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709 results on '"[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases"'

1. Sotrovimab to prevent severe COVID-19 in high-risk patients infected with Omicron BA.2

Author: Guillaume Martin-Blondel, Anne-Genevieve Marcelin, Cathia Soulié, Sofia Kaisaridi, Clovis Lusivika-Nzinga, Céline Dorival, Laura Nailler, Anaïs Boston, Cléa Melenotte, André Cabié, Christophe Choquet, François Coustillères, Jean-Philippe Martellosio, Géraldine Gaube, Albert Trinh-Duc, Anne-Marie Ronchetti, Valerie Pourcher, Marie Chauveau, Karine Lacombe, Nathan Peiffer-Smadja, Pierre Housset, Aurore Perrot, Gilles Pialoux, Aurélie Martin, Vincent Dubee, Mathilde Devaux, Jérôme Frey, Charles Cazanave, Roland Liblau, Fabrice Carrat, Youri Yordanov, Service Maladies infectieuses et tropicales [CHU Toulouse], Pôle Inflammation, infection, immunologie et loco-moteur [CHU Toulouse] (Pôle I3LM Toulouse), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [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), ANRS France Recherche Nord & sud Sida-hiv hépatites, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Accueil des Urgences (AGEN - SAU), Centre Hospitalier d'Agen, Centre Hospitalier Sud Francilien, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Hôtel-Dieu de Nantes, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Services de Maladies Infectieuses et Tropicales [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), CHR de Metz-Thionville, CHU Bordeaux [Bordeaux], Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service d'Allergologie et d'Immunologie [CHU Toulouse], Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), 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), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Urgences Adultes [CHU Saint-Antoine], and Gestionnaire, Hal Sorbonne Université
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, COVID-19, Humans, Antibodies, Monoclonal, Humanized, Antibodies, Neutralizing
Abstract: International audience; Before the Omicron era, the neutralizing antibody targeting the SARS-CoV2 Spike protein Sotrovimab has been shown to reduce the risk of COVID-19-related hospitalization in patients who are at high risk for progression (1, 2). We recently showed that early administration of Sotrovimab in Omicron-infected patients with very high-risk for progression was associated with a low rate of COVID-19-related hospitalization within one month after treatment administration (3%), and with no death (1). However, the dominance of the Omicron sublineage BA.2 led health agencies to suspend Sotrovimab emergency use authorizations because of its lower neutralizing ability in vitro compared to BA.1 sublineage (3, 4). Clinical efficiency of Sotrovimab to prevent COVID-19 related complications in high-risk patients with mild-to-moderate COVID-19 Omicron BA.2 remains unknown. Our aim was to compare the clinical and virological outcomes of Omicron BA.1 and BA.2-infected patients with mild-to-moderate COVID-19 who received 500 mg of Sotrovimab IV to prevent COVID-19-related complications.
Published: 2022
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2. High SARS-CoV-2 seroprevalence in HIV patients originating from sub-Saharan Africa in the Ile-de-France area

Author: Basma ABDI, Aude Laetitia NDOADOUMGUE, Siham DJEBARA, Karen ZAFILAZA, Romain PALICH, Stéphane MAROT, Luminata SCHNEIDER, Marc WIRDEN, Sophie SEANG, Yasmine DUDOIT, Elisa TEYSSOU, Roland TUBIANA, Cathia SOULIE, Marc Antoine VALANTIN, Christine KATLAMA, Vincent CALVEZ, Lambert ASSOUMOU, Anne-Geneviève MARCELIN, Valérie POURCHER, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Virologie [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), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], and ABDI, BASMA
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, seroprevalence, SARS-CoV-2, COVID-19, HIV, humoral immune response, Infectious Diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, risk factors, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; Objectives: We studied the kinetics of SARS-CoV-2 antibodies and identified the associated risk factors with the presence of these antibodies.Methods: In this longitudinal cohort study, we included all PLWHIV. Samples were tested for IgG targeting the nucleocapsid (N) and all positive samples were tested for IgG targeting the spike (S) and IgA targeting S.Results: 1,901 PLWHIV were included: 64.4% male, median age: 53 years (44-60). At inclusion, 254 (13.4%, 95% CI 11.9, 15.0) had positive IgG anti-N. Levels of IgG anti-N, IgG anti-S and IgA anti-S were 3.95 (standard error: 0.16), 199.4 BAU/mL (21.7) and 3.14 (0.21), respectively. Over one year, levels of IgG anti-N and anti-S decreased significantly (-2.83 p
Published: 2022
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3. Impact of Inflammation on Midazolam Metabolism in Severe COVID‐19 Patients

Author: Edouard Charles Le Carpentier, Emmanuel Canet, Damien Masson, Maëlle Martin, Guillaume Deslandes, Aurélie Gaultier, Éric Dailly, Ronan Bellouard, Matthieu Gregoire, NantesU M, Dépôt, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Intensive [CHU Nantes], Université de Rennes 1 - Faculté des sciences pharmaceutiques et biologiques (UR1 Pharmacie), Université de Rennes (UR), Service d'Epidémiologie et Biostatistique [Nantes], Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Université - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Rennes - Faculté des sciences pharmaceutiques et biologiques (UR Pharmacie), Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE)
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Pharmacology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Midazolam, [SDV]Life Sciences [q-bio], COVID-19 Drug Treatment, Isoenzymes, [SDV] Life Sciences [q-bio], C-Reactive Protein, Metabolism, Severe acute respiratory syndrome, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Sedation, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Glomerular filtration, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, Cytochrome P-450 CYP3A, Cytochrome P-450 CYP3A Inhibitors, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmacology (medical), Acute respiratory distress syndrome - ARDS, Coronavirus 2019 COVID-19
Abstract: International audience; Midazolam is a benzodiazepine frequently used for sedation in patients hospitalized in the intensive care unit (ICU) for coronavirus disease 2019 (COVID-19). This drug is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes. Several studies have suggested that inflammation, frequently observed in these patients, could modulate CYP3A activity. The objective of this work was to study the impact of inflammation on midazolam pharmacokinetics in patients with COVID-19. Forty-eight patients hospitalized in the ICU for COVID-19 and treated with midazolam administered by continuous infusion were included in this study. Midazolam and α-hydroxymidazolam concentrations were measured and patient data, including the use of CYP3A inhibitors, were collected. Total and unbound concentrations of midazolam and α-hydroxymidazolam were measured in plasma using a validated liquid-chromatography coupled with mass spectrometry method. Inflammatory condition was evaluated by C-reactive protein (CRP) level measurement. Both drug concentrations and CRP measurements were performed on 354 plasma samples. CRP elevation was significantly associated with the α-hydroxymidazolam/midazolam plasma ratio decrease, whether for the unbound fraction or for the total fraction. Conversely, inflammation was not associated with protein binding modifications. Logically, α-hydroxymidazolam/midazolam plasma ratio was significantly reduced when patients were treated with CYP3A inhibitors. In this study, we showed that inflammation probably reduces the metabolism of midazolam by CYP3A. These results suggest that molecules with narrow therapeutic margins and metabolized by CYP3A should be administrated with care in case of massive inflammatory situations.
Published: 2022
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4. Phenotypic Heterogeneity of Fulminant COVID-19--Related Myocarditis in Adults

Author: Petra Barhoum, Marc Pineton de Chambrun, Karim Dorgham, Mathieu Kerneis, Sonia Burrel, Paul Quentric, Christophe Parizot, Juliette Chommeloux, Nicolas Bréchot, Quentin Moyon, Guillaume Lebreton, Samia Boussouar, Matthieu Schmidt, Hans Yssel, Lucie Lefevre, Makoto Miyara, Jean-Luc Charuel, Stéphane Marot, Anne-Geneviève Marcelin, Charles-Edouard Luyt, Pascal Leprince, Zahir Amoura, Gilles Montalescot, Alban Redheuil, Alain Combes, Guy Gorochov, Guillaume Hékimian, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut E3M [CHU Pitié-Salpêtrière], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Dorgham, Karim
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Adult, Male, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Adolescent, SARS-CoV-2, COVID-19, Stroke Volume, Middle Aged, Systemic Inflammatory Response Syndrome, Ventricular Function, Left, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Myocarditis, Young Adult, Phenotype, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Cardiology and Cardiovascular Medicine, Autoantibodies, Retrospective Studies
Abstract: International audience; Background: Adults who have been infected with SARS-CoV-2 can develop a multisystem inflammatory syndrome (MIS-A), including fulminant myocarditis. Yet, several patients fail to meet MIS-A criteria, suggesting the existence of distinct phenotypes in fulminant COVID-19–related myocarditis.Objectives: This study sought to compare the characteristics and clinical outcome between patients with fulminant COVID-19–related myocarditis fulfilling MIS-A criteria (MIS-A+) or not (MIS-A−).Methods: A monocentric retrospective analysis of consecutive fulminant COVID-19–related myocarditis in a 26-bed intensive care unit (ICU).Results: Between March 2020 and June 2021, 38 patients required ICU admission (male 66%; mean age 32 ± 15 years) for suspected fulminant COVID-19–related myocarditis. In-ICU treatment for organ failure included dobutamine 79%, norepinephrine 60%, mechanical ventilation 50%, venoarterial extracorporeal membrane oxygenation 42%, and renal replacement therapy 29%. In-hospital mortality was 13%. Twenty-five patients (66%) met the MIS-A criteria. MIS-A− patients compared with MIS-A+ patients were characterized by a shorter delay between COVID-19 symptoms onset and myocarditis, a lower left ventricular ejection fraction, and a higher rate of in-ICU organ failure, and were more likely to require mechanical circulatory support with venoarterial extracorporeal membrane oxygenation (92% vs 16%; P < 0.0001). In-hospital mortality was higher in MIS-A− patients (31% vs 4%). MIS-A+ had higher circulating levels of interleukin (IL)-22, IL-17, and tumor necrosis factor-α (TNF-α), whereas MIS-A− had higher interferon-α2 (IFN-α2) and IL-8 levels. RNA polymerase III autoantibodies were present in 7 of 13 MIS-A− patients (54%) but in none of the MIS-A+ patients.Conclusion: MIS-A+ and MIS-A− fulminant COVID-19–related myocarditis patients have 2 distinct phenotypes with different clinical presentations, prognosis, and immunological profiles. Differentiating these 2 phenotypes is relevant for patients’ management and further understanding of their pathophysiology
Published: 2022
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5. Mental health symptoms are not correlated with peripheral inflammatory biomarkers concentrations in COVID-19-ARDS survivors

Author: Chean, Dara, Benarroch, Samuel, Pochard, Frédéric, Kentish-Barnes, Nancy, Azoulay, Élie, Resche-Rigon, Matthieu, Mégarbane, Bruno, Reuter, Danielle, Labbé, Vincent, Cariou, Alain, Géri, Guillaume, Meersch, Guillaume, Kouatchet, Achille, Guisset, Olivier, Bruneel, Fabrice, Reignier, Jean, Souppart, Virginie, Barbier, François, Argaud, Laurent, Quenot, Jean-Pierre, Papazian, Laurent, Guidet, Bertrand, Thiéry, Guillaume, Klouche, Kada, Lesieur, Olivier, Demoule, Alexandre, Guitton, Christophe, Capellier, Gilles, Mourvillier, Bruno, Biard, Lucie, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Mégarbane, Bruno
Subjects: [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience
Published: 2022
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6. Culture and identification of a 'Deltamicron' SARS‐CoV‐2 in a three cases cluster in southern France

Author: Philippe Colson, Pierre‐Edouard Fournier, Jeremy Delerce, Matthieu Million, Marielle Bedotto, Linda Houhamdi, Nouara Yahi, Jeremy Bayette, Anthony Levasseur, Jacques Fantini, Didier Raoult, Bernard La Scola, COMBE, Isabelle, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS - Inserm U1072), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Base Sequence, SARS-CoV-2, COVID-19, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Infectious Diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Phylogeny
Abstract: Multiple SARS-CoV-2 variants have successively, or concommitantly spread worldwide since summer 2020. A few co-infections with different variants were reported and genetic recombinations, common among coronaviruses, were reported or suspected based on co-detection of signature mutations of different variants in a given genome. Here we report three infections in southern France with a Delta 21J/AY.4-Omicron 21K/BA.1 “Deltamicron” recombinant. The hybrid genome harbors signature mutations of the two lineages, supported by a mean sequencing depth of 1,163-1,421 reads and mean nucleotide diversity of 0.1-0.6%. It is composed of the near full-length spike gene (from codons 156-179) of an Omicron 21K/BA.1 variant in a Delta 21J/AY.4 lineage backbone. Importantly, we cultured an isolate of this recombinant and sequenced its genome. It was observed by scanning electron microscopy. As it is misidentified with current variant screening qPCR, we designed and implemented for routine diagnosis a specific duplex qPCR. Finally, structural analysis of the recombinant spike suggested its hybrid content could optimize viral binding to the host cell membrane. These findings prompt further studies of the virological, epidemiological, and clinical features of this recombinant.
Published: 2022
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7. Factors associated with hospital admission and adverse outcome for COVID-19: Role of social factors and medical care

Author: Beaumont, Anne Lise, Vignes, Dorothée, Sterpu, Raluca, Bussone, Guillaume, Kansau, Imad, Pignon, Carole, Ben Ismail, R., Favier, Marion, Molitor, J. L., Braham, D., Fior, Renato, Roy, Sandrine, Mion, M., Meyer, Laurence, Andronikof, Marc, Damoisel, Charles, Chagué, Pierre, Aurégan, J. C., Bourgeois-Nicolaos, Nadège, Guillet-Caruba, Christelle, Téglas, Jean Paul, Abgrall, Sophie, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ligue Contre le Cancer, We would like to acknowledge all patients included in this research. We gratefully thank Dr. Rey Grégoire for sharing the FDEP score with us and for his advice. We would also like to thank the Ligue Nationale Contre le Cancer for sharing the French EDI score via the MapInMed platform (https://www.canceropole-nordouest.org/plateforme-mapinmed/) and Ludivine Launay for her help and availability., and HAL UVSQ, Équipe
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Male, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Hydrocortisone, SARS-CoV-2, COVID-19, Overweight, Hospitals, Socioeconomic deprivation, Hospitalization, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Geographical origin, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Corticosteroids, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Obesity, Social Factors
Abstract: International audience; Background: Beyond sex, age, and various comorbidities, geographical origin and socioeconomic deprivation are associated with Coronavirus Disease (COVID-19) morbidity and mortality in the general population. We aimed to assess factors associated with severe forms of COVID-19 after a hospital emergency department visit, focusing on socioeconomic factors. Methods: Patients with laboratory-confirmed COVID-19 attending the emergency department of Béclère Hospital (France) in March–April 2020 were included. Postal addresses were used to obtain two geographical deprivation indices at the neighborhood level. Factors associated with hospitalization and factors associated with adverse outcomes, i.e. mechanical ventilation or death, were studied using logistic and Cox analyses, respectively. Results: Among 399 included patients, 321 were hospitalized. Neither geographical origin nor socioeconomic deprivation was associated with any of the outcomes. Being male, older, overweight or obese, diabetic, or having a neuropsychiatric disorder were independent risk factors for hospitalization. Among 296 patients hospitalized at Béclère Hospital, 91 experienced an adverse outcome. Older age, being overweight or obese, desaturation and extent of chest CT scan lesions > 25% at admission (aHR: 2.2 [95% CI: 1.3–3.5]) and higher peak CRP levels and acute kidney failure (aHR: 2.0 [1.2–3.3]) during follow-up were independently associated with adverse outcomes, whereas treatment with hydrocortisone reduced the risk of mechanical ventilation or death by half (aHR: 0.5 [0.3–0.8]). Conclusion: No association between geographical origin or socioeconomic deprivation and the occurrence of a severe form of COVID-19 was observed in our population after arrival to the emergency department. Empirical corticosteroid use with hydrocortisone had a strong protective impact.
Published: 2022
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8. Pathogenesis of recent Lassa virus isolates from lineages II and VII in cynomolgus monkeys

Author: Mateo, Mathieu, Hortion, Jimmy, Perthame, Emeline, Picard, Caroline, Reynard, Stéphanie, Journeaux, Alexandra, Germain, Clara, Carnec, Xavier, Baillet, Nicolas, Borges-Cardoso, Virginie, Pietrosemoli, Natalia, Vallve, Audrey, Barron, Stéphane, Jourjon, Ophélie, Lacroix, Orianne, Duthey, Aurélie, Dirheimer, Manon, Daniau, Maïlys, Legras-Lachuer, Catherine, Jouvion, Gregory, Carbonnelle, Caroline, Raoul, Hervé, Baize, Sylvain, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), 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)-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)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), ViroScan3D SAS [Trévoux, France], Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), MATEO, MATHIEU, 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)-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)-Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Université Paris Cité (UPCité)
Subjects: Microbiology (medical), cynomolgus monkeys, Immunology, viral hemorrhagic fevers, MESH: Lassa Fever, Virus Replication, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Microbiology, Lassa Fever, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, MESH: Animals, Lassa virus, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Humans, pathogenesis, MESH: Virus Replication, MESH: Lassa virus, immune responses, Macaca fascicularis, Infectious Diseases, MESH: Macaca fascicularis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasitology
Abstract: We thank P. Regnard, P.H. Moreau, and L. Fellmann (SILABE, Strasbourg) for medical care given to the monkeys. We thank S. Mundweiller, S. Godard, E. Moissonnier, D. Thomas, S. Mely, B. Labrosse, D. Pannetier, and C. Leculier (P4 INSERM–Jean Merieux, US003, INSERM) for assistance in conducting the BSL-4 experiments. We thank M-A Dillies (HUB, Institut Pasteur) for helpful discussions. We thank G. Fourcaud and B. Lafoux (UBIVE, CIRI, Institut Pasteur) for technical help. We also thank L. Branco (Zalgen Labs) for providing recombinant proteins. We are grateful to the Coalition for Epidemic Preparedness and Innovations (R. Hatchett, G. Thiry, and M. Saville) and C. Gerke (Department of Innovation Development, Institut Pasteur) for invaluable support.; International audience; The area of Lassa virus (LASV) circulation is expanding, with the emergence of highly pathogenic new LASV lineages. Benin recently became an endemic country for LASV and has seen the emergence of a new LASV lineage (VII). The first two outbreaks in 2014 and 2016 showed a relatively high mortality rate compared to other outbreaks. We infected cynomolgus monkeys with two strains belonging to lineage II and lineage VII that were isolated from deceased patients during the 2016 outbreak in Benin. The lineage VII strain (L7) caused uniform mortality. Death was associated with uncontrolled viral replication, unbalanced inflammatory responses characterized by increased concentrations of pro- and anti-inflammatory mediators, and the absence of efficient immune responses, resembling the pathogenesis associated with the prototypic Josiah strain in monkeys. The lineage II strain (L2) showed apparently lower virulence than its counterpart, with a prolonged time to death and a lower mortality rate. Prolonged survival was associated with better control of viral replication, a moderate inflammatory response, and efficient T-cell responses. Transcriptomic analyses also highlighted important differences in the immune responses associated with the outcome. Both strains caused strong inflammation in several organs. Notably, meningitis and encephalitis were observed in the cerebral cortex and cerebellum in all monkeys, independently of the outcome. Due to their apparently high pathogenicity, emerging strains from lineage VII should be considered in preclinical vaccine testing. Lineage II would also be beneficial in pathogenesis studies to study the entire spectrum of Lassa fever severity.
Published: 2022
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9. Impact of <scp>SARS‐CoV‐</scp> 2 infection on risk of prematurity, birthweight and obstetric complications: A multivariate analysis from a nationwide, population‐based retrospective cohort study

Author: Emmanuel Simon, Jean‐Bernard Gouyon, Jonathan Cottenet, Sonia Bechraoui‐Quantin, Patrick Rozenberg, Anne‐Sophie Mariet, Catherine Quantin, HAL UVSQ, Équipe, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Études Périnatales de l'Océan Indien (CEPOI), Université de La Réunion (UR)-Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service Biostatistiques et Informatique Médicale (CHU de Dijon) (DIM), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Agence Nationale de la Recherche, ANR, and The project was funded by the French National Research Agency.
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, hypertension, pre-eclampsia, SARS-CoV-2, prematurity, Infant, Newborn, COVID-19, Obstetrics and Gynecology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Fetal Macrosomia, Cohort Studies, small for gestational age, [SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Pregnancy, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Multivariate Analysis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Birth Weight, Humans, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pregnancy Complications, Infectious, Retrospective Studies
Abstract: To determine the impact of maternal coronavirus disease 2019 (COVID-19) on prematurity, birthweight and obstetric complications.Nationwide, population-based retrospective cohort study.National Programme de Médicalisation des Systèmes d'Information database in France.All single births from March to December 2020: 510 387 deliveries, including 2927 (0.6%) with confirmed COVID-19 in the mother and/or the newborn.The group with COVID-19 was compared with the group without COVID-19 using the chi-square test or Fisher's exact test, and the Student's t test or Mann-Whitney U test. Logistic regressions were used to study the effect of COVID-19 on the risk of prematurity or macrosomia (birthweight ≥4500 g).Prematurity less than 37, less than 28, 28-31, or 32-36 weeks of gestation; birthweight; obstetric complications.In singleton pregnancies, COVID-19 was associated with obstetric complications such as hypertension (2.8% versus 2.0%, p 0.01), pre-eclampsia (3.6% versus 2.0%, p 0.01), diabetes (18.8% versus 14.4%, p 0.01) and caesarean delivery (26.8% versus 19.7%, p 0.01). Among pregnant women with COVID-19, there was more prematurity between 28 and 31 weeks of gestation (1.3% versus 0.6%, p 0.01) and between 32 and 36 weeks of gestation (7.7% versus 4.3%, p 0.01), and more macrosomia (1.0% versus 0.7%, p = 0.04), but there was no difference in small-for-gestational-age newborns (6.3% versus 8.7%, p = 0.15). Logistic regression analysis for prematurity showed an adjusted odds ratio (aOR) of 1.77 (95% CI 1.55-2.01) for COVID-19. For macrosomia, COVID-19 resulted in non-significant aOR of 1.38 (95% CI 0.95-2.00).COVID-19 is a risk factor for prematurity, even after adjustment for other risk factors.The risk of prematurity is twice as high in women with COVID-19 after adjustment for factors usually associated with prematurity.
Published: 2022
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10. Limited spread of a rare spike E484K-harboring SARS-CoV-2 in Marseille, France

Author: Philippe Colson, Jacques Fantini, Nouara Yahi, Jeremy Delerce, Anthony Levasseur, Pierre-Edouard Fournier, Jean-Christophe Lagier, Didier Raoult, Bernard La Scola, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS - Inserm U1072), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), and COMBE, Isabelle
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, Brief Report, COVID-19, General Medicine, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Mutation, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Guinea, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; We detected SARS-CoV-2 of PANGO lineage R.1 with the spike substitution E484K in three patients. Eleven other sequences in France and 8,831 worldwide were available from GISAID, 92% originating from Japan. The three genome sequences from our institute were phylogenetically closest to another from Guinea-Conakry, where one of the patients had travelled. These viruses did not exhibit any unusual features in cell culture. Spike structural predictions indicated a 1.3-time higher transmissibility index than for the globally spread B.1.1.7 variant but also an affinity loss for gangliosides that might have slowed dissemination. The spread of new SARS-CoV-2 mutants/variants is still not well understood and therefore difficult to predict, and this hinders implementation of effective preventive measures, including adapted vaccines.
Published: 2022
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11. Concurrent Nanopore Next-Generation Sequencing of Hepatitis B and Delta Virus Genomes Directly From Patient Plasma

Author: Anne Motte, Céline Boschi, Ludivine Brechard, Jessica Grace Bengone-Abogourin, Philippe Colson, Isabelle Allemand, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Gamétogénèse Apoptose et Génotoxicité - LGAG (Equipe - U967 INSERM), Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), European Project, Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), COMBE, Isabelle, Instituts Hospitalo-Universitaires - I.H.U. Méditerranée Infection - - Méditerranée Infection2010 - ANR-10-IAHU-0003 - IAHU - VALID, and FEDER PRIMI - INCOMING
Subjects: Delta, Hepatitis B virus, Clinical Biochemistry, Computational biology, Genome, Viral, Biology, Genome, DNA sequencing, Virus, 03 medical and health sciences, Nanopores, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Letter to the Editor, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 030306 microbiology, Biochemistry (medical), High-Throughput Nucleotide Sequencing, General Medicine, Hepatitis B, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Nanopore, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Diagnostic Genetics, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: International audience
Published: 2021
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12. Biosafety and biobanking: Current understanding and knowledge gaps

Author: Maissa Zeghidi, Zisis Kozlakidis, Julie Roux, Stephanie Villar, Retiveau, Nolwenn, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [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), and Université Catholique de Lyon (UCLy) (UCLy)
Subjects: Microbiology (medical), Best practice, Infectious and parasitic diseases, RC109-216, Article, Safety regulations, Biosafety, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Political science, Pandemic, Data safety, Global health, Biobank, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Public Health, Environmental and Occupational Health, Biological safety, Infectious Diseases, Work (electrical), Infectious disease (medical specialty), [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Engineering ethics, Public aspects of medicine, RA1-1270, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Physical security, Biotechnology
Abstract: International audience; Infectious disease outbreaks, such as 'Coronavirus disease 2019' (COVID-19), can constitute major global health threats with far-reaching consequences. As outbreaks develop, the international scientific community must provide high-quality scientific research-ready biological samples to solve the existing clinical and epidemiological questions to better combat the pandemic. Such examples are provided by dedicated biobank facilities, the latter collecting increasingly high volumes of biological samples. However, the more significant concentrations of infectious or potentially infectious biological materials can create a safety risk. The current short report describes the first attempt to identify the published scientific works on biobanking and safety. Three broad thematic areas have been identified: the physical security relevant to staff and sample integrity, the data safety aspects, and the governance parameters relating to the previous two. While the current publications reflect a broad alignment with existing standards and best practices in the biobanking field, they also demonstrate an opportunity for further in-depth work on this field in the post-COVID-19 era.
Published: 2021
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13. ICAM-1 Kilifi variant is not associated with cerebral and severe malaria pathogenesis in Beninese children

Author: Samuel Odarkwei Blankson, Danielle Seri Dadjé, Nadjla Traikia, Maroufou J. Alao, Serge Ayivi, Annick Amoussou, Philippe Deloron, Nicaise Tuikue Ndam, Jacqueline Milet, Leonardo K. Basco, Yaw Aniweh, Rachida Tahar, University of Ghana, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de la Mère et de l'Enfant Lagune (CHU-MEL), Centre National Hospitalier Universitaire Hubert K. Maga de Cotonou (CNHU-HKM), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), COMBE, Isabelle, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, ICAM-1, Plasmodium falciparum, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Malaria, Infectious Diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, ICAM-1kilifi, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasitology, cerebral malaria, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Polymorphism, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: Background Cytoadhesion and sequestration of Plasmodium falciparum infected red blood cells (iRBC) in the microvasculature of vital organs are a major cause of malaria pathology. Several studies have provided evidence on the implication of the human host intercellular adhesion molecule-1 (ICAM-1) as a major receptor for iRBCs binding to P. falciparum erythrocyte membrane protein 1 (PfEMP1) in the development of severe and cerebral malaria. The genetic polymorphism K29M in the immunoglobulin-like domain of ICAM-1, known as ICAM-1Kilifi, has been associated with either increased or decreased risk of developing cerebral malaria. Methods To provide more conclusive results, the genetic polymorphism of ICAM-1Kilifi was assessed by PCR and sequencing in blood samples from 215 Beninese children who presented with either mild or severe malaria including cerebral malaria. Results and conclusions The results showed that in this cohort of Beninese children, the ICAM-1kilifi variant is present at the frequencies of 0.27, similar to the frequency observed in other African countries. This ICAM-1kilifi variant was not associated with disease severity in agreement with other findings from the Gambia, Tanzania, Malawi, Gabon, and Thailand, suggesting no evidence of a direct link between this polymorphism and the pathogenesis of severe and cerebral malaria.
Published: 2022
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14. Putative native South Amerindian origin of head lice clade F: evidence from head lice nits infesting human shrunken heads

Author: Amanzougaghene, Nadia, Charlier, Philippe, Fenollar, Florence, Raoult, Didier, Mediannikov, Oleg, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Laboratoire Anthropologie, Archéologie, Biologie (LAAB), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Musée du quai Branly – Jacques Chirac (MQBJC), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), This study was supported by the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection, the National Research Agency under the program «Investissements d’avenir», reference ANR-10-IAHU-03, the Région Provence-Alpes-Côte d’Azur and European funding FEDER PRIM, ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), COMBE, Isabelle, Instituts Hospitalo-Universitaires - I.H.U. Méditerranée Infection - - Méditerranée Infection2010 - ANR-10-IAHU-0003 - IAHU - VALID, and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Phylogenetics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Molecular evolution, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: International audience; The head louse, Pediculus humanus capitis , is a strictly obligate human ectoparasite with a long history of association with humans. Here, 17 ancient head lice nits were recovered from six shrunken human heads (known as tsantsas ) of individuals from the Shuar/Jivaro tribe, a native Amazonian population from Ecuador, South America. Cytochrome b DNA analysis revealed the presence of three known mitochondrial clades. Clade A was the most frequent (52.94%), followed by F (35.29%), and B (11.76%). Eleven haplotypes were found in 17 samples, and nine of the haplotypes were novel, indicating an unusually high genetic diversity. In conclusion, we confirmed the presence of clades A, B and F in South Amerindian population. Moreover, the description of clade F, together with its previous reports in another Amerindian population from French Guiana, strongly support the hypothesis of a native South American origin for this clade, and probably derived from clade B which was carried to America by an ancestral Eurasian Beringian population. Further support to our conclusion and new insights might come from the analysis of a larger collection of modern and ancient native American lice.
Published: 2022
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15. Evolutionary trajectory of receptor binding specificity and promiscuity of the spike protein of SARS-CoV-2

Author: Cyril Planchais, Alejandra Reyes‐Ruiz, Robin Lacombe, Alessandra Zarantonello, Maxime Lecerf, Margot Revel, Lubka T. Roumenina, Boris P. Atanasov, Hugo Mouquet, Jordan D. Dimitrov, Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Bulgaria Academy of Sciences = Académie des Sciences de Bulgarie (BAS), This work was supported by Institut National de la Santé et de la Recherche Médicale (INSERM, France). Jordan D. Dimitrov is recipient of a grant from the European Research Council (Project CoBABATI ERC-StG-678905). Alejandra Reyes-Ruiz is recipient of fellowship from an Innovative Training Network (ITN) funded by the European Union's Horizon 2020 Programme under grant agreement No. 859974, project EDUC8. Alessandra Zarantonello is supported by the Danish Council for Independent Research (DFF-1025-00015B)., European Project: 678905,H2020-EU.1.1., ERC-StG-2015,CoBABATI(2016), European Project: 859974,H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions,EDUC8(2020), École pratique des hautes études (EPHE), Jordan, Dimitrov, Cofactor Binding Antibodies – Basic Aspects and Therapeutic Innovations - CoBABATI - - H2020-EU.1.1., ERC-StG-20152016-09-01 - 2021-08-31 - 678905 - VALID, and Early Stage Researchers EDUCational Program on Factor VIII Immunogenicity - EDUC8 - - H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions2020-04-01 - 2024-09-30 - 859974 - VALID
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, virus evolution, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, protein-protein interactions, COVID-19, Peptidyl-Dipeptidase A, binding promiscuity, Biochemistry, thermodynamics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, protein electrostatics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Angiotensin-Converting Enzyme 2, Molecular Biology, Protein Binding
Abstract: SARS-CoV-2 infects cells by attachment to its receptor – the angiotensin converting enzyme 2 (ACE2). Regardless of the wealth of structural data, little is known about the physicochemical mechanism of interactions of the viral spike (S) protein with ACE2 and how this mechanism has evolved during the pandemic. Here, we applied experimental and computational approaches to characterize the molecular interaction of S proteins from SARS-CoV-2 variants of concern (VOC). Data on kinetics, activation- and equilibrium thermodynamics of binding of the receptor binding domain (RBD) from VOC with ACE2 as well as data from computational protein electrostatics revealed a profound remodeling of the physicochemical characteristics of the interaction during the evolution. Thus, as compared to RBDs from Wuhan strain and other VOC, Omicron RBD presented as a unique protein in terms of conformational dynamics and types of non-covalent forces driving the complex formation with ACE2. Viral evolution resulted in a restriction of the RBD structural dynamics, and a shift to a major role of polar forces for ACE2 binding. Further, we investigated how the reshaping of the physicochemical characteristics of interaction affect the binding specificity of S proteins. Data from various binding assays revealed that SARS-CoV-2 Wuhan and Omicron RBDs manifest capacity for promiscuous recognition of unrelated human proteins, but they harbor distinct reactivity patterns. These findings might contribute for mechanistic understanding of the viral tropism, and capacity to evade immune responses during evolution.
Published: 2022
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16. Predicted Impacts of Booster, Immunity Decline, Vaccination Strategies, and Non-Pharmaceutical Interventions on COVID-19 Outcomes in France

Author: Simon, Pageaud, Anne, Eyraud-Loisel, Jean-Pierre, Bertoglio, Alexis, Bienvenüe, Nicolas, Leboisne, Catherine, Pothier, Christophe, Rigotti, Nicolas, Ponthus, Romain, Gauchon, François, Gueyffier, Philippe, Vanhems, Jean, Iwaz, Stéphane, Loisel, Pascal, Roy, On Behalf Of The CovDyn Group Covid Dynamics, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Laboratoire de Sciences Actuarielles et Financières [Lyon] (LSAF), Institut de Science Financière et d'Assurances (ISFA), Université de Lyon, Laboratoire de Mecanique des Fluides et d'Acoustique (LMFA), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), 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)-Centre National de la Recherche Scientifique (CNRS), Extraction de Caractéristiques et Identification (imagine), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Data Mining and Machine Learning (DM2L), Artificial Evolution and Computational Biology (BEAGLE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Lyon, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire de Tribologie et Dynamique des Systèmes (LTDS), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Ecole Nationale d'Ingénieurs de Saint Etienne (ENISE)-Centre National de la Recherche Scientifique (CNRS), 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), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), Service de Biostatistiques [Lyon], Institut Louis Bachelier, École Nationale des Travaux Publics de l'État (ENTPE), 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), and Rigotti, Christophe
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Pharmacology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, decision support techniques, Immunology, COVID-19, vaccination, agent-based model, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Infectious Diseases, booster, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Discovery, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Pharmacology (medical), [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology
Abstract: International audience; The major economic and health consequences of COVID-19 called for various protective measures and mass vaccination campaigns. A previsional model was used to predict the future impacts of various measure combinations on COVID-19 mortality over a 400-day period in France. Calibrated on previous national hospitalization and mortality data, an agent-based epidemiological model was used to predict individual and combined effects of booster doses, vaccination of refractory adults, and vaccination of children, according to infection severity, immunity waning, and graded non-pharmaceutical interventions (NPIs). Assuming a 1.5 hospitalization hazard ratio and rapid immunity waning, booster doses would reduce COVID-19-related deaths by 50–70% with intensive NPIs and 93% with moderate NPIs. Vaccination of initially-refractory adults or children ≥5 years would half the number of deaths whatever the infection severity or degree of immunity waning. Assuming a 1.5 hospitalization hazard ratio, rapid immunity waning, moderate NPIs and booster doses, vaccinating children ≥12 years, ≥5 years, and ≥6 months would result in 6212, 3084, and 3018 deaths, respectively (vs. 87,552, 64,002, and 48,954 deaths without booster, respectively). In the same conditions, deaths would be 2696 if all adults and children ≥12 years were vaccinated and 2606 if all adults and children ≥6 months were vaccinated (vs. 11,404 and 3624 without booster, respectively). The model dealt successfully with single measures or complex combinations. It can help choosing them according to future epidemic features, vaccination extensions, and population immune status.
Published: 2022
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17. Epidemiokinetic Tools to Monitor Lockdown Efficacy and Estimate the Duration Adequate to Control SARS-CoV-2 Spread

Author: Jean-Michel Scherrmann, Bruno Mégarbane, Fanchon Bourasset, Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris Cité (UPCité), and Mégarbane, Bruno
Subjects: medicine.medical_specialty, Population, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Epidemic half-life, law.invention, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Lockdown, Pandemic, Humans, Medicine, Operations management, Duration (project management), education, Pandemics, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Upstream (petroleum industry), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, SARS-CoV-2, business.industry, Public health, COVID-19, Intensive care unit, Hospitalization, Duration, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Communicable Disease Control, Commentary, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [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, Performance indicator, Simple linear regression, Prediction, business
Abstract: Various key performance indicators (KPIs) are communicated daily to the public by health authorities since the COVID-19 pandemic has started. “Upstream” KPIs mainly include the incidence of detected Sars-CoV-2-positive cases in the population, and “downstream” KPIs include daily hospitalizations, intensive care unit admissions and fatalities. Whereas “downstream” KPIs are essential to evaluate and adapt hospital organization, “upstream” KPIs are the most appropriate to decide on the strength of restrictions such as lockdown set up and evaluate their effectiveness. Here, we suggested tools derived from pharmacokinetic calculations to improve understanding the epidemic progression. From the time course of the number of new cases of SARS-coV-2 infection in the population, it is possible to calculate the infection rate constant using a simple linear regression and determine its corresponding half-life. This epidemic regression half-life is helpful to measure the potential benefits of restriction measures and to estimate the adequate duration of lockdown if implemented by policymakers in relation to the decided public health objectives. In France, during the first lockdown, we reported an epidemic half-life of 10 days. Our tools allow clearly acknowledging that the zero-COVID target is difficult to reach after a period of lockdown as seven half-lives are required to clear 99.2% of the epidemic and more than 10 half-lives to almost reach the objective of eliminating 100% of the contaminations.
Published: 2021
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18. Cardiac adipose tissue volume and IL-6 level at admission are complementary predictors of severity and short-term mortality in COVID-19 diabetic patients

Author: Franck Phan, Samia Boussouar, Olivier Lucidarme, Mohamed Zarai, Joe-Elie Salem, Nadjia Kachenoura, Khaoula Bouazizi, Etienne Charpentier, Yasmine Niati, Hasnae Bekkaoui, Zahir Amoura, Alexis Mathian, Olivier Benveniste, Patrice Cacoub, Yves Allenbach, David Saadoun, Jean-Marc Lacorte, Salma Fourati, Suzanne Laroche, Agnes Hartemann, Olivier Bourron, Fabrizio Andreelli, Alban Redheuil, COVID-19 APHP.SU Group, Service de Diabétologie [CHU Pitié-Salpétrière], 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), HAL-SU, Gestionnaire, Service de diabétologie [CHU Pitié-Salpétrière], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Service de pharmacologie médicale [CHU Pitié-Salpêtrière], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Unité de recherche sur les maladies cardiovasculaires et métaboliques, UMR S 1166, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Endocrinology, Diabetes and Metabolism, Adipose tissue, 030204 cardiovascular system & hematology, Severity of Illness Index, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Mass index, 030212 general & internal medicine, Hospital Mortality, Original Investigation, Outcome, 2. Zero hunger, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Cardiac adipose tissue, Diabetes, Heart, Organ Size, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Prognosis, 3. Good health, Intensive Care Units, Adipose Tissue, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Median body, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Cardiac computed tomography, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Intensive care, Severity of illness, medicine, Humans, Diseases of the circulatory (Cardiovascular) system, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Angiology, Aged, Inflammation, business.industry, SARS-CoV-2, Interleukin-6, Myocardium, COVID-19, medicine.disease, Obesity, Diabetes Mellitus, Type 2, RC666-701, business, Tomography, X-Ray Computed
Abstract: BackgroundCOVID-19 diabetic adults are at increased risk of severe forms irrespective of obesity. In patients with type-II diabetes, fat distribution is characterized by visceral and ectopic adipose tissues expansion, resulting in systemic inflammation, which may play a role in driving the COVID-19 cytokine storm. Our aim was to determine if cardiac adipose tissue, combined to interleukin-6 levels, could predict adverse short-term outcomes, death and ICU requirement, in COVID-19 diabetic patients during the 21 days after admission.MethodsEighty one consecutive patients with type-II diabetes admitted for COVID-19 were included. Interleukin-6 measurement and chest computed tomography with total cardiac adipose tissue index (CATi) measurement were performed at admission. The primary outcome was death during the 21 days following admission while intensive care requirement with or without early death (ICU-R) defined the secondary endpoint. Associations of CATi and IL-6 and threshold values to predict the primary and secondary endpoints were determined.ResultsOf the enrolled patients (median age 66 years [IQR: 59–74]), 73% male, median body mass index (BMI) 27 kg/m2[IQR: 24–31]) 20 patients had died from COVID-19, 20 required intensive care and 41 were in conventional care at day 21 after admission. Increased CATi and IL-6 levels were both significantly related to increased early mortality (respectively OR = 6.15, p = 0.002; OR = 18.2,p p = 0.01; OR = 4.86,p = 0.002). These associations remained significant independently of age, sex, BMI as well as troponin-T level and pulmonary lesion extension in CT. We combined CATi and IL-6 levels as a multiplicative interaction score (CATi*IL-6). The cut-point for this score was ≥ 6386 with a sensitivity of 0.90 and a specificity of 0.87 (AUC = 0.88) and an OR of 59.6 for early mortality (p ConclusionsCardiac adipose tissue index and IL-6 determination at admission could help physicians to better identify diabetic patients with a potentially severe and lethal short term course irrespective of obesity. Diabetic patients with high CATi at admission,a fortioriassociated with high IL-6 levels could be a relevant target population to promptly initiate anti-inflammatory therapies.
Published: 2021
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19. Non–C. difficileClostridioides Bacteremia in Intensive Care Patients, France

Author: Guillaume Morel, Romain Sonneville, Damien Contou, David Rousset, Djamel Mokart, Amélie Seguin, Bruno Mégarbane, Lucie Biard, Moustafa Abdel Nabey, Guillaume Dumas, Guillaume Voiriot, Anne-Sophie Moreau, Laura Platon, Yacine Tandjaoui, Elie Azoulay, Muriel Picard, Achille Kouatchet, Frédéric Pène, Guillaume Mulier, Lara Zafrani, Etienne Ghrenassia, Isabelle Oddou, Hôpital de Hautepierre [Strasbourg], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Avicenne [AP-HP], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Lapeyronie [Montpellier] (CHU), Hôpital Cochin [AP-HP], Hôpital Roger Salengro [Lille], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Victor Dupouy, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], CHU Tenon [AP-HP], CHU Strasbourg, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Mégarbane, Bruno
Subjects: Microbiology (medical), medicine.medical_specialty, Critical Care, Epidemiology, Infectious and parasitic diseases, RC109-216, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Clostridium, Clostridioides, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Intensive care, medicine, Humans, Non–C. difficile Clostridioides Bacteremia in Intensive Care Patients, France, bacteremia, bacteria, intensive care, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, business.industry, Research, medicine.disease, C difficile, biology.organism_classification, Hemolysis, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Infectious Diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Bacteremia, ICU, Clostridium Infections, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, France, hemolysis, business
Abstract: Article Summary: This multicenter study focusing on critically ill patients showed a strong relationship between hemolysis and mortality., Usually responsible for soft tissue infections, Clostridioides species can also cause bacteremia, life-threatening infections often requiring intensive care unit (ICU) admission. We conducted a multicenter retrospective study to investigate Clostridioides bacteremia in ICUs to describe the clinical and biologic characteristics and outcomes in critically ill patients. We identified 135 patients with Clostridioides bacteremia, which occurred almost exclusively (96%) in patients with underlying conditions. Septic shock and digestive symptoms were the hallmarks of Clostridioides bacteremia in the ICU. We identified 16 different species of Clostridioides, among which C. perfringens accounted for 31% of cases. Despite the high sensitivity of Clostridioides to common antimicrobial drugs, mortality rates were high: 52% for ICU patients and 71% overall at 3 months. In multivariate analysis, the most important factor associated with increased risk for death was the presence of hemolysis. Clostridioides bacteremia often leads to multiple organ failures, which have high mortality rates.
Published: 2021
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20. Statin Therapy to Improve Outcome of COVID-19 Patients: Useful or Not Useful?

Author: Bruno Mégarbane, INSERM UMRS-1144, Université Paris Cité, Réanimation Médicale et Toxicologique, Hôpital Lariboisière, and Mégarbane, Bruno
Subjects: [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine (miscellaneous), [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; About one year ago, the journal published a large population-based cohort study from South Korea investigating the potential benefits associated with statins at preventing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection or improving the outcome of hospitalized coronavirus disease-2019 (COVID-19) patients [...]
Published: 2022
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21. Persistence of neutrophil extracellular traps and anticardiolipin auto-antibodies in post-acute phase COVID-19 patients

Author: Ekaterina Pisareva, Stephanie Badiou, Lucia Mihalovičová, Alexia Mirandola, Brice Pastor, Andrei Kudriavtsev, Marie Berger, Camille Roubille, Pierre Fesler, Kada Klouche, Jean‐Paul Cristol, Alain R. Thierry, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and MORNET, Dominique
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity
Abstract: In the early phase of the pandemic, we were among the first to postulate that neutrophil extracellular traps (NETs) play a key role in COVID-19 pathogenesis. This exploratory prospective study based on 279 individuals showed that plasma levels of neutrophil elastase, myeloperoxidase and circulating DNA of nuclear and mitochondrial origins in nonsevere (NS), severe (S) and postacute phase (PAP) COVID-19 patients were statistically different as compared to the levels in healthy individuals, and revealed the high diagnostic power of these NETs markers in respect to the disease severity. The diagnostic power of NE, MPO, and cir-nDNA as determined by the Area Under Receiver Operating Curves (AUROC) was 0.95, 097, and 0.64; 0.99, 1.0, and 0.82; and 0.94, 1.0, and 0.93, in NS, S, and PAP patient subgroups, respectively. In addition, a significant fraction of NS, S as well as of PAP patients exhibited aCL IgM/IgG and anti-B2GP IgM/IgG positivity. We first demonstrate persistence of these NETs markers in PAP patients and consequently of sustained innate immune response imbalance, and a prolonged low-level pro-thrombotic potential activity highlighting the need to monitor these markers in all COVID-19 PAP individuals, to investigate postacute COVID-19 pathogenesis following intensive care, and to better identify which medical resources will ensure complete patient recovery.
Published: 2022
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22. Systematic MRI in persistent post-Covid-19 olfactory dysfunction should be reassessed

Author: Ioana Brudasca, Quentin Lisan, Romain Tournegros, Moustafa Bensafi, Camille Ferdenzi, Arnaud Fournel, Luna Denoix, Stéphane Tringali, Maxime Fieux, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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), Université de Lyon, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biomécanique & Appareil Respiratoire (BAR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), 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), and Ferdenzi, Camille
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, imaging, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Otorhinolaryngology, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, olfactory disorder, olfaction
Abstract: International audience; Background: Magnetic resonance imaging (MRI) is the gold standard in the etiological assessment of a persistent olfactory dysfunction (OD). While the utility of imaging in COVID-19-related OD has yet to be established, MRI is recommended in all patients with persistent OD. The high prevalence of the latter after SARS-CoV-2 infection means evaluating this strategy is an important public health matter.Methods:The main objective was to examine the impact of systematic MRI on the management of patients with OD. All adult patients consulting for persistent OD (>2 months) after primary SARS-COV-2 infection (PCR) between March 2020 and December 2021 were included (n = 67). The secondary objective was to evaluate the relationship between the severity of the OD as measured by psychophysical testing (ETOC) and the volume of the olfactory bulb (OB) measured by MRI.Results: All patients underwent MRI, and none led to a change in diagnosis or treatment. Among them, 82% (55/67) were considered normal by the radiologist on initial interpretation. There were no significant differences (visual analysis or OB volume) between groups (mild, moderate, and severe hyposmia).Conclusion: Systematic MRI may be unnecessary in patients whose persistent OD began soon (a few days) after confirmed SARS-CoV-2 infection.
Published: 2022
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23. The Challenge of Reaching Undocumented Migrants with COVID-19 Vaccination

Author: Stephen A. Matlin, Alyna C. Smith, Jessica Merone, Michele LeVoy, Jalpa Shah, Frank Vanbiervliet, Stéphanie Vandentorren, Joanna Vearey, Luciano Saso, Imperial College London, Università degli Studi di Padova = University of Padua (Unipd), Santé publique France - French National Public Health Agency [Saint-Maurice, France], 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), University of the Witwatersrand [Johannesburg] (WITS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), and Admin, Oskar
Subjects: Transients and Migrants, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, COVID-19 Vaccines, COVID-19 vaccination, SARS-CoV-2, Health, Toxicology and Mutagenesis, Vaccination, Public Health, Environmental and Occupational Health, COVID-19, Undocumented migrants, Health Services Accessibility, Supply- and demand-side access barriers, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Communicable Disease Control, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Equitable access, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Pandemics
Abstract: International audience; Access to vaccination against a health threat such as that presented by the COVID-19 pandemic is an imperative driven, in principle, by at least three compelling factors: (1) the right to health of all people, irrespective of their status; (2) humanitarian need of undocumented migrants, as well as of others including documented migrants, refugees and displaced people who are sometimes vulnerable and living in precarious situations; and (3) the need to ensure heath security globally and nationally, which in the case of a global pandemic requires operating on the basis that, for vaccination strategies to succeed in fighting a pandemic, the highest possible levels of vaccine uptake are required. Yet some population segments have had limited access to mainstream health systems, both prior to as well as during the COVID-19 pandemic. People with irregular resident status are among those who face extremely high barriers in accessing both preventative and curative health care. This is due to a range of factors that drive exclusion, both on the supply side (e.g., systemic and practical restrictions in service delivery) and the demand side (e.g., in uptake, including due to fears that personal data would be transmitted to immigration authorities). Moreover, undocumented people have often been at increased risk of infection due to their role as "essential workers", including those experiencing higher exposure to the SARS-CoV-2 virus due to frontline occupations while lacking protective equipment. Often, they have also been largely left out of social protection measures granted by governments to their populations during successive lockdowns. This article reviews the factors that serve as supply-side and demand-side barriers to vaccination for undocumented migrants and considers what steps need to be taken to ensure that inclusive approaches operate in practice.
Published: 2022
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24. Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat

Author: Camille Lagard, Dominique Vodovar, Lucie Chevillard, Jacques Callebert, Fabien Caillé, Géraldine Pottier, Hao Liang, Patricia Risède, Nicolas Tournier, Bruno Mégarbane, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Université Paris Cité (UPCité), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Biochimie et Biologie Moleculaire [AP-HP Hôpital Lariboisière] (IFR6), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Variabilité de réponse aux Psychotropes (VariaPsy - U1144), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, ANR-16-CE17-0011,ISOTOPK,Imagerie fonctionnelle des transporteurs SLCO (Solute Carrier O) chez l'Homme : implication dans la variabilité d'élimination et de distribution tissulaire des médicaments(2016), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Chevillard, Lucie, Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Mégarbane, Bruno, Imagerie fonctionnelle des transporteurs SLCO (Solute Carrier O) chez l'Homme : implication dans la variabilité d'élimination et de distribution tissulaire des médicaments - - ISOTOPK2016 - ANR-16-CE17-0011 - AAPG2016 - VALID, Laboratoire d’imagerie biomédicale multimodale [Orsay] (BioMaps), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Unité BioMaps (BIOMAPS)
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, tramadol, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, positron emission tomography, seizure, Pharmaceutical Science, GABA, overdose, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Drug Discovery, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Molecular Medicine, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: International audience; Tramadol overdose is frequently associated with the onset of seizures, usually considered as serotonin syndrome manifestations. Recently, the serotoninergic mechanism of tramadol-attributed seizures has been questioned. This study’s aim was to identify the mechanisms involved in tramadol-induced seizures in overdose in rats. The investigations included (1) the effects of specific pretreatments on tramadol-induced seizure onset and brain monoamine concentrations, (2) the interaction between tramadol and $\gamma$-aminobutyric acid (GABA)$_A$ receptors in vivo in the brain using positron emission tomography (PET) imaging and $^{11}$C-flumazenil. Diazepam abolished tramadol-induced seizures, in contrast to naloxone, cyproheptadine and fexofenadine pretreatments. Despite seizure abolishment, diazepam significantly enhanced tramadol-induced increase in the brain serotonin (p < 0.01), histamine (p < 0.01), dopamine (p < 0.05) and norepinephrine (p < 0.05). No displacement of $^{11}$C-flumazenil brain kinetics was observed following tramadol administration in contrast to diazepam, suggesting that the observed interaction was not related to a competitive mechanism between tramadol and flumazenil at the benzodiazepine-binding site. Our findings do not support the involvement of serotoninergic, histaminergic, dopaminergic, norepinephrine or opioidergic pathways in tramadol-induced seizures in overdose, but they strongly suggest a tramadol-induced allosteric change of the benzodiazepine-binding site of GABA$_A$ receptors. Management of tramadol-poisoned patients should take into account that tramadol-induced seizures are mainly related to a GABAergic pathway.
Published: 2022
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25. Atypical Borrelia garinii infection in an immunocompromised patient mimicking high-grade lymphoma

Author: Eiferman, Victor, Guenno, Guillaume Le, Boiret-Dupré, Nathalie, Barres, Bertrand, Luciani, Léa, Fournier, Pierre Edouard, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), and COMBE, Isabelle
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience
Published: 2022
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26. The emergence, spread and vanishing of a French SARS-CoV-2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule

Author: Philippe Colson, Philippe Gautret, Jeremy Delerce, Hervé Chaudet, Pierre Pontarotti, Patrick Forterre, Raphael Tola, Marielle Bedotto, Léa Delorme, Wahiba Bader, Anthony Levasseur, Jean‐Christophe Lagier, Matthieu Million, Nouara Yahi, Jacques Fantini, Bernard La Scola, Pierre‐Edouard Fournier, Didier Raoult, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS - Inserm U1072), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the French Government under the 'Investments for the Future' program managed by the National Agency for Research (ANR) (Méditerranée-Infection 10-IAHU-03), by the Région Provence Alpes Côte d'Azur and European funding FEDER PRIMMI (Fonds Européen de Développement Régional-Plateformes de Recherche et d'Innovation Mutualisées Méditerranée Infection) (FEDER PA 0000320 PRIMMI), and by the French Ministry of Higher Education, Research and Innovation (Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation) and the French Ministry of Solidarity and Health (Ministère des Solidarités et de la Santé)., ANR-10-IAHU-0003,Méditerranée Infection,I.H.U. Méditerranée Infection(2010), Pontarotti, Pierre, Instituts Hospitalo-Universitaires - I.H.U. Méditerranée Infection - - Méditerranée Infection2010 - ANR-10-IAHU-0003 - IAHU - VALID, and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, variants, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, ORF8, Pangolin B.1.1.160, epidemic, SARS‐CoV‐2, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Marseille‐4, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; The nature and dynamics of mutations associated with the emergence, spread, and vanishing of SARS-CoV-2 variants causing successive waves are complex. We determined the kinetics of the most common French variant (“Marseille-4”) for 10 months since its onset in July 2020. Here, we analyzed and classified into subvariants and lineages 7453 genomes obtained by next-generation sequencing. We identified two subvariants, Marseille-4A, which contains 22 different lineages of at least 50 genomes, and Marseille-4B. Their average lifetime was 4.1 ± 1.4 months, during which 4.1 ± 2.6 mutations accumulated. Growth rate was 0.079 ± 0.045, varying from 0.010 to 0.173. Most of the lineages exhibited a bell-shaped distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille-4B emerged when the other Marseille-4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in SARS-CoV-2 of mink and in the Alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.
Published: 2022
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27. Selection of Bis-Indolyl Pyridines and Triphenylamines as New Inhibitors of SARS-CoV-2 Cellular Entry by Modulating the Spike Protein/ACE2 Interfaces

Author: Delphine Lapaillerie, Cathy Charlier, Véronique Guyonnet-Dupérat, Emilie Murigneux, Henrique S. Fernandes, Fábio G. Martins, Rita P. Magalhães, Tatiana F. Vieira, Clémence Richetta, Frédéric Subra, Samuel Lebourgeois, Charlotte Charpentier, Diane Descamps, Benoît Visseaux, Pierre Weigel, Alexandre Favereaux, Claire Beauvineau, Frédéric Buron, Marie-Paule Teulade-Fichou, Sylvain Routier, Sarah Gallois-Montbrun, Laurent Meertens, Olivier Delelis, Sérgio F. Sousa, Vincent Parissi, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), TBM-Core [Bordeaux] (UMS3427 - INSERM US005), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Universidade do Porto = University of Porto, Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Chimie et modélisation pour la biologie du cancer (CMBC), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité en Sciences Biologiques et Biotechnologies de Nantes - UMR CNRS 6286 (US2B), Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005), and delelis, olivier
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Pharmacology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Pyridines, SARS-CoV-2, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, ACE2, COVID-19, spike, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Peptidyl-Dipeptidase A, Virus Internalization, COVID-19 Drug Treatment, inhibitor, Molecular Docking Simulation, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Spike Glycoprotein, Coronavirus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Pharmacology (medical), viral entry, Angiotensin-Converting Enzyme 2, Protein Binding
Abstract: International audience; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of viral replication. To identify chemical tools to further study these functional interfaces, 139,146 compounds from different chemical libraries were screened through an S/ACE2 in silico virtual molecular model. The best compounds were selected for further characterization using both cellular and biochemical approaches, reiterating SARS-CoV-2 entry and the S/ACE2 interaction. We report here two selected hits, bis-indolyl pyridine AB-00011778 and triphenylamine AB-00047476. Both of these compounds can block the infectivity of lentiviral vectors pseudotyped with the SARS-CoV-2 S protein as well as wild-type and circulating variant SARS-CoV-2 strains in various human cell lines, including pulmonary cells naturally susceptible to infection. AlphaLISA and biolayer interferometry confirmed a direct inhibitory effect of these drugs on the S/ACE2 association. A specific study of the AB-00011778 inhibitory properties showed that this drug inhibits viral replication with a 50% effective concentration (EC 50) between 0.1 and 0.5 mM depending on the cell lines. Molecular docking calculations of the interaction parameters of the molecules within the S/ACE2 complex from both wild-type and circulating variants of the virus showed that the molecules may target multiple sites within the S/ACE2 interface. Our work indicates that AB-00011778 constitutes a good tool for modulating this interface and a strong lead compound for further therapeutic purposes.
Published: 2022
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28. Co-Infection and Ventilator-Associated Pneumonia in Critically Ill COVID-19 Patients Requiring Mechanical Ventilation: A Retrospective Cohort Study

Author: Benjamine Sarton, Marion Grare, Fanny Vardon-Bounes, Anna Gaubert, Stein Silva, Laure Crognier, Béatrice Riu, Thierry Seguin, Bernard Georges, Vincent Minville, Stéphanie Ruiz, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Anesthésie Réanimation [CHU de Toulouse], and SEGUIN, Nathalie
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, SARS-CoV-2, COVID-19, Medicine (miscellaneous), intensive care unit, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, General Biochemistry, Genetics and Molecular Biology, ventilator-associated pneumonia, co-infection, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, influenza, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, H1N1
Abstract: International audience; Considering virus-related and drug-induced immunocompromised status of critically ill COVID-19 patients, we hypothesize that these patients would more frequently develop ventilator-associated pneumonia (VAP) than patients with ARDS from other viral causes. We conducted a retrospective observational study in two intensive care units (ICUs) from France, between 2017 and 2020. We compared bacterial co-infection at ICU admission and throughout the disease course of two retrospective longitudinally sampled groups of critically ill patients, who were admitted to ICU for either H1N1 or SARS-CoV-2 respiratory infection and depicted moderate-to-severe ARDS criteria upon admission. Sixty patients in the H1N1 group and 65 in the COVID-19 group were included in the study. Bacterial co-infection at the endotracheal intubation time was diagnosed in 33% of H1N1 and 16% COVID-19 patients (p = 0.08). The VAP incidence per 100 days of mechanical ventilation was 3.4 (2.2–5.2) in the H1N1 group and 7.2 (5.3–9.6) in the COVID-19 group (p < 0.004). The HR to develop VAP was of 2.33 (1.34–4.04) higher in the COVID-19 group (p = 0.002). Ten percent of H1N1 patients and 30% of the COVID-19 patients had a second episode of VAP (p = 0.013). COVID-19 patients have fewer bacterial co-infections upon admission, but the incidence of secondary infections increased faster in this group compared to H1N1 patients.
Published: 2022
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29. First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France

Author: Philippe Colson, Jérémy Delerce, Mamadou Beye, Anthony Levasseur, Céline Boschi, Linda Houhamdi, Hervé Tissot‐Dupont, Nouara Yahi, Matthieu Million, Bernard La Scola, Jacques Fantini, Didier Raoult, Pierre‐Edouard Fournier, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Unité de Neurobiologie des canaux Ioniques et de la Synapse (UNIS - Inserm U1072), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), COMBE, Isabelle, and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Nucleotides, SARS-CoV-2, COVID-19, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Infectious Diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Mutation, Spike Glycoprotein, Coronavirus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: The SARS-CoV-2 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants have recently emerged worldwide. To date, the 21L/BA.2 Omicron variant has remained very minority globally but became predominant in Denmark instead of the 21K/BA.1 variant. Here we describe the first cases diagnosed with this variant in south-eastern France. We identified thirteen cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travellers returning from Tanzania. Overall, viral genomes displayed a mean (±standard deviation) number of 65.9±2.5 (range, 61-69) nucleotide substitutions and 31.0±8.3 (27-50) nucleotide deletions, resulting in 49.6±2.2 (45-52) amino acid substitutions (including 28 in the spike protein) and 12.4±1.1 (12-15) amino acid deletions. Phylogeny showed the distribution in three different clusters of these genomes, which were most closely related to genomes from England and South Africa, from Singapore and Nepal, or from France and Denmark. Structural predictions pointed out a significant enlargement and flattening of the 21L/BA.2 N-terminal domain surface compared with that of the 21K/BA.2 Omicron variant, which may facilitate initial viral interactions with lipid rafts. Close surveillance is needed at global, country and center scales to monitor the incidence and clinical outcome of the 21L/BA.2 Omicron variant.
Published: 2022
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30. Human Q Fever on the Guiana Shield and Brazil: Recent Findings and Remaining Questions

Author: Gaëlle Walter, E. Beillard, Pauline Thill, Elba Regina Sampaio de Lemos, Vincent Pommier de Santi, María Mercedes Panizo, Loïc Epelboin, Magalie Demar, Alessia Melzani, S. Vreden, Philippe Abboud, Paule Letertre-Gibert, M. Boutrou, Carole Eldin, Julman Rosiris Cermeño, Félix Djossou, Jorlan Fernandes, Lucas Perez, Jacobus H. de Waard, Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Service Universitaire des Maladies Infectieuses et du Voyageur [Tourcoing], Centre Hospitalier Tourcoing, Centre d'épidémiologie et de santé publique des armées [Marseille] (CESPA), Service de Santé des Armées, Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles (UA), Instituto Oswaldo Cruz / Oswaldo Cruz Institute [Rio de Janeiro] (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Universidad Central de Venezuela (UCV), Instituto Nacional de Higiene 'Rafael Rangel' - National Institute of Hygiene Rafael Rangel [Caracas, Venezuela], Academic Hospital Paramaribo [Paramaribo, Suriname], Laboratoire de biologie médicale [Cayenne, Guyane française] (LBM), Institut Pasteur de la Guyane, Universidad de Oriente, COMBE, Isabelle, Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ)
Subjects: Bacterial zoonosis, Latin Americans, Community-acquired pneumonia, Amazonian, 030231 tropical medicine, Q fever, 03 medical and health sciences, Zoonosis, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, Amazonian Diseases in Isolate Populations (M Nacher, Section Editor), medicine, Immunology and Allergy, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Socioeconomics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Suriname, biology, 030306 microbiology, Amazonian forest, Coxiella burnetii, biology.organism_classification, medicine.disease, Venezuela, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, French Guiana, Infectious Diseases, Geography, Guiana Shield, Latin America, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Guyana, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Brazil
Abstract: Purpose of Review In this review, we report on the state of knowledge about human Q fever in Brazil and on the Guiana Shield, an Amazonian region located in northeastern South America. There is a contrast between French Guiana, where the incidence of this disease is the highest in the world, and other countries where this disease is practically non-existent. Recent Findings Recent findings are essentially in French Guiana where a unique strain MST17 has been identified; it is probably more virulent than those usually found with a particularly marked pulmonary tropism, a mysterious animal reservoir, a geographical distribution that raises questions. Summary Q fever is a bacterial zoonosis due to Coxiella burnetii that has been reported worldwide. On the Guiana Shield, a region mostly covered by Amazonian forest, which encompasses the Venezuelan State of Bolivar, Guyana, Suriname, French Guiana, and the Brazilian State of Amapá, the situation is very heterogeneous. While French Guiana is the region reporting the highest incidence of this disease in the world, with a single infecting clone (MST 117) and a unique epidemiological cycle, it has hardly ever been reported in other countries in the region. This absence of cases raises many questions and is probably due to massive under-diagnosis. Studies should estimate comprehensively the true burden of this disease in the region.
Published: 2021
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31. Comparison of Circulating Immune Cells Profiles and Kinetics Between Coronavirus Disease 2019 and Bacterial Sepsis*

Author: Etienne Gayat, Romain Barthélémy, Bruno Mégarbane, Caren Brumpt, Sehmi Mansouri, Sebastian Voicu, Candice Fontaine, Marie Neuwirth, Benjamin G. Chousterman, Alexandre Mebazaa, Charles de Roquetaillade, Matthieu Le Dorze, Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre hospitalier Saint-Joseph [Paris], Hôpital Lariboisière-Fernand-Widal [APHP], and Mégarbane, Bruno
Subjects: Male, CD14, Receptor expression, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, sepsis, Sepsis, coronavirus disease 2019, Immunophenotyping, Immune system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Immunologic Factors, Eosinophilia, Longitudinal Studies, Aged, Retrospective Studies, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, flow cytometry, Editorials, COVID-19, Middle Aged, immune endotypes, medicine.disease, Neutrophilia, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Intensive Care Units, Kinetics, Basophilia, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Female, France, medicine.symptom, business, severe acute respiratory syndrome coronavirus 2
Abstract: International audience; Objectives: Although clinical presentation of coronavirus disease 2019 has been extensively described, immune response to severe acute respiratory syndrome coronavirus 2 remains yet not fully understood. Similarities with bacterial sepsis were observed; however, few studies specifically addressed differences of immune response between both conditions. Here, we report a longitudinal analysis of the immune response in coronavirus disease 2019 patients, its correlation with outcome, and comparison between severe coronavirus disease 2019 patients and septic patients.Design: Longitudinal, retrospective observational study.Setting: Tertiary-care hospital during the first 2020 coronavirus disease 2019 outbreak in France.Patients: All successive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the emergency department, medical ward, and ICU with at least one available immunophenotyping performed during hospital stay.Measurements and main results: Between March and April 2020, 247 patients with coronavirus disease 2019 were included and compared with a historical cohort of 108 severe septic patients. Nonsevere coronavirus disease 2019 patients (n = 153) presented normal or slightly altered immune profiles. Severe coronavirus disease 2019 (n = 94) immune profile differed from sepsis. Coronavirus disease 2019 exhibited profound and prolonged lymphopenia (mostly on CD3, CD4, CD8, and NK cells), neutrophilia, and human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation. Surprisingly, coronavirus disease 2019 patients presented a unique profile of B cells expansion, basophilia, and eosinophilia. Lymphopenia, human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation, and neutrophilia were associated with a worsened outcome, whereas basophilia and eosinophilia were associated with survival. Circulating immune cell kinetics differed between severe coronavirus disease 2019 and sepsis, lack of correction of immune alterations in coronavirus disease 2019 patients during the first 2 weeks of ICU admission was associated with death and nosocomial infections.Conclusions: Circulating immune cells profile differs between mild and severe coronavirus disease 2019 patients. Severe coronavirus disease 2019 is associated with a unique immune profile as compared with sepsis. Several immune features are associated with outcome. Thus, immune monitoring of coronavirus disease 2019 might be of help for patient management.
Published: 2021
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32. Prolonged in‐hospital stay and higher mortality after Covid‐19 among patients with <scp>non‐Hodgkin</scp> lymphoma treated with B‐cell depleting immunotherapy

Author: Roberta Di Blasi, Laure Philippe, Thomas Hueso, Catherine Thieblemont, Karine Lacombe, Bénédicte Deau Fischer, Serge Bologna, Caroline Besson, Guillemette Fouquet, Sylvain Choquet, Milena Kohn, Rémy Duléry, Carole Soussain, Bernard Drenou, Pierre Feugier, Etienne Daguindau, Marc Delord, Nicolas Noel, Adrien Chauchet, Sylvain Lamure, Sandra Malak, Cédric Rossi, Bertrand Joly, Guillaume Cartron, Yassine Taoufik, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Département d’Hématologie Clinique [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier de Versailles André Mignot (CHV), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Gustave Roussy (IGR), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Saint-Cloud], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service d'Hématologie clinique [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), Centre d'Oncologie de Gentilly, Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Service d'Hématologie [CH Annecy], CH Annecy, Hôpital Bicêtre, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Roche, Takeda Pharmaceutical Company, TPC, We thank all the clinicians and patients in the participating centers for their contributions to this multicenter study. We are grateful to the Centre Hospitalier de Versailles, in particular Philippe Rousselot and Laure Morisset for promoting the research and for supporting the editing. We thank France Lymphome Espoir for reviewing the study material, LYSA for discussions on the design of this study, and Sophie Rigaudeau and C?cile Laur?ana for their contribution to the collection of the cases., Rémy Duléry reports personal fees from Takeda, Novartis, and Biotest and non‐financial support from Gilead outside the submitted work. Roberta Di Blasi reports personal fees from Gilead and Novartis outside the submitted work. Serge Bologna reports personal fees from Janssen and Roche outside the submitted work. Guillaume Cartron reports personal fees from Roche, Celgene, Sanofi, Gilead, Janssen, and Abbvie outside the submitted work. Karine Lacombe reports personal fees and non‐financial support from Gilead, MSD, Abbvie, ViiV Healthcare, and Janssen outside the submitted work. Caroline Besson reports research funding from Roche and non‐financial support from Takeda and Roche outside the submitted work., HAL UVSQ, Équipe, Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Groupe hospitalier de la région de Mulhouse et Sud-Alsace, Département d'Oncologie Médicale [Centre René-Huguenin, Saint-Cloud], Hôpital René HUGUENIN (Saint-Cloud), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, [SDV]Life Sciences [q-bio], MESH: COVID-19 / complications, Comorbidity, MESH: Lymphoma, Non-Hodgkin / complications, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, MESH: Age Factors, Young adult, Research Articles, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, B-Lymphocytes, education.field_of_study, Lymphoma, Non-Hodgkin, MESH: SARS-CoV-2, Hazard ratio, Age Factors, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, Combined Modality Therapy, MESH: Antigens, CD20 / immunology, 3. Good health, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Rituximab, B-cell depleting immunotherapy, Immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Research Article, medicine.drug, Adult, medicine.medical_specialty, Population, lymphoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, anti-CD20 therapy, Young Adult, MESH: Rituximab / administration & dosage, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH: COVID-19 / mortality, Internal medicine, medicine, Humans, education, MESH: B-Lymphocytes / drug effects, Survival analysis, Aged, Proportional Hazards Models, Retrospective Studies, MESH: Aged, 80 and over, SARS-CoV-2, Proportional hazards model, business.industry, COVID-19, Retrospective cohort study, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, MESH: Combined Modality Therapy, Length of Stay, vaccination, Antigens, CD20, medicine.disease, Survival Analysis, Lymphoma, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Drug Resistance, Neoplasm, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030215 immunology
Abstract: International audience; Prolonged Covid-19 is an emerging issue for patients with lymphoma or immune deficiency. We aimed to examine prolonged length of in-hospital stay (LOS) due to Covid-19 among patients with lymphoma and assess its determinants and outcomes. Adult patients with lymphoma admitted for Covid-19 to 16 French hospitals in March and April, 2020 were included. Length of in-hospital stay was analyzed as a competitor vs death. The study included 111 patients. The median age was 65 years (range, 19–92). Ninety-four patients (85%) had B-cell non-Hodgkin lymphoma. Within the 12 months prior to hospitalization for Covid-19, 79 patients (71%) were treated for their lymphoma. Among them, 63 (57%) received an anti-CD20 therapy. Fourteen patients (12%) had relapsed/refractory disease. The median LOS was 14 days (range, 1–235). After a median follow-up of 191 days (3–260), the 6-month overall survival was 69%. In multivariable analyses, recent administration of anti-CD20 therapy was associated with prolonged LOS (subdistribution hazard ratio 2.26, 95% confidence interval 1.42–3.6, p < 0.001) and higher risk of death (hazard ratio 2.17, 95% confidence interval 1.04–4.52, p = 0.039). An age ≥ 70 years and relapsed/refractory lymphoma were also associated with prolonged LOS and decreased overall survival. In conclusion, an age ≥ 70 years, a relapsed/refractory lymphoma and recent administration of anti-CD20 therapy are risk factors for prolonged LOS and death for lymphoma patients hospitalized for Covid-19. These findings may contribute to guide the management of lymphoma during the pandemic, support evaluating specific therapeutic approaches, and raise questions on the efficacy and timing of vaccination of this particular population.
Published: 2021
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33. Relationship between ventilator-associated pneumonia and mortality in COVID-19 patients: a planned ancillary analysis of the coVAPid cohort

Author: Nseir, Saad, Martin-Loeches, Ignacio, Povoa, Pedro, Metzelard, Matthieu, Du Cheyron, Damien, Lambiotte, Fabien, Tamion, Fabienne, Labruyere, Marie, Makris, Demosthenes, Boulle Geronimi, Claire, Pinetonde Chambrun, Marc, Nyunga, Martine, Pouly, Olivier, Mégarbane, Bruno, Saade, Anastasia, Gomà, Gemma, Magira, Eleni, Llitjos, Jean-François, Torres, Antoni, Ioannidou, Iliana, Pierre, Alexandre, Coelho, Luis, Reignier, Jean, Garot, Denis, Kreitmann, Louis, Baudel, Jean-Luc, Voiriot, Guillaume, Contou, Damien, Beurton, Alexandra, Asfar, Pierre, Boyer, Alexandre, Thille, Arnaud, Mekontso-Dessap, Armand, Tsolaki, Vassiliki, Vinsonneau, Christophe, Floch, Pierre-Edouard, Le Guennec, Loïc, Ceccato, Adrian, Artigas, Antonio, Bouchereau, Mathilde, Labreuche, Julien, Duhamel, Alain, Rouzé, Anahita, Favory, Raphaël, Préau, Sébastien, Jourdain, Mercé, Poissy, Julien, Leger, Piehr Saint, van der Linden, Thierry, Veinstein, Anne, Azoulay, Elie, Pene, Frédéric, Martin, Maelle, Razazi, Keyvan, Plantefeve, Gaëtan, Fartoukh, Muriel, Thevenin, Didier, Guidet, Bertrand, Weiss, Nicolas, Kouatchet, Achille, Salmon, Charlotte, Brunin, Guillaume, Nemlaghi, Safaa, Meguerditchian, David, Argaud, Laurent, Voicu, Sebastian, Luyt, Charles-Edouard, Kowalski, Benjamin, Moglia, Edgar, Morales, Luis, Koutsoukou, Antonia, Mentzelopoulos, Spyros, Nora, David, Boyd, Sean, Maizel, Julien, Cuchet, Pierre, Delforge, Quentin, Quenot, Jean-Pierre, Boyer, Déborah, Cilloniz, Catia, CHU Lille, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier [Valenciennes, Nord], CHU Rouen, Normandie Université (NU), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier [Douai, Nord], Institut de cardiologie [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), Centre Hospitalier de Roubaix, Hôpital Saint Philibert [Lomme], Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Cochin [AP-HP], Centre Hospitalier de Lens, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Centre Hospitalier Victor Dupouy, CHU Charles Foix [AP-HP], Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], Centre hospitalier universitaire de Poitiers (CHU Poitiers), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), 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 Henri Mondor, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Hôpital Duchenne, CH Boulogne sur Mer, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), coVAPid study group, Mégarbane, Bruno, and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil]
Subjects: Male, medicine.medical_treatment, Pneumònia, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pneumonia, Ventilator-Associated/epidemiology, Medicine, Hospital Mortality, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, COVID-19/mortality, Mortality rate, Ventilator-associated pneumonia, Pneumonia, Ventilator-Associated, Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Europe, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Intensive Care Units, Length of Stay/statistics & numerical data, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, medicine.medical_specialty, Respiration, Artificial/statistics & numerical data, Coronavirus disease 2019 (COVID-19), Population, Europe/epidemiology, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Mortalitat, Humans, Mortality, education, Aged, Retrospective Studies, Mechanical ventilation, business.industry, RC86-88.9, Research, COVID-19, 030208 emergency & critical care medicine, Retrospective cohort study, Pneumonia, Length of Stay, bacterial infections and mycoses, medicine.disease, Respiration, Artificial, respiratory tract diseases, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract: Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox’s regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 group (adjusted HR 1.65 (95% CI 1.11–2.46), p = 0.013), but not in influenza (1.74 (0.99–3.06), p = 0.052), or no viral infection groups (1.13 (0.68–1.86), p = 0.63). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.
Published: 2021
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34. Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup

Author: Mowry, James, Shepherd, Greene, Hoffman, Robert, Lavergne, Valery, Gosselin, Sophie, Nolin, Thomas, Vijayan, Anitha, Kielstein, Jan, Roberts, Darren, Ghannoum, Marc, Alhatali, Badria, Anseeuw, Kurt, Bird, Steven, Berling, Ingrid, Bouchard, Josée, Bunchman, Timothy, Calello, Diane, Chin, Paul, Doi, Kent, Galvao, Tais, Goldfarb, David, Hassanian, Hossein, Hoegberg, Lotte, Kallab, Siba, Kebede, Sofia, Lewington, Andrew, Li, Yi, Macedo, Etienne, Maclaren, Rob, Mégarbane, Bruno, Ostermann, Marlies, Peng, Ai, Roy, Jean‐philippe, Walsh, Steven, Wong, Anselm, Wood, David, Yates, Christopher, Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Extracorporeal Treatments in Poisoning workgroup: Badria Alhatali, Kurt Anseeuw, Steven Bird, Ingrid Berling, Josée Bouchard, Timothy E Bunchman, Diane P Calello, Paul K Chin, Kent Doi, Tais Galvao, David S Goldfarb, Hossein Hassanian, Lotte C Hoegberg, Siba Kallab, Sofia Kebede, Andrew Lewington, Yi Li, Etienne M Macedo, Rob MacLaren, Bruno Megarbane, Marlies E Ostermann, Ai Peng, Jean-Philippe Roy, Steven J Walsh, Anselm Wong, David M Wood, Christopher Yates, and Mégarbane, Bruno
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, 030106 microbiology, 030204 cardiovascular system & hematology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Extracorporeal, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Renal Dialysis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, Isoniazid, medicine, Animals, Humans, Pharmacology (medical), Dosing, Dialysis, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, Poisoning, Pyridoxine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Systematic review, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Practice Guidelines as Topic, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Hemodialysis, business, medicine.drug
Abstract: Isoniazid toxicity from self-poisoning or dosing errors remains common in regions of the world where tuberculosis is prevalent. Although the treatment of isoniazid poisoning is centered on supportive care and pyridoxine administration, extracorporeal treatments (ECTRs), such as hemodialysis, have been advocated to enhance elimination of isoniazid. No systematic reviews or evidence-based recommendations currently exist on the benefit of ECTRs for isoniazid poisoning. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup systematically collected and rated the available evidence on the effect of and indications for ECTRs in cases of isoniazid poisoning. We conducted a systematic review of the literature, screened studies, extracted data on study characteristics, outcomes, and measurement characteristics, summarized findings, and formulated recommendations following published EXTRIP methods. Forty-three studies (two animal studies, 34 patient reports or patient series, and seven pharmacokinetic studies) met inclusion criteria. Toxicokinetic or pharmacokinetic analysis was available for 60 patients, most treated with hemodialysis (n = 38). The workgroup assessed isoniazid as "Moderately Dialyzable" by hemodialysis for patients with normal kidney function (quality of evidence = C) and "Dialyzable" by hemodialysis for patients with impaired kidney function (quality of evidence = A). Clinical data for ECTR in isoniazid poisoning were available for 40 patients. Mortality of the cohort was 12.5%. Historical controls who received modern standard care including appropriately dosed pyridoxine generally had excellent outcomes. No benefit could be extrapolated from ECTR, although there was evidence of added costs and harms related to the double lumen catheter insertion, the extracorporeal procedure itself, and the extracorporeal removal of pyridoxine. The EXTRIP workgroup suggests against performing ECTR in addition to standard care (weak recommendation, very low quality of evidence) in patients with isoniazid poisoning. If standard dose pyridoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence).
Published: 2021
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35. SARS-CoV-2 variants of concern are associated with lower RT-PCR amplification cycles between January and March 2021 in France

Author: Vincent Foulongne, Mircea T. Sofonea, Bénédicte Roquebert, Samuel Alizon, Emmanuel Lecorche, Stéphanie Haim-Boukobza, Sonia Burrel, Laura Verdurme, Sabine Trombert-Paolantoni, Laboratoire CERBA [Saint Ouen l'Aumône], CHU Montpellier, 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), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), ANR-20-COVI-0098,PHYEPI,Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales(2020), Sofonea, Mircea T., Intégration de données de séquences et d'incidence pour analyser et contrôler les épidémies virales - - PHYEPI2020 - ANR-20-COVI-0098 - COVID-19 - VALID, and Génétique et évolution des maladies infectieuses (GEMI)
Subjects: Microbiology (medical), 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Short Communication, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Alpha (ethology), Infectious and parasitic diseases, RC109-216, Biology, law.invention, 03 medical and health sciences, 0302 clinical medicine, COVID-19 Testing, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Humans, 030212 general & internal medicine, 030304 developmental biology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, Cycle threshold, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, 030306 microbiology, Wild type, COVID-19, General Medicine, Virology, 3. Good health, Transmission (mechanics), Infectious Diseases, Real-time polymerase chain reaction, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: SARS-CoV-2 variants raise concern regarding the mortality caused by COVID-19 epidemics. We analyse 88,375 cycle amplification (Ct) values from variant-specific RT-PCR tests performed between January 26 and March 13, 2021. We estimate that on March 12, nearly 85% of the infections were caused by the V1 variant and that its transmission advantage over wild type strains was between 38 and 44%. We also find that tests positive for V1 and V2/V3 variants exhibit significantly lower cycle threshold (Ct) values.
Published: 2021
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36. Outbreak of NDM-1-producing Klebsiella pneumoniae in the intensive care unit during the COVID-19 pandemic: Another nightmare

Author: R. Amarsy, Manel Merimèche, Hervé Jacquier, Bruno Mégarbane, Béatrice Berçot, Anne-Lise Munier, Mégarbane, Bruno, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP]
Subjects: Epidemiology, Klebsiella pneumoniae, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Disease Outbreaks, law.invention, Enterobacterales, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Pandemic, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Transmission (medicine), Brief Report, Health Policy, Intensive care unit, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Anti-Bacterial Agents, Nightmare, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Intensive Care Units, Infectious Diseases, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine.symptom, Hospital infection control, medicine.medical_specialty, Microbial Sensitivity Tests, beta-Lactamases, Carbapenemase, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Bacterial Proteins, medicine, Transmission, Humans, Pandemics, SARS-CoV-2, business.industry, Public Health, Environmental and Occupational Health, COVID-19, Outbreak, biology.organism_classification, Dreams, Klebsiella Infections, Resistome, ICU, Emergency medicine, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Multilocus sequence typing, business, Multilocus Sequence Typing
Abstract: International audience; An outbreak of Klebsiella pneumoniae producing the carbapenemase NDM-1 occurred in our ICU during the last COVID-19 wave. Twelve patients were tested positive, seven remained asymptomatic whereas 5 developed an infection. Resistome and in silico multilocus sequence typing confirmed the clonal origin of the strains. The identification of a possible environmental reservoir suggested that difficulties in observing optimal bio-cleaning procedures due to workload and exhaustion contributed to the outbreak besides the inappropriate excessive glove use.
Published: 2021
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37. COVID-19 pandemic

Author: W. J. Fokkens, Jürgen Schwarze, Cezmi A. Akdis, J Mullol, W. Czarlewski, Claudia Traidl-Hoffmann, Claus Bachert, D. Larenas-Linnemann, Tomas Chivato, M. Gotua, Mateo Bonini, Ludger Klimek, Vincenzo Patella, A. A. Cruz, Stephanie Dramburg, Kari C. Nadeau, H W Fritsch, K. Ohta, Thomas Eiwegger, Robert M. Naclerio, Antti Lauerma, A. Yorgancioglu, Aslı Gelincik, Piotr Kuna, Oliver Pfaar, Carmen Riggioni, Violeta Kvedariene, Markus Ollert, Sinthia Bosnic-Anticevich, V. Cardona, S. Del Giacco, Sanna Toppila-Salmi, Helen A. Brough, Heimo Breiteneder, Valérie Hox, B. Samolinski, Zuzana Diamant, G.W. Canonica, Lihong Zhang, María José Torres, Y. Okamoto, Liam O'Mahony, Radosław Gawlik, Jolanta Walusiak-Skorupa, Sharon Chinthrajah, Winfried Rief, T. Haatela, M. Morais-Almeida, Ioana Agache, Manfred Schedlowski, I Skypala, R. Brehler, D. Y. Wang, João Fonseca, I. J. Ansotegui, Robyn E O'Hehir, Oscar Palomares, Charlotte G. Mortz, J. C. Ivancevich, C. Suppli Ulrik, M. T. Ventura, P M Matricardi, S Untersmayr, Gabrielle L. Onorato, Amir Hamzah Abdul Latiff, Frederico S. Regateiro, Vanitha Sampath, Arũnas Valiulis, Marek Jutel, Luisa Brussino, Pedro Carreiro-Martins, Jean Bousquet, Nikolaos G. Papadopoulos, A. Bedbrook, Torsten Zuberbier, Karin Hoffmann-Sommergruber, Edward F. Knol, Ear, Nose and Throat, AII - Inflammatory diseases, UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, UCL - (SLuc) Service d'oto-rhino-laryngologie, Philipps Universität Marburg = Philipps University of Marburg, Allergologie, Stimm und Sprachstörungen [Wiesbaden, Germany], Zentrum für Rhinologie und Allergologie [Wiesbaden, Germany], University of Wrocław [Poland] (UWr), ALL-MED, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), 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), Medizinische Universität Wien = Medical University of Vienna, Stanford University, Skane University Hospital [Malmo], Lund University [Lund], Charles University [Prague] (CU), University Medical Center Groningen [Groningen] (UMCG), Univ Toronto, Hosp Sick Children, Peter Gilgan Ctr Res & Learning, Mol Med, Toronto, ON M5G 0A4, Canada, The Hospital for sick children [Toronto] (SickKids), University of Toronto, Amsterdam UMC - Amsterdam University Medical Center, Alfred Health, Victoria University [Melbourne], University College Cork (UCC), Sean N. Parker Center for Allergy and Asthma Research [Stanford], Stanford Medicine, Stanford University-Stanford University, University Clinics of Essen, University of Essen, Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Helmholtz Zentrum München = German Research Center for Environmental Health, University Hospital Augsburg, National University of Singapore (NUS), Beijing Tongren Hospital, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Evelina London Children's Hospital, King‘s College London, CEU-San Pablo University and HM-Hospitals School of Medicine, University of Cagliari, Medical University of Silesia (SUM), Istanbul University, Cliniques Universitaires Saint-Luc [Bruxelles], University Medical Center [Utrecht], Helsinki University Central Hospital, University of Helsinki, Odense University Hospital (OUH), Luxembourg Institute of Health (LIH), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Hospital Sant Joan de Déu [Barcelona], Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], University of Edinburgh, NHS Foundation Trust [London], The Royal Marsden, Nofer Institute of Occupational Medicine (NIOM), Hospital Quirónsalud Bizkaia [Bilbao], Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], Woolcock Institute of Medical Research [Sydney], The University of Sydney, University of Turin, Mauriziano Umberto I Hospital, Humanitas University [Milan] (Hunimed), Vall d'Hebron University Hospital [Barcelona], Hospital de Dona Estefania, NOVA Medical School - Faculdade de Ciências Médicas (NMS), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Federal University of Bahia School of Medicine, Global Alliance Against Chronic Respiratory Diseases (GARD-WHO), Medical Consulting Czarlewski, Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, MEDIDA, Lda, David Tvildiani Medical University (DTMU), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Barlicki University Hospital, Vilnius University [Vilnius], Hospital Medica Sur [Mexico City, Mexico], Pantai Hospital [Kuala Lumpur], Hospital CUF Descobertas, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), CIBER de Epidemiología y Salud Pública (CIBERESP), Johns Hopkins University School of Medicine [Baltimore], Fukujuji Hospital, Tokyo National Hospital, Chiba Rosai Hospital, Chiba University Hospital, Royal Manchester Children's Hospital, University of Manchester [Manchester], General Children's Hospital of Athens P & A Kyriakou, 'Santa Maria della Speranza' Hospital, Centro Hospitalar e Universitário [Coimbra], Coimbra Institute for Clinical and Biomedical Research [Coimbra, Portugal] (iCBR - Faculty of Medicine), University of Coimbra [Portugal] (UC), Medical University of Warsaw - Poland, Hvidovre Hospital, University of Copenhagen = Københavns Universitet (UCPH), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Manisa Celal Bayar University, Transilvania University of Brasov, Salvy-Córdoba, Nathalie, Department of Dermatology, Allergology and Venereology, and HUS Inflammation Center
Subjects: 0301 basic medicine, viruses, Eaaci Position Paper, Medizin, Cochrane Library, GUIDELINES, FOOD ALLERGY, allergen immunotherapy, allergy clinic, anaphylaxis, asthma, clinical trials, COVID-19, Position Paper, psychological impact, SARS-CoV-2, Allergists, Health Personnel, Humans, Hypersensitivity, Information Technology, Patient Care Team, Triage, SARS‐CoV‐2, DESENSITIZATION, 0302 clinical medicine, MESH: Patient Care Team, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HDE ALER, Pandemic, Health care, Immunology and Allergy, ATOPIC-DERMATITIS, MESH: COVID-19, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, allergen immunotherapy (AIT), virus diseases, DRUG HYPERSENSITIVITY REACTIONS, 3. Good health, INFECTIONS, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Triage, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Allergen immunotherapy, medicine.medical_specialty, MESH: Information Technology, MESH: Hypersensitivity, Immunology, education, MEDLINE, DIAGNOSIS, psychological COVID, 03 medical and health sciences, MESH: Allergists, COVID‐19, medicine, MESH: SARS-CoV-2, ddc:610, RHINOSINUSITIS, MESH: Humans, business.industry, Clinical trial, Coronavirus, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Family medicine, 3121 General medicine, internal medicine and other clinical medicine, Position paper, MESH: Health Personnel, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: BackgroundThe Coronavirus disease 2019 (COVID‐19) has evolved as a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS‐CoV‐)2. Allergists and other health care providers (HCPs) in the field of allergies and associated airway diseases are in the front line, taking care of patients potentially infected with SARS‐CoV‐2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.MethodThe scientific information on COVID‐19 was analyzed by a literature search in Medline, Pubmed, national and international guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library and the Internet.ResultsBased on diagnostic and treatment standards developed by EAACI, on international information regarding COVID‐19, on guidelines of the World Health Organization (WHO) and other international organizations as well as on previous experience, a panel of experts including clinicians, psychologists, IT experts and basic scientists along with EAACI and the “Allergic Rhinitis and its Impact on Asthma (ARIA)” inititiative have developed recommendations for the optimal management of allergy clinics during the current COVID‐19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.ConclusionsThis international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients whilst ensuring necessary safety in the current COVID‐19 pandemic.
Published: 2021
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38. Effect of early treatment with polyvalent immunoglobulin on acute respiratory distress syndrome associated with SARS-CoV-2 infections (ICAR trial): study protocol for a randomized controlled trial

Author: Christine Rieu, Fernando A. Bozza, Letizia Mancusi, Aurélien Mazeraud, Philippe Aegerter, Tarek Sharshar, Bruno Gonçalves, Shidasp Siami, Khaoussou Sylla, HAL UVSQ, Équipe, GHU Paris Psychiatrie et Neurosciences, Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Instituto Estadual do cerebro Paulo Niemeyer, Centre Hospitalier Sud Essonnes, and This trial is funded by the Programme Hospitalier de Recherche Clinique. TheLaboratoire Français du Biofractionnement provided the drugs at no-cost.None of them had any role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Subjects: ARDS, medicine.medical_treatment, Medicine (miscellaneous), 030204 cardiovascular system & hematology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, Study Protocol, 0302 clinical medicine, Randomized controlled trial, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Activities of Daily Living, Pharmacology (medical), 030212 general & internal medicine, Randomized Controlled Trials as Topic, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Respiratory Distress Syndrome, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, lcsh:R5-920, Acute respiratory distress syndrome, Mortality rate, Immunoglobulins, Intravenous, Intensive care unit, Survival Rate, Intensive Care Units, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, lcsh:Medicine (General), medicine.medical_specialty, Lung injury, Placebo, 03 medical and health sciences, Double-Blind Method, Early Medical Intervention, Internal medicine, medicine, Humans, Immunologic Factors, Survival rate, Mechanical ventilation, business.industry, SARS-CoV-2, COVID-19, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Length of Stay, medicine.disease, Respiration, Artificial, Functional Status, Clinical Trials, Phase III as Topic, Polyvalent immunoglobulin, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business
Abstract: Background As of mid-June 2020, 7,500,000 people were infected with SARS-CoV-2 worldwide and 420,000 people died, mainly from coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS). COVID-19-related ARDS is subject to a mortality rate of 50% and prolonged period of mechanical ventilation, with no specific pharmacological treatment currently available (Infection au nouveau Coronavirus (SARS-CoV-2), COVID-19, France et Monde. https://www.santepubliquefrance.fr/dossiers/coronavirus-covid-19). Because of its immunomodulatory action, we propose to evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) administration in patients developing COVID-19-related ARDS. Methods The trial is a phase III double-blind, randomized, multicenter, parallel group, concurrent, controlled study in hospitalized participants with COVID-19 requiring mechanical ventilation using a sequential design. Participants in the treatment group will receive infusions of polyvalent immunoglobulin for 4 consecutive days, and the placebo group will receive an equivalent volume of sodium chloride 0.9% for the same duration. The primary outcome is the number of ventilator-free days up to the 28th day. Secondary objectives are to evaluate the effect of IVIG on (1) organ failure according to the Sequential Organ Failure Assessment (SOFA) score at 14 and 28 days, (2) lung injury score at 14 and 28 days, (3) the occurrence of grade 3 or 4 adverse events of IVIG, (4) length of intensive care unit (ICU) stay, (5) length of hospital stay, (6) functional outcomes at day 90 defined by the activities of daily living and instrumental activities of the daily living scales, and (7) 90-day survival. One hundred thirty-eight subjects will be randomized in a 1:1 ratio to IVIG or placebo groups (69 in each group), considering 90% power, alpha level 0.05 (two sides), and 0.67 effect size level. Discussion The ICAR trial investigates the effect of IVIG in COVID-19-related ARDS. We expect an increase in the survival rate and a reduction in the duration of mechanical ventilation, which is associated with significant morbidity. Trial registration EudraCT 2020-001570-30. ClinicalTrials.gov NCT04350580. Registered on 17 April 2020
Published: 2021
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39. Risk of COVID-19 variant importation – How useful are travel control measures?

Author: Evan M Milliken, Julien Arino, Pierre-Yves Boëlle, Stéphanie Portet, University of Manitoba [Winnipeg], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Louisville, HAL-SU, Gestionnaire, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Special issue on Modelling and Forecasting the 2019 Novel Coronavirus (2019-nCoV) Transmission, Edited by Prof. Carlos Castillo-Chavez, Prof. Gerardo Chowell-Puente, Prof. Ping Yan, Prof. Jianhong Wu, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Control (management), Importation risk, Infectious and parasitic diseases, RC109-216, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Time windows, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Quarantine, Econometrics, 030212 general & internal medicine, 030304 developmental biology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Applied Mathematics, Health Policy, Variants, COVID-19, New variant, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: We consider models for the importation of a new variant COVID-19 strain in a location already seeing propagation of a resident variant. By distinguishing contaminations generated by imported cases from those originating in the community, we are able to evaluate the contribution of importations to the dynamics of the disease in a community. We find that after an initial seeding, the role of importations becomes marginal compared to that of community-based propagation. We also evaluate the role of two travel control measures, quarantine and travel interruptions. We conclude that quarantine is an efficacious way of lowering importation rates, while travel interruptions have the potential to delay the consequences of importations but need to be applied within a very tight time window following the initial emergence of the variant.
Published: 2021
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40. Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial

Author: Lore, Vanderbeke, Nico A F, Janssen, Dennis C J J, Bergmans, Marc, Bourgeois, Jochem B, Buil, Yves, Debaveye, Pieter, Depuydt, Simon, Feys, Greet, Hermans, Oscar, Hoiting, Ben, van der Hoven, Cato, Jacobs, Katrien, Lagrou, Virginie, Lemiale, Piet, Lormans, Johan, Maertens, Philippe, Meersseman, Bruno, Mégarbane, Saad, Nseir, Jos A H, van Oers, Marijke, Reynders, Bart J A, Rijnders, Jeroen A, Schouten, Isabel, Spriet, Karin, Thevissen, Arnaud W, Thille, Ruth, Van Daele, Frank L, van de Veerdonk, Paul E, Verweij, Alexander, Wilmer, Roger J M, Brüggemann, Joost, Wauters, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Radboud University Medical Center [Nijmegen], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Ghent University Hospital, Canisius-Wilhelmina Hospital [Nijmegen, The Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Elisabeth-TweeSteden Hospital, Erasmus University Rotterdam, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Dutch-Belgian Mycosis Study Group: Bart Rijnders, Paul Verweij, Frank van de Veerdonk, Alexander Schauwvlieghe, Tom Wolfs, Joost Wauters, Katrien Lagrou, Mégarbane, Bruno, Intensive Care, Internal Medicine, MUMC+: MA Medische Staf IC (9), MUMC+: MA Arts Assistenten IC (9), and RS: NUTRIM - R2 - Liver and digestive health
Subjects: AZOLE RESISTANCE, Posaconazole, Original, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Critical Care and Intensive Care Medicine, Aspergillosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical endpoint, Invasive Pulmonary Aspergillosis, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Incidence (epidemiology), Intensive care unit, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Intensive Care Units, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, VIRUS, medicine.drug, Adult, medicine.medical_specialty, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Anesthesiology, SURVEILLANCE, Influenza, Human, medicine, Humans, education, FUMIGATUS, business.industry, Prophylaxis, 030208 emergency & critical care medicine, FLUCONAZOLE, Triazoles, medicine.disease, Influenza, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030228 respiratory system, Respiratory failure, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Critical illness
Abstract: Purpose Influenza-associated pulmonary aspergillosis (IAPA) is a frequent complication in critically ill influenza patients, associated with significant mortality. We investigated whether antifungal prophylaxis reduces the incidence of IAPA. Methods We compared 7 days of intravenous posaconazole (POS) prophylaxis with no prophylaxis (standard-of-care only, SOC) in a randomised, open-label, proof-of-concept trial in patients admitted to an intensive care unit (ICU) with respiratory failure due to influenza (ClinicalTrials.gov, NCT03378479). Adult patients with PCR-confirmed influenza were block randomised (1:1) within 10 days of symptoms onset and 48 h of ICU admission. The primary endpoint was the incidence of IAPA during ICU stay in patients who did not have IAPA within 48 h of ICU admission (modified intention-to-treat (MITT) population). Results Eighty-eight critically ill influenza patients were randomly allocated to POS or SOC. IAPA occurred in 21 cases (24%), the majority of which (71%, 15/21) were diagnosed within 48 h of ICU admission, excluding them from the MITT population. The incidence of IAPA was not significantly reduced in the POS arm (5.4%, 2/37) compared with SOC (11.1%, 4/36; between-group difference 5.7%; 95% CI − 10.8 to 21.7; p = 0.32). ICU mortality of early IAPA was high (53%), despite rapid antifungal treatment. Conclusion The higher than expected incidence of early IAPA precludes any definite conclusion on POS prophylaxis. High mortality of early IAPA, despite timely antifungal therapy, indicates that alternative management strategies are required. After 48 h, still 11% of patients developed IAPA. As these could benefit from prophylaxis, differentiated strategies are likely needed to manage IAPA in the ICU. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06431-0.
Published: 2021
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41. International electronic health record-derived post-acute sequelae profiles of COVID-19 patients

Author: Harrison G, Zhang, Arianna, Dagliati, Zahra, Shakeri Hossein Abad, Xin, Xiong, Clara-Lea, Bonzel, Zongqi, Xia, Bryce W Q, Tan, Paul, Avillach, Gabriel A, Brat, Chuan, Hong, Michele, Morris, Shyam, Visweswaran, Lav P, Patel, Alba, Gutiérrez-Sacristán, David A, Hanauer, John H, Holmes, Malarkodi Jebathilagam, Samayamuthu, Florence T, Bourgeois, Sehi, L'Yi, Sarah E, Maidlow, Bertrand, Moal, Shawn N, Murphy, Zachary H, Strasser, Antoine, Neuraz, Kee Yuan, Ngiam, Ne Hooi Will, Loh, Gilbert S, Omenn, Andrea, Prunotto, Lauren A, Dalvin, Jeffrey G, Klann, Petra, Schubert, Fernando J Sanz, Vidorreta, Vincent, Benoit, Guillaume, Verdy, Ramakanth, Kavuluru, Hossein, Estiri, Yuan, Luo, Alberto, Malovini, Valentina, Tibollo, Riccardo, Bellazzi, Kelly, Cho, Yuk-Lam, Ho, Amelia L M, Tan, Byorn W L, Tan, Nils, Gehlenborg, Sara, Lozano-Zahonero, Vianney, Jouhet, Luca, Chiovato, Bruce J, Aronow, Emma M S, Toh, Wei Gen Scott, Wong, Sara, Pizzimenti, Kavishwar B, Wagholikar, Mauro, Bucalo, Tianxi, Cai, Andrew M, South, Isaac S, Kohane, Griffin M, Weber, Admin, Oskar, Harvard Medical School [Boston] (HMS), Columbia University [New York], Università degli Studi di Pavia = University of Pavia (UNIPV), Harvard T.H. Chan School of Public Health, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), National University Hospital [Singapore] (NUH), Duke University [Durham], University of Kansas Medical Center [Kansas City, KS, USA], University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Pennsylvania, University of Michigan System, CHU Bordeaux [Bordeaux], Massachusetts General Hospital [Boston], Université Paris Cité (UPCité), Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), National University Health System [Singapore] (NUHS), University of Freiburg [Freiburg], Mayo Clinic [Rochester], VA Boston Healthcare System, University of California [Los Angeles] (UCLA), University of California (UC), University of Kentucky (UK), Northwestern University [Chicago, Ill. USA], Istituti Clinici Scientifici Maugeri [Pavia] (IRCCS Pavia - ICS Maugeri), 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), Cincinnati Children's Hospital Medical Center, National University of Singapore (NUS), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, BIOMERIS [Pavia], Wake Forest School of Medicine [Winston-Salem], and Wake Forest Baptist Medical Center
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Health Information Management, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine (miscellaneous), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Health Informatics, Computer Science Applications
Abstract: The risk profiles of post-acute sequelae of COVID-19 (PASC) have not been well characterized in multi-national settings with appropriate controls. We leveraged electronic health record (EHR) data from 277 international hospitals representing 414,602 patients with COVID-19, 2.3 million control patients without COVID-19 in the inpatient and outpatient settings, and over 221 million diagnosis codes to systematically identify new-onset conditions enriched among patients with COVID-19 during the post-acute period. Compared to inpatient controls, inpatient COVID-19 cases were at significant risk for angina pectoris (RR 1.30, 95% CI 1.09–1.55), heart failure (RR 1.22, 95% CI 1.10–1.35), cognitive dysfunctions (RR 1.18, 95% CI 1.07–1.31), and fatigue (RR 1.18, 95% CI 1.07–1.30). Relative to outpatient controls, outpatient COVID-19 cases were at risk for pulmonary embolism (RR 2.10, 95% CI 1.58–2.76), venous embolism (RR 1.34, 95% CI 1.17–1.54), atrial fibrillation (RR 1.30, 95% CI 1.13–1.50), type 2 diabetes (RR 1.26, 95% CI 1.16–1.36) and vitamin D deficiency (RR 1.19, 95% CI 1.09–1.30). Outpatient COVID-19 cases were also at risk for loss of smell and taste (RR 2.42, 95% CI 1.90–3.06), inflammatory neuropathy (RR 1.66, 95% CI 1.21–2.27), and cognitive dysfunction (RR 1.18, 95% CI 1.04–1.33). The incidence of post-acute cardiovascular and pulmonary conditions decreased across time among inpatient cases while the incidence of cardiovascular, digestive, and metabolic conditions increased among outpatient cases. Our study, based on a federated international network, systematically identified robust conditions associated with PASC compared to control groups, underscoring the multifaceted cardiovascular and neurological phenotype profiles of PASC.
Published: 2022
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42. BTN3A Targeting Vγ9Vδ2 T Cells Antimicrobial Activity Against Coxiella burnetii-Infected Cells

Author: Gay, Laetitia, Mezouar, Soraya, Cano, Carla, Foucher, Etienne, Gabriac, Mélanie, Fullana, Marie, Madakamutil, Loui, Mège, Jean-Louis, Olive, Daniel, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), ImCheck Therapeutics [Marseille], Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), and COMBE, Isabelle
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, butyrophilin, antimicrobial immunity, Immunology, therapeutic approaches, Vγ9Vδ2 T cells, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Coxiella burnetii, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: Vγ9Vδ2 T cells have been reported to participate to the immune response against infectious diseases such as the Q fever caused by Coxiella burnetii infection. Indeed, the number and proportion of Vγ9Vδ2 T cells are increased during the acute phase of Q fever. Human Vγ9Vδ2 T cell responses are triggered by phosphoantigens (pAgs) produced by pathogens and malignant cells, that are sensed via the membrane receptors butyrophilin-3A1 (BTN3A1) and -2A1 (BTN2A1). Here, by using CRISPR-Cas9 inactivation in THP-1 cells, we show that BTN3A and BTN2A are required to Vγ9Vδ2 T cell response to C. burnetii infection, though not directly involved in the infection process. Furthermore, C. burnetii-infected monocytes display increased BTN3A and BTN2A expression and induce Vγ9Vδ2 T cell activation that can be inhibited by specific antagonist mAb. More importantly, we show that the antimicrobial functions of Vγ9Vδ2 T cells towards C. burnetii are enhanced in the presence of an BTN3A activating antibody. This supports the role of Vγ9Vδ2 T cells in the control of C. burnetii infection and argues in favor of targeting these cells as an alternative treatment strategy for infectious diseases caused by intracellular bacteria.
Published: 2022
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43. Epigenetic alterations in gut and brain of adult rats after oral administration of miR-320-3p and miR-375-3p at mid-lactation, and preventive potential of miR-320-3p on early weaning stress

Author: Gabriel A Tavares, Amada Torres, Gwenola Le Drean, Maïwenn Queignec, Blandine Castellano, Laurent Tesson, Séverine Remy, Ignacio Annegone, Sandra L de Souza, Bruno Pitard, Bertrand Kaeffer, KAEFFER, BERTRAND, Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Santé - François Bonamy, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Federal University of Pernambuco [Recife], Immunology and New Concepts in ImmunoTherapy (INCIT), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE)
Subjects: [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract: AimTo investigate if the artificial delivery of microRNAs naturally present in the breastmilk can impact the gut and brain of young rats according to weaning.MethodsAnimals from a new transgenic rat line expressing green-fluorescent protein in the endocrine lineage (cholecystokinin expressing cells) received at Day-12, near neural diversification, a single oral bolus of mir-320-3p or miR-375-3p, embedded in DiOleyl-Succinyl-Paromomycin (DOSP), and were further early (Day-15) or regularly (Day-30) weaned. Relevant miRNA (miR-320-3p, miR-375-3p, miR-375-5p, miR-16-5p, miR-132-3p, miR-504), polr3d, hspb6, inflammation, enteroendocrine, and circadian clock-related mRNAs, chromatin complexes, and duodenal cell density were assayed at 8h post-inoculation and at Day-45.ResultsThe miR-320-3p/DOSP induced immediate effects on H3K4me3 chromatin complexes with polr3d promoter (pConclusionAddressing oral miRNA-320-3p loads to duodenal cell lineage is paving the way for the design of new therapeutics, manipulating long term consequences of early life stress.
Published: 2022
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44. Mental Disorders Are Associated With Leukocytes Telomere Shortening Among People Who Inject Drugs

Author: Mélusine Durand, Nicolas Nagot, Laurent Michel, Sao Mai Le, Huong Thi Duong, Roselyne Vallo, Amélie Vizeneux, Delphine Rapoud, Hoang Thi Giang, Catherine Quillet, Nham Thi Tuyet Thanh, Khuat Thi Hai Oanh, Vu Hai Vinh, Jonathan Feelemyer, Philippe Vande Perre, Khue Pham Minh, Didier Laureillard, Don Des Jarlais, Jean-Pierre Molès, Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), Université des Antilles (UA), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Pierre Nicole [Paris], Hai Phong University of Medicine and Pharmacy [Hai Phong, Vietnam], Supporting Community Development Initiatives [Hanoï, Vietnam], Viet Tiep Hospital [Hai Phong, Vietnam], New York University [New York] (NYU), NYU System (NYU), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), and DIAMANT-BERGER, Valérie
Subjects: hepatitis C virus, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Psychiatry and Mental health, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, telomere shortening, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, depression, aging, psychotic syndrome, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, mitochondrial DNA, drug use
Abstract: International audience; Premature biological aging, assessed by shorter telomere length (TL) and mitochondrial DNA (mtDNA) alterations, has been reported among people with major depressive disorders or psychotic disorders. However, these markers have never been assessed together among people who inject drugs (PWIDs), although mental disorders are highly prevalent in this population, which, in addition, is subject to other aggravating exposures. Diagnosis of mental disorders was performed by a psychiatrist using the Mini International Neuropsychiatric Interview test among active PWIDs in Haiphong, Vietnam. mtDNA copy number (MCN), mtDNA deletion, and TL were assessed by quantitative PCR and compared to those without any mental disorder. We next performed a multivariate analysis to identify risk factors associated with being diagnosed with a major depressive episode (MDE) or a psychotic syndrome (PS). In total, 130 and 136 PWIDs with and without psychiatric conditions were analyzed. Among PWIDs with mental disorders, 110 and 74 were diagnosed with MDE and PS, respectively. TL attrition was significantly associated with hepatitis C virus-infected PWIDs with MDE or PS (adjusted odds ratio [OR]: 0.53 [0.36; 0.80] and 0.59 [0.39; 0.88], respectively). TL attrition was even stronger when PWIDs cumulated at least two episodes of major depressive disorders. On the other hand, no difference was observed in mtDNA alterations between groups. The telomeric age difference with drug users without a diagnosis of psychiatric condition was estimated during 4.2-12.8 years according to the number of MDEs, making this group more prone to age-related diseases.
Published: 2022
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45. Impaired skin microvascular endothelial reactivity in critically ill COVID-19 patients

Author: Lisa Raia, Tomas Urbina, Paul Gabarre, Vincent Bonny, Geoffroy Hariri, Sebastien Ehrminger, Naïke Bigé, Jean-Luc Baudel, Bertrand Guidet, Eric Maury, Jeremie Joffre, Hafid Ait-Oufella, Gestionnaire, Hal Sorbonne Université, Service de Réanimation Médicale [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, Endothelial reactivity, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Tissue perfusion, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive care medicine, Critical Care and Intensive Care Medicine
Abstract: Background Some clinical and histological studies have reported that SARS-CoV-2 infection may damage the endothelium. However, the impact of this virus on endothelial function in vivo remains poorly characterized. In this single-center pilot observational study, we performed iontophoresis of acetylcholine coupled with Laser doppler to investigate microvascular endothelial reactivity in COVID-19 patients compared to patients with non-COVID-19 bacterial pneumonia (NCBP) patients. Results During three consecutive months, 32 COVID-19 patients and 11 control NCBP patients with acute respiratory failure were included. The median age was 59 [50–68] and 69 [57–75] years in COVID-19 and NCBP groups, respectively (P = 0.11). There was no significant difference in comorbidities or medications between the two groups, except for body mass index, which was higher in COVID-19 patients. NCBP patients had a higher SAPS II score compared to COVID-19 patients (P P = 0.51). Global hemodynamic and peripheral tissue perfusion parameters were not different between groups. COVID-19 patients had significantly lower skin microvascular basal blood flow than NCBP patients (P = 0.02). In addition, endothelium-dependent microvascular reactivity was threefold lower in COVID-19 patients than NCBP patients (P = 0.008). Conclusions Both baseline skin microvascular blood flow and skin endothelial-dependent microvascular reactivity were impaired in critically ill COVID-19 patients compared to NCBP patients, despite a lower disease severity score supporting a specific pathogenic role of SARS-CoV-2 on the endothelium.
Published: 2022
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46. Publisher Correction: Heterogeneous SARS-CoV-2 humoral response after COVID-19 vaccination and/or infection in the general population

Author: Carrat, Fabrice, Villarroel, Paola Mariela Saba, Lapidus, Nathanael, Fourié, Toscane, Blanché, Hélène, Dorival, Céline, Nicol, Jérôme, Deleuze, Jean-François, Robineau, Olivier, Touvier, Mathilde, Severi, Gianluca, Zins, Marie, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre d'Etude du Polymorphisme Humain (CEPH), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset-Université Paris Cité (UPCité), Fondation Jean Dausset CEPH, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-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), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Università degli Studi di Firenze = University of Florence (UniFI), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), SAPRIS-SERO Study Group: Fabrice Carrat, Marie Zins, Gianluca Severi, Mathilde Touvier, Hélène Blanché, Jean-François Deleuze, Xavier de Lamballerie, Clovis Lusivika-Nzinga, Gregory Pannetier, Nathanael Lapidus, Isabelle Goderel, Céline Dorival, Jérôme Nicol, Olivier Robineau, Sofiane Kab, Adeline Renuy, Stéphane Le-Got, Céline Ribet, Mireille Pellicer, Emmanuel Wiernik, Marcel Goldberg, Fanny Artaud, Pascale Gerbouin-Rérolle, Mélody Enguix, Camille Laplanche, Roselyn Gomes-Rima, Lyan Hoang, Emmanuelle Correia, Alpha Amadou Barry, Nadège Senina, Julien Allegre, Fabien Szabo de Edelenyi, Nathalie Druesne-Pecollo, Younes Esseddik, Serge Hercberg, Mélanie Deschasaux, Hélène Blanché, Jean-Marc Sébaoun, Jean-Christophe Beaudoin, Laetitia Gressin, Valérie Morel, Ouissam Ouili, Jean-François Deleuze, Laetitia Ninove, Stéphane Priet, Paola Mariela Saba Villarroel, Toscane Fourié, Souand Mohamed Ali, Abdenour Amroun, Morgan Seston, Nazli Ayhan, Boris Pastorino, and CARRAT, FABRICE
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Multidisciplinary
Abstract: International audience; No abstract available
Published: 2022
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47. Rapidly adapting primary care sentinel surveillance across seven countries in Europe for COVID-19 in the first half of 2020: strengths, challenges, and lessons learned

Author: Bagaria, Jayshree, Jansen, Tessa, Marques, Diogo Fp, Hooiveld, Mariette, McMenamin, Jim, de Lusignan, Simon, Vilcu, Ana-Maria, Meijer, Adam, Rodrigues, Ana-Paula, Brytting, Mia, Mazagatos, Clara, Cogdale, Jade, van der Werf, Sylvie, Dijkstra, Frederika, Guiomar, Raquel, Enkirch, Theresa, Valenciano, Marta, I-MOVE-COVID-19 study team, Larrauri, Amparo, Pozo Sanchez, Francisco, Casas Flecha, Inmaculada, Unión Europea. Comisión Europea. H2020, Public Health Scotland [Glasgow], Netherlands Institute for Health Services Research [Utrecht] (NIVEL), EpiConcept [Paris], University of Oxford, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), Public Health Agency of Sweden, Institute of Health Carlos III, UK Health Security Agency (UKHSA), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673., MOVE-COVID-19 study team: Esther Kissling, Lisa Domegan, Joan O'Donnell, Josephine Murray, Virginia Sandonis Martín, Iván Martínez-Baz, Ausenda Machado, Itziar Casado, Sylvie Behillil, Amparo Larrauri, Ruby Tsang, Marit de Lange, Maximilian Riess, Jesús Castilla, Mark Hamilton, Alessandra Falchi, Francisco Pozo, Linda Dunford, Cristina Burgui, Debbie Sigerson, Thierry Blanchon, Eva María Martínez Ochoa, Jeff Connell, Joanna Ellis, Rianne van Gageldonk-Lafeber, Irina Kislaya, Angela Mc Rose, Jamie Lopez Bernal, Nick Andrews, Inmaculada Casas Flecha, Janine Thoulass, Baltazar Nunes, Verónica Gomez, Rita Sa Machado, Vincent Enouf, Pedro Licinio Pinto Leite, Anna Molesworth, Adele McKenna, Janine Thoulass, European Project: 101003673,H2020-SC1-PHE-CORONAVIRUS-2020,I-MOVE-COVID-19(2020), HAL-SU, Gestionnaire, Multidisciplinary European network for research, prevention and control of the COVID-19 Pandemic - I-MOVE-COVID-19 - - H2020-SC1-PHE-CORONAVIRUS-20202020-03-16 - 2022-06-15 - 101003673 - VALID, UK Health Security Agency [London] (UKHSA), and Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur)
Subjects: Epidemiology, Sentinel surveillance, primary care, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Influenza, Human, Humans, Influenza-Like Illness, Pandemics, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Primary Health Care, SARS-CoV-2, Cuidados de Saúde, Public Health, Environmental and Occupational Health, Influenza-Like Illness (ILI), COVID-19, Estados de Saúde e de Doença, Primary care, Europe, Vigilância Epidemiológica, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Influenza Vaccines, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sentinel Surveillance
Abstract: I-MOVE-COVID-19 study team: Esther Kissling, Lisa Domegan, Joan O’Donnell, Josephine Murray, Virginia Sandonis Martín, Iván Martínez-Baz, Ausenda Machado, Itziar Casado, Sylvie Behillil, Amparo Larrauri, Ruby Tsang, Marit de Lange, Maximilian Riess, Jesús Castilla, Mark Hamilton, Alessandra Falchi, Francisco Pozo, Linda Dunford, Cristina Burgui, Debbie Sigerson, Thierry Blanchon, Eva María Martínez Ochoa, Jeff Connell, Joanna Ellis, Rianne van Gageldonk-Lafeber, Irina Kislaya, Angela MC Rose, Jamie Lopez Bernal, Nick Andrews, Inmaculada Casas Flecha, Janine Thoulass, Baltazar Nunes, Verónica Gomez, Rita Sa Machado, Vincent Enouf, Pedro Licinio Pinto Leite, Anna Molesworth, Adele McKenna, Janine Thoulass As the COVID-19 pandemic began in early 2020, primary care influenza sentinel surveillance networks within the Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE) consortium rapidly adapted to COVID-19 surveillance. This study maps system adaptations and lessons learned about aligning influenza and COVID-19 surveillance following ECDC / WHO/Europe recommendations and preparing for other diseases possibly emerging in the future. Using a qualitative approach, we describe the adaptations of seven sentinel sites in five European Union countries and the United Kingdom during the first pandemic phase (March–September 2020). Adaptations to sentinel systems were substantial (2/7 sites), moderate (2/7) or minor (3/7 sites). Most adaptations encompassed patient referral and sample collection pathways, laboratory testing and data collection. Strengths included established networks of primary care providers, highly qualified testing laboratories and stakeholder commitments. One challenge was the decreasing number of samples due to altered patient pathways. Lessons learned included flexibility establishing new routines and new laboratory testing. To enable simultaneous sentinel surveillance of influenza and COVID-19, experiences of the sentinel sites and testing infrastructure should be considered. The contradicting aims of rapid case finding and contact tracing, which are needed for control during a pandemic and regular surveillance, should be carefully balanced. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673. info:eu-repo/semantics/publishedVersion
Published: 2022
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48. Measuring Basic Reproduction Number to Assess Effects of Nonpharmaceutical Interventions on Nosocomial SARS-CoV-2 Transmission

Author: George, Shirreff, Jean-Ralph, Zahar, Simon, Cauchemez, Laura, Temime, Lulla, Opatowski, Cynthia, Tamandjou, Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), 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 de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-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 Paris Cité (UPCité), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, This work was supported directly by internal resources from the French National Institute for Health and Medical Research, the Institut Pasteur, the Conservatoire National des Arts et Métiers, and the University of Versailles-Saint-Quentin-en-Yvelines/University of Paris-Saclay. This study received funding through the MODCOV project from the Fondation de France (grant no. 106059) as part of the alliance framework 'Tous unis contre le virus,' the Université Paris-Saclay (no. AAP Covid-19 2020) and the French government through its National Research Agency (project no. SPHINX-17-CE36-0008-01)., ANR-17-CE36-0008,SPHINx,Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation(2017), Bertram, Marie-Liesse, Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation - - SPHINx2017 - ANR-17-CE36-0008 - AAPG2017 - VALID, Modélisation mathématique des maladies infectieuses - Mathematical modelling of Infectious Diseases, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Microbiology (medical), [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Cross Infection, Infection Control, Epidemiology, SARS-CoV-2, Basic Reproduction Number, COVID-19, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; Outbreaks of SARS-CoV-2 infection frequently occur in hospitals. Preventing nosocomial infection requires insight into hospital transmission. However, estimates of the basic reproduction number (R0) in care facilities are lacking. Analyzing a closely monitored SARS-CoV-2 outbreak in a hospital in early 2020, we estimated the patient-to-patient transmission rate and R0. We developed a model for SARS-CoV-2 nosocomial transmission that accounts for stochastic effects and undetected infections and fit it to patient test results. The model formalizes changes in testing capacity over time, and accounts for evolving PCR sensitivity at different stages of infection. R0 estimates varied considerably across wards, ranging from 3 to 15 in different wards. During the outbreak, the hospital introduced a contact precautions policy. Our results strongly support a reduction in the hospital-level R0 after this policy was implemented, from 8.7 to 1.3, corresponding to a policy efficacy of 85% and demonstrating the effectiveness of nonpharmaceutical interventions.
Published: 2022
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49. Diagnostic Accuracy of LDBIO-Toxo II IgG and IgM Western Blot in Suspected Seroconversion in Pregnancy: A Multicentre Study

Author: Valeria Meroni, Francesca Genco, Luigia Scudeller, Marie-Pierre Brenier-Pinchart, Hélène Fricker-Hidalgo, Coralie L’Ollivier, Luc Paris, Hervé Pelloux, Università degli Studi di Pavia = University of Pavia (UNIPV), Fondazione IRCCS Policlinico San Matteo [Pavia], Sant'Orsola-Malpighi Hospital [Bologna, Italy], Centre Hospitalier Universitaire [Grenoble] (CHU), Université Grenoble Alpes (UGA), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and COMBE, Isabelle
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Microbiology (medical), [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, IgM, western blot, General Immunology and Microbiology, IgG, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, toxoplasmosis, seroconversion, pregnancy, Infectious Diseases, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Molecular Biology, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: International audience; The high sensitivity of the automated tests used for Toxoplasma gondii serology can yield false-positive IgM results due to aspecific reactions. On the other hand, specific therapy can delay IgG production and, therefore, the diagnosis of seroconversion. There is a need for confirmation tests to early detect seroconversions during pregnancy. We conducted a multicentre study to evaluate the diagnostic accuracy of the Toxo II IgG and a new, not yet commercialised Toxo II IgM western blot (WB) (LDBio diagnostics Lyon France) on 229 sera corresponding to 93 patients with seroconversions and 158 sera corresponding to 68 patients with nonspecific IgM. Sensitivity was 97.8% for IgM WB and 98.9% for IgG WB. Specificity was 89.7% and 100%, respectively. The concordance between IgM and IgG Toxo WB with the final diagnosis was very good, K = 0.89 and K = 0.99, respectively. In 5 cases (5.4%), the appearance of IgM, and in 55 cases (59.1%), the appearance of IgG was recorded by WB earlier than by traditional tests. In 10 cases (10.8%), IgM was detected after the traditional tests and in 2 cases (2.2%) for IgG. The association of IgG and IgM WB on the same sample not only detected all seroconversions but also correctly identified most of the false-positive results.
Published: 2022
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50. The economic, medical and psychosocial consequences of whole genome sequencing for the genetic diagnosis of patients with intellectual disability: The DEFIDIAG study protocol

Author: Catherine Lejeune, Charley Robert-Viard, Nicolas Meunier-Beillard, Myriam Alice Borel, Léna Gourvès, Stéphanie Staraci, Anne-Laure Soilly, Francis Guillemin, Valerie Seror, Hamza Achit, Marion Bouctot, Marie-Laure Asensio, Anne-Sophie Briffaut, Christelle Delmas, Ange-Line Bruel, Alexia Benoit, Alban Simon, Bénédicte Gerard, Hamza Hadj Abdallah, Stanislas Lyonnet, Laurence Faivre, Christel Thauvin-Robinet, Sylvie Odent, Delphine Heron, Damien Sanlaville, Thierry Frebourg, Jean Muller, Yannis Duffourd, Anne Boland, Jean-François Deleuze, Hélène Espérou, Christine Binquet, Hélène Dollfus, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Délégation à la recherche clinique et à l'innovation [CHU Dijon] (DRCI), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), 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), Pôle de Recherche Clinique [Paris] (PRC), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bourgogne Franche-Comté [COMUE] (UBFC), FHU TRANSLAD (CHU de Dijon), Equipe GAD (LNC - U1231), Institut de génétique médicale, Les Hôpitaux Universitaires de Strasbourg (HUS), Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre de référence Maladies Rares CLAD-Ouest [Rennes], Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Rouen, Normandie Université (NU), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), TheDEFIDIAG study is funded by grants from the French Ministry of Health in the framewok of the national French initiative for genomic medicine. Institut national de la santé et de la recherche médicale (Inserm) is the sponsor of the DEFDIAG study., COMBE, Isabelle, and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, micro-costing, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, genome sequencing, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, intellectual disability, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Molecular Medicine, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, cost-effectiveness, Genetics (clinical), [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, qualitative stud
Abstract: Introduction: Like other countries, France has invested in a national medical genomics program. Among the four pilot research studies, the DEFIDIAG project focuses on the use of whole genome sequencing (WGS) for patients with intellectual disability (ID), a neurodevelopmental condition affecting 1–3% of the general population but due to a plethora of genes. However, the access to genomic analyses has many potential individual and societal issues in addition to the technical challenges. In order to help decision-makers optimally introduce genomic testing in France, there is a need to identify the socio-economic obstacles and leverages associated with the implementation of WGS.Methods and Analysis: This humanities and social sciences analysis is part of the DEFIDIAG study. The main goal of DEFIDIAG is to compare the percentage of causal genetic diagnoses obtained by trio WGS (including the patient and both parents) (WGST) to the percentage obtained using the minimal reference strategy currently used in France (Fragile-X testing, chromosomal microarray analysis, and gene panel strategy including 44 ID genes) for patients with ID having their first clinical genetics consultation. Additionally, four complementary studies will be conducted. First, a cost-effectiveness analysis will be undertaken in a subsample of 196 patients consulting for the first time for a genetic evaluation; in a blinded fashion, WGST and solo (index case, only) genomic analysis (WGSS) will be compared to the reference strategy. In addition, quantitative studies will be conducted: the first will estimate the cost of the diagnostic odyssey that could potentially be avoidable with first-line WGST in all patients previously investigated in the DEFIDIAG study; the second will estimate changes in follow-up of the patients in the year after the return of the WGST analysis compared to the period before inclusion. Finally, through semi-directive interviews, we will explore the expectations of 60 parents regarding genomic analyses.Discussion: Humanities and social sciences studies can be used to demonstrate the efficiency of WGS and assess the value that families associate with sequencing. These studies are thus expected to clarify trade-offs and to help optimize the implementation of genomic sequencing in France.Ethics Statement: The protocol was approved by the Ethics Committee Sud Méditerranée I (June 2019)—identification number: 2018-A00680-55 and the French data privacy commission (CNIL, authorization 919361).Clinical Trial Registration: (ClinicalTrials.gov), identifier (NCT04154891).
Published: 2022
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