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1. Relationship between molecular pathogen detection and clinical disease in febrile children across Europe: a multicentre, prospective observational studyResearch in context

Author

Priyen Shah, Marie Voice, Leonides Calvo-Bado, Irene Rivero-Calle, Sophie Morris, Ruud Nijman, Claire Broderick, Tisham De, Irini Eleftheriou, Rachel Galassini, Aakash Khanijau, Laura Kolberg, Mojca Kolnik, Aleksandra Rudzate, Manfred G. Sagmeister, Nina A. Schweintzger, Fatou Secka, Clare Thakker, Fabian van der Velden, Clementien Vermont, Katarina Vincek, Philipp K.A. Agyeman, Aubrey J. Cunnington, Ronald De Groot, Marieke Emonts, Katy Fidler, Taco W. Kuijpers, Marine Mommert-Tripon, Karen Brengel-Pesce, Francois Mallet, Henriette Moll, Stéphane Paulus, Marko Pokorn, Andrew Pollard, Luregn J. Schlapbach, Ching-Fen Shen, Maria Tsolia, Effua Usuf, Michiel van der Flier, Ulrich von Both, Shunmay Yeung, Dace Zavadska, Werner Zenz, Victoria Wright, Enitan D. Carrol, Myrsini Kaforou, Federico Martinon-Torres, Colin Fink, Michael Levin, Jethro Herberg, Irene Rivero Calle, Manfred Sagmeister, Nina Schweintzger, Fabian Van der Velden, Taco Kuijpers, Michiel Van der Flier, Ulrich Von Both, Lucas Baumard, Evangelos Bellos, Lachlan Coin, Giselle D'Souza, Dominic Habgood-Coote, Shea Hamilton, Cllive Hoggart, Sara Hourmat, Heather Jackson, Naomi Lin, Stephanie Menikou, Samuel Nichols, Ivonne Pena Paz, Oliver Powell, Ortensia Vito, Clare Wilson, Amina Abdulla, Ladan Ali, Sarah Darnell, Rikke Jorgensen, Ian Maconochie, Sobia Mustafa, Salina Persand, Ben Walsh, Molly Stevens, Nayoung Kim, Eunjung Kim, Benjamin Pierce, Julia Dudley, Vivien Richmond, Emma Tavliavini, Ching-Chuan Liu, Shih-Min Wang, Fernando Álves González, Cristina Balo Farto, Ruth Barral-Arca, María Barreiro Castro, Xabier Bello, Mirian Ben García, Sandra Carnota, Miriam Cebey-López, María José Curras-Tuala, Carlos Durán Suárez, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Pilar Leboráns Iglesias, Nazareth Martinón-Torres, José María Martinón Sánchez, Belén Mosquera Pérez, Jacobo Pardo-Seco, Lidia Piñeiro Rodríguez, Sara Pischedda, Sara Ray Vázquez, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Miguel Sadiki Ora, Antonio Sallas, Sonia Serén Fernández, Cristina Serén Trasorras, Marisol Vilas Iglesias, Anda Balode, Arta Bãrdzdina, Dãrta Deksne, Dace Gardovska, Dagne Grãvele, Ilze Grope, Anija Meiere, Ieve Nokalna, Jana Pavãre, Zanda Pučuka, Katrīna Selecka, Dace Svile, Urzula Nora Urbãne, Kalifa Bojang, Syed M.A. Zaman, Suzanne Anderson, Anna Roca, Isatou Sarr, Momodou Saidykhan, Saffiatou Darboe, Samba Ceesay, Umberto D'alessandro, Dorine M. Borensztajn, Nienke N. Hagedoorn, Chantal Tal, Joany Zachariasse, W. Dik, Christoph Aebi, Christoph Berger, Verena Wyss, Mariama Usman, Eric Giannoni, Martin Stocker, Klara M. Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Giancarlo Natalucci, Christa Relly, Thomas Riedel, Elizabeth Cocklin, Rebecca Jennings, Joanne Johnson, Simon Leigh, Karen Newall, Sam Romaine, Maria Tambouratzi, Antonis Marmarinos, Marietta Xagorari, Kelly Syggelou, Nikos Spyridis, Jennifer Blackmore, Rebekah Harrison, Benno Kohlmaier, Daniela S. Kohlfürst, Christoph Zurl, Alexander Binder, Susanne Hösele, Manuel Leitner, Lena Pölz, Glorija Rajic, Sebastian Bauchinger, Hinrich Baumgart, Martin Benesch, Astrid Ceolotto, Ernst Eber, Siegfried Gallisti, Gunther Gores, Harald Haidl, Almuthe Hauer, Christa Hude, Markus Keldorfer, Larissa Krenn, Heidemarie Pilch, Andreas Pfleger, Klaus Pfurtscheller, Gudrun Nordberg, Tobias Niedrist, Siegfried Rödl, Andrea Skrabl-Baumgartner, Matthias Sperl, Laura Stampfer, Volker Strenger, Holger Till, Andreas Trobisch, Sabine Löffler, Juan Emmanuel Dewez, Martin Hibberd, David Bath, Alec Miners, Elizabeth Fitchett, Catherine Wedderburn, Anne Meierford, Baptiste Leurent, Marien I. De Jonge, Koen van Aerde, Wynand Alkema, Bryan van den Broek, Jolein Gloerich, Alain J. Van Gool, Stefanie Henriet, Martijn Huijnen, Ria Philipsen, Esther Willems, G.P.J.M. Gerrits, M. Van Leur, J. Heidema, L. De Haan, C.J. Miedema, C. Neeleman, C.C. Obihara, G.A. Tramper-Stranders, Rama Kandasamy, Michael J. Carter, Daniel O'Connor, Sagida Bibi, Dominic F. Kelly, Meeru Gurung, Stephen Throson, Imran Ansari, David R. Murdoch, Shrijana Shrestha, Zoe Oliver, Emma Lim, Lucille Valentine, Karen Allen, Kathryn Bell, Adora Chan, Stephen Crulley, Kirsty Devine, Daniel Fabian, Sharon King, Paul McAlinden, Sam McDonald, Anne McDonell, Alisa Pickering, Evelyn Thomson, Amanda Wood, Diane Wallia, Phil Woodsford, Frances Baxter, Ashley Bell, Mathew Rhodes, Rachel Agbeko, Christine Mackerness, Bryan Baas, Lieke Kloosterhuis, Wilma Oosthoek, Tasnim Arif, Joshua Bennet, Kalvin Collings, Ilona Van der Giessen, Alex Martin, Aqeela Rashid, Emily Rowlands, Joshua Soon, Gabriella De Vries, Mike Martin, Ravi Mistry, Manuela Zwerenz, Judith Buschbeck, Christoph Bidlingmaier, Vera Binder, Katharina Danhauser, Nikolaus Haas, Matthias Griese, Matthias Kappler, Eberhard Lurz, Georg Muench, Karl Reiter, Carola Schoen, Alexandre Pachot, Marine Mommert, Tina Plankar Srovin, Natalija Bahovec, Petra Prunk, Veronika Osterman, Tanja Avramoska, Ilse Jongerius, J.M. van den Berg, D. Schonenberg, A.M. Barendregt, D. Pajkrt, M. van der Kuip, A.M. van Furth, Evelien Sprenkeler, Judith Zandstra, G. van Mierlo, and J. Geissler

Subjects
Molecular diagnostics, Diagnostic, Febrile illness, Infectious disease, Bacterial, Viral, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The PERFORM study aimed to understand causes of febrile childhood illness by comparing molecular pathogen detection with current clinical practice. Methods: Febrile children and controls were recruited on presentation to hospital in 9 European countries 2016–2020. Each child was assigned a standardized diagnostic category based on retrospective review of local clinical and microbiological data. Subsequently, centralised molecular tests (CMTs) for 19 respiratory and 27 blood pathogens were performed. Findings: Of 4611 febrile children, 643 (14%) were classified as definite bacterial infection (DB), 491 (11%) as definite viral infection (DV), and 3477 (75%) had uncertain aetiology. 1061 controls without infection were recruited. CMTs detected blood bacteria more frequently in DB than DV cases for N. meningitidis (OR: 3.37, 95% CI: 1.92–5.99), S. pneumoniae (OR: 3.89, 95% CI: 2.07–7.59), Group A streptococcus (OR 2.73, 95% CI 1.13–6.09) and E. coli (OR 2.7, 95% CI 1.02–6.71). Respiratory viruses were more common in febrile children than controls, but only influenza A (OR 0.24, 95% CI 0.11–0.46), influenza B (OR 0.12, 95% CI 0.02–0.37) and RSV (OR 0.16, 95% CI: 0.06–0.36) were less common in DB than DV cases. Of 16 blood viruses, enterovirus (OR 0.43, 95% CI 0.23–0.72) and EBV (OR 0.71, 95% CI 0.56–0.90) were detected less often in DB than DV cases. Combined local diagnostics and CMTs respectively detected blood viruses and respiratory viruses in 360 (56%) and 161 (25%) of DB cases, and virus detection ruled-out bacterial infection poorly, with predictive values of 0.64 and 0.68 respectively. Interpretation: Most febrile children cannot be conclusively defined as having bacterial or viral infection when molecular tests supplement conventional approaches. Viruses are detected in most patients with bacterial infections, and the clinical value of individual pathogen detection in determining treatment is low. New approaches are needed to help determine which febrile children require antibiotics. Funding: EU Horizon 2020 grant 668303.

Published
2023
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2. Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Author

Esther Willems, Jolein Gloerich, Anouk Suppers, Michiel van der Flier, Lambert P. van den Heuvel, Nicole van de Kar, Ria H.L.A. Philipsen, Maurice van Dael, Myrsini Kaforou, Victoria J. Wright, Jethro A. Herberg, Federico Martinon Torres, Michael Levin, Ronald de Groot, Alain J. van Gool, Dirk J. Lefeber, Hans J.C.T. Wessels, Marien I. de Jonge, Amina Abdulla, Christoph Aebi, Koen van Aerde, Rachel Agbeko, Philipp Agyeman, Umberto D’alessandro, Ladan Ali, Wynand Alkema, Karen Allen, Fernando Álvez González, Suzanne Anderson, Imran Ansari, Tasnim Araf, Tanja Avramoska, Bryan Baas, Natalija Bahovec, Cristina Balo Farto, Anda Balode, A.M. Barendregt, Ruth Barral-Arca, María Barreiro Castro, Arta Bārzdiņa, David Bath, Sebastian Bauchinger, Lucas Baumard, Hinrich Baumgart, Frances Baxter, Ashley Bell, Kathryn Bell, Xabier Bello, Evangelos Bellos, Martin Benesch, Mirian Ben García, Joshua Bennet, Christoph Berger, J.M. van den Berg, Sara Bernhard-Stirnemann, Sagida Bibi, Christoph Bidlingmaier, Alexander Binder, Vera Binder, Kalifa Bojang, Dorine M. Borensztajn, Ulrich von Both, Karen Brengel-Pesce, Bryan van den Broek, Judith Buschbeck, Leo Calvo-Bado, Sandra Carnota, Enitan D. Carrol, Michael J. Carter, Miriam Cebey-López, Samba Ceesay, Astrid Ceolotto, Adora Chan, Elizabeth Cocklin, Kalvin Collings, Stephen Crulley, Aubrey Cunnington, María José Curras-Tuala, Katharina Danhauser, Saffiatou Darboe, Sarah Darnell, Tisham De, Dārta Deksne, Kirsty Devine, Juan Emmanuel Dewez, Julia Dudley, Carlos Durán Suárez, Ernst Eber, Irini Eleftheriou, Marieke Emonts, Daniel Fabian, Tobias Feuchtinger, Katy Fidler, Colin Fink, A.M. van Furth, Rachel Galassini, Siegfried Gallistl, Luisa García Vicente, Dace Gardovska, J. Geissler, G.P.J.M. Gerrits, Eric Giannoni, Ilona van der Giessen, Alberto Gómez-Carballa, Jose Gómez Rial, Gunther Gores, Dagne Grāvele, Matthias Griese, Ilze Grope, Meeru Gurung, L. de Haan, Nikolaus Haas, Dominic Habgood-Coote, Nienke N. Hagedoorn, Harald Haidl, Shea Hamilton, Almuthe Hauer, J. Heidema, Ulrich Heininger, Stefanie Henriet, Jethro Herberg, Clive Hoggart, Susanne Hösele, Sara Hourmat, Christa Hude, Martijn Huijnen, Heather Jackson, Rebecca Jennings, Joanne Johnston, Ilse Jongerius, Rikke Jorgensen, Christian Kahlert, Rama Kandasamy, Matthias Kappler, Julia Keil, Markus Keldorfer, Dominic F. Kell, Eunjung Kim, Sharon King, Lieke Kloosterhuis, Daniela S. Kohlfürst, Benno Kohlmaier, Laura Kolberg, Mojca Kolnik, Larissa Krenn, Taco Kuijpers, M. van der Kuip, Pilar Leboráns Iglesias, Simon Leigh, Manuel Leitner, M. van Leur, Emma Lim, Naomi Lin, Ching-Chuan Liu, Sabine Löffler, Eberhard Lurz, Ian Maconochie, Christine Mackerness, François Mallet, Federico Martinón-Torres, Antonis Marmarinos, Alex Martin, Mike Martin, José María Martinón Sánchez, Nazareth Martinón-Torres, Paul McAlinden, Anne McDonnell, Sam McDonald, C.J. Miedema, Anija Meiere, Stephanie Menikou, G. van Mierlo, Alec Miners, Ravi Mistry, Henriëtte A. Moll, Marine Mommert, Belén Mosquera Pérez, David R. Murdoch, Sobia Mustafa, Giancarlo Natalucci, C. Neeleman, Karen Newall, Samuel Nichols, Tobias Niedrist, Anita Niederer-Loher, Ruud Nijman, Ieva Nokalna, Urzula Nora Urbāne, Gudrun Nordberg, C.C. Obihara, Daniel O'Connor, Wilma Oosthoek, Veronika Osterman, Alexandre Pachot, D. Pajkrt, Jacobo Pardo-Seco, Stéphane Paulus, Jana Pavāre, Ivonne Pena Paz, Salina Persand, Andreas Pfleger, Klaus Pfurtscheller, Ria Philipsen, Ailsa Pickering, Benjamin Pierce, Heidemarie Pilch, Lidia Piñeiro Rodríguez, Sara Pischedda, Tina Plankar Srovin, Marko Pokorn, Andrew J. Pollard, Lena Pölz, Klara M. Posfay-Barbe, Petra Prunk, Zanda Pučuka, Glorija Rajic, Aqeela Rashid, Lorenzo Redondo-Collazo, Christa Relly, Irene Rivero Calle, Sara Rey Vázquez, Mathew Rhodes, Vivien Richmond, Thomas Riedel, Anna RocaIsatou Sarr, Siegfried Rödl, Carmen Rodríguez-Tenreiro, Sam Romaine, Emily Rowlands, Miguel Sadiki Ora, Manfred G. Sagmeister, Momodou Saidykhan, Antonio Salas, Luregn J. Schlapbach, D. Schonenberg, Fatou Secka, Katrīna Selecka, Sonia Serén Fernández, Cristina Serén Trasorras, Priyen Shah, Ching-Fen Shen, Shrijana Shrestha, Aleksandra Sidorova, Andrea Skrabl-Baumgartner, Giselle D’Souza, Matthias Sperl, Evelien Sprenkeler, Nina A. Schweintzger, Laura Stampfer, Molly Stevens, Martin Stocker, Volker Strenger, Dace Svile, Kelly Syggelou, Maria Tambouratzi, Chantal Tan, Emma Tavliavini, Evelyn Thomson, Stephen Thorson, Holger Till, G.A. Tramper-Stranders, Andreas Trobisch, Maria Tsolia, Effua Usuf, Lucille Valentine, Clementien L. Vermont, Marisol Vilas Iglesias, Katarina Vincek, Marie Voice, Gabriella de Vries, Diane Wallia, Shih-Min Wang, Clare Wilson, Amanda Wood, Phil Woodsford, Victoria Wright, Marietta Xagorari, Shunmay Yeung, Joany Zachariasse, Dace Zavadska, Syed M.A. Zaman, Judith Zandstra, Werner Zenz, Christoph Zurl, and Manuela Zwerenz

Subjects
Health sciences, Glycobiology, Immunology, Glycomics, Science
Abstract

Summary: Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection.

Published
2023
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3. TIPICO XI: report of the first series and podcast on infectious diseases and vaccines (aTIPICO)

Author

Federico Martinón-Torres, Adolfo García-Sastre, Andrew J. Pollard, Carlos Martín, Albert Osterhaus, Shamez N Ladhani, Octavio Ramilo, Jose Gómez Rial, Antonio Salas, F Xavier Bosch, María Martinón-Torres, Michael J. Mina, and James Cherry

Subjects
infectious disease, vaccine-preventable disease, covid-19 pandemic, control of transmission, vaccine-immunity response, severe acute respiratory syndrome coronavirus-2 (sars-cov-2), Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

TIPiCO is an annual expert meeting and workshop on infectious diseases and vaccination. The edition of 2020 changed its name and format to aTIPiCO, the first series and podcasts on infectious diseases and vaccines. A total of 13 prestigious experts from different countries participated in this edition launched on the 26 November 2020. The state of the art of coronavirus disease-2019 (COVID-19) and the responsible pathogen, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the options to tackle the pandemic situation were discussed in light of the knowledge in November 2020. Despite COVID-19, the status of other infectious diseases, including influenza infections, respiratory syncytial virus disease, human papillomavirus infection, measles, pertussis, tuberculosis, meningococcal disease, and pneumococcal disease, were also addressed. The essential lessons that can be learned from these diseases and their vaccines to use in the COVID-19 pandemic were also commented with the experts.

Published
2021
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4. Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis

Author

Navin P. Boeddha, MD, PhD, Gertjan J. Driessen, MD, PhD, Nienke N. Hagedoorn, MD, Daniela S. Kohlfuerst, MD, Clive J. Hoggart, PhD, Angelique L. van Rijswijk, MSc, Ebru Ekinci, MD, Debby Priem, BSc, Luregn J. Schlapbach, MD, PhD, Jethro A. Herberg, MD, PhD, Ronald de Groot, MD, PhD, Suzanne T. Anderson, MD, PhD, Colin G. Fink, PhD, Enitan D. Carrol, MD, PhD, Michiel van der Flier, MD, PhD, Federico Martinón-Torres, MD, PhD, Michael Levin, MD, PhD, Frank W. Leebeek, MD, PhD, Werner Zenz, MD, PhD, Moniek P. M. de Maat, PhD, Jan A. Hazelzet, MD, PhD, Marieke Emonts, MD, PhD, Willem A. Dik, PhD, on behalf of the EUCLIDS consortium, Michael Levin, Lachlan Coin, Stuart Gormley, Shea Hamilton, Jethro Herberg, Bernardo Hourmat, Clive Hoggart, Myrsini Kaforou, Vanessa Sancho-Shimizu, Victoria Wright, Amina Abdulla, Paul Agapow, Maeve Bartlett, Evangelos Bellos, Hariklia Eleftherohorinou, Rachel Galassini, David Inwald, Meg Mashbat, Stefanie Menikou, Sobia Mustafa, Simon Nadel, Rahmeen Rahman, Clare Thakker, S Bokhandi, Sue Power, Heather Barham, N Pathan, Jenna Ridout, Deborah White, Sarah Thurston, S Faust, S Patel, Jenni McCorkell, P Davies, Lindsey Crate, Helen Navarra, Stephanie Carter, R Ramaiah, Rekha Patel, Catherine Tuffrey, Andrew Gribbin, Sharon McCready, Mark Peters, Katie Hardy, Fran Standing, Lauren O’Neill, Eugenia Abelake, Akash Deep, Eniola Nsirim, A Pollard, Louise Willis, Zoe Young, C Royad, Sonia White, PM Fortune, Phil Hudnott, Federico Martinón-Torres, Antonio Salas, Fernando Álvez González, Ruth Barral-Arca, Miriam Cebey-López, María José CurrasTuala, Natalia García, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Andrea Grela Beiroa, Antonio Justicia Grande, Pilar Leboráns Iglesias, Alba Elena Martínez Santos, Nazareth Martinón-Torres, José María Martinón Sánchez, Beatriz Morillo Gutiérrez, Belén Mosquera Pérez, Pablo Obando Pacheco, Jacobo Pardo-Seco, Sara Pischedda, Irene Rivero Calle, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Antonio Salas Ellacuriaga, Sonia Serén Fernández, María del Sol Porto Silva, Ana Vega, Lucía Vilanova Trillo, Susana Beatriz Reyes, María Cruz León León, Álvaro Navarro Mingorance, Xavier Gabaldó Barrios, Eider Oñate Vergara, Andrés Concha Torre, Ana Vivanco, Reyes Fernández, Francisco Giménez Sánchez, Miguel Sánchez Forte, Pablo Rojo, J.Ruiz Contreras, Alba Palacios, Cristina Epalza Ibarrondo, Elizabeth Fernández Cooke, Marisa Navarro, Cristina Álvarez Álvarez, María José Lozano, Eduardo Carreras, Sonia Brió Sanagustín, Olaf Neth, Mª del Carmen Martínez Padilla, Luis Manuel Prieto Tato, Sara Guillén, Laura Fernández Silveira, David Moreno, R. de Groot, A.M. Tutu van Furth, M. van der Flier, N.P. Boeddha, G.J.A. Driessen, M. Emonts, J.A. Hazelzet, T.W. Kuijpers, D. Pajkrt, E.A.M. Sanders, D. van de Beek, A. van der Ende, H.L.A. Philipsen, A.O.A. Adeel, M.A. Breukels, D.M.C. Brinkman, C.C.M.M. de Korte, E. de Vries, W.J. de Waal, R. Dekkers, A. Dings-Lammertink, R.A. Doedens, A.E. Donker, M. Dousma, T.E. Faber, G.P.J.M. Gerrits, J.A.M. Gerver, J. Heidema, J. Homan-van der Veen, M.A.M. Jacobs, N.J.G. Jansen, P. Kawczynski, K. Klucovska, M.C.J. Kneyber, Y. Koopman-Keemink, V.J. Langenhorst, J. Leusink, B.F. Loza, I.T. Merth, C.J. Miedema, C. Neeleman, J.G. Noordzij, C.C. Obihara, A.L.T. van Overbeek – van Gils, G.H. Poortman, S.T. Potgieter, J. Potjewijd, P.P.R. Rosias, T. Sprong, G.W. ten Tussher, B.J. Thio, G.A. Tramper-Strander, M. van Deuren, H. van der Meer, A.J.M. van Kuppevelt, A.M. van Wermeskerken, W.A. Verwijs, T.F.W. Wolfs, Luregn J Schlapbach, Philipp Agyeman, Christoph Aebi, Eric Giannoni, Martin Stocker, Klara M Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Paul Hasters, Christa Relly, Walter Baer, Christoph Berger, Enitan Carrol, Stéphane Paulus, Hannah Frederick, Rebecca Jennings, Joanne Johnston, Rhian Kenwright, Colin G Fink, Elli Pinnock, Marieke Emonts, Rachel Agbeko, Suzanne Anderson, Fatou Secka, Kalifa Bojang, Isatou Sarr, Ngane Kebbeh, Gibbi Sey, Momodou Saidykhan, Fatoumatta Cole, Gilleh Thomas, Martin Antonio, Werner Zenz, Daniela S. Klobassa, Alexander Binder, Nina A. Schweintzger, Manfred Sagmeister, Hinrich Baumgart, Markus Baumgartner, Uta Behrends, Ariane Biebl, Robert Birnbacher, Jan-Gerd Blanke, Carsten Boelke, Kai Breuling, Jürgen Brunner, Maria Buller, Peter Dahlem, Beate Dietrich, Ernst Eber, Johannes Elias, Josef Emhofer, Rosa Etschmaier, Sebastian Farr, Ylenia Girtler, Irina Grigorow, Konrad Heimann, Ulrike Ihm, Zdenek Jaros, Hermann Kalhoff, Wilhelm Kaulfersch, Christoph Kemen, Nina Klocker, Bernhard Köster, Benno Kohlmaier, Eleni Komini, Lydia Kramer, Antje Neubert, Daniel Ortner, Lydia Pescollderungg, Klaus Pfurtscheller, Karl Reiter, Goran Ristic, Siegfried Rödl, Andrea Sellner, Astrid Sonnleitner, Matthias Sperl, Wolfgang Stelzl, Holger Till, Andreas Trobisch, Anne Vierzig, Ulrich Vogel, Christina Weingarten, Stefanie Welke, Andreas Wimmer, Uwe Wintergerst, Daniel Wüller, Andrew Zaunschirm, Ieva Ziuraite, and Veslava Žukovskaja

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

IMPORTANCE:. A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking. OBJECTIVES:. To study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome. DESIGN:. Data from two prospective cohort studies. SETTING AND PARTICIPANTS:. Cohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission). MAIN OUTCOMES AND MEASURES:. Primary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay. RESULTS:. In cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis. CONCLUSIONS AND RELEVANCE:. In children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms.

Published
2021
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5. Role and Diagnostic Performance of Host Epigenome in Respiratory Morbidity after RSV Infection: The EPIRESVi Study

Author

Sara Pischedda, Irene Rivero-Calle, Alberto Gómez-Carballa, Miriam Cebey-López, Ruth Barral-Arca, Jose Gómez-Rial, Jacobo Pardo-Seco, María-José Curras-Tuala, Sandra Viz-Lasheras, Xabier Bello, Ana B. Crujeiras, Angel Diaz-Lagares, María Teresa González-López, Federico Martinón-Torres, Antonio Salas, and GENDRES consortium

Subjects
RSV, DNA methylation, immune system, respiratory sequelae, recurrent wheezing, asthma, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundRespiratory syncytial virus (RSV) infection has been associated with the subsequent development of recurrent wheezing and asthma, although the mechanisms involved are still unknown. We investigate the role of epigenetics in the respiratory morbidity after infection by comparing methylation patterns from children who develop recurrent wheezing (RW-RSV), subsequent asthma (AS-RVS), and those experiencing complete recovery (CR-RSV).MethodsProspective, observational study of infants aged < 2 years with RSV respiratory infection admitted to hospital and followed-up after discharge for at least three years. According to their clinical course, patients were categorized into subgroups: RW-RSV (n = 36), AS-RSV (n = 9), and CR-RSV (n = 32). The DNA genome-wide methylation pattern was analyzed in whole blood samples, collected during the acute phase of the infection, using the Illumina Infinium Methylation EPIC BeadChip (850K CpG sites). Differences in methylation were determined through a linear regression model adjusted for age, gender and cell composition.ResultsPatients who developed respiratory sequelae showed a statistically significant higher proportion of NK and CD8T cells (inferred through a deconvolution approach) than those with complete recovery. We identified 5,097 significant differentially methylated positions (DMPs) when comparing RW-RSV and AS-RVS together against CR-RSV. Methylation profiles affect several genes involved in airway inflammation processes. The most significant DMPs were found to be hypomethylated in cases and therefore generally leading to overexpression of affected genes. The lead CpG position (cg24509398) falls at the gene body of EYA3 (P-value = 2.77×10-10), a tyrosine phosphatase connected with pulmonary vascular remodeling, a key process in the asthma pathology. Logistic regression analysis resulted in a diagnostic epigenetic signature of 3-DMPs (involving genes ZNF2698, LOC102723354 and RPL15/NKIRAS1) that allows to efficiently differentiate sequelae cases from CR-RSV patients (AUC = 1.00). Enrichment pathway analysis reveals the role of the cell cycle checkpoint (FDR P-value = 4.71×10-2), DNA damage (FDP-value = 2.53×10-2), and DNA integrity checkpoint (FDR P-value = 2.56×10-2) in differentiating sequelae from CR-RSV patients.ConclusionsEpigenetic mechanisms might play a fundamental role in the long-term sequelae after RSV infection, contributing to explain the different phenotypes observed.

Published
2022
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6. Seroprevalence of SARS-CoV-2 Among Pediatric Healthcare Workers in Spain

Author

Ana Dacosta-Urbieta, Irene Rivero-Calle, Jacobo Pardo-Seco, Lorenzo Redondo-Collazo, Antonio Salas, Jose Gómez-Rial, and Federico Martinón-Torres

Subjects
seroprevalance, COVID-19, healthcare worker (HCW), SARS-CoV-2, rapid test for COVID-19, Pediatrics, RJ1-570
Abstract

Spain is one of the countries most severely affected by the SARS-CoV-2 pandemic, with almost 190,000 cases as of April 18, 2020. As healthcare workers (HCW) are one of the groups hardest hit by the infection, it is important to know the seroprevalence of antibodies against SARS-CoV-2 in pediatric departments. We performed 175 immunoglobulin (Ig)M and IgG immunochromatographic rapid tests in the personnel working at the Pediatric Department of the Hospital Clínico Universitario of Santiago de Compostela (Spain), including pediatricians, residents, nurses, and other staff, on days 31–33 since the lockdown started. Seven out of the 175 tests were positive, including four for IgM and three for IgG, leading to a seroprevalence of 4.0% (95% CI: 1.1–6.9%). Only one of them had symptoms at the time of testing (sore throat). All seropositive cases yielded negative RT-PCR of the upper and lower respiratory tract. This is the first SARS-CoV-2 serological survey among HCWs reported in Spain. Notwithstanding the test limitations, our results reveal that personal protection policy and lockdown measures have been effective to limit population exposure. The low seroprevalence rate poses a significant challenge for the next strategic steps of pandemic control.

Published
2020
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7. Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology

Author

Jose Gómez-Rial, Maria José Currás-Tuala, Irene Rivero-Calle, Alberto Gómez-Carballa, Miriam Cebey-López, Carmen Rodríguez-Tenreiro, Ana Dacosta-Urbieta, Carmen Rivero-Velasco, Nuria Rodríguez-Núñez, Rocio Trastoy-Pena, Javier Rodríguez-García, Antonio Salas, and Federico Martinón-Torres

Subjects
COVID-19, monocyte, sCD14, sCD163, immunopathology, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundEmerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind.MethodsFifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group.ResultssCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not.ConclusionsMonocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients.

Published
2020
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8. TIPICO XI: report of the first series and podcast on infectious diseases and vaccines (aTIPICO)

Author

Shamez N Ladhani, Andrew J. Pollard, Carlos Martin, Michael J. Mina, Antonio Salas, James D. Cherry, F Xavier Bosch, Albert D. M. E. Osterhaus, Adolfo García-Sastre, Jose Gómez Rial, María Martinón-Torres, Octavio Ramilo, and Federico Martinón-Torres

Subjects
Pharmacology, medicine.medical_specialty, Tuberculosis, business.industry, SARS-CoV-2, education, Immunology, COVID-19, medicine.disease, medicine.disease_cause, Meningococcal disease, Measles, Communicable Diseases, Vaccination, Infectious disease (medical specialty), Influenza Vaccines, Family medicine, Pandemic, medicine, Immunology and Allergy, Humans, business, Pathogen, Pandemics, Coronavirus
Abstract

TIPiCO is an annual expert meeting and workshop on infectious diseases and vaccination. The edition of 2020 changed its name and format to aTIPiCO, the first series and podcasts on infectious diseases and vaccines. A total of 13 prestigious experts from different countries participated in this edition launched on the 26 November 2020. The state of the art of coronavirus disease-2019 (COVID-19) and the responsible pathogen, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the options to tackle the pandemic situation were discussed in light of the knowledge in November 2020. Despite COVID-19, the status of other infectious diseases, including influenza infections, respiratory syncytial virus disease, human papillomavirus infection, measles, pertussis, tuberculosis, meningococcal disease, and pneumococcal disease, were also addressed. The essential lessons that can be learned from these diseases and their vaccines to use in the COVID-19 pandemic were also commented with the experts. © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.

Published
2021

9. Role of Monocytes/Macrophages in Covid-19 Pathogenesis: Implications for Therapy

Author

Jose, Gómez-Rial, Irene, Rivero-Calle, Antonio, Salas, and Federico, Martinón-Torres

Subjects
viruses, coronavirus, Review, monocyte/macrophage, anti-GM-CSF, COVID-19 infection
Abstract

cov-Abstract Emerging studies from SARS-CoV-2-infected patients indicate a preponderant role of monocytes/macrophages in the pathogenesis of this viral infection, in a similar way to that previously observed in other coronavirus outbreaks (SARS and MERS). The clinical presentation of severe patients resembles viral-associated hemophagocytic syndrome, a rare condition previously seen during lethal influenza pandemics and during previous SARS and MERS coronavirus outbreaks. SARS-CoV-2 infection triggers an over-exuberant inflammatory response due to the development of a cytokine storm and the depletion of the adaptative immune compartment, which may prelude sepsis in many cases. The present review summarizes past evidence on the role of monocytes/macrophages in previous coronavirus outbreaks and the emerging knowledge on their role in COVID-19 pathogenesis. Treatment strategies incorporating the blockade of migration and differentiation of monocyte-macrophage, such as granulocyte macrophage-colony stimulating factor inhibitors, might enhance the promising results seen so far with selective cytokine blockade.

Published
2020

10. Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study

Author

Federico Martinón-Torres, Antonio Salas, Irene Rivero-Calle, Miriam Cebey-López, Jacobo Pardo-Seco, Jethro A Herberg, Navin P Boeddha, Daniela S Klobassa, Fatou Secka, Stephane Paulus, Ronald de Groot, Luregn J Schlapbach, Gertjan J Driessen, Suzanne T Anderson, Marieke Emonts, Werner Zenz, Enitan D Carrol, Michiel Van der Flier, Michael Levin, Lachlan Coin, Stuart Gormley, Shea Hamilton, Jethro Herberg, Bernardo Hourmat, Clive Hoggart, Myrsini Kaforou, Vanessa Sancho-Shimizu, Victoria Wright, Amina Abdulla, Paul Agapow, Maeve Bartlett, Evangelos Bellos, Hariklia Eleftherohorinou, Rachel Galassini, David Inwald, Meg Mashbat, Stefanie Menikou, Sobia Mustafa, Simon Nadel, Rahmeen Rahman, Clare Thakker, Sumit Bokhandi, Sue Power, Heather Barham, Nazima Pathan, Jenna Ridout, Deborah White, Sarah Thurston, Saul Faust, Sanjay Patel, Jenni McCorkell, Patrick Davies, Lindsey Crate, Helen Navarra, Stephanie Carter, Raghu Ramaiah, Rekha Patel, Catherine Tuffrey, Andrew Gribbin, Sharon McCready, Mark Peters, Katie Hardy, Fran Standing, Lauren O'Neill, Eugenia Abelake, Akash Deep, Eniola Nsirim, Andrew Pollard, Louise Willis, Zoe Young, C Royad, Sonia White, Peter Marc Fortune, Phil Hudnott, Antonio Salas Ellacuriaga, Fernando Álvez González, Ruth Barral-Arca, María José Curras-Tuala, Natalia García, Luisa García Vicente, Alberto Gómez-Carballa, Jose Gómez Rial, Andrea Grela Beiroa, Antonio Justicia Grande, Pilar Leboráns Iglesias, Alba Elena Martínez Santos, Nazareth Martinón-Torres, José María Martinón Sánchez, Beatriz Morillo Gutiérrez, Belén Mosquera Pérez, Pablo Obando Pacheco, Sara Pischedda, Carmen Rodríguez-Tenreiro, Lorenzo Redondo-Collazo, Sonia Serén Fernández, María del Sol Porto Silva, Ana Vega, Lucía Vilanova Trillo, Susana Beatriz Reyes, María Cruz León León, Álvaro Navarro Mingorance, Xavier Gabaldó Barrios, Eider Oñate Vergara, Andrés Concha Torre, Ana Vivanco, Reyes Fernández, Francisco Giménez Sánchez, Miguel Sánchez Forte, Pablo Rojo, Jesús Ruiz Contreras, Alba Palacios, Cristina Epalza Ibarrondo, Elizabeth Fernández Cooke, Marisa Navarro, Cristina Álvarez Álvarez, María José Lozano, Eduardo Carreras, Sonia Brió Sanagustín, Olaf Neth, María del Carmen Martínez Padilla, Luis Manuel Prieto Tato, Sara Guillén, Laura Fernández Silveira, David Moreno, A. Marceline van Furth, Michiel van der Flier, Navin Prekash Boeddha, Gertjan JA Driessen, Jan A Hazelzet, Taco W Kuijpers, Dasja Pajkrt, Elisabeth AM Sanders, Diederik van de Beek, Arie van der Ende, Ria LA Philipsen, Abdul OA Adeel, Meike A Breukels, Danielle MC Brinkman, Carla CMM de Korte, Esther de Vries, Wouter J de Waal, Roel Dekkers, Anouk Dings-Lammertink, Rienus A Doedens, Albertine E Donker, Mieke Dousma, Tina E Faber, G Peter JM Gerrits, Jan AM Gerver, Jojanneke Heidema, Jenneke Homan-van der Veen, Monique AM Jacobs, Nicolaas JG Jansen, Pawel Kawczynski, Kristine Klucovska, Martin CJ Kneyber, Yvonne Koopman-Keemink, Veerle J Langenhorst, José Leusink, Bettina F Loza, Istvan T Merth, Carien J Miedema, Chris Neeleman, Jeroen G Noordzij, Charles C Obihara, A Lidy T van Overbeek - van Gils, Geriska H Poortman, Steph T Potgieter, Joke Potjewijd, Philippe PR Rosias, Tom Sprong, Gavin W ten Tussher, Boony J Thio, Gerdien A Tramper-Stranders, Marcel van Deuren, Henny van der Meer, Andre JM van Kuppevelt, Anne-Marie van Wermeskerken, Wim A Verwijs, Tom FW Wolfs, Luregn Jan Schlapbach, Philipp Agyeman, Christoph Aebi, Christoph Berger, Eric Giannoni, Martin Stocker, Klara M Posfay-Barbe, Ulrich Heininger, Sara Bernhard-Stirnemann, Anita Niederer-Loher, Christian Kahlert, Paul Hasters, Christa Relly, Walter Baer, Enitan Carrol, Stéphane Paulus, Hannah Frederick, Rebecca Jennings, Joanne Johnston, Rhian Kenwright, Colin G Fink, Elli Pinnock, Rachel Sarah Agbeko, Kalifa A Bojang, Isatou Sarr, Ngange Kebbeh, Gibbi Sey, Momodou Saidykhan, Fatoumata Cole, Gilleh Thomas, Martin Antonio, Daniela Sabine Klobassa, Alexander Binder, Nina Alexandra Schweintzger, Manfred Sagmeister, Hinrich Baumgart, Markus Baumgartner, Uta Behrends, Ariane Biebl, Robert Birnbacher, Jan-Gerd Blanke, Carsten Boelke, Kai Breuling, Jürgen Brunner, Maria Buller, Peter Dahlem, Beate Dietrich, Ernst Eber, Johannes Elias, Josef Emhofer, Rosa Etschmaier, Sebastian Farr, Ylenia Girtler, Irina Grigorow, Konrad Heimann, Ulrike Ihm, Zdenek Jaros, Hermann Kalhoff, Wilhelm Kaulfersch, Christoph Kemen, Nina Klocker, Bernhard Köster, Benno Kohlmaier, Eleni Komini, Lydia Kramer, Antje Neubert, Daniel Ortner, Lydia Pescollderungg, Klaus Pfurtscheller, Karl Reiter, Goran Ristic, Siegfried Rödl, Andrea Sellner, Astrid Sonnleitner, Matthias Sperl, Wolfgang Stelzl, Holger Till, Andreas Trobisch, Anne Vierzig, Ulrich Vogel, Christina Weingarten, Stefanie Welke, Andreas Wimmer, Uwe Wintergerst, Daniel Wüller, Andrew Zaunschirm, Ieva Ziuraite, Veslava Žukovskaja, Posfay Barbe, Klara, Pediatrics, Huisarts & Ziekenhuis, Tranzo, Scientific center for care and wellbeing, ARD - Amsterdam Reproduction and Development, AII - Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, ANS - Neuroinfection & -inflammation, Neurology, Medical Microbiology and Infection Prevention, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), The European Society for Paediatric Infectious Diseases, Meningitis Research Foundation, Imperial College Healthcare NHS Trust- BRC Funding, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), University of Zurich, and Martinón-Torres, Federico

Subjects
Male, Pediatrics, RJ101, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Severity of Illness Index, Cohort Studies, 0302 clinical medicine, Cost of Illness, Developmental and Educational Psychology, 030212 general & internal medicine, Prospective Studies, Sepsis/epidemiology, Prospective cohort study, Child, media_common, ddc:618, Bacterial Infections, Europe, Child, Preschool, Cohort, Female, Algorithms, Cohort study, medicine.medical_specialty, 610 Medicine & health, Europe/epidemiology, Sepsis, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, 030225 pediatrics, Severity of illness, medicine, media_common.cataloged_instance, Humans, 2735 Pediatrics, Perinatology and Child Health, European union, Preschool, Disease burden, 3204 Developmental and Educational Psychology, business.industry, Infant, Newborn, Infant, medicine.disease, Newborn, Pneumonia, 10036 Medical Clinic, Pediatrics, Perinatology and Child Health, business, Bacterial Infections/epidemiology
Abstract

Background Sepsis and severe focal infections represent a substantial disease burden in children admitted to hospital. We aimed to understand the burden of disease and outcomes in children with life-threatening bacterial infections in Europe. Methods The European Union Childhood Life-threatening Infectious Disease Study (EUCLIDS) was a prospective, multicentre, cohort study done in six countries in Europe. Patients aged 1 month to 18 years with sepsis (or suspected sepsis) or severe focal infections, admitted to 98 participating hospitals in the UK, Austria, Germany, Lithuania, Spain, and the Netherlands were prospectively recruited between July 1, 2012, and Dec 31, 2015. To assess disease burden and outcomes, we collected demographic and clinical data using a secured web-based platform and obtained microbiological data using locally available clinical diagnostic procedures. Findings 2844 patients were recruited and included in the analysis. 1512 (53·2%) of 2841 patients were male and median age was 39·1 months (IQR 12·4–93·9). 1229 (43·2%) patients had sepsis and 1615 (56·8%) had severe focal infections. Patients diagnosed with sepsis had a median age of 27·6 months (IQR 9·0–80·2), whereas those diagnosed with severe focal infections had a median age of 46·5 months (15·8–100·4; pInterpretation Mortality in children admitted to hospital for sepsis or severe focal infections is low in Europe. The disease burden is mainly in children younger than 5 years and is largely due to vaccine-preventable meningococcal and pneumococcal infections. Despite the availability and application of clinical procedures for microbiological diagnosis, the causative organism remained unidentified in approximately 50% of patients.

Published
2018
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11. Whole Exome Sequencing reveals new candidate genes in host genomic susceptibility to Respiratory Syncytial Virus Disease

Author

Jacobo Pardo-Seco, Laura Moreno-Galarraga, Rosaura Leis, Lorenzo Redondo Collazo, Sara Pischedda, Ignacio Oulego-Erroz, Jorge Amigo, MARIA LUZ GARCIA-GARCIA, Pablo Obando-Pacheco, Cristina Calvo, Federico Martinon-Torres, Irene Rivero Calle, Ruth Barral Arca, Jose Gómez Rial, Beatriz Morillo Gutierrez, Alberto Gómez-Carballa, María José Currás Tuala, Antonio Salas, Máximo Fraga Rodríguez, and Miriam Cebey-López

Subjects
0301 basic medicine, Candidate gene, lcsh:Medicine, Respiratory Syncytial Virus Infections, Biology, Genome, Polymorphism, Single Nucleotide, Virus, Article, Whole Exome Sequencing, 03 medical and health sciences, 0302 clinical medicine, Exome Sequencing, medicine, Humans, Genetic Predisposition to Disease, 1000 Genomes Project, lcsh:Science, Gene, Exome, Exome sequencing, Genetic Association Studies, Genetics, Multidisciplinary, Genome, Human, lcsh:R, Infant, Newborn, Infant, medicine.disease, Virology, 030104 developmental biology, Gene Ontology, Bronchiolitis, Case-Control Studies, Respiratory Syncytial Virus, Human, Host-Pathogen Interactions, lcsh:Q, 030217 neurology & neurosurgery
Abstract

Respiratory syncytial virus (RSV) is an important cause of serious lower respiratory tract disease in infants. Several studies have shown evidence pointing to the genome of the host as an important factor determining susceptibility to respiratory disease caused by RSV. We sequenced the complete exomes of 54 patients infected by RSV that needed hospitalization due to development of severe bronchiolitis. The Iberian sample (IBS) from The 1000 Genomes Project (1000G) was used as control group; all the association results were pseudo-replicated using other 1000G-European controls and Spanish controls. The study points to SNP rs199665292 in the olfactory receptor (OR) gene OR13C5 as the best candidate variant (P-value = 1.16 × 10−12; OR = 5.56). Genetic variants at HLA genes (HLA-DQA1, HLA-DPB1), and in the mucin 4 gene (MUC4) also emerge as susceptibility candidates. By collapsing rare variants in genes and weighing by pathogenicity, we obtained confirmatory signals of association in the OR gene OR8U1/OR8U8, the taste receptor TAS2R19, and another mucin gene (MUC6). Overall, we identified new predisposition variants and genes related to RSV infection. Of special interest is the association of RSV to olfactory and taste receptors; this finding is in line with recent evidence pointing to their role in viral infectious diseases.

Published
2017

12. Characterisation of the blood RNA host response underpinning severity in COVID-19 patients

Author

Heather Jackson, Irene Rivero Calle, Claire Broderick, Dominic Habgood-Coote, Giselle D’Souza, Samuel Nichols, Ortensia Vito, Jose Gómez-Rial, Carmen Rivero-Velasco, Nuria Rodríguez-Núñez, Gema Barbeito-Castiñeiras, Hugo Pérez-Freixo, Manuel Barreiro-de Acosta, Aubrey J. Cunnington, Jethro A. Herberg, Victoria J. Wright, Alberto Gómez-Carballa, Antonio Salas, Michael Levin, Federico Martinon-Torres, Myrsini Kaforou, PERFORM consortium, and GEN-COVID (www.gencovid.eu) study group

Subjects
Medicine, Science
Abstract

Abstract Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. In this study, for the first time, we show how immunomodulatory treatments commonly administered to COVID-19 patients greatly alter the transcriptome. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.

Published
2022
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13. TIPICO X: report of the 10th interactive infectious disease workshop on infectious diseases and vaccines

Author

Irene Rivero-Calle, Jose Gómez-Rial, Louis Bont, Bradford D. Gessner, Melvin Kohn, Ron Dagan, Daniel C. Payne, Laia Bruni, Andrew J. Pollard, Adolfo García-Sastre, Denise L. Faustman, Albert Osterhaus, Robb Butler, Francisco Giménez Sánchez, Francisco Álvarez, Myrsini Kaforou, Xabier Bello, and Federico Martinón-Torres

Subjects
infectious disease, vaccine-preventable diseases, off-target effects, emergent virus, zoonoses, rna gene signatures, transcriptomics, big data, vaccine hesitancy, vaccine resilience, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950
Abstract

TIPICO is an expert meeting and workshop that aims to provide the most recent evidence in the field of infectious diseases and vaccination. The 10th Interactive Infectious Disease TIPICO workshop took place in Santiago de Compostela, Spain, on November 21–22, 2019. Cutting-edge advances in vaccination against respiratory syncytial virus, Streptococcus pneumoniae, rotavirus, human papillomavirus, Neisseria meningitidis, influenza virus, and Salmonella Typhi were discussed. Furthermore, heterologous vaccine effects were updated, including the use of Bacillus Calmette-Guérin (BCG) vaccine as potential treatment for type 1 diabetes. Finally, the workshop also included presentations and discussion on emergent virus and zoonoses, vaccine resilience, building and sustaining confidence in vaccination, approaches to vaccine decision-making, pros and cons of compulsory vaccination, the latest advances in decoding infectious diseases by RNA gene signatures, and the application of big data approaches.

Published
2021
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