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1. Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells

Author: Rosado-Olivieri, E.A., primary, Razooky, B., additional, Le Pen, J., additional, De Santis, R., additional, Barrows, D., additional, Sabry, Z., additional, Hoffmann, H.-H., additional, Park, J., additional, Carroll, T.S., additional, Poirier, J.T., additional, Rice, C.M., additional, and Brivanlou, A.H., additional
Published: 2023
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2. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author: Zhang Q., Liu Z., Moncada-Velez M., Chen J., Ogishi M., Bigio B., Yang R., Arias A. A., Zhou Q., Han J. E., Ugurbil A. C., Zhang P., Rapaport F., Li J., Spaan A. N., Boisson B., Boisson-Dupuis S., Bustamante J., Puel A., Ciancanelli M. J., Zhang S. -Y., Beziat V., Jouanguy E., Abel L., Cobat A., Casanova J. -L., Bastard P., Korol C., Rosain J., Philippot Q., Chbihi M., Lorenzo L., Bizien L., Neehus A. -L., Kerner G., Seeleuthner Y., Manry J., Le Voyer T., Le Pen J., Schneider W. M., Razooky B. S., Hoffmann H. -H., Michailidis E., Rice C. M., Sabli I. K. D., Hodeib S., Sancho-Shimizu V., Bilguvar K., Ye J., Maniatis T., Bolze A., Zhang Y., Notarangelo L. D., Su H. C., Onodi F., Korniotis S., Karpf L., Soumelis V., Bonnet-Madin L., Amara A., Dorgham K., Gorochov G., Smith N., Duffy D., Moens L., Meyts I., Meade P., Garcia-Sastre A., Krammer F., Corneau A., Masson C., Schmitt Y., Schluter A., Pujol A., Khan T., Marr N., Fellay J., Roussel L., Vinh D. C., Shahrooei M., Alosaimi M. F., Alsohime F., Hasanato R., Mansouri D., Al-Saud H., Almourfi F., Al-Mulla F., Al-Muhsen S. Z., Al Turki S., van de Beek D., Biondi A., Bettini L. R., D'Angio M., Bonfanti P., Imberti L., Sottini A., Paghera S., Quiros-Roldan E., Rossi C., Oler A. J., Tompkins M. F., Alba C., Dalgard C. L., Vandernoot I., Smits G., Goffard J. -C., Migeotte I., Haerynck F., Soler-Palacin P., Martin-Nalda A., Colobran R., Morange P. -E., Keles S., Colkesen F., Ozcelik T., Yasar K. K., Senoglu S., Karabela S. N., Rodriguez-Gallego C., Novelli G., Hraiech S., Tandjaoui-Lambiotte Y., Duval X., Laouenan C., Snow A. L., Milner J. D., Mogensen T. H., Nussenzweig M., Lifton R. P., Foti G., Bellani G., Citerio G., Contro E., Pesci A., Valsecchi M. G., Cazzaniga M., Abad J., Blanco I., Rodrigo C., Aguilera-Albesa S., Akcan O. M., Darazam I. A., Aldave J. C., Ramos M. A., Nadji S. A., Alkan G., Allardet-Servent J., Allende L. M., Alsina L., Alyanakian M. -A., Amador-Borrero B., Mouly S., Sene D., Amoura Z., Mathian A., Antoli A., Blanch G. R., Riera J. S., Moreno X. S., Arslan S., Assant S., Auguet T., Azot A., Bajolle F., Levy R., Oualha M., Baldolli A., Ballester M., Feldman H. B., Barrou B., Beurton A., Bilbao A., Blanchard-Rohner G., Blandinieres A., Rivet N., Blazquez-Gamero D., Bloomfield M., Bolivar-Prados M., Clave P., Borie R., Bosteels C., Lambrecht B. N., van Braeckel E., Bousfiha A. A., Bouvattier C., Vincent A., Boyarchuk O., Bueno M. R. P., Castro M. V., Matos L. R. B., Zatz M., Agra J. J. C., Calimli S., Capra R., Carrabba M., Fabio G., Casasnovas C., Velez-Santamaria V., Caseris M., Falck A., Poncelet G., Castelle M., Castelli F., de Vera M. C., Catherinot E., Chalumeau M., Toubiana J., Charbit B., Li Z., Pellegrini S., Cheng M. P., Clotet B., Codina A., Comarmond C., Dalmau D., Darley D. R., Dauby N., Dauger S., Le Bourgeois F., Levy M., de Pontual L., Dehban A., Delplancq G., Demoule A., Diehl J. -L., Dobbelaere S., Durand S., Mircher C., Rebillat A. -S., Vilaire M. E., Eldars W., Elgamal M., Elnagdy M. H., Emiroglu M., Erdeniz E. H., Aytekin S. E., Euvrard R., Evcen R., Faivre L., Fartoukh M., Faure M., Arquero M. F., Flores C., Francois B., Fumado V., Fusco F., Ursini M. V., Solis B. G., de Diego R. P., van Den Rym A. M., Gaussem P., Gil-Herrera J., Gilardin L., Alarcon M. G., Girona-Alarcon M., Gok F., Yosunkaya A., Gonzalez-Montelongo R., Inigo-Campos A., Lorenzo-Salazar J. M., Munoz-Barrera A., Guerder A., Gul Y., Guner S. N., Gut M., Hadjadj J., Halwani R., Hammarstrom L., Hatipoglu N., Hernandez-Brito E., Heijmans C., Holanda-Pena M. S., Horcajada J. P., Hoste L., Hoste E., Humbert L., Mordacq C., Thumerelle C., Vuotto F., Iglesias A. D., Jamme M., Arranz M. J., Jordan I., Jorens P., Kanat F., Kapakli H., Kara I., Karbuz A., Demirkol Y. K., Klocperk A., Krol Z. J., Kuentz P., Kwan Y. W. M., Lagier J. -C., Lau Y. -L., Leung D., Leo Y. -S., Young B. E., Lopez R. L., Levin M., Linglart A., Loeys B., Louapre C., Lubetzki C., Luyt C. -E., Lye D. C., Marjani M., Pereira J. M., Martin A., Pueyo D. M., Martinez-Picado J., Marzana I., Matthews G. V., Mayaux J., Parizot C., Quentric P., Mege J. -L., Raoult D., Melki I., Meritet J. -F., Metin O., Mezidi M., Taccone F., Millereux M., Mirault T., Mirsaeidi M., Melian A. M., Martinez A. M., Morange P., Morelle G., Naesens L., Nafati C., Neves J. F., Ng L. F. P., Medina Y. N., Cuadros E. N., Gonzalo Ocejo-Vinyals J., Orbak Z., Pan-Hammarstrom Q., Pascreau T., Paz-Artal E., Philippe A., Planas-Serra L., Ploin D., Viel S., Poissy J., Pouletty M., Reisli I., Ricart P., Richard J. -C., Riviere J. G., Rodriguez-Palmero A., Romero C. S., Rothenbuhler A., Rozenberg F., del Prado M. Y. R., Sanchez O., Sanchez-Ramon S., Schmidt M., Schweitzer C. E., Scolari F., Sediva A., Seijo L. M., Seppanen M. R. J., Ilovich A. S., Slabbynck H., Smadja D. M., Sobh A., Sole-Violan J., Soler C., Stepanovskiy Y., Stoclin A., Taupin J. -L., Tavernier S. J., Terrier B., Tomasoni G., Alvarez J. T., Trouillet-Assant S., Troya J., Tucci A., Uzunhan Y., Vabres P., Valencia-Ramos J., van de Velde S., van Praet J., Vatansev H., Vilain C., Voiriot G., Yucel F., Zannad F., Belot A., Bole-Feysot C., Lyonnet S., Nitschke P., Pouliet A., Tores F., Zarhrate M., Andrejak C., Angoulvant F., Bachelet D., Bhavsar K., Bouadma L., Chair A., Couffignal C., Silveira C. D., Debray M. -P., Eloy P., Esposito-Farese M., Ettalhaoui N., Gault N., Ghosn J., Gorenne I., Hoffmann I., Kafif O., Kali S., Khalil A., Laribi S., Le M., Le Hingrat Q., Lescure F. -X., Lucet J. C., Mentre F., Mullaert J., Peiffer-Smadja N., Peytavin G., Roy C., Schneider M., Mohammed N. S., Tagherset L., Tardivon C., Tellier M. -C., Timsit J. -F., Trioux T., Tubiana S., Basmaci R., Behillil S., Beluze M., Benkerrou D., Dorival C., Meziane A., Teoule F., Bompart F., Bouscambert M., Gaymard A., Lina B., Rosa-Calatrava M., Terrier O., Caralp M., Cervantes-Gonzalez M., D'Ortenzio E., Puechal O., Semaille C., Coelho A., Diouf A., Hoctin A., Mambert M., Couffin-Cadiergues S., Deplanque D., Descamps D., Visseaux B., Desvallees M., Khan C., Diallo A., Mercier N., Paul C., Petrov-Sanchez V., Dubos F., Enouf V. V. E., Mouquet H., Esperou H., Jaafoura S., Papadopoulos A., Etienne M., Gigante T., Rossignol B., Guedj J., Le Nagard H., Lingas G., Neant N., Kaguelidou F., Levy Y., Wiedemann A., Levy-Marchal C., Malvy D., Noret M., Pages J., Picone O., Rossignol P., Tual C., Veislinger A., van der Werf S., Vanel N., Yazdanpanah Y., Alavoine L., Costa Y., Ecobichon J. -L., Frezouls W., Ilic-Habensus E., Leclercq A., Lehacaut J., Letrou S., Mandic M., Nouroudine M., Quintin C., Rexach J., Vignali V., Amat K. K. A., Enouf V., Bielicki J., Bruijning P., Burdet C., Caumes E., Charpentier C., Damond F., Coignard B., Delmas C., Roufai L., Dechanet A., Houhou N., Kikoine J., Manchon P., Piquard V., Postolache A., Terzian Z., Lebeaux D., Lucet J. -C., Meghadecha M., Motiejunaite J., Thy M., van Agtmael M., Bomers M., Chouchane O., Geerlings S., Goorhuis B., Grobusch M. P., Harris V., Hermans S. M., Hovius J. W., Nellen J., Peters E., van der Poll T., Prins J. M., Reijnders T., Schinkel M., Sigaloff K., Stijnis C. S., van der Valk M., van Vugt M., Joost Wiersinga W., Algera A. G., van Baarle F., Bos L., Botta M., de Bruin S., Bulle E., Elbers P., Fleuren L., Girbes A., Hagens L., Heunks L., Horn J., van Mourik N., Paulus F., Raasveld J., Schultz M. J., Smit M., Stilma W., Thoral P., Tsonas A., de Vries H., Bax D., Cloherty A., Beudel M., Brouwer M. C., Koning R., Bogaard H. J., de Brabander J., de Bree G., Bugiani M., Geerts B., Hollmann M. W., Preckel B., Veelo D., Geijtenbeek T., Hafkamp F., Hamann J., Hemke R., de Jong M. D., Schuurman A., Teunissen C., Vlaar A. P. J., Wouters D., Zwinderman A. H., Aiuti A., Muhsen S. A., Anderson M. S., Bogunovic D., Itan Y., Cirulli E., Barrett K. S., Washington N., Bondarenko A., Brodin P., Bryceson Y., Bustamante C. D., Butte M., Casari G., Chakravorty S., Christodoulou J., Le Mestre S., Condino-Neto A., Cooper M. A., David A., DeRisi J. L., Desai M., Drolet B. A., Espinosa S., Franco J. L., Gregersen P. K., Hagin D., Heath J., Henrickson S. E., Hsieh E., Imai K., Karamitros T., Kisand K., Ku C. -L., Ling Y., Lucas C. L., Marodi L., Milner J., Mironska K., Mogensen T., Morio T., Novelli A., O'Farrelly C., Okada S., Planas A. M., Prando C., Quintana-Murci L., Renia L., Renieri A., Sankaran V., Snow A., Tangye S., Turvey S., Uddin F., Uddin M. J., Vazquez S. E., von Bernuth H., Zawadzki P., Jing H., Tung W., Meguro K., Shaw E., Shafer S., Zheng L., Zhang Z., Kubo S., Chauvin S. D., Lenardo M., Luthers C. R., Bauman B. M., Lack J., Karlins E., Hupalo D. M., Rosenberger J., Sukumar G., Wilkerson M. D., Zhang X., Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), R01AI088364, National Institutes of Health, Howard Hughes Medical Institute, UL1 TR001866, NIH Clinical and Translational Science Award, fast grant, Emergent Ventures, St. Giles Foundation, National Center for Advancing Translational Sciences, Rockefeller University, ANR-10-IAHU-01, Agence Nationale de la Recherche, UM1HG006504 and U24HG008956, National Human Genome Research Institute, ANR-10-LABX-62-IBEID, the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, EQU201903007798, the French Foundation for Medical Research, Özçelik, Tayfun, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Virologie (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-17-CE15-0003,DENDRISEPSIS,Analyse systémique des cellules présentatrices d'antigène dans le sepsis humain(2017), ANR-20-COVI-0025,iCovid,Immunopathologie du COVID-19 à l'Assistance Publique Hôpitaux de Paris(2020), Zhang, Qian, Bastard, Paul, Le Pen, Jeremie, Moncada-Velez, Marcela, Ogishi, Masato, Sabli, Ira K. D., Hodeib, Stephanie, Korol, Cecilia, Bilguvar, Kaya, Bolze, Alexandre, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Smith, Nikaïa, Schneider, William M., Razooky, Brandon S., Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Han, Jin Eun, Lorenzo, Lazaro, Bizien, Lucy, Meade, Philip, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Kerner, Gaspard, Zhang, Peng, Rapaport, Franck, Manry, Jérémy, Masson, Cecile, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Fellay, Jacques, Roussel, Lucie, Alosaimi, Mohammed F., Al-Mulla, Fahd, Almourfi, Feras, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, Beek, Diederik van der, Bettini, Laura Rachele, Bonfanti, Paolo, Oler, Andrew J., Tompkins, Miranda F., Alba, Camille, Smits, Guillaume, Soler-Palacín, Pere, Martin-Nalda, Andrea, Colobran, Roger, Çölkesen, Fatma, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Rodríguez-Gallego, Carlos, Novelli, Giuseppe, Tandjaoui-Lambiotte, Yacine, Laouénan, Cédric, Zhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, Ogishi, M, Sabli, I, Hodeib, S, Korol, C, Rosain, J, Bilguvar, K, Ye, J, Bolze, A, Bigio, B, Yang, R, Arias, A, Zhou, Q, Zhang, Y, Onodi, F, Korniotis, S, Karpf, L, Philippot, Q, Chbihi, M, Bonnet-Madin, L, Dorgham, K, Smith, N, Schneider, W, Razooky, B, Hoffmann, H, Michailidis, E, Moens, L, Han, J, Lorenzo, L, Bizien, L, Meade, P, Neehus, A, Ugurbil, A, Corneau, A, Kerner, G, Zhang, P, Rapaport, F, Seeleuthner, Y, Manry, J, Masson, C, Schmitt, Y, Schlüter, A, Le Voyer, T, Khan, T, Li, J, Fellay, J, Roussel, L, Shahrooei, M, Alosaimi, M, Mansouri, D, Al-Saud, H, Al-Mulla, F, Almourfi, F, Al-Muhsen, S, Alsohime, F, Al Turki, S, Hasanato, R, van de Beek, D, Biondi, A, Bettini, L, D'Angio, M, Bonfanti, P, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Oler, A, Tompkins, M, Alba, C, Vandernoot, I, Goffard, J, Smits, G, Migeotte, I, Haerynck, F, Soler-Palacin, P, Martin-Nalda, A, Colobran, R, Morange, P, Keles, S, Çölkesen, F, Ozcelik, T, Yasar, K, Senoglu, S, Karabela, Ş, Gallego, C, Novelli, G, Hraiech, S, Tandjaoui-Lambiotte, Y, Duval, X, Laouénan, C, Snow, A, Dalgard, C, Milner, J, Vinh, D, Mogensen, T, Marr, N, Spaan, A, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, M, Meyts, I, Maniatis, T, Soumelis, V, Amara, A, Nussenzweig, M, García-Sastre, A, Krammer, F, Pujol, A, Duffy, D, Lifton, R, Zhang, S, Gorochov, G, Béziat, V, Jouanguy, E, Sancho-Shimizu, V, Rice, C, Abel, L, Notarangelo, L, Cobat, A, Su, H, Casanova, J, Pesci, A, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Infectious diseases, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, ACS - Microcirculation, UKRI Future Leader's Fellowship, Internal medicine, Pulmonary medicine, Intensive care medicine, Pathology, Medical Microbiology and Infection Prevention, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Neuroinfection & -inflammation, Laboratory Medicine, APH - Quality of Care, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic Effort, NIAID-USUHS/TAGC COVID Immunity Group, Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Abad, J., Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Amoura, Z., Antolí, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, M., Borie, R., Bosteels, C., Bousfiha, A.A., Bouvattier, C., Boyarchuk, O., Bueno, MRP, Bustamante, J., Cáceres Agra, J.J., Calimli, S., Capra, R., Carrabba, M., Casasnovas, C., Caseris, M., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Catherinot, E., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Colkesen, F., Çölkesen, F., Colobran, R., Comarmond, C., Dalmau, D., Darley, D.R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Diehl, J.L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Flores, C., Francois, B., Fumadó, V., Fusco, F., Solis, B.G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Goffard, J.C., Gok, F., González-Montelongo, R., Guerder, A., Gul, Y., Guner, S.N., Gut, M., Hadjadj, J., Haerynck, F., Halwani, R., Hammarström, L., Hatipoglu, N., Hernandez-Brito, E., Heijmans, C., Holanda-Peña, M.S., Horcajada, J.P., Hoste, L., Hoste, E., Hraiech, S., Humbert, L., Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jordan, I., Jorens, P., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K.K., Keles, S., Demirkol, Y.K., Klocperk, A., Król, Z.J., Kuentz, P., Kwan, YWM, Lagier, J.C., Lambrecht, B.N., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Linglart, A., Loeys, B., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Luyt, C.E., Lye, D.C., Mansouri, D., Marjani, M., Pereira, J.M., Martin, A., Pueyo, D.M., Martinez-Picado, J., Marzana, I., Mathian, A., Matos, LRB, Matthews, G.V., Mayaux, J., Mège, J.L., Melki, I., Meritet, J.F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melián, A.M., Martinez, A.M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Muñoz-Barrera, A., Naesens, L., Nafati, C., Neves, J.F., Ng, LFP, Medina, Y.N., Cuadros, E.N., Ocejo-Vinyals, J.G., Orbak, Z., Oualha, M., Özçelik, T., Pan-Hammarström, Q., Parizot, C., Pascreau, T., Paz-Artal, E., Pellegrini, S., de Diego, R.P., Philippe, A., Philippot, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A.S., Reisli, I., Ricart, P., Richard, J.C., Rivet, N., Rivière, J.G., Blanch, G.R., Rodrigo, C., Rodriguez-Gallego, C., Rodríguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Rozenberg, F., Ruiz Del Prado, M.Y., Riera, J.S., Sanchez, O., Sánchez-Ramón, S., Schluter, A., Schmidt, M., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L.M., Sene, D., Senoglu, S., Seppänen, MRJ, Ilovich, A.S., Shahrooei, M., Slabbynck, H., Smadja, D.M., Sobh, A., Moreno, X.S., Solé-Violán, J., Soler, C., Soler-Palacín, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiotte, Y., Taupin, J.L., Tavernier, S.J., Terrier, B., Thumerelle, C., Tomasoni, G., Toubiana, J., 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Rodríguez-Gallego, C., Sancho-Shimizu, V., Sankaran, V., Barrett, K.S., Snow, A., Spaan, A.N., Tangye, S., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., Vinh, D.C., von Bernuth, H., Washington, N., Zawadzki, P., Su, H.C., Casanova, J.L., Jing, H., Tung, W., Luthers, C.R., Bauman, B.M., Shafer, S., Zheng, L., Zhang, Z., Kubo, S., Chauvin, S.D., Meguro, K., Shaw, E., Lenardo, M., Lack, J., Karlins, E., Hupalo, D.M., Rosenberger, J., Sukumar, G., Wilkerson, M.D., Zhang, X., Children's Hospital, HUS Children and Adolescents, Clinicum, Department of Medicine, Zhang, Q., Liu, Z., Moncada-Velez, M., Chen, J., Ogishi, M., Bigio, B., Yang, R., Arias, A. A., Zhou, Q., Han, J. E., Ugurbil, A. C., Zhang, P., Rapaport, F., Li, J., Spaan, A. N., Boisson, B., Boisson-Dupuis, S., Puel, A., Ciancanelli, M. J., Zhang, S. -Y., Beziat, V., Jouanguy, E., Cobat, A., Casanova, J. -L., Bastard, P., Korol, C., Rosain, J., Chbihi, M., Lorenzo, L., Bizien, L., Neehus, A. -L., Kerner, G., Seeleuthner, Y., Manry, J., Le Voyer, T., Le Pen, J., Schneider, W. M., Razooky, B. S., Hoffmann, H. -H., Michailidis, E., Rice, C. M., Sabli, I. K. D., Hodeib, S., Bilguvar, K., Ye, J., Zhang, Y., Notarangelo, L. D., Su, H. C., Onodi, F., Korniotis, S., Karpf, L., Soumelis, V., Bonnet-Madin, L., Amara, A., Dorgham, K., Gorochov, G., Smith, N., Duffy, D., Moens, L., Meade, P., Garcia-Sastre, A., Krammer, F., Corneau, A., Khan, T., Marr, N., Roussel, L., Vinh, D. C., Alosaimi, M. F., Alsohime, F., Hasanato, R., Al-Saud, H., Almourfi, F., Al-Muhsen, S. Z., Al Turki, S., Biondi, A., Bettini, L. R., D'Angio, M., Bonfanti, P., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Oler, A. J., Tompkins, M. F., Alba, C., Dalgard, C. L., Smits, G., Goffard, J. -C., Soler-Palacin, P., Martin-Nalda, A., Morange, P. -E., Yasar, K. K., Karabela, S. N., Laouenan, C., Snow, A. L., Milner, J. D., Mogensen, T. H., Nussenzweig, M., Lifton, R. P., Valsecchi, M. G., Akcan, O. M., Darazam, I. A., Aldave, J. C., Ramos, M. A., Nadji, S. A., Allende, L. M., Alyanakian, M. -A., Antoli, A., Blanch, G. R., Riera, J. S., Moreno, X. S., Levy, R., Feldman, H. B., Blandinieres, A., Clave, P., Lambrecht, B. N., van Braeckel, E., Bousfiha, A. A., Bueno, M. R. P., Castro, M. V., Matos, L. R. B., Agra, J. J. C., Velez-Santamaria, V., de Vera, M. C., Cheng, M. P., Darley, D. R., Diehl, J. -L., Rebillat, A. -S., Vilaire, M. E., Elnagdy, M. H., Erdeniz, E. H., Aytekin, S. E., Arquero, M. F., Fumado, V., Ursini, M. V., Solis, B. G., de Diego, R. P., van Den Rym, A. M., Alarcon, M. G., Girona-Alarcon, M., Gonzalez-Montelongo, R., Inigo-Campos, A., Lorenzo-Salazar, J. M., Munoz-Barrera, A., Guner, S. N., Hammarstrom, L., Holanda-Pena, M. S., Horcajada, J. P., Iglesias, A. D., Arranz, M. J., Demirkol, Y. K., Krol, Z. J., Kwan, Y. W. M., Lagier, J. -C., Lau, Y. -L., Leo, Y. -S., Young, B. E., Lopez, R. L., Luyt, C. -E., Lye, D. C., Pereira, J. M., Pueyo, D. M., Matthews, G. V., Mege, J. -L., Meritet, J. -F., Melian, A. M., Martinez, A. M., Neves, J. F., Ng, L. F. P., Medina, Y. N., Cuadros, E. N., Gonzalo Ocejo-Vinyals, J., Pan-Hammarstrom, Q., Richard, J. -C., Riviere, J. G., Rodriguez-Palmero, A., Romero, C. S., del Prado, M. Y. R., Sanchez-Ramon, S., Schweitzer, C. E., Seijo, L. M., Seppanen, M. R. J., Ilovich, A. S., Smadja, D. M., Sole-Violan, J., Taupin, J. -L., Tavernier, S. J., Alvarez, J. T., van de Velde, S., van Praet, J., Silveira, C. D., Debray, M. -P., Lescure, F. -X., Lucet, J. C., Mentre, F., Mohammed, N. S., Tellier, M. -C., Timsit, J. -F., Teoule, F., Puechal, O., Desvallees, M., Enouf, V. V. E., Levy, Y., Ecobichon, J. -L., Amat, K. K. A., Lucet, J. -C., Grobusch, M. P., Hermans, S. M., Hovius, J. W., Prins, J. M., Stijnis, C. S., Joost Wiersinga, W., Algera, A. G., Schultz, M. J., Brouwer, M. C., Bogaard, H. J., Hollmann, M. W., de Jong, M. D., Vlaar, A. P. J., Zwinderman, A. H., Muhsen, S. A., Anderson, M. S., Barrett, K. S., Bustamante, C. D., Cooper, M. A., Derisi, J. L., Drolet, B. A., Franco, J. L., Gregersen, P. K., Henrickson, S. E., Ku, C. -L., Lucas, C. L., Planas, A. M., Uddin, M. J., Vazquez, S. E., Chauvin, S. D., Luthers, C. R., Bauman, B. M., Hupalo, D. M., Wilkerson, M. D., Zhang, Qian [0000-0002-9040-3289], Bastard, Paul [0000-0002-5926-8437], Le Pen, Jeremie [0000-0001-7025-9526], Moncada-Velez, Marcela [0000-0002-3073-5345], Ogishi, Masato [0000-0003-2421-7389], Sabli, Ira K. D. [0000-0002-0170-2990], Hodeib, Stephanie [0000-0002-5978-6189], Korol, Cecilia [0000-0002-0023-8823], Bilguvar, Kaya [0000-0002-7313-7652], Bolze, Alexandre [0000-0001-7399-2766], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Arias, Andrés Augusto [0000-0002-9478-8403], Zhou, Qinhua [0000-0002-5112-3727], Chbihi, Marwa [0000-0002-2771-851X], Bonnet-Madin, Lucie [0000-0002-9848-3287], Dorgham, Karim [0000-0001-9539-3203], Smith, Nikaïa [0000-0002-0202-612X], Schneider, William M. [0000-0001-9407-6118], Razooky, Brandon S. [0000-0002-5263-1512], Hoffmann, Hans-Heinrich [0000-0003-0554-0244], Michailidis, Eleftherios [0000-0002-9907-4346], Han, Jin Eun [0000-0003-1112-9320], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Meade, Philip [0000-0002-6754-7209], Neehus, Anna-Lena [0000-0002-8573-6820], Ugurbil, Aileen Camille [0000-0002-9450-3092], Kerner, Gaspard [0000-0003-0146-9428], Zhang, Peng [0000-0002-6129-567X], Rapaport, Franck [0000-0001-6553-2110], Manry, Jérémy [0000-0001-5998-2051], Masson, Cecile [0000-0001-7870-7821], Schlüter, Agatha [0000-0001-6732-1528], Le Voyer, Tom [0000-0002-0630-8626], Khan, Taushif [0000-0002-7917-8965], Fellay, Jacques [0000-0002-8240-939X], Roussel, Lucie [0000-0001-5355-702X], Alosaimi, Mohammed F. [0000-0002-8025-3491], Al-Mulla, Fahd [0000-0001-5409-3829], Almourfi, Feras [0000-0002-5166-4662], Alsohime, Fahad [0000-0002-4979-3895], Al Turki, Saeed [0000-0001-7017-336X], Hasanato, Rana [0000-0002-4697-2222], Beek, Diederik van der [0000-0002-4571-044X], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Oler, Andrew J. [0000-0002-6310-0434], Tompkins, Miranda F. [0000-0003-2941-7515], Alba, Camille [0000-0002-0458-1629], Smits, Guillaume [0000-0003-2845-6758], Soler-Palacín, Pere [0000-0002-0346-5570], Martin-Nalda, Andrea [0000-0002-3590-0186], Colobran, Roger [0000-0002-5964-536X], Çölkesen, Fatma [0000-0001-9545-5179], Yasar, Kadriye Kart [0000-0003-2963-4894], Senoglu, Sevtap [0000-0003-4796-9583], Karabela, Şemsi Nur [0000-0003-2562-3004], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Novelli, Giuseppe [0000-0002-7781-602X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], and Laouénan, Cédric [0000-0002-3681-6314]
Subjects: Male, COVID19, Interferon Regulatory Factor-7, [SDV]Life Sciences [q-bio], NF-KAPPA-B, Receptor, Interferon alpha-beta, SUSCEPTIBILITY, susceptibility, Interferon alpha-beta, CoV-Contact Cohort, 0302 clinical medicine, Interferon, Loss of Function Mutation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 80 and over, Medicine and Health Sciences, Viral, Online, Imagine COVID Group, Child, Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Asymptomatic Infections, Betacoronavirus, COVID-19, Child, Preschool, Coronavirus Infections/genetics, Coronavirus Infections/immunology, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Infant, Interferon Regulatory Factor-7/deficiency, Interferon Regulatory Factor-7/genetics, Interferon Type I/immunology, Middle Aged, Pandemics, Pneumonia, Viral/genetics, Pneumonia, Viral/immunology, Receptor, Interferon alpha-beta/deficiency, Receptor, Interferon alpha-beta/genetics, SARS-CoV-2, Toll-Like Receptor 3/deficiency, Toll-Like Receptor 3/genetics, Young Adult, Research Articles, 0303 health sciences, Multidisciplinary, COVID Clinicians, deficiency, 3. Good health, Multidisciplinary Sciences, DEFICIENCY, Settore MED/03, 030220 oncology & carcinogenesis, Interferon Type I, Science & Technology - Other Topics, medicine.symptom, Coronavirus Infections, Receptor, medicine.drug, NIAID-USUHS, Research Article, General Science & Technology, HERPES-SIMPLEX ENCEPHALITIS, French COVID Cohort Study Group, Pneumonia, Viral, Immunology, Asymptomatic, Virus, 03 medical and health sciences, Immunity, nf-kappa-b, medicine, Genetics, Preschool, COVID Human Genetic Effort, 030304 developmental biology, Biobank, Science & Technology, business.industry, R-Articles, TAGC COVID Immunity Group, Médecine pathologie humaine, herpes-simplex encephalitis, Pneumonia, Amsterdam UMC Covid-19, medicine.disease, COVID-STORM Clinicians, Toll-Like Receptor 3, 3121 General medicine, internal medicine and other clinical medicine, IRF7, 3111 Biomedicine, business, Interferon type I, Interferon regulatory factors
Abstract: COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani 1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT, COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Cédric Bosteels33, Ahmed A. Bousfiha34, Claire Bouvattier35, Oksana Boyarchuk36, Maria Rita P. Bueno37, Jacinta Bustamante20, Juan José Cáceres Agra38, Semra Calimli39, Ruggero Capra40, Maria Carrabba41, Carlos Casasnovas42, Marion Caseris43, Martin Castelle44, Francesco Castelli45, Martín Castillo de Vera46, Mateus V. Castro37, Emilie Catherinot47, Martin Chalumeau48, Bruno Charbit49, Matthew P. Cheng50, Père Clavé31, Bonaventura Clotet51, Anna Codina52, Fatih Colkesen53, Fatma Çölkesen54, Roger Colobran55, Cloé Comarmond56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Jean-Luc Diehl65, Stephanie Dobbelaere66, Sophie Durand67, Waleed Eldars68, Mohamed Elgamal69, Marwa H. Elnagdy70, Melike Emiroglu71, Emine Hafize Erdeniz72, Selma Erol Aytekin73, Romain Euvrard74, Recep Evcen75, Giovanna Fabio41, Laurence Faivre76, Antonin Falck43, Muriel Fartoukh77, Morgane Faure78, Miguel Fernandez Arquero79, Carlos Flores80, Bruno Francois81, Victoria Fumadó82, Francesca Fusco83, Blanca Garcia Solis84, Pascale Gaussem85, Juana Gil-Herrera86, Laurent Gilardin87, Monica Girona Alarcon88, Mònica Girona-Alarcón88, Jean-Christophe Goffard89, Funda Gok90, Rafaela González-Montelongo91, Antoine Guerder92, Yahya Gul93, Sukru Nail Guner93, Marta Gut94, Jérôme Hadjadj95, Filomeen Haerynck96, Rabih Halwani97, Lennart Hammarström98, Nevin Hatipoglu99, Elisa Hernandez-Brito100, Cathérine Heijmans101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Levi Hoste104, Eric Hoste105, Sami Hraiech106, Linda Humbert107, Alejandro D. Iglesias108, Antonio Íñigo-Campos91, Matthieu Jamme109, María Jesús Arranz110, Iolanda Jordan111, Philippe Jorens112, Fikret Kanat113, Hasan Kapakli114, Iskender Kara115, Adem Karbuz116, Kadriye Kart Yasar117, Sevgi Keles118, Yasemin Kendir Demirkol119, Adam Klocperk120, Zbigniew J. Król121, Paul Kuentz122, Yat Wah M. Kwan123, Jean-Christophe Lagier124, Bart N. Lambrecht33, Yu-Lung Lau125, Fleur Le Bourgeois60, Yee-Sin Leo126, Rafael Leon Lopez127, Daniel Leung125, Michael Levin128, Michael Levy60, Romain Lévy20, Zhi Li49, Agnes Linglart129, Bart Loeys130, José M. Lorenzo-Salazar91, Céline Louapre131, Catherine Lubetzki131, Charles-Edouard Luyt132, David C. Lye133, Davood Mansouri134, Majid Marjani135, Jesus Marquez Pereira136, Andrea Martin137, David Martínez Pueyo138, Javier Martinez-Picado139, Iciar Marzana140, Alexis Mathian14, Larissa R. B. Matos37, Gail V. Matthews141, Julien Mayaux142, Jean-Louis Mège143, Isabelle Melki144, Jean-François Meritet145, Ozge Metin146, Isabelle Meyts147, Mehdi Mezidi148, Isabelle Migeotte149, Maude Millereux150, Tristan Mirault151, Clotilde Mircher67, Mehdi Mirsaeidi152, Abián Montesdeoca Melián153, Antonio Morales Martinez154, Pierre Morange155, Clémence Mordacq107, Guillaume Morelle156, Stéphane Mouly13, Adrián Muñoz-Barrera91, Leslie Naesens157, Cyril Nafati158, João Farela Neves159, Lisa FP. Ng160, Yeray Novoa Medina161, Esmeralda Nuñez Cuadros162, J. Gonzalo Ocejo-Vinyals163, Zerrin Orbak164, Mehdi Oualha20, Tayfun Özçelik165, Qiang Pan-Hammarström166, Christophe Parizot142, Tiffany Pascreau167, Estela Paz-Artal168, Sandra Pellegrini49, Rebeca Pérez de Diego84, Aurélien Philippe169, Quentin Philippot77, Laura Planas-Serra170, Dominique Ploin171, Julien Poissy172, Géraldine Poncelet43, Marie Pouletty173, Paul Quentric142, Didier Raoult143, Anne-Sophie Rebillat67, Ismail Reisli174, Pilar Ricart175, Jean-Christophe Richard176, Nadia Rivet28, Jacques G. Rivière177, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego178, Agustí Rodríguez-Palmero179, Carolina Soledad Romero180, Anya Rothenbuhler181, Flore Rozenberg182, Maria Yolanda Ruiz del Prado183, Joan Sabater Riera15, Oliver Sanchez184, Silvia Sánchez-Ramón185, Agatha Schluter170, Matthieu Schmidt186, Cyril E. Schweitzer187, Francesco Scolari188, Anna Sediva189, Luis M. Seijo190, Damien Sene13, Sevtap Senoglu117, Mikko R. J. Seppänen191, Alex Serra Ilovich192, Mohammad Shahrooei62, Hans Slabbynck193, David M. Smadja194, Ali Sobh195, Xavier Solanich Moreno15, Jordi Solé-Violán196, Catherine Soler197, Pere Soler-Palacín137, Yuri Stepanovskiy198, Annabelle Stoclin199, Fabio Taccone149, Yacine Tandjaoui-Lambiotte200, Jean-Luc Taupin201, Simon J. Tavernier202, Benjamin Terrier203, Caroline Thumerelle107, Gabriele Tomasoni204, Julie Toubiana48, Josep Trenado Alvarez205, Sophie Trouillet-Assant206, Jesús Troya207, Alessandra Tucci208, Matilde Valeria Ursini‬83, Yurdagul Uzunhan209, Pierre Vabres210, Juan Valencia-Ramos211, Eva Van Braeckel33, Stijn Van de Velde212, Ana Maria Van Den Rym84, Jens Van Praet213, Isabelle Vandernoot214, Hulya Vatansev215, Valentina Vélez-Santamaria42, Sébastien Viel171, Cédric Vilain216, Marie E. Vilaire67, Audrey Vincent35, Guillaume Voiriot217, Fanny Vuotto107, Alper Yosunkaya90, Barnaby E. Young126, Fatih Yucel218, Faiez Zannad219, Mayana Zatz37, Alexandre Belot220*, Imagine COVID Group Christine Bole-Feysot, Stanislas Lyonnet*, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID Group., French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric D’Ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent VE Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Trioux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases Initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, Paris, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22CHU Rouen–SMIT, Rouen, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d’Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28CHU de Bordeaux–SMIT, Bordeaux, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Hôpital Louis Mourier–Gynécologie, Colombes, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35Hôpital la Timone, Marseille, France. 36Bichat–SMIT, Paris, France., CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cadiergues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d’Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M’Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children’s Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris, France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France. 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, Bordeaux, France. 16Hôpital Hotel Dieu, APHP, Paris, France. 17Service des Explorations Fonctionnelles, Hôpital Bichat–Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve de Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P.J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek4* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC Consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Alessia David21, Joseph L. DeRisi22, Murkesh Desai23, Beth A. Drolet24, Sara Espinosa25, Jacques Fellay26, Carlos Flores27, Jose Luis Franco28, Peter K. Gregersen29, Filomeen Haerynck30, David Hagin31, Rabih Halwani32, Jim Heath33, Sarah E. Henrickson34, Elena Hsieh35, Kohsuke Imai36, Yuval Itan8, Timokratis Karamitros37, Kai Kisand38, Cheng-Lung Ku39, Yu-Lung Lau40, Yun Ling41, Carrie L. Lucas42, Tom Maniatis43, Davoud Mansouri44, Laszlo Marodi45, Isabelle Meyts46, Joshua Milner47, Kristina Mironska48, Trine Mogensen49, Tomohiro Morio50, Lisa FP. Ng51, Luigi D. Notarangelo52, Antonio Novelli53, Giuseppe Novelli54, Cliona O’Farrelly55, Satoshi Okada56, Tayfun Ozcelik57, Rebeca Perez de Diego58, Anna M. Planas59, Carolina Prando60, Aurora Pujol61, Lluis Quintana-Murci62, Laurent Renia63, Alessandra Renieri64, Carlos Rodríguez-Gallego65, Vanessa Sancho-Shimizu66, Vijay Sankaran67, Kelly Schiabor Barrett9, Mohammed Shahrooei68, Andrew Snow69, Pere Soler-Palacín70, András N. Spaan71, Stuart Tangye72, Stuart Turvey73, Furkan Uddin74, Mohammed J. Uddin75, Diederik van de Beek76, Sara E. Vazquez77, Donald C. Vinh78, Horst von Bernuth79, Nicole Washington9, Pawel Zawadzki80, Helen C. Su52, Jean-Laurent Casanova81 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Departement, Faculty of Medicine and Pharmacy, Averroes University Hospital; LICIA Laboratoire d’Immunologie Clinique, d’Inflammation et d’Allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory University Department of Pediatrics and Children’s Healthcare of Atlanta, Atlanta, GA, USA. 17Murdoch Children’s Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21Centre for Bioinformatics and System Biology, Department of Life Sciences, Imperial College London, South Kensington Campus, London, UK. 22University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. 23Bai Jerbai Wadia Hospital for Children, Mumbai, India. 24School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 25Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 26Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 27Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 28University of Antioquia, Medellín, Colombia. 29Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 30Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 31The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 32Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 33Institute for Systems Biology, Seattle, WA, USA. 34Children’s Hospital of Philadelphia, Philadelphia, PA, USA. 35Anschutz Medical Campus, Aurora, CO, USA. 36Riken, Tokyo, Japan. 37Hellenic Pasteur Institute, Athens, Greece. 38University of Tartu, Tartu, Estonia. 39Chang Gung University, Taoyuan County, Taiwan. 40The University of Hong Kong, Hong Kong, China. 41Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 42Yale School of Medicine, New Haven, CT, USA. 43New York Genome Center, New York, NY, USA. 44Shahid Beheshti University of Medical Sciences, Tehran, Iran. 45Semmelweis University Budapest, Budapest, Hungary. 46KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 47Columbia University Medical Center, New York, NY, USA. 48University Clinic for Children’s Diseases, Skopje, North Macedonia. 49Aarhus University, Aarhus, Denmark. 50Tokyo Medical & Dental University Hospital, Tokyo, Japan. 51Singapore Immunology Network, Singapore. 52National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 53Bambino Gesù Children’s Hospital, Rome, Italy. 54Department of Biomedicine and Prevention, University of Rome “Tor Vergata,” Rome, Italy. 55Trinity College, Dublin, Ireland. 56Hiroshima University, Hiroshima, Japan. 57Bilkent University, Ankara, Turkey. 58Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 59IIBB-CSIC, IDIBAPS, Barcelona, Spain. 60Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 61Neurometabolic Diseases Laboratory, IDIBELL–Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 62Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 63Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 64Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Italy; GEN-COVID Multicenter Study. 65Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Canary Islands, Spain. 66Imperial College London, London, UK. 67Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA. 68Saeed Pathobiology and Genetic Lab, Tehran, Iran. 69Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 70Hospital Universitari Vall d’Hebron, Barcelona, Spain. 71University Medical Center Utrecht, Amsterdam, The Netherlands. 72Garvan Institute of Medical Research, Sydney, Australia. 73The University of British Columbia, Vancouver, Canada. 74Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children’s Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children’s Healthcare, Dhaka, Bangladesh. 75Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 76Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, The Netherlands. 77University of California, San Francisco, CA, USA. 78McGill University Health Centre, Montreal, Canada. 79Charité–Berlin University Hospital Center, Berlin, Germany. 80Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 81Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., NIAID-USUHS/TAGC COVID Immunity Group Huie Jing1,2, Wesley Tung1,2, Christopher R. Luthers3, Bradly M. Bauman3, Samantha Shafer2,4, Lixin Zheng2,4, Zinan Zhang2,4, Satoshi Kubo2,4, Samuel D. Chauvin2,4, Kazuyuki Meguro1,2, Elana Shaw1,2, Michael Lenardo2,4, Justin Lack5, Eric Karlins6, Daniel M. Hupalo7, John Rosenberger7, Gauthaman Sukumar7, Matthew D. Wilkerson7, Xijun Zhang7 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD, USA. 3Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 4Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 5NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. 6Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 7The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection., We thank the generous donation from Fisher Center for Alzheimer’s Research Foundation for our research. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Paris. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”), and the Intramural Research Program of the NIAID, NIH. The laboratory of Genomes & Cell Biology of Disease is supported by “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID), the “Fondation pour la Recherche Medicale” (grant FRM - EQU202003010193), the “Agence Nationale de la Recherche” (ANR FLASH COVID project IDISCOVR cofounded by the “Fondation pour la Recherche Médicale”), University of Paris (“Plan de Soutien Covid-19”: RACPL20FIR01-COVID-SOUL). IM is a senior clinical investigator with the FWO Vlaanderen; IM and LM are supported by FWO G0C8517N – GOB5120N. The VS team was supported by “Agence Nationale de la Recherche” (ANR-17-CE15-0003, ANR-17-CE15-0003-01), and by Université de Paris “PLAN D’URGENCE COVID19”. LK was supported by a fellowship from the French Ministry of Research. VS-S is supported by a UKRI Future Leaders Fellowship (MR/S032304/1). SZA-M is supported by the Elite Journals Program at King Saud University through grant number PEJP-16-107. JM lab is supported by Columbia University COVID biobank and grant: UL1TR001873. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. JLP is supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). Work at the Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 824110 (EasiGenomics grant COVID-19/ PID12342) to A.P., and Roche and Illumina Covid Match Funds to M.G.. C.R.G and colleagues are supported by cInstituto de Salud Carlos III (COV20_01333 and COV20_01334), Spanish Ministry of Science and Innovation, with the funding of European Regional Development Fund-European Social Fund -FEDER-FSE; (RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. Helen Su is adjunct faculty at the University of Pennsylvania. A-L.N. was supported by the Foundation Bettencourt Schueller. The Amsterdam UMC Covid-19 Biobank was funded by the Netherlands Organization for Health Research and Development (ZonMw, NWO-vici 91819627), The Corona Research Fund (Amsterdam UMC), Dr. J. C. Vaillantfonds, and Amsterdam UMC. Work on COVID-19 at the AG-S lab is partly supported by NIH supplements to grants U19AI135972, U19AI142733 and R35 HL135834, and to contract HHSN272201800048C, by a DoD supplement to grant W81XWH-20-1-0270, by DARPA project HR0011-19-2-0020, by CRIP (Center for Research on Influenza Pathogenesis), a NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400008C), by an NIAID funded Collaborative Influenza Vaccine Innovation Center (SEM-CIVIC, contract 75N93019C00051) and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611(5384)) and anonymous donors. The Virscan analysis presented in fig. S11 was performed with financial support from Sidra Medicine
Published: 2020

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

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

4. Human hepatocyte PNPLA3 148M exacerbates rapid non-alcoholic steatohepatitis development in chimeric mice

Author: Luis Chiriboga, de Jong Yp, Le Pen J, Gadi Lalazar, Neil D. Theise, Eleftherios Michailidis, Zou C, Briana Zeck, Hiroshi Suemizu, Brandon S. Razooky, Serkan Belkaya, Alison W. Ashbrook, Robert Copenhaver, Ansgar F. Stenzel, Corrine Quirk, Markus Grompe, Sandra Steensels, Lander Foquet, William M. Schneider, Yupu Liang, Inna Ricardo-Lax, Meredith E. Pittman, Devisscher L, Mohanmmad Kabbani, David E. Cohen, Baran A. Ersoy, Clifton G. Fulmer, Charles M. Rice, Tardelli M, Joseph M. Luna, and Philip Meuleman
Subjects: medicine.medical_specialty, Methionine, business.industry, Fatty liver, Microvesicular Steatosis, Phospholipase, medicine.disease, Impaired glucose tolerance, chemistry.chemical_compound, Endocrinology, chemistry, Fibrosis, Internal medicine, medicine, Steatohepatitis, business, Dyslipidemia
Abstract: Advanced non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging global health problem associated with pre-disposing genetic polymorphisms, most strikingly an isoleucine to methionine substitution in patatin-like phospholipase domain-containing protein 3 (PNPLA3-I148M). Here, we study how human hepatocytes with PNPLA3 148I and 148M variants engrafted in the livers of chimeric mice respond to a hypercaloric Western-style diet. As early as 4 weeks, mice developed dyslipidemia, impaired glucose tolerance, and steatohepatitis selectively in the human graft, followed by pericellular fibrosis after 8 weeks of hypercaloric feeding. The PNPLA3 148M variant, either from a homozygous 148M human donor or overexpressed in a homozygous 148I donor background, caused widespread microvesicular steatosis and even more severe steatohepatitis. We conclude that PNPLA3 148M in human hepatocytes exacerbates NAFLD. These models will facilitate mechanistic studies into human genetic variants associated with advanced fatty liver diseases.
Published: 2020

5. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author: Zhang, Q, Liu, Z, Moncada-Velez, M, Chen, J, Ogishi, M, Bigio, B, Yang, R, Arias, AA, Zhou, Q, Han, JE, Ugurbil, AC, Zhang, P, Rapaport, F, Li, J, Spaan, AN, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, MJ, Zhang, SY, Béziat, V, Jouanguy, E, Abel, L, Cobat, A, Casanova, JL, Bastard, P, Korol, C, Rosain, J, Philippot, Q, Chbihi, M, Lorenzo, L, Bizien, L, Neehus, AL, Kerner, G, Seeleuthner, Y, Manry, J, Le Voyer, T, Le Pen, J, Schneider, WM, Razooky, BS, Hoffmann, HH, Michailidis, E, Rice, CM, Sabli, IKD, Hodeib, S, Sancho-Shimizu, V, Bilguvar, K, Ye, J, Maniatis, T, Bolze, A, Zhang, Y, Notarangelo, LD, Su, HC, Onodi, F, Korniotis, S, Karpf, L, Soumelis, V, Bonnet-Madin, L, Amara, A, Dorgham, K, Gorochov, G, Smith, N, Duffy, D, Moens, L, Meyts, I, Zhang, Q, Liu, Z, Moncada-Velez, M, Chen, J, Ogishi, M, Bigio, B, Yang, R, Arias, AA, Zhou, Q, Han, JE, Ugurbil, AC, Zhang, P, Rapaport, F, Li, J, Spaan, AN, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, MJ, Zhang, SY, Béziat, V, Jouanguy, E, Abel, L, Cobat, A, Casanova, JL, Bastard, P, Korol, C, Rosain, J, Philippot, Q, Chbihi, M, Lorenzo, L, Bizien, L, Neehus, AL, Kerner, G, Seeleuthner, Y, Manry, J, Le Voyer, T, Le Pen, J, Schneider, WM, Razooky, BS, Hoffmann, HH, Michailidis, E, Rice, CM, Sabli, IKD, Hodeib, S, Sancho-Shimizu, V, Bilguvar, K, Ye, J, Maniatis, T, Bolze, A, Zhang, Y, Notarangelo, LD, Su, HC, Onodi, F, Korniotis, S, Karpf, L, Soumelis, V, Bonnet-Madin, L, Amara, A, Dorgham, K, Gorochov, G, Smith, N, Duffy, D, Moens, L, and Meyts, I
Abstract: Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
Published: 2020

6. Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Author: Bastard, P, Rosen, LB, Zhang, Q, Michailidis, E, Hoffmann, HH, Zhang, Y, Dorgham, K, Philippot, Q, Rosain, J, Béziat, V, Manry, J, Shaw, E, Haljasmägi, L, Peterson, P, Lorenzo, L, Bizien, L, Trouillet-Assant, S, Dobbs, K, de Jesus, AA, Belot, A, Kallaste, A, Catherinot, E, Tandjaoui-Lambiotte, Y, Le Pen, J, Kerner, G, Bigio, B, Seeleuthner, Y, Yang, R, Bolze, A, Spaan, AN, Delmonte, OM, Abers, MS, Aiuti, A, Casari, G, Lampasona, V, Piemonti, L, Ciceri, F, Bilguvar, K, Lifton, RP, Vasse, M, Smadja, DM, Migaud, M, Hadjadj, J, Terrier, B, Duffy, D, Quintana-Murci, L, van de Beek, D, Roussel, L, Vinh, DC, Tangye, SG, Haerynck, F, Dalmau, D, Martinez-Picado, J, Brodin, P, Nussenzweig, MC, Boisson-Dupuis, S, Rodríguez-Gallego, C, Vogt, G, Mogensen, TH, Oler, AJ, Gu, J, Burbelo, PD, Cohen, JI, Biondi, A, Bettini, LR, DÁngio, M, Bonfanti, P, Rossignol, P, Mayaux, J, Rieux-Laucat, F, Husebye, ES, Fusco, F, Ursini, MV, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Castagnoli, R, Montagna, D, Licari, A, Marseglia, GL, Duval, X, Ghosn, J, Tsang, JS, Goldbach-Mansky, R, Kisand, K, Lionakis, MS, Puel, A, Zhang, SY, Holland, SM, Gorochov, G, Jouanguy, E, Rice, CM, Cobat, A, Notarangelo, LD, Abel, L, Su, HC, Casanova, JL, Arias, AA, Bastard, P, Rosen, LB, Zhang, Q, Michailidis, E, Hoffmann, HH, Zhang, Y, Dorgham, K, Philippot, Q, Rosain, J, Béziat, V, Manry, J, Shaw, E, Haljasmägi, L, Peterson, P, Lorenzo, L, Bizien, L, Trouillet-Assant, S, Dobbs, K, de Jesus, AA, Belot, A, Kallaste, A, Catherinot, E, Tandjaoui-Lambiotte, Y, Le Pen, J, Kerner, G, Bigio, B, Seeleuthner, Y, Yang, R, Bolze, A, Spaan, AN, Delmonte, OM, Abers, MS, Aiuti, A, Casari, G, Lampasona, V, Piemonti, L, Ciceri, F, Bilguvar, K, Lifton, RP, Vasse, M, Smadja, DM, Migaud, M, Hadjadj, J, Terrier, B, Duffy, D, Quintana-Murci, L, van de Beek, D, Roussel, L, Vinh, DC, Tangye, SG, Haerynck, F, Dalmau, D, Martinez-Picado, J, Brodin, P, Nussenzweig, MC, Boisson-Dupuis, S, Rodríguez-Gallego, C, Vogt, G, Mogensen, TH, Oler, AJ, Gu, J, Burbelo, PD, Cohen, JI, Biondi, A, Bettini, LR, DÁngio, M, Bonfanti, P, Rossignol, P, Mayaux, J, Rieux-Laucat, F, Husebye, ES, Fusco, F, Ursini, MV, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Castagnoli, R, Montagna, D, Licari, A, Marseglia, GL, Duval, X, Ghosn, J, Tsang, JS, Goldbach-Mansky, R, Kisand, K, Lionakis, MS, Puel, A, Zhang, SY, Holland, SM, Gorochov, G, Jouanguy, E, Rice, CM, Cobat, A, Notarangelo, LD, Abel, L, Su, HC, Casanova, JL, and Arias, AA
Abstract: Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
Published: 2020

7. Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Author: Bastard, P., Zhang, Q., Michailidis, E., Hoffmann, H.H., Zhang, Y., Dorgham, Karim, Philippot, Q., Rosain, J., Béziat, V., Manry, J., Shaw, E., Haljasmägi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A.A., Belot, A., Kallaste, A., Catherinot, E., Tandjaoui-Lambiotte, Y., Le Pen, J., Kerner, G., Bigio, B., Seeleuthner, Y., Yang, R., Bolze, A., Spaan, A.N., Delmonte, O.M., Abers, M.S., Aiuti, A., Casari, G., Lampasona, V., Piemonti, L., Ciceri, F., Bilguvar, K., Lifton, R.P., Vasse, M., Smadja, D.M., Migaud, M., Hadjadj, J., Terrier, B., Duffy, D., Quintana-Murci, L., van de Beek, D., Roussel, L., Vinh, D.C., Tangye, S., Haerynck, F., Dalmau, D., Martinez-Picado, J., Brodin, P., Nussenzweig, M.C., Boisson-Dupuis, S., Rodríguez-Gallego, C., Vogt, G., Mogensen, T.H., Oler, A.J., Gu, J., Burbelo, P.D., Cohen, J.I., Biondi, A., Bettini, L.R., DÁngio, M., Bonfanti, P., Rossignol, P., Mayaux, J., Rieux-Laucat, F., Husebye, E.S., Fusco, F., Ursini, M.V., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Castagnoli, R., Montagna, D., Licari, A., Marseglia, G.L., Duval, X., Ghosn, J., Tsang, J.S., Goldbach-Mansky, R., Kisand, K., Lionakis, M.S., Puel, A., Zhang, S.Y., Holland, S.M., Gorochov, G., Jouanguy, E., Rice, C.M., Cobat, A., Notarangelo, L.D., Abel, L., Su, H.C., Casanova, J.L., Arias, A.A., Boisson, B., Boucherit, S., Bustamante, J., Chbihi, M., Chen, J., Chrabieh, M., Kochetkov, T., Le Voyer, T., Liu, D., Nemirovskaya, Y., Ogishi, M., Papandrea, D., Patissier, C., Rapaport, F., Roynard, M., Vladikine, N., Woollett, M., Zhang, P., Kashyap, A., Ding, L., Bosticardo, M., Wang, Q., Ochoa, S., Liu, H., Chauvin, S.D., Stack, M., Koroleva, G., Bansal, N., Dalgard, C.L., Snow, A.L., Abad Capa, Jorge, Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Amoura, Z., Antolí, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, Mireia, Borie, R., Bousfiha, A.A., Bouvattier, C., Boyarchuk, O., Bueno, M.R.P., Agra, J.J.C., Calimli, S., Capra, R., Carrabba, M., Casasnovas, Carlos, Caseris, M., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Colkesen, F., Colobrán Oriol, Roger, Comarmond, C., Corsico, A.G., Darley, D.R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Di Sabatino, A., Diehl, J.L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Flores, Carlos, Francois, B., Fumadó, V., Solis, B.G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Goffard, J.C., Gok, F., González-Montelongo, R., Guerder, A., Gul, Y., Guner, S.N., Gut, M., Halwani, R., Hammarström, L., Hatipoglu, N., Hernandez-Brito, E., Holanda-Peña, M.S., Horcajada, J.P., Hraiech, S., Humbert, L., Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jordan, I., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K.K., Keles, S., Demirkol, Y.K., Klocperk, A., Król, Z.J., Kuentz, P., Kwan, Y.W.M., Lagier, J.C., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Linglart, A., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Luyt, C.E., Lye, D.C., Mansouri, D., Marjani, M., Pereira, J.M., Martin, A., Pueyo, D.M., Marzana, I., Mathian, A., Matos, L.R.B., Matthews, G.V., Mège, J.L., Melki, I., Meritet, J.F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melián, A.M., Martinez, A.M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Muñoz-Barrera, A., Nafati, C., Neves, J.F., Ng, L.F.P., Medina, Y.N., Cuadros, E.N., Gonzalo Ocejo-Vinyals, J., Orbak, Z., Oualha, M., Ozcelik, T., Hammarström, Q.P., Parizot, C., Pascreau, T., Paz-Artal, E., de Diego, R.P., Philippe, A., Philippota, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A.S., Reisli, I., Ricart, P., Richard, J.C., Rivet, N., Rivière, J.G., Blanch, G.R., Rodrigo, C., Rodriguez-Gallego, C., Rodríguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Rozenberg, F., del Prado, M.Y.R., Riera, J.S., Sanchez, O., Sánchez-Ramón, S., Schluter, A., Schmidt, M., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L.M., Sene, D., Senoglu, S., Seppänen, M.R.J., Ilovich, A.S., Shahrooei, M., Smadja, D., Sobh, A., Moreno, X.S., Solé-Violán, J., Soler, C., Soler-Palacín, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiottea, Y., Taupin, J.L., Tavernier, S.J., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J.T., Trouillet-Assanta, S., Troya, J., Tucci, A., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., van Den Rym, A.M., Vandernoot, I., Vatansev, H., Vélez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M.E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B.E., Yucel, F., Zannad, F., Zatz, M., Belota, A., Foti, Giuseppe, Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abela, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'ortenzio, E., da Silveira, C., Debray, M.P., Deplanque, D., Descamps, D., Desvallées, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Eloy, P., Enouf, V.V.E., Espérou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouénan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F.X., Lévy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J.C., Malvy, D., Mambert, M., Mentré, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Roy, C., Schneider, M., Semaille, C., Mohammed, N.S., Tagherset, L., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Treoux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Abelc, L., Alcover, A., Aschard, H., Astrom, K., Bousso, P., Bruhns, P., Cumano, A., Demangel, C., Deriano, L., Santo, J.D., Dromer, F., Eberl, G., Enninga, J., Fellay, Jacques, Gomperts-Boneca, I., Hasan, M., Hercberg, S., Lantz, O., Patin, E., Pellegrini, S., Pol, S., Rausell, A., Rogge, L., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M.N., Albert, M.L., Alavoine, L., Amat, K.K.A., Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J.L., Enouf, V., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A.G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bos, Lieuwe D, Botta, M., de Brabander, J., Bree, G., Brouwer, M.C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M.W., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J.M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M.J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C.S., Stilma, Willemke, Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, A.P.J., de Vries, H., van Vugt, M., Joost Wiersinga, W., Wouters, D., Zwinderman, A.H., Abelb, L., Iuti, F., Muhsen, S.A., Al-Mulla, F., Anderson, M.S., Bogunovic, D., Bondarenko, A., Bryceson, Y., Bustamante, C.D., Butte, M., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M.A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Franco, J.L., Gregersen, P.K., Hagin, D., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisanda, K., Ku, C.L., Ling, Y., Lucas, C.L., Maniatis, T., Marodi, L., Milner, J.D., Mironska, K., Morio, T., Notarangeloa, L.D., Novelli, G., Novelli, A., O'Farrelly, C., Okada, S., Planas, A.M., Prando, C., Pujol, A., Renia, L., Renieri, A., Sancho-Shimizu, V., Sankaran, V., Barrett, K.S., Snow, A., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., von Bernuth, H., Washington, N., Zawadzki, P., Sua, H.C., Casanovaa, J.L., Rosen, L.B., Universitat Autònoma de Barcelona, Bastard, P., Zhang, Q., Michailidis, E., Hoffmann, H.H., Zhang, Y., Dorgham, Karim, Philippot, Q., Rosain, J., Béziat, V., Manry, J., Shaw, E., Haljasmägi, L., Peterson, P., Lorenzo, L., Bizien, L., Trouillet-Assant, S., Dobbs, K., de Jesus, A.A., Belot, A., Kallaste, A., Catherinot, E., Tandjaoui-Lambiotte, Y., Le Pen, J., Kerner, G., Bigio, B., Seeleuthner, Y., Yang, R., Bolze, A., Spaan, A.N., Delmonte, O.M., Abers, M.S., Aiuti, A., Casari, G., Lampasona, V., Piemonti, L., Ciceri, F., Bilguvar, K., Lifton, R.P., Vasse, M., Smadja, D.M., Migaud, M., Hadjadj, J., Terrier, B., Duffy, D., Quintana-Murci, L., van de Beek, D., Roussel, L., Vinh, D.C., Tangye, S., Haerynck, F., Dalmau, D., Martinez-Picado, J., Brodin, P., Nussenzweig, M.C., Boisson-Dupuis, S., Rodríguez-Gallego, C., Vogt, G., Mogensen, T.H., Oler, A.J., Gu, J., Burbelo, P.D., Cohen, J.I., Biondi, A., Bettini, L.R., DÁngio, M., Bonfanti, P., Rossignol, P., Mayaux, J., Rieux-Laucat, F., Husebye, E.S., Fusco, F., Ursini, M.V., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Castagnoli, R., Montagna, D., Licari, A., Marseglia, G.L., Duval, X., Ghosn, J., Tsang, J.S., Goldbach-Mansky, R., Kisand, K., Lionakis, M.S., Puel, A., Zhang, S.Y., Holland, S.M., Gorochov, G., Jouanguy, E., Rice, C.M., Cobat, A., Notarangelo, L.D., Abel, L., Su, H.C., Casanova, J.L., Arias, A.A., Boisson, B., Boucherit, S., Bustamante, J., Chbihi, M., Chen, J., Chrabieh, M., Kochetkov, T., Le Voyer, T., Liu, D., Nemirovskaya, Y., Ogishi, M., Papandrea, D., Patissier, C., Rapaport, F., Roynard, M., Vladikine, N., Woollett, M., Zhang, P., Kashyap, A., Ding, L., Bosticardo, M., Wang, Q., Ochoa, S., Liu, H., Chauvin, S.D., Stack, M., Koroleva, G., Bansal, N., Dalgard, C.L., Snow, A.L., Abad Capa, Jorge, Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Amoura, Z., Antolí, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, Mireia, Borie, R., Bousfiha, A.A., Bouvattier, C., Boyarchuk, O., Bueno, M.R.P., Agra, J.J.C., Calimli, S., Capra, R., Carrabba, M., Casasnovas, Carlos, Caseris, M., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Colkesen, F., Colobrán Oriol, Roger, Comarmond, C., Corsico, A.G., Darley, D.R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Di Sabatino, A., Diehl, J.L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Flores, Carlos, Francois, B., Fumadó, V., Solis, B.G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Goffard, J.C., Gok, F., González-Montelongo, R., Guerder, A., Gul, Y., Guner, S.N., Gut, M., Halwani, R., Hammarström, L., Hatipoglu, N., Hernandez-Brito, E., Holanda-Peña, M.S., Horcajada, J.P., Hraiech, S., Humbert, L., Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jordan, I., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K.K., Keles, S., Demirkol, Y.K., Klocperk, A., Król, Z.J., Kuentz, P., Kwan, Y.W.M., Lagier, J.C., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Linglart, A., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Luyt, C.E., Lye, D.C., Mansouri, D., Marjani, M., Pereira, J.M., Martin, A., Pueyo, D.M., Marzana, I., Mathian, A., Matos, L.R.B., Matthews, G.V., Mège, J.L., Melki, I., Meritet, J.F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melián, A.M., Martinez, A.M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Muñoz-Barrera, A., Nafati, C., Neves, J.F., Ng, L.F.P., Medina, Y.N., Cuadros, E.N., Gonzalo Ocejo-Vinyals, J., Orbak, Z., Oualha, M., Ozcelik, T., Hammarström, Q.P., Parizot, C., Pascreau, T., Paz-Artal, E., de Diego, R.P., Philippe, A., Philippota, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A.S., Reisli, I., Ricart, P., Richard, J.C., Rivet, N., Rivière, J.G., Blanch, G.R., Rodrigo, C., Rodriguez-Gallego, C., Rodríguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Rozenberg, F., del Prado, M.Y.R., Riera, J.S., Sanchez, O., Sánchez-Ramón, S., Schluter, A., Schmidt, M., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L.M., Sene, D., Senoglu, S., Seppänen, M.R.J., Ilovich, A.S., Shahrooei, M., Smadja, D., Sobh, A., Moreno, X.S., Solé-Violán, J., Soler, C., Soler-Palacín, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiottea, Y., Taupin, J.L., Tavernier, S.J., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J.T., Trouillet-Assanta, S., Troya, J., Tucci, A., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., van Den Rym, A.M., Vandernoot, I., Vatansev, H., Vélez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M.E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B.E., Yucel, F., Zannad, F., Zatz, M., Belota, A., Foti, Giuseppe, Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abela, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'ortenzio, E., da Silveira, C., Debray, M.P., Deplanque, D., Descamps, D., Desvallées, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Eloy, P., Enouf, V.V.E., Espérou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouénan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F.X., Lévy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J.C., Malvy, D., Mambert, M., Mentré, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Roy, C., Schneider, M., Semaille, C., Mohammed, N.S., Tagherset, L., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Treoux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Abelc, L., Alcover, A., Aschard, H., Astrom, K., Bousso, P., Bruhns, P., Cumano, A., Demangel, C., Deriano, L., Santo, J.D., Dromer, F., Eberl, G., Enninga, J., Fellay, Jacques, Gomperts-Boneca, I., Hasan, M., Hercberg, S., Lantz, O., Patin, E., Pellegrini, S., Pol, S., Rausell, A., Rogge, L., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Tangy, F., Toubert, A., Touvier, M., Ungeheuer, M.N., Albert, M.L., Alavoine, L., Amat, K.K.A., Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J.L., Enouf, V., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A.G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bos, Lieuwe D, Botta, M., de Brabander, J., Bree, G., Brouwer, M.C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M.W., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J.M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M.J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C.S., Stilma, Willemke, Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, A.P.J., de Vries, H., van Vugt, M., Joost Wiersinga, W., Wouters, D., Zwinderman, A.H., Abelb, L., Iuti, F., Muhsen, S.A., Al-Mulla, F., Anderson, M.S., Bogunovic, D., Bondarenko, A., Bryceson, Y., Bustamante, C.D., Butte, M., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M.A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Franco, J.L., Gregersen, P.K., Hagin, D., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisanda, K., Ku, C.L., Ling, Y., Lucas, C.L., Maniatis, T., Marodi, L., Milner, J.D., Mironska, K., Morio, T., Notarangeloa, L.D., Novelli, G., Novelli, A., O'Farrelly, C., Okada, S., Planas, A.M., Prando, C., Pujol, A., Renia, L., Renieri, A., Sancho-Shimizu, V., Sankaran, V., Barrett, K.S., Snow, A., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., von Bernuth, H., Washington, N., Zawadzki, P., Sua, H.C., Casanovaa, J.L., Rosen, L.B., and Universitat Autònoma de Barcelona
Abstract: Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
Published: 2020

8. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author: Zhang, Q., Liu, Z., Moncada-Velez, M., Chen, J., Ogishi, M., Bigio, B., Yang, R., Arias, A.A., Zhou, Q., Han, J.E., Ugurbil, A.C., Zhang, P., Rapaport, F., Li, J., Spaan, A.N., Boisson, B., Boisson-Dupuis, S., Bustamante, J., Puel, A., Ciancanelli, M.J., Zhang, S.Y., Béziat, V., Jouanguy, E., Abel, L., Cobat, A., Casanova, J.L., Bastard, P., Korol, C., Rosain, J., Philippot, Q., Chbihi, M., Lorenzo, L., Bizien, L., Neehus, A.L., Kerner, G., Seeleuthner, Y., Manry, J., Le Voyer, T., Le Pen, J., Schneider, W.M., Razooky, B.S., Hoffmann, H.H., Michailidis, E., Rice, C.M., Sabli, I.K.D., Hodeib, S., Sancho-Shimizu, V., Bilguvar, K., Ye, J., Maniatis, T., Bolze, A., Zhang, Y., Notarangelo, L.D., Su, H.C., Onodi, F., Korniotis, S., Karpf, L., Soumelis, V., Bonnet-Madin, L., Amara, A., Dorgham, Karim, Gorochov, G., Smith, N., Duffy, D., Moens, L., Meyts, I., Meade, P., Garcia-Sastre, Adolfo, Krammer, F., Corneau, A., Masson, C., Schmitt, Y., Schluter, A., Pujol, A., Khan, T., Marr, N., Fellay, Jacques, Roussel, L., Vinh, D.C., Shahrooei, M., Alosaimi, M.F., Alsohime, F., Hasanato, R., Mansouri, D., Al-Saud, H., Almourfi, F., Al-Mulla, F., Al-Muhsen, S.Z., Al Turki, S., van de Beek, D., Biondi, A., Bettini, L.R., D'Angio, M., Bonfanti, P., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Oler, A.J., Tompkins, M.F., Alba, C., Dalgard, C.L., Vandernoot, I., Smits, G., Goffard, J.C., Migeotte, I., Haerynck, F., Soler-Palacín, P., Martin-Nalda, A., Colobrán Oriol, Roger, Morange, P.E., Keles, S., Çölkesen, F., Ozcelik, T., Yasar, K.K., Senoglu, S., Karabela, Ş.N., Rodríguez-Gallego, C., Novelli, G., Hraiech, S., Tandjaoui-Lambiotte, Y., Duval, X., Laouénan, C., Snow, A., Milner, J.D., Mogensen, T.H., Nussenzweig, M., Lifton, R.P., Foti, Giuseppe, Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Abad Capa, Jorge, Blanco, I., Rodrigo, C., Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Mouly, S., Sene, D., Amoura, Z., Mathian, A., Antolí, A., Blanch, G.R., Riera, J.S., Moreno, X.S., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Lévy, R., Oualha, M., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blandinières, A., Rivet, N., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, Mireia, Clavé, P., Bosteels, C., Lambrecht, B.N., van Braeckel, E., Bousfiha, A.A., Bouvattier, C., Vincent, A., Boyarchuk, O., Bueno, M.R.P., Castro, M.V., Matos, L.R.B., Zatz, M., Agra, J.J.C., Calimli, S., Capra, R., Carrabba, M., Fabio, G., Casasnovas, Carlos, Vélez-Santamaria, V., Caseris, M., Falck, A., Poncelet, G., Castelle, M., Castelli, F., de Vera, M.C., Catherinot, E., Chalumeau, M., Toubiana, J., Charbit, B., Li, Z., Pellegrini, S., Cheng, M.P., Clotet, B., Codina, A., Colkesen, F., Comarmond, C., Dalmau, D., Darley, D.R., Dauby, N., Dauger, S., Le Bourgeois, F., Levy, M., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Diehl, J.L., Dobbelaere, S., Durand, S., Mircher, C., Rebillat, A.S., Vilaire, M.E., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Faivre, L., Fartoukh, M., Faure, M., Arquero, M.F., Flores, Carlos, Francois, B., Fumadó, V., Fusco, F., Ursini, M.V., Solis, B.G., de Diego, R.P., van Den Rym, A.M., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Gok, F., Yosunkaya, A., Thy, M., van Agtmael, M., Bomers, M., Chouchane, O., Geerlings, S., Goorhuis, B., Grobusch, M.P., Harris, V., Hermans, S.M., Hovius, J.W., Nellen, J., Peters, E., van der Poll, T., Prins, J.M., Reijnders, T., Schinkel, M., Sigaloff, K., Stijnis, C.S., van der Valk, M., van Vugt, M., Joost Wiersinga, W., Algera, A.G., van Baarle, F., Bos, Lieuwe D, Botta, M., de Bruin, S., Bulle, E., Elbers, P., Fleuren, L., Girbes, A., Hagens, L., Heunks, L., Horn, J., van Mourik, N., Paulus, F., Raasveld, J., Schultz, M.J., Smit, M., Stilma, Willemke, Thoral, P., Tsonas, A., de Vries, H., Bax, D., Cloherty, A., Beudel, M., Brouwer, M.C., Koning, R., Bogaard, H.J., de Brabander, J., de Bree, G., Bugiani, M., Geerts, B., Hollmann, M.W., Preckel, B., Veelo, D., Geijtenbeek, T., Hafkamp, F., Hamann, J., Hemke, R., de Jong, M.D., Schuurman, A., Teunissen, C., Vlaar, A.P.J., Wouters, D., Zwinderman, A.H., Aiuti, A., Muhsen, S.A., Anderson, M.S., Bogunovic, D., Itan, Y., Cirulli, E., Barrett, K.S., Washington, N., Bondarenko, A., Brodin, P., Bryceson, Y., Bustamante, C.D., Butte, M., Casari, G., Chakravorty, S., Christodoulou, J., Le Mestre, S., Condino-Neto, A., Cooper, M.A., David, A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Franco, J.L., Gregersen, P.K., Hagin, D., Halwani, R., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Karamitros, T., Kisand, K., Ku, C.L., Lau, Y.L., Ling, Y., Lucas, C.L., Marodi, L., Milner, J., Mironska, K., Morio, T., Novelli, A., O'Farrelly, C., Okada, S., Planas, A.M., Prando, C., Quintana-Murci, L., Renia, L., Renieri, A., Sankaran, V., Tangye, S., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., von Bernuth, H., Zawadzki, P., Jing, H., Tung, W., Meguro, K., Shaw, E., Shafer, S., Zheng, L., Zhang, Z., Kubo, S., Chauvin, S.D., Lenardo, M., Luthers, C.R., Bauman, B.M., Lack, J., Karlins, E., Hupalo, D.M., Rosenberger, J., Sukumar, G., Wilkerson, M.D., Zhang, X., Universitat Autònoma Barcelona, Zhang, Q., Liu, Z., Moncada-Velez, M., Chen, J., Ogishi, M., Bigio, B., Yang, R., Arias, A.A., Zhou, Q., Han, J.E., Ugurbil, A.C., Zhang, P., Rapaport, F., Li, J., Spaan, A.N., Boisson, B., Boisson-Dupuis, S., Bustamante, J., Puel, A., Ciancanelli, M.J., Zhang, S.Y., Béziat, V., Jouanguy, E., Abel, L., Cobat, A., Casanova, J.L., Bastard, P., Korol, C., Rosain, J., Philippot, Q., Chbihi, M., Lorenzo, L., Bizien, L., Neehus, A.L., Kerner, G., Seeleuthner, Y., Manry, J., Le Voyer, T., Le Pen, J., Schneider, W.M., Razooky, B.S., Hoffmann, H.H., Michailidis, E., Rice, C.M., Sabli, I.K.D., Hodeib, S., Sancho-Shimizu, V., Bilguvar, K., Ye, J., Maniatis, T., Bolze, A., Zhang, Y., Notarangelo, L.D., Su, H.C., Onodi, F., Korniotis, S., Karpf, L., Soumelis, V., Bonnet-Madin, L., Amara, A., Dorgham, Karim, Gorochov, G., Smith, N., Duffy, D., Moens, L., Meyts, I., Meade, P., Garcia-Sastre, Adolfo, Krammer, F., Corneau, A., Masson, C., Schmitt, Y., Schluter, A., Pujol, A., Khan, T., Marr, N., Fellay, Jacques, Roussel, L., Vinh, D.C., Shahrooei, M., Alosaimi, M.F., Alsohime, F., Hasanato, R., Mansouri, D., Al-Saud, H., Almourfi, F., Al-Mulla, F., Al-Muhsen, S.Z., Al Turki, S., van de Beek, D., Biondi, A., Bettini, L.R., D'Angio, M., Bonfanti, P., Imberti, L., Sottini, A., Paghera, S., Quiros-Roldan, E., Rossi, C., Oler, A.J., Tompkins, M.F., Alba, C., Dalgard, C.L., Vandernoot, I., Smits, G., Goffard, J.C., Migeotte, I., Haerynck, F., Soler-Palacín, P., Martin-Nalda, A., Colobrán Oriol, Roger, Morange, P.E., Keles, S., Çölkesen, F., Ozcelik, T., Yasar, K.K., Senoglu, S., Karabela, Ş.N., Rodríguez-Gallego, C., Novelli, G., Hraiech, S., Tandjaoui-Lambiotte, Y., Duval, X., Laouénan, C., Snow, A., Milner, J.D., Mogensen, T.H., Nussenzweig, M., Lifton, R.P., Foti, Giuseppe, Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Abad Capa, Jorge, Blanco, I., Rodrigo, C., Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Mouly, S., Sene, D., Amoura, Z., Mathian, A., Antolí, A., Blanch, G.R., Riera, J.S., Moreno, X.S., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Lévy, R., Oualha, M., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blandinières, A., Rivet, N., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, Mireia, Clavé, P., Bosteels, C., Lambrecht, B.N., van Braeckel, E., Bousfiha, A.A., Bouvattier, C., Vincent, A., Boyarchuk, O., Bueno, M.R.P., Castro, M.V., Matos, L.R.B., Zatz, M., Agra, J.J.C., Calimli, S., Capra, R., Carrabba, M., Fabio, G., Casasnovas, Carlos, Vélez-Santamaria, V., Caseris, M., Falck, A., Poncelet, G., Castelle, M., Castelli, F., de Vera, M.C., Catherinot, E., Chalumeau, M., Toubiana, J., Charbit, B., Li, Z., Pellegrini, S., Cheng, M.P., Clotet, B., Codina, A., Colkesen, F., Comarmond, C., Dalmau, D., Darley, D.R., Dauby, N., Dauger, S., Le Bourgeois, F., Levy, M., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Diehl, J.L., Dobbelaere, S., Durand, S., Mircher, C., Rebillat, A.S., Vilaire, M.E., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Faivre, L., Fartoukh, M., Faure, M., Arquero, M.F., Flores, Carlos, Francois, B., Fumadó, V., Fusco, F., Ursini, M.V., Solis, B.G., de Diego, R.P., van Den Rym, A.M., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Gok, F., Yosunkaya, A., Thy, M., van Agtmael, M., Bomers, M., Chouchane, O., Geerlings, S., Goorhuis, B., Grobusch, M.P., Harris, V., Hermans, S.M., Hovius, J.W., Nellen, J., Peters, E., van der Poll, T., Prins, J.M., Reijnders, T., Schinkel, M., Sigaloff, K., Stijnis, C.S., van der Valk, M., van Vugt, M., Joost Wiersinga, W., Algera, A.G., van Baarle, F., Bos, Lieuwe D, Botta, M., de Bruin, S., Bulle, E., Elbers, P., Fleuren, L., Girbes, A., Hagens, L., Heunks, L., Horn, J., van Mourik, N., Paulus, F., Raasveld, J., Schultz, M.J., Smit, M., Stilma, Willemke, Thoral, P., Tsonas, A., de Vries, H., Bax, D., Cloherty, A., Beudel, M., Brouwer, M.C., Koning, R., Bogaard, H.J., de Brabander, J., de Bree, G., Bugiani, M., Geerts, B., Hollmann, M.W., Preckel, B., Veelo, D., Geijtenbeek, T., Hafkamp, F., Hamann, J., Hemke, R., de Jong, M.D., Schuurman, A., Teunissen, C., Vlaar, A.P.J., Wouters, D., Zwinderman, A.H., Aiuti, A., Muhsen, S.A., Anderson, M.S., Bogunovic, D., Itan, Y., Cirulli, E., Barrett, K.S., Washington, N., Bondarenko, A., Brodin, P., Bryceson, Y., Bustamante, C.D., Butte, M., Casari, G., Chakravorty, S., Christodoulou, J., Le Mestre, S., Condino-Neto, A., Cooper, M.A., David, A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Franco, J.L., Gregersen, P.K., Hagin, D., Halwani, R., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Karamitros, T., Kisand, K., Ku, C.L., Lau, Y.L., Ling, Y., Lucas, C.L., Marodi, L., Milner, J., Mironska, K., Morio, T., Novelli, A., O'Farrelly, C., Okada, S., Planas, A.M., Prando, C., Quintana-Murci, L., Renia, L., Renieri, A., Sankaran, V., Tangye, S., Turvey, S., Uddin, F., Uddin, M.J., Vazquez, S.E., von Bernuth, H., Zawadzki, P., Jing, H., Tung, W., Meguro, K., Shaw, E., Shafer, S., Zheng, L., Zhang, Z., Kubo, S., Chauvin, S.D., Lenardo, M., Luthers, C.R., Bauman, B.M., Lack, J., Karlins, E., Hupalo, D.M., Rosenberger, J., Sukumar, G., Wilkerson, M.D., Zhang, X., and Universitat Autònoma Barcelona
Abstract: Afegiu 653 1_, Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
Published: 2020

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

Author: Universitat Rovira i Virgili, Bastard P; Rosen LB; Zhang Q; Michailidis E; Hoffmann HH; Zhang Y; Dorgham K; Philippot Q; Rosain J; Béziat V; Manry J; Shaw E; Haljasmägi L; Peterson P; Lorenzo L; Bizien L; Trouillet-Assant S; Dobbs K; de Jesus AA; Belot A; Kallaste A; Catherinot E; Tandjaoui-Lambiotte Y; Le Pen J; Kerner G; Bigio B; Seeleuthner Y; Yang R; Bolze A; Spaan AN; Delmonte OM; Abers MS; Aiuti A; Casari G; Lampasona V; Piemonti L; Ciceri F; Bilguvar K; Lifton RP; Vasse M; Smadja DM; Migaud M; Hadjadj J; Terrier B; Duffy D; Quintana-Murci L; van de Beek D; Roussel L; Vinh DC; Tangye SG; Haerynck F; Dalmau D; Martinez-Picado J; Brodin P; Nussenzweig MC; Boisson-Dupuis S; Rodríguez-Gallego C; Vogt G; Mogensen TH; Oler AJ; Gu J; Burbelo PD; Cohen J; Biondi A; Bettini LR; D'Angio M; Bonfanti P; Rossignol P; Mayaux J; Rieux-Laucat F; Husebye ES; Fusco F; Ursini MV; Imberti L; Sottini A; Paghera S; Quiros-Roldan E; Rossi C; Castagnoli R; Montagna D; Licari A; Marseglia GL; Duval X; Ghosn J; HGID Lab; NIAID-USUHS Immune Response to COVID Group; COVID Clinicians; COVID-STORM Clinicians; Imagine COVID Group; French COVID Cohort Study Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort; Tsang JS; Goldbach-Mansky R; Kisand K; Lionakis MS; Puel A; Zhang SY; Holland SM; Gorochov G; Jouanguy E; Rice CM; Cobat A; Notarangelo LD; Abel L; Su HC; Casanova JL, Universitat Rovira i Virgili, and Bastard P; Rosen LB; Zhang Q; Michailidis E; Hoffmann HH; Zhang Y; Dorgham K; Philippot Q; Rosain J; Béziat V; Manry J; Shaw E; Haljasmägi L; Peterson P; Lorenzo L; Bizien L; Trouillet-Assant S; Dobbs K; de Jesus AA; Belot A; Kallaste A; Catherinot E; Tandjaoui-Lambiotte Y; Le Pen J; Kerner G; Bigio B; Seeleuthner Y; Yang R; Bolze A; Spaan AN; Delmonte OM; Abers MS; Aiuti A; Casari G; Lampasona V; Piemonti L; Ciceri F; Bilguvar K; Lifton RP; Vasse M; Smadja DM; Migaud M; Hadjadj J; Terrier B; Duffy D; Quintana-Murci L; van de Beek D; Roussel L; Vinh DC; Tangye SG; Haerynck F; Dalmau D; Martinez-Picado J; Brodin P; Nussenzweig MC; Boisson-Dupuis S; Rodríguez-Gallego C; Vogt G; Mogensen TH; Oler AJ; Gu J; Burbelo PD; Cohen J; Biondi A; Bettini LR; D'Angio M; Bonfanti P; Rossignol P; Mayaux J; Rieux-Laucat F; Husebye ES; Fusco F; Ursini MV; Imberti L; Sottini A; Paghera S; Quiros-Roldan E; Rossi C; Castagnoli R; Montagna D; Licari A; Marseglia GL; Duval X; Ghosn J; HGID Lab; NIAID-USUHS Immune Response to COVID Group; COVID Clinicians; COVID-STORM Clinicians; Imagine COVID Group; French COVID Cohort Study Group; Milieu Intérieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort; Tsang JS; Goldbach-Mansky R; Kisand K; Lionakis MS; Puel A; Zhang SY; Holland SM; Gorochov G; Jouanguy E; Rice CM; Cobat A; Notarangelo LD; Abel L; Su HC; Casanova JL
Abstract: Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-omega (IFN-omega) (13 patients), against the 13 types of IFN-alpha (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for lifethreatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
Published: 2020

10. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author: Universitat Rovira i Virgili, Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ?N, Gallego CR, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan C,, Snow AL, Dalgard CL, Milner J, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli M, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton R, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, Casanova JL COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19, Biobank, COVID Human Genetic Effort, NIAID-USUHS, TAGC COVID Immunity Group, Universitat Rovira i Virgili, and Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ?N, Gallego CR, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan C,, Snow AL, Dalgard CL, Milner J, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli M, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton R, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, Casanova JL COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19, Biobank, COVID Human Genetic Effort, NIAID-USUHS, TAGC COVID Immunity Group
Abstract: Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.Copyright © 2020, American Association for the Advancement of Science.
Published: 2020

11. Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines.

Author: Hernandez, N, Bucciol, G, Moens, L, Le Pen, J, Shahrooei, M, Goudouris, E, Shirkani, A, Changi-Ashtiani, M, Rokni-Zadeh, H, Sayar, EH, Reisli, I, Lefevre-Utile, A, Zijlmans, D, Jurado, A, Pholien, R, Drutman, S, Belkaya, S, Cobat, A, Boudewijns, R, Jochmans, D, Neyts, J, Seeleuthner, Y, Lorenzo-Diaz, L, Enemchukwu, C, Tietjen, I, Hoffmann, H-H, Momenilandi, M, Pöyhönen, L, Siqueira, MM, de Lima, SMB, de Souza Matos, DC, Homma, A, Maia, MDLS, da Costa Barros, TA, de Oliveira, PMN, Mesquita, EC, Gijsbers, R, Zhang, S-Y, Seligman, SJ, Abel, L, Hertzog, P, Marr, N, Martins, RDM, Meyts, I, Zhang, Q, MacDonald, MR, Rice, CM, Casanova, J-L, Jouanguy, E, Bossuyt, X, Hernandez, N, Bucciol, G, Moens, L, Le Pen, J, Shahrooei, M, Goudouris, E, Shirkani, A, Changi-Ashtiani, M, Rokni-Zadeh, H, Sayar, EH, Reisli, I, Lefevre-Utile, A, Zijlmans, D, Jurado, A, Pholien, R, Drutman, S, Belkaya, S, Cobat, A, Boudewijns, R, Jochmans, D, Neyts, J, Seeleuthner, Y, Lorenzo-Diaz, L, Enemchukwu, C, Tietjen, I, Hoffmann, H-H, Momenilandi, M, Pöyhönen, L, Siqueira, MM, de Lima, SMB, de Souza Matos, DC, Homma, A, Maia, MDLS, da Costa Barros, TA, de Oliveira, PMN, Mesquita, EC, Gijsbers, R, Zhang, S-Y, Seligman, SJ, Abel, L, Hertzog, P, Marr, N, Martins, RDM, Meyts, I, Zhang, Q, MacDonald, MR, Rice, CM, Casanova, J-L, Jouanguy, E, and Bossuyt, X
Abstract: Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2, STAT1, or STAT2). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function IFNAR1 variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients' fibroblast phenotypes are rescued with WT IFNAR1 Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals.
Published: 2019

12. Terminal uridylyltransferases target RNA viruses as part of the innate immune system in animals

Author: Dónal O'Carroll, Joanna Kosalka, Emma Kneuss, Eric A. Miska, Di Domenico T, Rudolph Klm, Dong-Mei Wang, Marcos Morgan, Le Pen J, Anton J. Enright, Christian Much, and Hongbing Jiang
Subjects: 0303 health sciences, Orsay virus, Messenger RNA, Innate immune system, RNA, Biology, medicine.disease_cause, Virology, 03 medical and health sciences, RNA silencing, 0302 clinical medicine, RNA interference, Interferon, medicine, Influenza A virus, 030217 neurology & neurosurgery, 030304 developmental biology, medicine.drug
Abstract: RNA viruses are a major threat to animals and plants. RNA interference (RNAi) and the interferon response provide innate antiviral defense against RNA viruses. Here we performed a large-scale screen using C. elegans and its natural pathogen, the Orsay virus (OrV), and identified cde-1 as important for antiviral defense. CDE-1 is a homologue of the mammalian TUT4/7 terminal uridylyltransferases; its catalytic activity is required for its antiviral function. CDE-1 uridylates the 3′ end of the OrV RNA genome and promotes its degradation, independently of the RNAi pathway. Likewise, TUT4/7 uridylate influenza A virus (IAV) mRNAs in mammalian cells. Deletion of TUT4/7 leads to increased IAV mRNA and protein levels. We have defined 3′ terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.
Published: 2017
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13. Antiviral RNA Interference against Orsay Virus Is neither Systemic nor Transgenerational in Caenorhabditis elegans

Author: Ashe, A, Sarkies, P, Le Pen, J, Tanguy, M, Miska, EA, Miska, Eric A [0000-0002-4450-576X], and Apollo - University of Cambridge Repository
Subjects: C. ELEGANS, MECHANISM, DEFENSE, Molecular Sequence Data, Inheritance Patterns, DOUBLE-STRANDED-RNA, SILENCING SIGNALS, INHERITANCE, Virology, GERMLINE, Animals, Nodaviridae, Caenorhabditis elegans, Science & Technology, Base Sequence, Sequence Analysis, RNA, TRANSMEMBRANE PROTEIN SID-1, fungi, Models, Immunological, AMPLIFICATION, 11 Medical And Health Sciences, 06 Biological Sciences, Microarray Analysis, Immunity, Innate, CELLS, RNA Interference, 07 Agricultural And Veterinary Sciences, Life Sciences & Biomedicine
Abstract: UNLABELLED: Antiviral RNA-mediated silencing (RNA interference [RNAi]) acts as a powerful innate immunity defense in plants, invertebrates, and mammals. In Caenorhabditis elegans, RNAi is systemic; i.e., RNAi silencing signals can move between cells and tissues. Furthermore, RNAi effects can be inherited transgenerationally and may last for many generations. Neither the biological relevance of systemic RNAi nor transgenerational RNAi is currently understood. Here we examined the role of both pathways in the protection of C. elegans from viral infection. We studied the Orsay virus, a positive-strand RNA virus related to Nodaviridae and the first and only virus known to infect C. elegans. Immunity to Orsay virus infection requires the RNAi pathway. Surprisingly, we found that genes required for systemic or transgenerational RNAi did not have a role in antiviral defense. Furthermore, we found that Orsay virus infection did not elicit a systemic RNAi response even when a target for RNAi was provided by using transgenes. Finally, we show that viral siRNAs, the effectors of RNAi, are not inherited to a level that provides any significant resistance to viral infection in the next generation. We conclude that systemic or transgenerational RNAi does not play a role in the defense against natural Orsay virus infection. Furthermore, our data suggest that there is a qualitative difference between experimental RNAi and antiviral RNAi. Our data are consistent with a model of systemic and transgenerational RNAi that requires a nuclear or germ line component that is lacking in almost all RNA virus infections. IMPORTANCE: Since its discovery in Caenorhabditis elegans, RNAi has proven a valuable scientific tool in many organisms. In C. elegans, exogenous RNAi spreads throughout the organism and can be passed between generations; however, there has been controversy as to the endogenous role(s) that the RNAi pathway plays. One endogenous role for which spreading both within the infected organism and between generations would be advantageous is a role in viral defense. In plants, antiviral RNAi is systemic and the spread of RNAi between cells provides protection against subsequent viral infection. Here we investigated this by using the only naturally occurring virus known to infect C. elegans, Orsay virus, and surprisingly found that, in contrast to the exogenous RNAi pathway, the antiviral RNAi response targeted against this virus does not spread systemically throughout the organism and cannot be passed between generations. These results suggest that there are differences between the two pathways that remain to be discovered.
Published: 2015

14. Erratum: Constitutive p53 heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors of BCL-xL

Author: Le Pen, J, primary, Maillet, L, additional, Sarosiek, K, additional, Vuillier, C, additional, Gautier, F, additional, Montessuit, S, additional, Martinou, J C, additional, Letaï, A, additional, Braun, F, additional, and Juin, P P, additional
Published: 2017
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15. Constitutive p53 heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors of BCL-xL

Author: Le Pen, J, primary, Laurent, M, additional, Sarosiek, K, additional, Vuillier, C, additional, Gautier, F, additional, Montessuit, S, additional, Martinou, J C, additional, Letaï, A, additional, Braun, F, additional, and Juin, P P, additional
Published: 2016
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16. A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity

Author: Ashe A, Bxe9licard T, Le Pen J, Sarkies P, Frxe9zal L, Lehrbach N. J, Fxe9lix M.-A, and Miska E. A.
Published: 2013

17. pRb/E2F-1-mediated caspase-dependent induction of Noxa amplifies the apoptotic effects of the Bcl-2/Bcl-xL inhibitor ABT-737

Author: Bertin-Ciftci, J, primary, Barré, B, additional, Le Pen, J, additional, Maillet, L, additional, Couriaud, C, additional, Juin, P, additional, and Braun, F, additional
Published: 2013
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18. A genome-wide arrayed CRISPR screen identifies PLSCR1 as an intrinsic barrier to SARS-CoV-2 entry that recent virus variants have evolved to resist.

Author: Le Pen J, Paniccia G, Kinast V, Moncada-Velez M, Ashbrook AW, Bauer M, Hoffmann HH, Pinharanda A, Ricardo-Lax I, Stenzel AF, Rosado-Olivieri EA, Dinnon KH 3rd, Doyle WC, Freije CA, Hong SH, Lee D, Lewy T, Luna JM, Peace A, Schmidt C, Schneider WM, Winkler R, Yip EZ, Larson C, McGinn T, Menezes MR, Ramos-Espiritu L, Banerjee P, Poirier JT, Sànchez-Rivera FJ, Cobat A, Zhang Q, Casanova JL, Carroll TS, Glickman JF, Michailidis E, Razooky B, MacDonald MR, and Rice CM
Subjects: Humans, HEK293 Cells, CRISPR-Cas Systems genetics, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus metabolism, Serine Endopeptidases genetics, Serine Endopeptidases metabolism, Interferons metabolism, Interferons genetics, Clustered Regularly Interspaced Short Palindromic Repeats genetics, Antigens, Differentiation, SARS-CoV-2 genetics, Virus Internalization, COVID-19 virology, COVID-19 genetics
Abstract: Interferons (IFNs) play a crucial role in the regulation and evolution of host-virus interactions. Here, we conducted a genome-wide arrayed CRISPR knockout screen in the presence and absence of IFN to identify human genes that influence Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. We then performed an integrated analysis of genes interacting with SARS-CoV-2, drawing from a selection of 67 large-scale studies, including our own. We identified 28 genes of high relevance in both human genetic studies of Coronavirus Disease 2019 (COVID-19) patients and functional genetic screens in cell culture, with many related to the IFN pathway. Among these was the IFN-stimulated gene PLSCR1. PLSCR1 did not require IFN induction to restrict SARS-CoV-2 and did not contribute to IFN signaling. Instead, PLSCR1 specifically restricted spike-mediated SARS-CoV-2 entry. The PLSCR1-mediated restriction was alleviated by TMPRSS2 overexpression, suggesting that PLSCR1 primarily restricts the endocytic entry route. In addition, recent SARS-CoV-2 variants have adapted to circumvent the PLSCR1 barrier via currently undetermined mechanisms. Finally, we investigate the functional effects of PLSCR1 variants present in humans and discuss an association between PLSCR1 and severe COVID-19 reported recently., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Le Pen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Published: 2024
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19. SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Author: Chan YH, Lundberg V, Le Pen J, Yuan J, Lee D, Pinci F, Volpi S, Nakajima K, Bondet V, Åkesson S, Khobrekar NV, Bodansky A, Du L, Melander T, Mariaggi AA, Seeleuthner Y, Saleh TS, Chakravarty D, Marits P, Dobbs K, Vonlanthen S, Hennings V, Thörn K, Rinchai D, Bizien L, Chaldebas M, Sobh A, Özçelik T, Keles S, AlKhater SA, Prando C, Meyts I, Wilson MR, Rosain J, Jouanguy E, Aubart M, Abel L, Mogensen TH, Pan-Hammarström Q, Gao D, Duffy D, Cobat A, Berg S, Notarangelo LD, Harschnitz O, Rice CM, Studer L, Casanova JL, Ekwall O, and Zhang SY
Subjects: Humans, Male, Adolescent, Encephalitis, Viral genetics, Encephalitis, Viral pathology, Encephalitis, Viral virology, Fibroblasts metabolism, Rhombencephalon metabolism, SARS-CoV-2 genetics, COVID-19 genetics, COVID-19 virology, Brain Stem pathology, Brain Stem virology, Brain Stem metabolism, Neurons metabolism, Neurons pathology
Abstract: Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2., (© 2024 Chan et al.)
Published: 2024
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20. The antiviral state of the cell: lessons from SARS-CoV-2.

Author: Le Pen J and Rice CM
Subjects: Humans, Virus Internalization, Host-Pathogen Interactions immunology, Virus Replication, Animals, Antiviral Agents therapeutic use, Interferons metabolism, Interferons immunology, SARS-CoV-2 immunology, SARS-CoV-2 physiology, COVID-19 immunology, COVID-19 virology
Abstract: In this review, we provide an overview of the intricate host-virus interactions that have emerged from the study of SARS-CoV-2 infection. We focus on the antiviral mechanisms of interferon-stimulated genes (ISGs) and their modulation of viral entry, replication, and release. We explore the role of a selection ISGs, including BST2, CD74, CH25H, DAXX, IFI6, IFITM1-3, LY6E, NCOA7, PLSCR1, OAS1, RTP4, and ZC3HAV1/ZAP, in restricting SARS-CoV-2 infection and discuss the virus's countermeasures. By synthesizing the latest research on SARS-CoV-2 and host antiviral responses, this review aims to provide a deeper understanding of the antiviral state of the cell under SARS-CoV-2 and other viral infections, offering insights for the development of novel antiviral strategies and therapeutics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Published: 2024
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21. Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children.

Author: Lee D, Le Pen J, Yatim A, Dong B, Aquino Y, Ogishi M, Pescarmona R, Talouarn E, Rinchai D, Zhang P, Perret M, Liu Z, Jordan I, Elmas Bozdemir S, Bayhan GI, Beaufils C, Bizien L, Bisiaux A, Lei W, Hasan M, Chen J, Gaughan C, Asthana A, Libri V, Luna JM, Jaffré F, Hoffmann HH, Michailidis E, Moreews M, Seeleuthner Y, Bilguvar K, Mane S, Flores C, Zhang Y, Arias AA, Bailey R, Schlüter A, Milisavljevic B, Bigio B, Le Voyer T, Materna M, Gervais A, Moncada-Velez M, Pala F, Lazarov T, Levy R, Neehus AL, Rosain J, Peel J, Chan YH, Morin MP, Pino-Ramirez RM, Belkaya S, Lorenzo L, Anton J, Delafontaine S, Toubiana J, Bajolle F, Fumadó V, DeDiego ML, Fidouh N, Rozenberg F, Pérez-Tur J, Chen S, Evans T, Geissmann F, Lebon P, Weiss SR, Bonnet D, Duval X, Pan-Hammarström Q, Planas AM, Meyts I, Haerynck F, Pujol A, Sancho-Shimizu V, Dalgard CL, Bustamante J, Puel A, Boisson-Dupuis S, Boisson B, Maniatis T, Zhang Q, Bastard P, Notarangelo L, Béziat V, Perez de Diego R, Rodriguez-Gallego C, Su HC, Lifton RP, Jouanguy E, Cobat A, Alsina L, Keles S, Haddad E, Abel L, Belot A, Quintana-Murci L, Rice CM, Silverman RH, Zhang SY, and Casanova JL
Subjects: Child, Humans, RNA, Double-Stranded, COVID-19 immunology, Cytokines genetics, Cytokines immunology, Endoribonucleases genetics, Endoribonucleases metabolism, SARS-CoV-2 genetics, Systemic Inflammatory Response Syndrome genetics
Abstract: Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1 , OAS2 , or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.
Published: 2023
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22. Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria.

Author: Rosain J, Neehus AL, Manry J, Yang R, Le Pen J, Daher W, Liu Z, Chan YH, Tahuil N, Türel Ö, Bourgey M, Ogishi M, Doisne JM, Izquierdo HM, Shirasaki T, Le Voyer T, Guérin A, Bastard P, Moncada-Vélez M, Han JE, Khan T, Rapaport F, Hong SH, Cheung A, Haake K, Mindt BC, Pérez L, Philippot Q, Lee D, Zhang P, Rinchai D, Al Ali F, Ahmad Ata MM, Rahman M, Peel JN, Heissel S, Molina H, Kendir-Demirkol Y, Bailey R, Zhao S, Bohlen J, Mancini M, Seeleuthner Y, Roelens M, Lorenzo L, Soudée C, Paz MEJ, González ML, Jeljeli M, Soulier J, Romana S, L'Honneur AS, Materna M, Martínez-Barricarte R, Pochon M, Oleaga-Quintas C, Michev A, Migaud M, Lévy R, Alyanakian MA, Rozenberg F, Croft CA, Vogt G, Emile JF, Kremer L, Ma CS, Fritz JH, Lemon SM, Spaan AN, Manel N, Abel L, MacDonald MR, Boisson-Dupuis S, Marr N, Tangye SG, Di Santo JP, Zhang Q, Zhang SY, Rice CM, Béziat V, Lachmann N, Langlais D, Casanova JL, Gros P, and Bustamante J
Subjects: Child, Humans, Interferon-gamma, SARS-CoV-2, Interferon-alpha, Interferon Regulatory Factor-1, COVID-19, Mycobacterium
Abstract: Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity., Competing Interests: Declaration of interests J.-L.C. serves on the scientific advisory boards of ADMA Biologics Inc., Kymera Therapeutics, and Elixiron Immunotherapeutics., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)
Published: 2023
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23. ER-associated RNA silencing promotes ER quality control.

Author: Efstathiou S, Ottens F, Schütter LS, Ravanelli S, Charmpilas N, Gutschmidt A, Le Pen J, Gehring NH, Miska EA, Bouças J, and Hoppe T
Subjects: RNA Interference, Endoplasmic Reticulum genetics
Abstract: The endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the accumulation of misfolded proteins in the ER, but the physiological regulation of this process remains poorly characterized. Here, in a genetic screen using an ERAD model substrate in Caenorhabditis elegans, we identified an anti-viral RNA interference pathway, referred to as ER-associated RNA silencing (ERAS), which acts together with ERAD to preserve ER homeostasis and function. Induced by ER stress, ERAS is mediated by the Argonaute protein RDE-1/AGO2, is conserved in mammals and promotes ER-associated RNA turnover. ERAS and ERAD are complementary, as simultaneous inactivation of both quality-control pathways leads to increased ER stress, reduced protein quality control and impaired intestinal integrity. Collectively, our findings indicate that ER homeostasis and organismal health are protected by synergistic functions of ERAS and ERAD., (© 2022. The Author(s).)
Published: 2022
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24. Human hepatocyte PNPLA3-148M exacerbates rapid non-alcoholic fatty liver disease development in chimeric mice.

Author: Kabbani M, Michailidis E, Steensels S, Fulmer CG, Luna JM, Le Pen J, Tardelli M, Razooky B, Ricardo-Lax I, Zou C, Zeck B, Stenzel AF, Quirk C, Foquet L, Ashbrook AW, Schneider WM, Belkaya S, Lalazar G, Liang Y, Pittman M, Devisscher L, Suemizu H, Theise ND, Chiriboga L, Cohen DE, Copenhaver R, Grompe M, Meuleman P, Ersoy BA, Rice CM, and de Jong YP
Subjects: Acyltransferases, Animals, Hepatocytes metabolism, Humans, Lipase genetics, Lipase metabolism, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, Phospholipases A2, Calcium-Independent, Non-alcoholic Fatty Liver Disease genetics
Abstract: Advanced non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging global health problem associated with pre-disposing genetic polymorphisms, most strikingly an isoleucine to methionine substitution in patatin-like phospholipase domain-containing protein 3 (PNPLA3-I148M). Here, we study how human hepatocytes with PNPLA3 148I and 148M variants engrafted in the livers of broadly immunodeficient chimeric mice respond to hypercaloric diets. As early as four weeks, mice developed dyslipidemia, impaired glucose tolerance, and steatosis with ballooning degeneration selectively in the human graft, followed by pericellular fibrosis after eight weeks of hypercaloric feeding. Hepatocytes with the PNPLA3-148M variant, either from a homozygous 148M donor or overexpressed in a 148I donor background, developed microvesicular and severe steatosis with frequent ballooning degeneration, resulting in more active steatohepatitis than 148I hepatocytes. We conclude that PNPLA3-148M in human hepatocytes exacerbates NAFLD. These models will facilitate mechanistic studies into human genetic variant contributions to advanced fatty liver diseases., Competing Interests: Declaration of interests L.F., R.C., and M.G. have financial interest in Yecuris Corporation. All others declare no competing interests., (Copyright © 2022. Published by Elsevier Inc.)
Published: 2022
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25. Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia.

Author: Zhang Q, Matuozzo D, Le Pen J, Lee D, Moens L, Asano T, Bohlen J, Liu Z, Moncada-Velez M, Kendir-Demirkol Y, Jing H, Bizien L, Marchal A, Abolhassani H, Delafontaine S, Bucciol G, Bayhan GI, Keles S, Kiykim A, Hancerli S, Haerynck F, Florkin B, Hatipoglu N, Ozcelik T, Morelle G, Zatz M, Ng LFP, Lye DC, Young BE, Leo YS, Dalgard CL, Lifton RP, Renia L, Meyts I, Jouanguy E, Hammarström L, Pan-Hammarström Q, Boisson B, Bastard P, Su HC, Boisson-Dupuis S, Abel L, Rice CM, Zhang SY, Cobat A, and Casanova JL
Subjects: Adult, Child, Humans, Inheritance Patterns, SARS-CoV-2, COVID-19 genetics, Interferon Type I, Pneumonia
Abstract: Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5-13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10-11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children., (© 2022 ZHANG et al.)
Published: 2022
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26. Replication and single-cycle delivery of SARS-CoV-2 replicons.

Author: Ricardo-Lax I, Luna JM, Thao TTN, Le Pen J, Yu Y, Hoffmann HH, Schneider WM, Razooky BS, Fernandez-Martinez J, Schmidt F, Weisblum Y, Trüeb BS, Berenguer Veiga I, Schmied K, Ebert N, Michailidis E, Peace A, Sánchez-Rivera FJ, Lowe SW, Rout MP, Hatziioannou T, Bieniasz PD, Poirier JT, MacDonald MR, Thiel V, and Rice CM
Subjects: Animals, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Antiviral Agents pharmacology, Cell Line, Humans, Interferons pharmacology, Microbial Sensitivity Tests, Mutation, Plasmids, RNA, Viral metabolism, Replicon genetics, Reverse Genetics, SARS-CoV-2 drug effects, SARS-CoV-2 physiology, Saccharomyces cerevisiae genetics, Spike Glycoprotein, Coronavirus genetics, Viral Nonstructural Proteins genetics, Viral Nonstructural Proteins metabolism, Viral Pseudotyping, Virion genetics, Virion physiology, Virus Replication, RNA, Viral genetics, Replicon physiology, SARS-CoV-2 genetics
Abstract: Molecular virology tools are critical for basic studies of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and for developing new therapeutics. Experimental systems that do not rely on viruses capable of spread are needed for potential use in lower-containment settings. In this work, we use a yeast-based reverse genetics system to develop spike-deleted SARS-CoV-2 self-replicating RNAs. These noninfectious self-replicating RNAs, or replicons, can be trans-complemented with viral glycoproteins to generate replicon delivery particles for single-cycle delivery into a range of cell types. This SARS-CoV-2 replicon system represents a convenient and versatile platform for antiviral drug screening, neutralization assays, host factor validation, and viral variant characterization.
Published: 2021
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27. Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.

Author: Hoffmann HH, Sánchez-Rivera FJ, Schneider WM, Luna JM, Soto-Feliciano YM, Ashbrook AW, Le Pen J, Leal AA, Ricardo-Lax I, Michailidis E, Hao Y, Stenzel AF, Peace A, Zuber J, Allis CD, Lowe SW, MacDonald MR, Poirier JT, and Rice CM
Subjects: CRISPR-Cas Systems, Coronavirus 229E, Human genetics, Coronavirus 229E, Human metabolism, Coronavirus NL63, Human genetics, Coronavirus NL63, Human metabolism, Coronavirus OC43, Human, Genes, Viral, Host-Pathogen Interactions, Humans, SARS-CoV-2 genetics, Viral Proteins genetics, Viral Proteins metabolism, COVID-19 virology, SARS-CoV-2 metabolism
Abstract: The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has devastated the global economy and claimed more than 1.7 million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen SARS-CoV-2 at two physiologically relevant temperatures along with three related coronaviruses (human coronavirus 229E [HCoV-229E], HCoV-NL63, and HCoV-OC43), allowing us to probe this interactome at a much higher resolution than genome-scale studies. This approach yielded several insights, including potential virus-specific differences in Rab GTPase requirements and glycosylphosphatidylinositol (GPI) anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating coronavirus disease 2019 (COVID-19) and help prepare for future coronavirus outbreaks., Competing Interests: Declaration of interests C.D.A. is a co-founder of Chroma Therapeutics and Constellation Pharmaceuticals and a Scientific Advisory Board member of EpiCypher. S.W.L. is an advisor for and has equity in the following biotechnology companies: ORIC Pharmaceuticals, Faeth Therapeutics, Blueprint Medicines, Geras Bio, Mirimus Inc., PMV Pharmaceuticals, and Constellation Pharmaceuticals. C.M.R. is a founder of Apath LLC, a Scientific Advisory Board member of Imvaq Therapeutics, Vir Biotechnology, and Arbutus Biopharma and is an advisor for Regulus Therapeutics and Pfizer. The remaining authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
Published: 2021
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28. Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks.

Author: Schneider WM, Luna JM, Hoffmann HH, Sánchez-Rivera FJ, Leal AA, Ashbrook AW, Le Pen J, Ricardo-Lax I, Michailidis E, Peace A, Stenzel AF, Lowe SW, MacDonald MR, Rice CM, and Poirier JT
Subjects: A549 Cells, Cell Line, Clustered Regularly Interspaced Short Palindromic Repeats, Coronavirus 229E, Human physiology, Coronavirus Infections virology, Coronavirus NL63, Human physiology, Coronavirus OC43, Human physiology, Gene Knockout Techniques, HEK293 Cells, Host-Pathogen Interactions drug effects, Humans, Membrane Proteins metabolism, Metabolic Networks and Pathways drug effects, Protein Interaction Mapping, Coronavirus Infections genetics, Genome-Wide Association Study, SARS-CoV-2 physiology
Abstract: The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity. The cellular host factors and pathways co-opted during SARS-CoV-2 and related coronavirus life cycles remain ill defined. To address this gap, we performed genome-scale CRISPR knockout screens during infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E). These screens uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, sterol regulatory element-binding protein (SREBP) signaling, bone morphogenetic protein (BMP) signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VMP1, TMEM41, and TMEM64 (VTT) domain-containing protein transmembrane protein 41B (TMEM41B) for infection by SARS-CoV-2 and three seasonal coronaviruses. This human coronavirus host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics., Competing Interests: Declaration of Interests S.W.L. is an advisor for and has equity in the following biotechnology companies: ORIC Pharmaceuticals, Faeth Therapeutics, Blueprint Medicines, Geras Bio, Mirimus Inc., PMV Pharmaceuticals, and Constellation Pharmaceuticals. C.M.R. is a founder of Apath LLC; a Scientific Advisory Board member of Imvaq Therapeutics; Vir Biotechnology, and Arbutus Biopharma; and an advisor for Regulus Therapeutics and Pfizer., (Copyright © 2020 Elsevier Inc. All rights reserved.)
Published: 2021
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29. The deubiquitinase TRABID stabilizes the K29/K48-specific E3 ubiquitin ligase HECTD1.

Author: Harris LD, Le Pen J, Scholz N, Mieszczanek J, Vaughan N, Davis S, Berridge G, Kessler BM, Bienz M, and Licchesi JDF
Subjects: Amino Acid Sequence genetics, Animals, COS Cells, Chlorocebus aethiops, Dogs, Endopeptidases chemistry, HEK293 Cells, Humans, Madin Darby Canine Kidney Cells, Point Mutation genetics, Proteolysis, Signal Transduction genetics, Substrate Specificity genetics, Ubiquitin chemistry, Ubiquitin-Protein Ligases chemistry, Endopeptidases genetics, Proteomics, Ubiquitin genetics, Ubiquitin-Protein Ligases genetics, Ubiquitination genetics
Abstract: Ubiquitin is a versatile posttranslational modification, which is covalently attached to protein targets either as a single moiety or as a ubiquitin chain. In contrast to K48 and K63-linked chains, which have been extensively studied, the regulation and function of most atypical ubiquitin chains are only starting to emerge. The deubiquitinase TRABID/ZRANB1 is tuned for the recognition and cleavage of K29 and K33-linked chains. Yet, substrates of TRABID and the cellular functions of these atypical ubiquitin signals remain unclear. We determined the interactome of two TRABID constructs rendered catalytic dead either through a point mutation in the catalytic cysteine residue or through removal of the OTU catalytic domain. We identified 50 proteins trapped by both constructs and which therefore represent candidate substrates of TRABID. The E3 ubiquitin ligase HECTD1 was then validated as a substrate of TRABID and used UbiCREST and Ub-AQUA proteomics to show that HECTD1 preferentially assembles K29- and K48-linked ubiquitin chains. Further in vitro autoubiquitination assays using ubiquitin mutants established that while HECTD1 can assemble short homotypic K29 and K48-linked chains, it requires branching at K29/K48 in order to achieve its full ubiquitin ligase activity. We next used transient knockdown and genetic knockout of TRABID in mammalian cells in order to determine the functional relationship between TRABID and HECTD1. This revealed that upon TRABID depletion, HECTD1 is readily degraded. Thus, this study identifies HECTD1 as a mammalian E3 ligase that assembles branched K29/K48 chains and also establishes TRABID-HECTD1 as a DUB/E3 pair regulating K29 linkages., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2021
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30. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Author: Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schlüter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D'Angio' M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Çölkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela ŞN, Rodríguez-Gallego C, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouénan C, Snow AL, Dalgard CL, Milner JD, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli MJ, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, García-Sastre A, Krammer F, Pujol A, Duffy D, Lifton RP, Zhang SY, Gorochov G, Béziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, and Casanova JL
Subjects: Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Asymptomatic Infections, Betacoronavirus, COVID-19, Child, Child, Preschool, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Infant, Interferon Regulatory Factor-7 deficiency, Interferon Regulatory Factor-7 genetics, Male, Middle Aged, Pandemics, Receptor, Interferon alpha-beta deficiency, Receptor, Interferon alpha-beta genetics, SARS-CoV-2, Toll-Like Receptor 3 deficiency, Toll-Like Receptor 3 genetics, Young Adult, Coronavirus Infections genetics, Coronavirus Infections immunology, Interferon Type I immunology, Loss of Function Mutation, Pneumonia, Viral genetics, Pneumonia, Viral immunology
Abstract: Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Published: 2020
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31. Autoantibodies against type I IFNs in patients with life-threatening COVID-19.

Author: Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, Dorgham K, Philippot Q, Rosain J, Béziat V, Manry J, Shaw E, Haljasmägi L, Peterson P, Lorenzo L, Bizien L, Trouillet-Assant S, Dobbs K, de Jesus AA, Belot A, Kallaste A, Catherinot E, Tandjaoui-Lambiotte Y, Le Pen J, Kerner G, Bigio B, Seeleuthner Y, Yang R, Bolze A, Spaan AN, Delmonte OM, Abers MS, Aiuti A, Casari G, Lampasona V, Piemonti L, Ciceri F, Bilguvar K, Lifton RP, Vasse M, Smadja DM, Migaud M, Hadjadj J, Terrier B, Duffy D, Quintana-Murci L, van de Beek D, Roussel L, Vinh DC, Tangye SG, Haerynck F, Dalmau D, Martinez-Picado J, Brodin P, Nussenzweig MC, Boisson-Dupuis S, Rodríguez-Gallego C, Vogt G, Mogensen TH, Oler AJ, Gu J, Burbelo PD, Cohen JI, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Rossignol P, Mayaux J, Rieux-Laucat F, Husebye ES, Fusco F, Ursini MV, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Castagnoli R, Montagna D, Licari A, Marseglia GL, Duval X, Ghosn J, Tsang JS, Goldbach-Mansky R, Kisand K, Lionakis MS, Puel A, Zhang SY, Holland SM, Gorochov G, Jouanguy E, Rice CM, Cobat A, Notarangelo LD, Abel L, Su HC, and Casanova JL
Subjects: Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing blood, Asymptomatic Infections, Betacoronavirus, COVID-19, Case-Control Studies, Critical Illness, Female, Humans, Immunoglobulin G blood, Male, Middle Aged, Pandemics, SARS-CoV-2, Autoantibodies blood, Coronavirus Infections immunology, Interferon Type I immunology, Interferon alpha-2 immunology, Pneumonia, Viral immunology
Abstract: Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Published: 2020
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32. Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks.

Author: Schneider WM, Luna JM, Hoffmann HH, Sánchez-Rivera FJ, Leal AA, Ashbrook AW, Le Pen J, Michailidis E, Ricardo-Lax I, Peace A, Stenzel AF, Lowe SW, MacDonald MR, Rice CM, and Poirier JT
Abstract: The COVID-19 pandemic has claimed the lives of more than one million people worldwide. The causative agent, SARS-CoV-2, is a member of the Coronaviridae family, which are viruses that cause respiratory infections of varying severity. The cellular host factors and pathways co-opted by SARS-CoV-2 and other coronaviruses in the execution of their life cycles remain ill-defined. To develop an extensive compendium of host factors required for infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E), we performed parallel genome-scale CRISPR knockout screens. These screens uncovered multiple host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, SREBP signaling, and glycosylphosphatidylinositol biosynthesis, as well as an unexpected requirement for several poorly characterized proteins. We identified an absolute requirement for the VTT-domain containing protein TMEM41B for infection by SARS-CoV-2 and all other coronaviruses. This human Coronaviridae host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus spillover events., Highlights: Genome-wide CRISPR screens for SARS-CoV-2, HCoV-OC43, HCoV-NL63, and HCoV-229E coronavirus host factors.Parallel genome-wide CRISPR screening uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles.Coronaviruses co-opt multiple biological pathways, including glycosaminoglycan biosynthesis, SREBP signaling, and glycosylphosphatidylinositol biosynthesis and anchoring, among others.TMEM41B - a poorly understood factor with roles in autophagy and lipid mobilization - is a critical pan-coronavirus host factor.
Published: 2020
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33. Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.

Author: Hoffmann HH, Schneider WM, Sánchez-Rivera FJ, Luna JM, Ashbrook AW, Soto-Feliciano YM, Leal AA, Le Pen J, Ricardo-Lax I, Michailidis E, Hao Y, Stenzel AF, Peace A, Allis CD, Lowe SW, MacDonald MR, Poirier JT, and Rice CM
Abstract: The ongoing SARS-CoV-2 pandemic has devastated the global economy and claimed nearly one million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen four related coronaviruses (HCoV-229E, HCoV-NL63, HCoV-OC43 and SARS-CoV-2) at two physiologically relevant temperatures (33 °C and 37 °C), allowing us to probe this interactome at a much higher resolution relative to genome scale studies. This approach yielded several new insights, including unexpected virus and temperature specific differences in Rab GTPase requirements and GPI anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating COVID-19, and help prepare for future coronavirus outbreaks., Highlights: Focused CRISPR screens targeting host factors in the SARS-CoV-2 interactome were performed for SARS-CoV-2, HCoV-229E, HCoV-NL63, and HCoV-OC43 coronaviruses.Focused interactome CRISPR screens achieve higher resolution compared to genome-wide screens, leading to the identification of critical factors missed by the latter.Parallel CRISPR screens against multiple coronaviruses uncover host factors and pathways with pan-coronavirus and virus-specific functional roles.The number of host proteins that interact with a viral bait protein is not proportional to the number of functional interactors.Novel SARS-CoV-2 host factors are expressed in relevant cell types in the human airway.
Published: 2020
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34. High-Throughput Quantitative RT-PCR in Single and Bulk C. elegans Samples Using Nanofluidic Technology.

Author: Chauve L, Le Pen J, Hodge F, Todtenhaupt P, Biggins L, Miska EA, Andrews S, and Casanueva O
Subjects: Animals, Caenorhabditis elegans Proteins genetics, DNA Primers, DNA, Complementary, DNA, Helminth, Heat-Shock Proteins genetics, Oligonucleotide Array Sequence Analysis, RNA, Messenger metabolism, Caenorhabditis elegans genetics, Real-Time Polymerase Chain Reaction methods, Reverse Transcriptase Polymerase Chain Reaction methods
Abstract: This paper presents a high-throughput reverse transcription quantitative PCR (RT-qPCR) assay for Caenorhabditis elegans that is fast, robust, and highly sensitive. This protocol obtains precise measurements of gene expression from single worms or from bulk samples. The protocol presented here provides a novel adaptation of existing methods for complementary DNA (cDNA) preparation coupled to a nanofluidic RT-qPCR platform. The first part of this protocol, named 'Worm-to-CT', allows cDNA production directly from nematodes without the need for prior mRNA isolation. It increases experimental throughput by allowing the preparation of cDNA from 96 worms in 3.5 h. The second part of the protocol uses existing nanofluidic technology to run high-throughput RT-qPCR on the cDNA. This paper evaluates two different nanofluidic chips: the first runs 96 samples and 96 targets, resulting in 9,216 reactions in approximately 1.5 days of benchwork. The second chip type consists of six 12 x 12 arrays, resulting in 864 reactions. Here, the Worm-to-CT method is demonstrated by quantifying mRNA levels of genes encoding heat shock proteins from single worms and from bulk samples. Provided is an extensive list of primers designed to amplify processed RNA for the majority of coding genes within the C. elegans genome.
Published: 2020
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35. Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines.

Author: Hernandez N, Bucciol G, Moens L, Le Pen J, Shahrooei M, Goudouris E, Shirkani A, Changi-Ashtiani M, Rokni-Zadeh H, Sayar EH, Reisli I, Lefevre-Utile A, Zijlmans D, Jurado A, Pholien R, Drutman S, Belkaya S, Cobat A, Boudewijns R, Jochmans D, Neyts J, Seeleuthner Y, Lorenzo-Diaz L, Enemchukwu C, Tietjen I, Hoffmann HH, Momenilandi M, Pöyhönen L, Siqueira MM, de Lima SMB, de Souza Matos DC, Homma A, Maia MLS, da Costa Barros TA, de Oliveira PMN, Mesquita EC, Gijsbers R, Zhang SY, Seligman SJ, Abel L, Hertzog P, Marr N, Martins RM, Meyts I, Zhang Q, MacDonald MR, Rice CM, Casanova JL, Jouanguy E, and Bossuyt X
Subjects: Adolescent, Alleles, Child, Female, Humans, Immunity, Infant, Interferon Type I metabolism, Male, Measles Vaccine immunology, Mutant Proteins metabolism, Mutation genetics, Pedigree, Receptor, Interferon alpha-beta genetics, Signal Transduction, Yellow Fever Vaccine immunology, Inheritance Patterns genetics, Measles Vaccine adverse effects, Receptor, Interferon alpha-beta deficiency, Yellow Fever Vaccine adverse effects
Abstract: Vaccination against measles, mumps, and rubella (MMR) and yellow fever (YF) with live attenuated viruses can rarely cause life-threatening disease. Severe illness by MMR vaccines can be caused by inborn errors of type I and/or III interferon (IFN) immunity (mutations in IFNAR2 , STAT1 , or STAT2 ). Adverse reactions to the YF vaccine have remained unexplained. We report two otherwise healthy patients, a 9-yr-old boy in Iran with severe measles vaccine disease at 1 yr and a 14-yr-old girl in Brazil with viscerotropic disease caused by the YF vaccine at 12 yr. The Iranian patient is homozygous and the Brazilian patient compound heterozygous for loss-of-function IFNAR1 variations. Patient-derived fibroblasts are susceptible to viruses, including the YF and measles virus vaccine strains, in the absence or presence of exogenous type I IFN. The patients' fibroblast phenotypes are rescued with WT IFNAR1 Autosomal recessive, complete IFNAR1 deficiency can result in life-threatening complications of vaccination with live attenuated measles and YF viruses in previously healthy individuals., (© 2019 Hernandez et al.)
Published: 2019
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36. Friend and foe, HNRNPC takes on immunostimulatory RNAs in breast cancer cells.

Author: Sarbanes SL, Le Pen J, and Rice CM
Subjects: Heterogeneous-Nuclear Ribonucleoprotein Group C, Humans, Interferons, RNA, Double-Stranded, Antiviral Agents, Breast Neoplasms
Published: 2018
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37. Terminal uridylyltransferases target RNA viruses as part of the innate immune system.

Author: Le Pen J, Jiang H, Di Domenico T, Kneuss E, Kosałka J, Leung C, Morgan M, Much C, Rudolph KLM, Enright AJ, O'Carroll D, Wang D, and Miska EA
Subjects: A549 Cells, Animals, Caenorhabditis elegans genetics, Humans, RNA Interference, RNA Viruses immunology, RNA Viruses physiology, RNA, Viral metabolism, Transcriptome, Virus Replication, Caenorhabditis elegans enzymology, Caenorhabditis elegans virology, Immunity, Innate, RNA Nucleotidyltransferases metabolism, RNA Viruses metabolism
Abstract: RNA viruses are a major threat to animals and plants. RNA interference (RNAi) and the interferon response provide innate antiviral defense against RNA viruses. Here, we performed a large-scale screen using Caenorhabditis elegans and its natural pathogen the Orsay virus (OrV), and we identified cde-1 as important for antiviral defense. CDE-1 is a homolog of the mammalian TUT4 and TUT7 terminal uridylyltransferases (collectively called TUT4(7)); its catalytic activity is required for its antiviral function. CDE-1 uridylates the 3' end of the OrV RNA genome and promotes its degradation in a manner independent of the RNAi pathway. Likewise, TUT4(7) enzymes uridylate influenza A virus (IAV) mRNAs in mammalian cells. Deletion of TUT4(7) leads to increased IAV mRNA and protein levels. Collectively, these data implicate 3'-terminal uridylation of viral RNAs as a conserved antiviral defense mechanism.
Published: 2018
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38. Constitutive p53 heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors of BCL-xL.

Author: Le Pen J, Maillet L, Sarosiek K, Vuillier C, Gautier F, Montessuit S, Martinou JC, Letaï A, Braun F, and Juin PP
Published: 2017
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39. Tight Sequestration of BH3 Proteins by BCL-xL at Subcellular Membranes Contributes to Apoptotic Resistance.

Author: Pécot J, Maillet L, Le Pen J, Vuillier C, Trécesson SC, Fétiveau A, Sarosiek KA, Bock FJ, Braun F, Letai A, Tait SWG, Gautier F, and Juin PP
Subjects: Apoptosis Regulatory Proteins metabolism, Bcl-2-Like Protein 11 genetics, Cell Survival genetics, Cell-Free System, HCT116 Cells, Humans, Mitochondria metabolism, Neoplasms drug therapy, Peptide Fragments administration & dosage, Proto-Oncogene Proteins administration & dosage, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins c-bcl-2 genetics, bcl-X Protein metabolism, Apoptosis genetics, Apoptosis Regulatory Proteins genetics, Mitochondria genetics, Neoplasms genetics, bcl-X Protein genetics
Abstract: Anti-apoptotic BCL-2 family members bind to BH3-only proteins and multidomain BAX/BAK to preserve mitochondrial integrity and maintain survival. Whereas inhibition of these interactions is the biological basis of BH3-mimetic anti-cancer therapy, the actual response of membrane-bound protein complexes to these compounds is currently ill-defined. Here, we find that treatment with BH3 mimetics targeting BCL-xL spares subsets of cells with the highest levels of this protein. In intact cells, sequestration of some pro-apoptotic activators (including PUMA and BIM) by full-length BCL-xL is much more resistant to derepression than previously described in cell-free systems. Alterations in the BCL-xL C-terminal anchor that impacts subcellular membrane-targeting and localization dynamics restore sensitivity. Thus, the membrane localization of BCL-xL enforces its control over cell survival and, importantly, limits the pro-apoptotic effects of BH3 mimetics by selectively influencing BCL-xL binding to key pro-apoptotic effectors., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2016
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40. Antiviral RNA Interference against Orsay Virus Is neither Systemic nor Transgenerational in Caenorhabditis elegans.

Author: Ashe A, Sarkies P, Le Pen J, Tanguy M, and Miska EA
Subjects: Animals, Base Sequence, Caenorhabditis elegans immunology, Microarray Analysis, Molecular Sequence Data, Sequence Analysis, RNA, Caenorhabditis elegans virology, Immunity, Innate immunology, Inheritance Patterns immunology, Models, Immunological, Nodaviridae immunology, RNA Interference immunology
Abstract: Unlabelled: Antiviral RNA-mediated silencing (RNA interference [RNAi]) acts as a powerful innate immunity defense in plants, invertebrates, and mammals. In Caenorhabditis elegans, RNAi is systemic; i.e., RNAi silencing signals can move between cells and tissues. Furthermore, RNAi effects can be inherited transgenerationally and may last for many generations. Neither the biological relevance of systemic RNAi nor transgenerational RNAi is currently understood. Here we examined the role of both pathways in the protection of C. elegans from viral infection. We studied the Orsay virus, a positive-strand RNA virus related to Nodaviridae and the first and only virus known to infect C. elegans. Immunity to Orsay virus infection requires the RNAi pathway. Surprisingly, we found that genes required for systemic or transgenerational RNAi did not have a role in antiviral defense. Furthermore, we found that Orsay virus infection did not elicit a systemic RNAi response even when a target for RNAi was provided by using transgenes. Finally, we show that viral siRNAs, the effectors of RNAi, are not inherited to a level that provides any significant resistance to viral infection in the next generation. We conclude that systemic or transgenerational RNAi does not play a role in the defense against natural Orsay virus infection. Furthermore, our data suggest that there is a qualitative difference between experimental RNAi and antiviral RNAi. Our data are consistent with a model of systemic and transgenerational RNAi that requires a nuclear or germ line component that is lacking in almost all RNA virus infections., Importance: Since its discovery in Caenorhabditis elegans, RNAi has proven a valuable scientific tool in many organisms. In C. elegans, exogenous RNAi spreads throughout the organism and can be passed between generations; however, there has been controversy as to the endogenous role(s) that the RNAi pathway plays. One endogenous role for which spreading both within the infected organism and between generations would be advantageous is a role in viral defense. In plants, antiviral RNAi is systemic and the spread of RNAi between cells provides protection against subsequent viral infection. Here we investigated this by using the only naturally occurring virus known to infect C. elegans, Orsay virus, and surprisingly found that, in contrast to the exogenous RNAi pathway, the antiviral RNAi response targeted against this virus does not spread systemically throughout the organism and cannot be passed between generations. These results suggest that there are differences between the two pathways that remain to be discovered., (Copyright © 2015 Ashe et al.)
Published: 2015
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41. TE-Tracker: systematic identification of transposition events through whole-genome resequencing.

Author: Gilly A, Etcheverry M, Madoui MA, Guy J, Quadrana L, Alberti A, Martin A, Heitkam T, Engelen S, Labadie K, Le Pen J, Wincker P, Colot V, and Aury JM
Subjects: DNA Methylation, Humans, Arabidopsis genetics, DNA Transposable Elements genetics, Genes, Plant genetics, Genome, Plant, High-Throughput Nucleotide Sequencing methods, Software
Abstract: Background: Transposable elements (TEs) are DNA sequences that are able to move from their location in the genome by cutting or copying themselves to another locus. As such, they are increasingly recognized as impacting all aspects of genome function. With the dramatic reduction in cost of DNA sequencing, it is now possible to resequence whole genomes in order to systematically characterize novel TE mobilization in a particular individual. However, this task is made difficult by the inherently repetitive nature of TE sequences, which in some eukaryotes compose over half of the genome sequence. Currently, only a few software tools dedicated to the detection of TE mobilization using next-generation-sequencing are described in the literature. They often target specific TEs for which annotation is available, and are only able to identify families of closely related TEs, rather than individual elements., Results: We present TE-Tracker, a general and accurate computational method for the de-novo detection of germ line TE mobilization from re-sequenced genomes, as well as the identification of both their source and destination sequences. We compare our method with the two classes of existing software: specialized TE-detection tools and generic structural variant (SV) detection tools. We show that TE-Tracker, while working independently of any prior annotation, bridges the gap between these two approaches in terms of detection power. Indeed, its positive predictive value (PPV) is comparable to that of dedicated TE software while its sensitivity is typical of a generic SV detection tool. TE-Tracker demonstrates the benefit of adopting an annotation-independent, de novo approach for the detection of TE mobilization events. We use TE-Tracker to provide a comprehensive view of transposition events induced by loss of DNA methylation in Arabidopsis. TE-Tracker is freely available at http://www.genoscope.cns.fr/TE-Tracker ., Conclusions: We show that TE-Tracker accurately detects both the source and destination of novel transposition events in re-sequenced genomes. Moreover, TE-Tracker is able to detect all potential donor sequences for a given insertion, and can identify the correct one among them. Furthermore, TE-Tracker produces significantly fewer false positives than common SV detection programs, thus greatly facilitating the detection and analysis of TE mobilization events.
Published: 2014
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42. Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.

Author: Sarkies P, Ashe A, Le Pen J, McKie MA, and Miska EA
Subjects: Animals, Caenorhabditis elegans immunology, Caenorhabditis elegans virology, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins metabolism, Gene Ontology, Genome, Helminth, Host-Pathogen Interactions, Immunity, Innate genetics, MicroRNAs genetics, MicroRNAs metabolism, Multigene Family, Transcriptome, Up-Regulation, Caenorhabditis elegans genetics, Nodaviridae genetics, RNA Interference, RNA, Viral genetics
Abstract: Positive-strand RNA viruses encompass more than one-third of known virus genera and include many medically and agriculturally relevant human, animal, and plant pathogens. The nematode Caenorhabditis elegans and its natural pathogen, the positive-strand RNA virus Orsay, have recently emerged as a new animal model to understand the mechanisms and evolution of innate immune responses. In particular, the RNA interference (RNAi) pathway is required for C. elegans resistance to viral infection. Here we report the first genome-wide analyses of gene expression upon viral infection in C. elegans. Using the laboratory strain N2, we identify a novel C. elegans innate immune response specific to viral infection. A subset of these changes is driven by the RNAi response to the virus, which redirects the Argonaute protein RDE-1 from its endogenous small RNA cofactors, leading to loss of repression of endogenous RDE-1 targets. Additionally, we show that a C. elegans wild isolate, JU1580, has a distinct gene expression signature in response to viral infection. This is associated with a reduction in microRNA (miRNA) levels and an up-regulation of their target genes. Intriguingly, alterations in miRNA levels upon JU1580 infection are associated with a transformation of the antiviral transcriptional response into an antibacterial-like response. Together our data support a model whereby antiviral RNAi competes with endogenous small RNA pathways, causing widespread transcriptional changes. This provides an elegant mechanism for C. elegans to orchestrate its antiviral response, which may have significance for the relationship between small RNA pathways and immune regulation in other organisms.
Published: 2013
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43. piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans.

Author: Ashe A, Sapetschnig A, Weick EM, Mitchell J, Bagijn MP, Cording AC, Doebley AL, Goldstein LD, Lehrbach NJ, Le Pen J, Pintacuda G, Sakaguchi A, Sarkies P, Ahmed S, and Miska EA
Subjects: Animals, Caenorhabditis elegans metabolism, Cell Nucleus genetics, Cell Nucleus metabolism, Female, Germ Cells metabolism, Male, Transgenes, Caenorhabditis elegans genetics, Epigenomics, RNA Interference, RNA, Helminth metabolism, RNA, Small Interfering metabolism
Abstract: Transgenerational effects have wide-ranging implications for human health, biological adaptation, and evolution; however, their mechanisms and biology remain poorly understood. Here, we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain stable inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches, we find that a core set of nuclear RNAi and chromatin factors is required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 ortholog HPL-2, and two putative histone methyltransferases, SET-25 and SET-32. piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present a multigenerational epigenetic inheritance mechanism induced by piRNAs., (Copyright © 2012 Elsevier Inc. All rights reserved.)
Published: 2012
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