finke J, Gedde-Dahl T, Hébert J, Höglund M, Kaare A, Lazarevic V, Möllgård L, Remes K, Ritchie D, Spyridonidis A, Sabloff M, Spearing R, Wallhult E, and Ljungman P
Abstract: The aim of this prospective, international multicenter, pseudorandomized study comparing RICT HCT to standard-of-care chemotherapy in intermediate- or high-risk AML patients 50-70 years using the donor versus no-donor concept. Part 1 included only patients with potential family donors (RD) at the date of HLA-typing of the first potential sibling or CR-date, if later. Part 2 allowed the inclusion of patients without a possible sibling donor using the start of an unrelated donor (URD) search as inclusion date. 360 patients were registered and 309 analyzed. The median follow-up was 47 months (1-168). There was no difference in overall survival (OS) between the RD (n = 124) and the Control (n = 77) groups (p = 0.50, 3-year OS RD: 0.41(95% CI; 0.32-0.50); Controls: 0.49 (95% CI; 0.37-0.59)). The main cause of death was relapse (67% RD; 88% Controls). In Part 2, the 3-year OS was 0.60 (95% CI 0.50-0.70) for URD-HCT (n = 86) and 0.37 (95% CI 0.13-0.62) for Controls (n = 20), respectively (p = 0.10). When analyzing transplanted patients (Part 2), the OS at 3-years was higher for URD-HCT than RD-HCT (0.67 (0.55-0.76) vs. 0.42 (0.26-0.57; p = 0.005). This study doesn't support elderly HLA-identical siblings as donors for older AML patients undergoing a RICT allogeneic HCT in first CR., (© 2024. The Author(s).)
Published: 2024
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32. Autosomal recessive leber hereditary optic neuropathy in a choroideremia carrier. A case report.

Author: Roomets E and Mauring L
Subjects: Humans, Female, Visual Acuity physiology, DNA Mutational Analysis, Mutation, Heterozygote, Child, HSP40 Heat-Shock Proteins genetics, Tomography, Optical Coherence, Genes, Recessive, Genetic Testing, Visual Fields physiology, Optic Atrophy, Hereditary, Leber genetics, Optic Atrophy, Hereditary, Leber diagnosis, Optic Atrophy, Hereditary, Leber drug therapy, Choroideremia genetics, Choroideremia diagnosis, DNA, Mitochondrial genetics
Abstract: Background: Leber hereditary optic neuropathy (LHON) is an inherited progressive optic neuropathy usually caused by mitochondrial DNA mutations. Recently, autosomal recessive (arLHON), which is caused by biallelic mutations in the DNAJC30 gene (usually c.152A > G), has been described. The onset of LHON before the age of 12 is uncommon and it is typically associated with a more variable clinical course and a more favorable visual prognosis than adult-onset LHON., Materials and Methods: Detailed clinical findings of a female child with vision loss due to arLHON together with choroideremia (CHM) carrier state are presented., Results: Genetic testing for the three most common mitochondrial LHON pathogenic variants was negative. On suspicion of arLHON, genetic testing was continued with the next-generation sequencing (NGS) of the nuclear DNA, identifying a homozygous pathogenic variant in DNAJC3° c.152A > G, p.(Tyr51Cys), but no alterations in the CHM gene. Idebenone treatment was started 4.5 months after the first evaluation. Clinical diagnosis of the CHM carrier state was confirmed by multiplex ligation-dependent probe amplification (MLPA) assay, which revealed a heterozygous deletion of all exons of the CHM ., Conclusions: In children with acute or subacute, simultaneous, or sequential vision loss that is unresponsive to immunomodulatory treatment, LHON should be considered as a possible diagnosis. Our case emphasizes the diagnostic advantage of sequencing DNAJC30 in parallel with the mitochondrial DNA, especially in Eastern European descent patients. Genomic rearrangement testing should be considered for patients with a CHM carrier phenotype who have negative results on sequencing tests., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2024
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33. Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

Author: Scelo G, Tran TN, Le TT, Fagerås M, Dorscheid D, Busby J, Al-Ahmad M, Al-Lehebi R, Altraja A, Beastall A, Bergeron C, Bjermer L, Bjerrum AS, Cano-Rosales DJ, Canonica GW, Carter V, Charriot J, Christoff GC, Cosio BG, Denton E, Fernandez-Sanchez MJ, Fonseca JA, Gibson PG, Goh C, Heaney LG, Heffler E, Hew M, Iwanaga T, Katial R, Koh MS, Kuna P, Larenas-Linnemann D, Lehtimäki L, Mahboub B, Martin N, Matsumoto H, Menzies-Gow AN, Papadopoulos NG, Patel P, Perez-De-Llano L, Peters M, Pfeffer PE, Popov TA, Porsbjerg CM, Rhee CK, Sadatsafavi M, Taillé C, Torres-Duque CA, Tsai MJ, Ulrik CS, Upham JW, von Bülow A, Wang E, Wechsler ME, and Price DB
Subjects: Humans, Male, Female, Middle Aged, Adult, Longitudinal Studies, Treatment Outcome, Severity of Illness Index, Adrenal Cortex Hormones therapeutic use, Registries, Aged, Cohort Studies, Asthma drug therapy, Asthma physiopathology, Biological Products therapeutic use, Anti-Asthmatic Agents therapeutic use
Abstract: Background: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging., Objective: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response., Methods: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV 1 . Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis., Results: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria., Conclusions: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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34. Correction: Genome-wide meta-analysis identifies novel loci conferring risk of acne vulgaris.

Author: Teder-Laving M, Kals M, Reigo A, Ehin R, Objärtel T, Vaht M, Nikopensius T, Metspalu A, and Kingo K
Published: 2024
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35. Genome-wide meta-analysis identifies novel loci conferring risk of acne vulgaris.

Author: Teder-Laving M, Kals M, Reigo A, Ehin R, Objärtel T, Vaht M, Nikopensius T, Metspalu A, and Kingo K
Subjects: Humans, Polymorphism, Single Nucleotide, Genetic Loci, Genetic Predisposition to Disease, Male, Multifactorial Inheritance, Female, Acne Vulgaris genetics, Acne Vulgaris pathology, Genome-Wide Association Study
Abstract: Acne vulgaris is a common chronic skin disorder presenting with comedones, cystic structures forming within the distal hair follicle, and in most cases additionally with inflammatory skin lesions on the face and upper torso. We performed a genome-wide association study and meta-analysis of data from 34,422 individuals with acne and 364,991 controls from three independent European-ancestry cohorts. We replicated 19 previously implicated genome-wide significant risk loci and identified four novel loci [11q12.2 (FADS2), 12q21.1 (LGR5), 17q25.3 (FASN), and 22q12.1 (ZNRF3-KREMEN1)], bringing the total number of reported acne risk loci to 50. Our meta-analysis results explain 9.4% of the phenotypic variance of acne. A polygenic model of acne risk variants showed that individuals in the top 5% of the risk percentiles had a 1.62-fold (95% CI 1.47-1.78) increased acne risk relative to individuals with average risk (20-80% on the polygenic risk score distribution). Our findings highlight the Wnt and MAPK pathways as key factors in the genetic predisposition to acne vulgaris, together with the effects of genetic variation on the structure and maintenance of the hair follicle and pilosebaceous unit. Two novel loci, 11q12.2 and 17q25.3, contain genes encoding key enzymes involved in lipid biosynthesis pathways., (© 2023. The Author(s).)
Published: 2024
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36. Voice and Swallowing Disorders After Thyroid Surgery.

Author: Sõber L, Lepner U, Kirsimägi Ü, Puksa L, and Kasenõmm P
Subjects: Humans, Male, Female, Middle Aged, Prospective Studies, Adult, Time Factors, Aged, Treatment Outcome, Laryngoscopy, Phonation, Stroboscopy, Disability Evaluation, Electromyography, Recovery of Function, Video Recording, Laryngeal Nerve Injuries etiology, Laryngeal Nerve Injuries physiopathology, Young Adult, Acoustics, Speech Acoustics, Voice Quality, Thyroidectomy adverse effects, Deglutition Disorders physiopathology, Deglutition Disorders etiology, Deglutition Disorders diagnosis, Deglutition, Voice Disorders etiology, Voice Disorders physiopathology, Voice Disorders diagnosis, Vocal Cord Paralysis physiopathology, Vocal Cord Paralysis etiology, Vocal Cord Paralysis diagnosis
Abstract: Objective: The aim of the study was to evaluate voice and swallowing function following thyroid surgery, to identify dynamic changes during the follow-up period of 12-18 month and to find possible indicative signs of permanent or temporary vocal fold palsy., Methods: All participants (N = 110) were prospectively enrolled from the preoperative thyroid surgery patients between September 2013 and December 2016. All subjects underwent preoperatively, first week and 12-18 month postoperatively videolaryngostroboscopy, filled in subjective evaluation of voice (voice handicap index, [VHI]) and swallowing (swallowing impairment score) complaints. Acoustic voice analysis (AVA), maximum phonation time (MPT) measurement and perceptual voice evaluation were conducted. In the presence of laryngeal damage, additional first and sixth-month follow-up visits were planned. Patients, whom we suspected laryngeal nerve damage, underwent laryngeal electromyography 4 weeks after the operation., Results: On first postoperative week evaluation, no objective voice changes within patients with postoperatively intact laryngeal nerves were found. Subjective evaluations showed decline in VHI physical domain and increased strain in postoperative voice. Patients with postoperative nerve damage had a drastic decline in subjective voice quality (VHI all subscales and total score), AVA parameter jitter, MPT and perceptual voice quality. Subjective evaluation of swallowing revealed disturbances in all patients regardless of the nerve damage. We noticed remarkable differences in first week and first month visits between patients with permanent and temporary palsy in VHI total score and physical domain, MPT and perceptual breathiness and asthenia in voice. Regardless of the nerve injury, by the end of the follow-up period all changes had become statistically insignificant with the exception of perceptual evaluation of voice quality., Conclusions: Patients with postoperative laryngeal nerve damage experience substantial deterioration of both subjective and objective voice quality with more extensive impairment in patients with permanent paralysis. Thyroid surgery causes subjective swallowing changes irrespective of laryngeal nerve damage. In patients without laryngeal nerve damage, swallowing function improves following thyroidectomy. Possible indicators for permanent paralysis are delayed recovery in the values of MPT and jitter and persistent perceptual breathiness and asthenia., (Copyright © 2022 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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37. Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry.

Author: Abd ElHafeez S, Kramer A, Arici M, Arnol M, Åsberg A, Bell S, Belliere J, Corte CD, Fresnedo GF, Hemmelder M, Heylen L, Hommel K, Kerschbaum J, Naumović R, Nitsch D, Santamaria R, Finne P, Palsson R, Pippias M, Resic H, Rosenberg M, de Pablos CS, Segelmark M, Sørensen SS, Soler MJ, Vidal E, Jager KJ, Ortiz A, and Stel VS
Subjects: Humans, Incidence, Female, Male, Europe epidemiology, Middle Aged, Adult, Aged, Survival Rate, Young Adult, Adolescent, Glomerulonephritis epidemiology, Glomerulonephritis complications, Kidney Failure, Chronic epidemiology, Kidney Failure, Chronic therapy, Kidney Failure, Chronic mortality, Registries statistics & numerical data, Renal Replacement Therapy statistics & numerical data
Abstract: Background: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death., Methods: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence and survival., Results: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. Immunoglobulin A nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidences, of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had 5-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death [adjusted hazard ratio 1.8 (95% confidence interval 1.6-1.9)] compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%)., Conclusion: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)
Published: 2024
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38. Genome-wide association study of copy number variations in Parkinson's disease.

Author: Landoulsi Z, Sreelatha AAK, Schulte C, Bobbili DR, Montanucci L, Leu C, Niestroj LM, Hassanin E, Domenighetti C, Pavelka L, Sugier PE, Radivojkov-Blagojevic M, Lichtner P, Portugal B, Edsall C, Kru Ger J, Hernandez DG, Blauwendraat C, Mellick GD, Zimprich A, Pirker W, Tan M, Rogaeva E, Lang AE, Koks S, Taba P, Lesage S, Brice A, Corvol JC, Chartier-Harlin MC, Mutez E, Brockmann K, Deutschländer AB, Hadjigeorgiou GM, Dardiotis E, Stefanis L, Simitsi AM, Valente EM, Petrucci S, Straniero L, Zecchinelli A, Pezzoli G, Brighina L, Ferrarese C, Annesi G, Quattrone A, Gagliardi M, Burbulla LF, Matsuo H, Nakayama A, Hattori N, Nishioka K, Chung SJ, Kim YJ, Kolber P, van de Warrenburg BP, Bloem BR, Singleton AB, Toft M, Pihlstrom L, Guedes LC, Ferreira JJ, Bardien S, Carr J, Tolosa E, Ezquerra M, Pastor P, Wirdefeldt K, Pedersen NL, Ran C, Belin AC, Puschmann A, Clarke CE, Morrison KE, Krainc D, Farrer MJ, Lal D, Elbaz A, Gasser T, Krüger R, Sharma M, and May P
Abstract: Objective: Our study investigates the impact of copy number variations (CNVs) on Parkinson's disease (PD) pathogenesis using genome-wide data, aiming to uncover novel genetic mechanisms and improve the understanding of the role of CNVs in sporadic PD., Methods: We applied a sliding window approach to perform CNV-GWAS and conducted genome-wide burden analyses on CNV data from 11,035 PD patients (including 2,731 early-onset PD (EOPD)) and 8,901 controls from the COURAGE-PD consortium., Results: We identified 14 genome-wide significant CNV loci associated with PD, including one deletion and 13 duplications. Among these, duplications in 7q22.1, 11q12.3 and 7q33 displayed the highest effect. Two significant duplications overlapped with PD-related genes SNCA and VPS13C , but none overlapped with recent significant SNP-based GWAS findings. Five duplications included genes associated with neurological disease, and four overlapping genes were dosage-sensitive and intolerant to loss-of-function variants. Enriched pathways included neurodegeneration, steroid hormone biosynthesis, and lipid metabolism. In early-onset cases, four loci were significantly associated with EOPD, including three known duplications and one novel deletion in PRKN . CNV burden analysis showed a higher prevalence of CNVs in PD-related genes in patients compared to controls (OR=1.56 [1.18-2.09], p=0.0013), with PRKN showing the highest burden (OR=1.47 [1.10-1.98], p=0.026). Patients with CNVs in PRKN had an earlier disease onset. Burden analysis with controls and EOPD patients showed similar results., Interpretation: This is the largest CNV-based GWAS in PD identifying novel CNV regions and confirming the significant CNV burden in EOPD, primarily driven by the PRKN gene, warranting further investigation.
Published: 2024
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39. Heritability of cough across two generations: the RHINESSA study.

Author: Emilsson ÖI, Johansson H, Johannessen A, Janson C, Palm A, Franklin KA, Oudin A, Gómez Real F, Holm M, Gislason T, Lindberg E, Jõgi R, Schlünssen V, Callejas-González FJ, Zhang J, Malinovschi A, Svanes C, and Ekström M
Abstract: Aim: Heritability of cough has not yet been studied. We aimed to evaluate if individuals with cough are more likely to have offspring who develop cough, and if these associations differ by type of cough (productive/nonproductive)., Methods: The RHINESSA Generation Study (Respiratory Health In Northern Europe, Spain and Australia) includes 7155 parents (initially aged 30-54) answering detailed questionnaires in 2000 and 2010, and 8176 offspring ≥20 years answering similar questionnaires in 2012-2019. Chronic cough was categorised as productive or nonproductive (dry) cough. Associations between parental and offspring cough were analysed using mixed-effects logistic regression, adjusting for offspring age, sex, body mass index, smoking history, education level, current asthma, rhinitis, nocturnal gastroesophageal reflux; parent sex and smoking history; centre and family., Results: Among parents with nonproductive cough, 11% of their offspring reported nonproductive cough, compared with 7% of offspring to parents without nonproductive cough, adjusted odds ratio (aOR) 1.59 (95% confidence interval 1.20-2.10). Among parents with productive cough, 14% of their offspring reported productive cough, compared with 11% of offspring to parents without productive cough, aOR 1.34 (1.07-1.67). No associations were found between parent productive cough-offspring nonproductive cough, nor between parent nonproductive cough-offspring productive cough., Conclusions: Parents with chronic cough are more likely to have offspring with chronic cough independent of parental asthma, suggesting cough to be a separate heritable trait. The type of cough is important, as the nonproductive cough in parent associates only with nonproductive cough in offspring, and the same applied for productive cough., Competing Interests: Conflict of interest: Ö.I. Emilsson has participated in advisory boards with MSD Sweden, not related to this manuscript. The other authors have no other competing interests to declare., (Copyright ©The authors 2024.)
Published: 2024
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40. Prospective evaluation of thin-layer agar colour test in routine diagnosis of multidrug-resistant TB.

Author: Klaos K, Agejeva A, Hurt K, Kummik T, Kurve A, Nirk J, Pehme L, Remets O, Sasi S, Tann A, and Altraja A
Subjects: Humans, Prospective Studies, Agar, Bronchoalveolar Lavage Fluid microbiology, Female, Adult, Time Factors, Male, Pleural Effusion microbiology, Pleural Effusion diagnosis, Culture Media, Middle Aged, Mycobacterium tuberculosis isolation & purification, Mycobacterium tuberculosis drug effects, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant drug therapy, Microbial Sensitivity Tests, Sputum microbiology, Antitubercular Agents pharmacology, Sensitivity and Specificity
Abstract: BACKGROUNDThis study evaluated the diagnostic performance of the thin-layer agar MDR/XDR-TB Colour Test (CT), a Mycobacterium tuberculosis complex (MTBC) detection and direct drug susceptibility testing (DST) method with routine sputum, bronchoalveolar lavage and pleural fluid specimen.METHODSIn a prospective study, the time and rate of MTBC detection were compared between CT, Löwenstein-Jensen, and MGIT media. Times until DST result, sensitivities, and specificities were evaluated between CT and MGIT 960 indirect DST.RESULTSThe cultivation of 177 pulmonary specimens resulted in 83 MTBC-positive cultures. The sensitivity of CT for MTBC detection was 81.3% with a median time of 20 days compared to 13 days and 93.5% for MGIT. The sensitivity of CT for DST results was 100% for isoniazid and levofloxacin and 94.7% for rifampicin. The specificities for isoniazid and rifampicin DST were 97.3% and 98.0% for levofloxacin. The median time until a DST result was significantly shorter with CT than the BACTEC MGIT 960 system, 20 and 27 days, respectively, independent of the specimen type used.CONCLUSIONSThe CT is a highly accurate and fast initial diagnostic test for high-incidence settings and could also be used as a first culture and direct DST in peripheral settings..
Published: 2024
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41. HPV self-sampling in organized cervical cancer screening program: A randomized pilot study in Estonia in 2021.

Author: Hallik R, Innos K, Jänes J, Jõers K, Ratnik K, and Veerus P
Abstract: Background: Cervical cancer incidence in Estonia ranks among the highest in Europe, but screening attendance has remained low. This randomized study aimed to evaluate the impact of opt-in and opt-out human papillomavirus (HPV) self-sampling options on participation in organized screening., Methods: A random sample of 25,591 women were drawn from the cervical cancer screening target population who were due to receive a reminder in autumn 2021 and thereafter randomly allocated to two equally sized intervention arms (opt-out and opt-in) receiving a choice between HPV self-sampling or clinician sampling. In the opt-out arm, a self-sampler was sent to home address by regular mail; the opt-in arm received an e-mail containing a link to order a self-sampler online. The remaining 30,102 women in the control group received a standard reminder for conventional screening. Participation by intervention arm, age and region of residence was calculated; a questionnaire was used to assess self-sampling user experience., Results: A significant difference in participation was seen between opt-out (41.7%) (19.8% chose self-sampling and 21.9% clinician sampling), opt-in (34.1%) (7.9% self-sampling, 26.2% clinician sampling) and control group (29.0%, clinician sampling only). All age groups and regions in the intervention arms showed higher participation compared to the control group, but the size of the effect varied. Among self-sampling users, 99% agreed that the device was easy to use and only 3.5% preferred future testing at the clinic., Conclusion: Providing women with a choice between self-sampling and clinician sampling significantly increased participation in cervical cancer screening. Opt-in and opt-out options had a different effect across age groups, suggesting the need to adapt strategies., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2024
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42. Vascular syndrome predicts the development and course of epilepsy after perinatal stroke.

Author: Vaher U, Ilves N, Ilves N, Laugesaar R, Männamaa M, Loorits D, Kool P, and Ilves P
Subjects: Humans, Female, Male, Adolescent, Child, Follow-Up Studies, Child, Preschool, Ischemic Stroke complications, Ischemic Stroke physiopathology, Ischemic Stroke diagnostic imaging, Ischemic Stroke etiology, Stroke complications, Stroke physiopathology, Stroke diagnostic imaging, Stroke etiology, Magnetic Resonance Imaging, Infarction, Middle Cerebral Artery physiopathology, Infarction, Middle Cerebral Artery diagnostic imaging, Infarction, Middle Cerebral Artery complications, Infant, Infant, Newborn, Epilepsy etiology, Epilepsy physiopathology
Abstract: Objective: Epilepsy develops in one third of the patients after perinatal stroke. It is still unclear which vascular syndrome of ischemic stroke carries higher risk of epilepsy. The aim of the current study was to evaluate the risk of epilepsy according to the vascular syndrome of perinatal stroke., Methods: The study included 39 children with perinatal arterial ischemic stroke (13 with anterior or posterior trunk of the distal middle cerebral artery occlusion, 23 with proximal or distal M1 middle cerebral artery occlusion and three with lenticulostriate arteria infarction), and 44 children with presumed perinatal venous infarction. Magnetic resonance imaging obtained at the chronic stage was used to evaluate the vascular syndrome of stroke., Results: The median follow-up time was 15.1 years (95% CI: 12.4-16.5 years), epilepsy developed in 19/83 (22.9%) patients. The cumulative probability to be without epilepsy at 15 years was 75.4% (95% CI: 65.8-86.4). The probability of having epilepsy was higher in the group of proximal or distal M1 artery occlusion compared to patients with periventricular venous infarction (HR 7.2, 95% CI: 2.5-26, p = .0007). Patients with periventricular venous infarction had significantly more often status epilepticus or spike-wave activation in sleep ≥85% of it compared to patients with anterior or posterior trunk of the distal middle cerebral artery occlusion (OR = 81; 95% CI: 1.3-5046, p = .029)., Significance: The emphasis of this study is placed on classifying the vascular syndrome of perinatal stroke and on the targeted follow-up of patients for epilepsy until young adulthood. The risk for having epilepsy after perinatal stroke is the highest in children with proximal or distal M1 middle cerebral artery occlusion. Patients with periventricular venous infarction have a more severe course of epilepsy., (© 2024 The Authors. Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Published: 2024
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43. Lung Cancer in Estonia.

Author: Laisaar T, Innos K, Jaal J, Oselin K, Sarana B, Vanakesa T, and Laisaar KT
Subjects: Humans, Estonia epidemiology, Male, Female, Lung Neoplasms pathology
Abstract: Competing Interests: Disclosure Dr. T. Laisaar reports receiving grants from Roche Estonia and Estonian Health Insurance Fund; and funding support from AstraZeneca. Prof. Jaal reports receiving consulting fees from AstraZeneca; honoraria for lectures from AstraZeneca, Pfizer, and Roche; support for travels and meeting from MSD and AstraZeneca; and is a board member of the Estonian Society of Clinical Oncologists. Dr. Oselin reports receiving research grants from Optellum and Pfizer; consulting fees from MSD, Roche, Johnson & Johnson, Amgen, Takeda, and Servier; honoraria for MSD; and support for attending international conferences from MSD, Roche, and Astra Zeneca. Dr. Innos reports receiving institutional grant from the Estonian Research Council (grant no PRG722). Dr. K-T. Laisaar reports receiving grant funding from the European Commission and Estonian Health Insurance Fund, payment for expert testimony from the Estonian Health Insurance Fund; and is a member of the Steering Group Committee at the Estonian Ministry of Social Affairs. The remaining authors declare no conflict of interest.
Published: 2024
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44. Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis.

Author: Mackay DJG, Gazdagh G, Monk D, Brioude F, Giabicani E, Krzyzewska IM, Kalish JM, Maas SM, Kagami M, Beygo J, Kahre T, Tenorio-Castano J, Ambrozaitytė L, Burnytė B, Cerrato F, Davies JH, Ferrero GB, Fjodorova O, Manero-Azua A, Pereda A, Russo S, Tannorella P, Temple KI, Õunap K, Riccio A, de Nanclares GP, Maher ER, Lapunzina P, Netchine I, Eggermann T, Bliek J, and Tümer Z
Subjects: Humans, Genetic Testing methods, Genomic Imprinting genetics, DNA Methylation genetics
Abstract: Background: Imprinting disorders are rare diseases resulting from altered expression of imprinted genes, which exhibit parent-of-origin-specific expression patterns regulated through differential DNA methylation. A subgroup of patients with imprinting disorders have DNA methylation changes at multiple imprinted loci, a condition referred to as multi-locus imprinting disturbance (MLID). MLID is recognised in most but not all imprinting disorders and is also found in individuals with atypical clinical features; the presence of MLID often alters the management or prognosis of the affected person. Some cases of MLID are caused by trans-acting genetic variants, frequently not in the patients but their mothers, which have counselling implications. There is currently no consensus on the definition of MLID, clinical indications prompting testing, molecular procedures and methods for epigenetic and genetic diagnosis, recommendations for laboratory reporting, considerations for counselling, and implications for prognosis and management. The purpose of this study is thus to cover this unmet need., Methods: A comprehensive literature search was conducted resulting in identification of more than 100 articles which formed the basis of discussions by two working groups focusing on clinical diagnosis (n = 12 members) and molecular testing (n = 19 members). Following eight months of preparations and regular online discussions, the experts from 11 countries compiled the preliminary documentation and determined the questions to be addressed during a face-to-face meeting which was held with the attendance of the experts together with four representatives of patient advocacy organisations., Results: In light of available evidence and expert consensus, we formulated 16 propositions and 8 recommendations as interim guidance for the clinical and molecular diagnosis of MLID., Conclusions: MLID is a molecular designation, and for patients with MLID and atypical phenotypes, we propose the alternative term multi-locus imprinting syndrome. Due to the intrinsic variability of MLID, the guidelines underscore the importance of involving experts from various fields to ensure a confident approach to diagnosis, counselling, and care. The authors advocate for global, collaborative efforts in both basic and translational research to tackle numerous crucial questions that currently lack answers, and suggest reconvening within the next 3-5 years to evaluate the research advancements and update this guidance as needed., (© 2024. The Author(s).)
Published: 2024
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45. Genetic counselling legislation and practice in cancer in EU Member States.

Author: McCrary JM, Van Valckenborgh E, Poirel HA, de Putter R, van Rooij J, Horgan D, Dierks ML, Antonova O, Brunet J, Chirita-Emandi A, Colas C, Dalmas M, Ehrencrona H, Grima C, Janavičius R, Klink B, Koczok K, Krajc M, Lace B, Leitsalu L, Mistrik M, Paneque M, Primorac D, Roetzer KM, Ronez J, Slámová L, Spanou E, Stamatopoulos K, Stoklosa T, Strang-Karlsson S, Szakszon K, Szczałuba K, Turner J, van Dooren MF, van Zelst-Stams WAG, Vassallo LM, Wadt KAW, Žigman T, Ripperger T, Genuardi M, Van den Bulcke M, and Bergmann AK
Subjects: Humans, Genetic Testing legislation & jurisprudence, European Union, Genetic Counseling legislation & jurisprudence, Neoplasms genetics
Abstract: Background: Somatic and germline genetic alterations are significant drivers of cancer. Increasing integration of new technologies which profile these alterations requires timely, equitable and high-quality genetic counselling to facilitate accurate diagnoses and informed decision-making by patients and their families in preventive and clinical settings. This article aims to provide an overview of genetic counselling legislation and practice across European Union (EU) Member States to serve as a foundation for future European recommendations and action., Methods: National legislative databases of all 27 Member States were searched using terms relevant to genetic counselling, translated as appropriate. Interviews with relevant experts from each Member State were conducted to validate legislative search results and provide detailed insights into genetic counselling practice in each country., Results: Genetic counselling is included in national legislative documents of 22 of 27 Member States, with substantial variation in legal mechanisms and prescribed details (i.e. the 'who, what, when and where' of counselling). Practice is similarly varied. Workforce capacity (25 of 27 Member States) and genetic literacy (all Member States) were common reported barriers. Recognition and/or better integration of genetic counsellors and updated legislation and were most commonly noted as the 'most important change' which would improve practice., Conclusions: This review highlights substantial variability in genetic counselling across EU Member States, as well as common barriers notwithstanding this variation. Future recommendations and action should focus on addressing literacy and capacity challenges through legislative, regulatory and/or strategic approaches at EU, national, regional and/or local levels., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)
Published: 2024
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46. Biomarkers In Prediction of Acute Mesenteric Ischaemia: a prospective multicentre study (BIPAMI study): a study protocol.

Author: Tamme K, Acosta S, Biloslavo A, Björck M, Casian D, Damaskos D, Forbes A, Kase K, Kisand K, Lakbar I, Mihnovitš V, Murruste M, Mändul M, Nuzzo A, Padar M, Starkopf J, Visconti D, and Reintam Blaser A
Subjects: Adult, Humans, Acute Disease, Predictive Value of Tests, Prospective Studies, Multicenter Studies as Topic, Biomarkers blood, Mesenteric Ischemia diagnosis, Mesenteric Ischemia blood
Abstract: Background: Acute mesenteric ischaemia (AMI) is a life-threatening disease where early diagnosis is critical to avoid morbidity and mortality from extensive irreversible bowel necrosis. Appropriate prediction of presence of bowel necrosis is currently not available but would help to choose the optimal method of treatment. The study aims to identify combinations of biomarkers that can reliably identify AMI and distinguish between potentially reversible and irreversible bowel ischaemia., Methods: This is a prospective multicentre study. Adult patients with clinical suspicion of AMI (n = 250) will be included. Blood will be sampled on admission, at and after interventions, or during the first 48 h of suspicion of AMI if no intervention undertaken. Samples will be collected and the following serum or plasma biomarkers measured at Tartu University Hospital laboratory: intestinal fatty acid-binding protein (I-FABP), alpha-glutathione S-transferase (Alpha- GST), interleukin 6 (IL-6), procalcitonin (PCT), ischaemia-modified albumin (IMA), D-lactate, D-dimer, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and lipopolysaccharide-binding protein (LBP). Additionally, more common laboratory markers will be measured in routine clinical practice at study sites. Diagnosis of AMI will be confirmed by computed tomography angiography, surgery, endoscopy or autopsy. Student's t or Wilcoxon rank tests will be used for comparisons between transmural vs. suspected (but not confirmed) AMI (comparison A), confirmed AMI of any stage vs suspected AMI (comparison B) and non-transmural AMI vs transmural AMI (comparison C). Optimal cut-off values for each comparison will be identified based on the AUROC analysis and likelihood ratios calculated. Positive likelihood ratio > 10 (> 5) and negative likelihood ratio < 0.1 (< 0.2) indicate high (moderate) diagnostic accuracy, respectively. All biomarkers with at least moderate accuracy will be entered as binary covariates (using the best cutoffs) into the multivariable stepwise regression analysis to identify the best combination of biomarkers for all comparisons separately. The best models for each comparison will be used to construct a practical score to distinguish between no AMI, non-transmural AMI and transmural AMI., Discussion: As a result of this study, we aim to propose a score including set of biomarkers that can be used for diagnosis and decision-making in patients with suspected AMI., Trial Registration: NCT06212921 (Registration Date 19-01-2024)., (© 2024. The Author(s).)
Published: 2024
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47. Classification and Treatment of Pediatric Capitellar Fractures.

Author: Yang D, Baghdadi S, Värk PR, Buttrick E, and Shah AS
Subjects: Humans, Child, Male, Retrospective Studies, Female, Adolescent, Reproducibility of Results, Treatment Outcome, Child, Preschool, Elbow Joint surgery, Elbow Joint diagnostic imaging, Observer Variation, Humeral Fractures surgery, Humeral Fractures diagnostic imaging, Humeral Fractures classification, Elbow Injuries
Abstract: Background: Fractures of the capitellum are rare in children. The purpose of this study was to report fracture characteristics, treatment, and outcomes of pediatric capitellar fractures at a single children's hospital. We also aimed to update the classification of these fractures based on a large sample size by revising the Murthy (Boston) classification., Methods: In a retrospective study at a single tertiary care children's hospital, fractures of the capitellum in patients below 18 years of age were queried and reviewed for demographics, injury characteristics, imaging, treatment, outcomes, and complications. Three surgeons reviewed all imaging to classify the fractures and assess interobserver and intraobserver reliability., Results: Forty-four patients (25 male) with capitellar fractures with a mean age of 11.7±3.7 years were identified. Seven fractures did not belong to an existing type and were grouped into a new type IV capitellar fracture, defined as LCL avulsions with extension to the articular surface of the capitellum. We found good to excellent inter-rater and intrarater reliability for the new classification system. Our raters believed that cross-sectional imaging was essential to classifying fractures in 84% of the cases. Thirty-three of 44 patients underwent early surgical intervention, with favorable outcomes. Five patients presented late with substantial elbow contracture and malunion and were treated surgically with the excision of the fragment., Conclusions: The new classification of pediatric capitellar fractures is more comprehensive and offers good to excellent reliability. We found excellent outcomes in the majority of cases with early diagnosis and management, but substantial risk for complications with missed and delayed diagnosis. Malunion and subsequent loss of ROM were the most common presentations of a missed diagnosis, which can be surgically treated with favorable outcomes., Level of Evidence: Level III-retrospective cohort study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2024
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48. In vitro experimental conditions and tools can influence the safety and biocompatibility results of antimicrobial electrospun biomaterials for wound healing.

Author: Põhako-Palu K, Lorenz K, Randmäe K, Putrinš M, Kingo K, Tenson T, and Kogermann K
Subjects: Animals, Humans, Cell Line, Materials Testing, Cricetinae, Polyesters chemistry, Fibroblasts drug effects, Anti-Infective Agents pharmacology, Polyethylene Glycols chemistry, Chloramphenicol pharmacology, Wound Healing drug effects, Biocompatible Materials chemistry, Biocompatible Materials pharmacology, Bandages
Abstract: Electrospun (ES) fibrous nanomaterials have been widely investigated as novel biomaterials. These biomaterials have to be safe and biocompatible; hence, they need to be tested for cytotoxicity before being administered to patients. The aim of this study was to develop a suitable and biorelevant in vitro cytotoxicity assay for ES biomaterials (e.g. wound dressings). We compared different in vitro cytotoxicity assays, and our model wound dressing was made from polycaprolactone and polyethylene oxide and contained chloramphenicol as the active pharmaceutical ingredient. Baby Hamster Kidney cells (BHK-21), human primary fibroblasts and MTS assays together with real-time cell analysis were selected. The extract exposure and direct contact safety evaluation setups were tested together with microscopic techniques. We found that while extract exposure assays are suitable for the initial testing, the biocompatibility of the biomaterial is revealed in in vitro direct contact assays where cell interactions with the ES wound dressing are evaluated. We observed significant differences in the experimental outcome, caused by the experimental set up modification such as cell line choice, cell medium and controls used, conducting the phosphate buffer washing step or not. A more detailed technical protocol for the in vitro cytotoxicity assessment of ES wound dressings was developed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Põhako-Palu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2024
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49. Comparison of the ABC and ACMG systems for variant classification.

Author: Houge G, Bratland E, Aukrust I, Tveten K, Žukauskaitė G, Sansovic I, Brea-Fernández AJ, Mayer K, Paakkola T, McKenna C, Wright W, Markovic MK, Lildballe DL, Konecny M, Smol T, Alhopuro P, Gouttenoire EA, Obeid K, Todorova A, Jankovic M, Lubieniecka JM, Stojiljkovic M, Buisine MP, Haukanes BI, Lorans M, Roomere H, Petit FM, Haanpää MK, Beneteau C, Pérez B, Plaseska-Karanfilska D, Rath M, Fuhrmann N, Ferreira BI, Stephanou C, Sjursen W, Maver A, Rouzier C, Chirita-Emandi A, Gonçalves J, Kuek WCD, Broly M, Haer-Wigman L, Thong MK, Tae SK, Hyblova M, den Dunnen JT, and Laner A
Subjects: Humans, Genetic Testing standards, Genetic Testing methods, Genetic Variation
Abstract: The ABC and ACMG variant classification systems were compared by asking mainly European clinical laboratories to classify variants in 10 challenging cases using both systems, and to state if the variant in question would be reported as a relevant result or not as a measure of clinical utility. In contrast to the ABC system, the ACMG system was not made to guide variant reporting but to determine the likelihood of pathogenicity. Nevertheless, this comparison is justified since the ACMG class determines variant reporting in many laboratories. Forty-three laboratories participated in the survey. In seven cases, the classification system used did not influence the reporting likelihood when variants labeled as "maybe report" after ACMG-based classification were included. In three cases of population frequent but disease-associated variants, there was a difference in favor of reporting after ABC classification. A possible reason is that ABC step C (standard variant comments) allows a variant to be reported in one clinical setting but not another, e.g., based on Bayesian-based likelihood calculation of clinical relevance. Finally, the selection of ACMG criteria was compared between 36 laboratories. When excluding criteria used by less than four laboratories (<10%), the average concordance rate was 46%. Taken together, ABC-based classification is more clear-cut than ACMG-based classification since molecular and clinical information is handled separately, and variant reporting can be adapted to the clinical question and phenotype. Furthermore, variants do not get a clinically inappropriate label, like pathogenic when not pathogenic in a clinical context, or variant of unknown significance when the significance is known., (© 2024. The Author(s).)
Published: 2024
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50. Diagnosing missed cases of spinal muscular atrophy in genome, exome, and panel sequencing datasets.

Author: Weisburd B, Sharma R, Pata V, Reimand T, Ganesh VS, Austin-Tse C, Osei-Owusu I, O'Heir E, O'Leary M, Pais L, Stafki SA, Daugherty AL, Folland C, Perić S, Fahmy N, Udd B, Horakova M, Łusakowska A, Manoj R, Nalini A, Karcagi V, Polavarapu K, Lochmüller H, Horvath R, Bönnemann CG, Donkervoort S, Haliloğlu G, Herguner O, Kang PB, Ravenscroft G, Laing N, Scott HS, Töpf A, Straub V, Pajusalu S, Õunap K, Tiao G, Rehm HL, and O'Donnell-Luria A
Abstract: Spinal muscular atrophy (SMA) is a genetic disorder that causes progressive degeneration of lower motor neurons and the subsequent loss of muscle function throughout the body. It is the second most common recessive disorder in individuals of European descent and is present in all populations. Accurate tools exist for diagnosing SMA from genome sequencing data. However, there are no publicly available tools for GRCh38-aligned data from panel or exome sequencing assays which continue to be used as first line tests for neuromuscular disorders. This deficiency creates a critical gap in our ability to diagnose SMA in large existing rare disease cohorts, as well as newly sequenced exome and panel datasets. We therefore developed and extensively validated a new tool - SMA Finder - that can diagnose SMA not only in genome, but also exome and panel sequencing samples aligned to GRCh37, GRCh38, or T2T-CHM13. It works by evaluating aligned reads that overlap the c.840 position of SMN1 and SMN2 in order to detect the most common molecular causes of SMA. We applied SMA Finder to 16,626 exomes and 3,911 genomes from heterogeneous rare disease cohorts sequenced at the Broad Institute Center for Mendelian Genomics as well as 1,157 exomes and 8,762 panel sequencing samples from Tartu University Hospital. SMA Finder correctly identified all 16 known SMA cases and reported nine novel diagnoses which have since been confirmed by clinical testing, with another four novel diagnoses undergoing validation. Notably, out of the 29 total SMA positive cases, 23 had an initial clinical diagnosis of muscular dystrophy, congenital myasthenic syndrome, or myopathy. This underscored the frequency with which SMA can be misdiagnosed as other neuromuscular disorders and confirmed the utility of using SMA Finder to reanalyze phenotypically diverse neuromuscular disease cohorts. Finally, we evaluated SMA Finder on 198,868 individuals that had both exome and genome sequencing data within the UK Biobank (UKBB) and found that SMA Finder's overall false positive rate was less than 1 / 200,000 exome samples, and its positive predictive value (PPV) was 97%. We also observed 100% concordance between UKBB exome and genome calls. This analysis showed that, even though it is located within a segmental duplication, the most common causal variant for SMA can be detected with comparable accuracy to monogenic disease variants in non-repetitive regions. Additionally, the high PPV demonstrated by SMA Finder, the existence of treatment options for SMA in which early diagnosis is imperative for therapeutic benefit, as well as widespread availability of clinical confirmatory testing for SMA, warrants the addition of SMN1 to the ACMG list of genes with reportable secondary findings after genome and exome sequencing., Competing Interests: HLR receives research funding from Microsoft and previously received funding from Illumina to support rare disease gene discovery and diagnosis. AODL has consulted for Tome Biosciences, Ono Pharma USA Inc, and Addition Therapeutics, and is member of the scientific advisory board for Congenica Inc and the Simons Foundation SPARK for Autism study. AL received honoraria for speaking at educational events for Biogen, PTC and Roche, is a subinvestigator in clinical trials by Roche and PTC, and is involved in a project supported by Biogen (POL-SMA-17-11166). PBK has received research support from ML Bio and Sarepta Therapeutics, and has consulted for Lupin, Neurogene, NS Pharma, and Teneofour.
Published: 2024
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