Zhang, Qian, Pizzorno, Andrés, Miorin, Lisa, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Manry, Jeremy, Rosain, Jérémie, Philippot, Quentin, Goavec, Kelian, Wroblewski, Isabelle, Husebye, Eystein, Fellay, Jacques, Pothier, Pierre, Morand, Patrice, Navarrete, Nicolás, Franco, José Luis, Uddin, Mohammed J., Carratalà, Jordi, Merino Díaz, Laura, Palomo, Virginia, Seppänen, Mikko R.J., Särekannu, Karita, Aiuti, Alessandro, Retamar Gentil, Pilar, Debette, Stéphanie, Belot, Alexandre, Abel, Laurent, Soler Palacín, Pere, Abad Arranz, Maria, Aguilar Guisado, Manuela, Meyts, Isabelle, Casanova, Jean-Laurent, Gonzalez Granado, Luis L., Butte, Manish J., Itan, Yuval, Escoresca Ortega, Ana, Morio, Tomohiro, Padey, Blandine, Niubó, Jordi, Gallardo Ríos, Rafaela, Lau, Yu-lung, Triantafyllia, Vasiliki, Briones, Marisa, Saker, Kahina, Richard, Pascale, Drolet, Beth A., Espinosa Padilla, Sara, Wauters, Joost, Peigue Lafeuille, Helene, Valiente, Adoración, El Baghdadi, Jamila, Tiberghien, Pierre, Balsera-manzanero, María, Zins, Marie, Hammarström, Lennart, Andreakos, Evangelos, Notarangelo, Luigi D., Prando, Carolina, Condino-neto, Antonio, Dominguez Pinilla, Nerea, Aydillo, Teresa, Okamoto, Keisuke, Soumaré, Aïcha, Karamitros, Timokratis, Medina, Rafael A., Kisand, Kai, Ramírez Duque, Nieves, Feys, Simon, Romero Oraa, Laura, Kuo, Chen-yen, Lei, Wei-te, Quintana Murci, Lluis, Milner, Joshua D., Ku, Cheng-lung, Van De Beek, Diederik, Hsieh, Elena W.Y., Tal, Galit, Fournet, Thomas, Cerba Healthcare Group, Patural, Hugues, Novelli, Giuseppe, Lyon Antigrippe Working Group, Arias, Andrés A., Rovina, Nikoletta, Rodríguez-gallego, Carlos, Puel, Anne, Jouanguy, Emmanuelle, Vinh, Donald C., Henny, Joseph, Mogensen, Trine H., Cobat, Aurélie, Casari, Giorgio, Ramaswamy, Sathishkumar, Abelenda Alonso, Gabriela, Morel, Pascal, Trouillet Assant, Sophie, Tzourio, Christophe, Gallian, Pierre, Reipi Inf Working Group, García Sastre, Adolfo, Constantinescu, Stefan N., Hamzeh Cognasse, Hind, Haerynck, Filomeen, Flores, Carlos, Bousfiha, Ahmed A., García Salum, Tamara, Shahrooei, Mohammed, Slaby, Ondrej, Fragkou, Paraskevi C., Argaud, Laurent, Shcherbina, Anna, Al-muhsen, Saleh, Biggs, Catherine M., Bogunovic, Dusan, Planas, Anna M., Heath, James R., Von Bernuth, Horst, Dufouil, Carole, Bolze, Alexandre, Boeuf, Benoit, Rodríguez Gallego, Carlos, Christodoulou, John, Bondarenko, Anastasiia, Martin, Fernando, Koltsida, Ourania, Sediva, Anna, Ruiz Hernandez, José Juan, Bonneaudeau, Brigitte, Cannet, Dorothée, Etablissement Français Du Sang Study Group, Froidure, Antoine, Laurent, Emilie, Galani, Ioanna Evdokia, Gregersen, Peter K., Lemonnier, Sylvie, Spaan, András N., Darmon, Michael, Grimbacher, Bodo, Del Mar Muñoz Garcia, Maria, Zawadzki, Pawel, Henrickson, Sarah E., O'farrelly, Cliona, Rosa Calatrava, Manuel, Lachaize, Morgane, Okada, Satoshi, Vanker, Martti, Bryceson, Yenan, Ling, Yun, Cooper, Megan A., Lucas, Carrie L., Maniatis, Tom, Romero Vázquez, Gloria María, Mansouri, Davood, Castagnoli, Riccardo, Maródi, László, Mironska, Kristina, Rapti, Vasiliki, Baris Feldman, Hagit, Pozzetto, Bruno, Renia, Laurent, Tancevski, Ivan, Imai, Kohsuke, Ozcelik, Tayfun, Pan-hammarström, Qiang, Al-mulla, Fahd, Pape, Jean W., Etzioni, Amos, Souweine, Bertrand, Perez De Diego, Rebeca, Sánchez Cordero, Maria Jose, Solé Violán, Jordi, Perlin, David S., Queromes, Gregory, Anderson, Mark S., Resnick, Igor, Pesole, Graziano, Su, Helen C., Vanderbeke, Lore, Hagin, David, Jeanne, Michel, Desai, Murkesh, Ferres, Marcela, Sánchez Céspedes, Javier, Perroquin, Magali, Ng, Lisa F.P., Abou Tayoun, Ahmad, Le Corre, Nicole, Snow, Andrew L., Temel, Şehime Gülsün, Tsiodras, Sotirios, Coeuret Pellicer, Mireille, Javouhey, Etienne, Turvey, Stuart E., Covid Human Genetic Effort, Rombauts, Alexander, Zatz, Mayana, Uddin, K.m. Furkan, Fievet, Nathalie, Jarvis, Erich D., Rodríguez De Castro, Felipe, Ferreres, José, Flaig, Amandine, Pujol, Aurora, Cognasse, Fabrice, Sancho Shimizu, Vanessa, Nadif, Rachel, Hanna, Suhair, Constances Cohort, Goldberg, Marcel, Brodin, Petter, Le Got, Stéphane, Ozguler, Anna, Quenot, Jean Pierre, Novelli, Antonio, Cordero, Elisa, Colomb, Benoit, Cupic, Anastasija, Mehlal Sedkaoui, Souad, Sallette, Jérôme, Hernu, Romain, Bustamante, Carlos D., Lina, Bruno, Halwani, Rabih, Casalegno, Jean Sebastien, Schwebel, Carole, Salamanca Rivera, Celia, 3C-Dijon Study, Tangye, Stuart G., Dalgard, Clifton L., Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), European Commission, Square Foundation, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Institut National de la Santé et de la Recherche Médicale (France), Université Paris Cité, Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), Center of Excellence for Influenza Research and Response (US) CEIRR, Agencia Nacional de Investigación y Desarrollo (Chile), Centre National de la Recherche Scientifique (France), Ministère des Solidarités et de la Santé (France), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Sociedad Española de Neumología y Cirugía Torácica, Cabildo de Tenerife, Hellenic Foundation for Research and Innovation, Fondation pour la Recherche Médicale, Fondation Bettencourt Schueller, Ministerio de Ciencia, Innovación y Universidades (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Junta de Andalucía, Research Foundation - Flanders, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 01057100, HORIZON-HLTH-2021-DISEASE-04, MESRI-COVID-19, ANR-10-LABX-62-IBEID, P18-RT-3320, CGIEU0000219140, RTC-2017-6471-1, REIPI RD16/0016/0009, National Institutes of Health, NIH: R01AI088364, R01AI163029, Howard Hughes Medical Institute, HHMI, National Institute of Allergy and Infectious Diseases, NIAID: 75N93021C00014, U19AI135972, U19AI142733, U19AI168631, Jeffrey Modell Foundation, JMF, Glenn Foundation for Medical Research, GFMR: ANRS-COV05, EA20170638020, EQU201903007798, Pfizer, Albert Ellis Institute, AEI, National Center for Advancing Translational Sciences, NCATS: UL1 TR001866, JPB Foundation, JPBF, Horizon 2020 Framework Programme, H2020: 824110, Fondation du Souffle, FdS, College of Natural Resources and Sciences, Humboldt State University, CNRS, Ministerio de Ciencia, Innovación y Universidades, MCIU, Instituto Tecnológico y de Energías Renovables, ITER, SCOR Corporate Foundation for Science, Agence Nationale de la Recherche, ANR: ANR-10-IAHU-01, Institut National de la Santé et de la Recherche Médicale, Inserm, Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT: 1161971, 1212023, Association Nationale de la Recherche et de la Technologie, ANRT, Fonds Wetenschappelijk Onderzoek, FWO: G0B5120N, G0C8517N, G0E8420N, KU Leuven: C16/18/007, Instituto de Salud Carlos III, ISCIII: COV20_01333, COV20_01334, PI12/01565, European Regional Development Fund, ERDF: CB21/13/00006, University of the East, UE, Hellenic Foundation for Research and Innovation, ΕΛ.ΙΔ.Ε.Κ, Université de Paris, SINOVAC outside the submitted work. P. Retamar-Gentil reported personal fees from Merck outside the submitted work. I. Meyts reported grants from CSL-Behring outside the submitted work. E. Andreakos reported grants from Janssen Pharmaceuticals during the conduct of the study. J. Wauters reported grants and personal fees from Pfizer and Gilead outside the submitted work. L. Vanderbeke reported grants from Research Foundation Flanders and non-financial support from Pfizer outside the submitted work. S. Feys reported grants from Pfizer outside the submitted work. J. Casalegno reported 'other' from Pfizer and grants from Sanofi outside the submitted work. M. Rosa-Calatrava reported a patent to WO2016/146836 licensed (Signia Therapeutics), a patent to WO2017/174593 licensed (Signia Therapeutics), and a patent to WO2019/224489 licensed (Signia Therapeutics), and is the co-founder of Signia Therapeutics SAS. S. Trouillet-Assant reported non-financial support from BioMérieux outside the submitted work. A. Garcia-Sastre reported 'other' from Vivaldi Biosciences, Pagoda, Contrafect, Vaxalto, Accurius, Curelab oncology, and Curelab veterinary, personal fees from Avimex, 7Hills, Esperovax, Pfizer, Farmak, Applied Biological Laboratories, Paratus, Pharmamar, Pfizer, and Synairgen, grants from Pfizer, Pharmamar, Blade Therapeutics, Avimex, Accurius, Dyna-vax, Kenall Manufacturing, ImmunityBio, Nanocomposix, Merck, Model Medicines, Atea Pharma, Shenwa Biosciences, Johnson & Johnson, 7 Hills, Hexamer, N-fold LLC, and Applied Biological Laboratories outside the submitted work, in addition, A. Garcia-Sastre had a patent for influenza virus vaccines and uses thereof issued, and invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca. J. Casanova reported a patent to PCT/US2021/ 042741 pending. No other disclosures were reported., We thank Dr. Cato Jacobs for her contribution to the sampling of UZLeuven patients in Belgium. 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 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, 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 (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Sci-ence, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmis-sion, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cab-ildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Eu-rope', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University. Author contributions: Q. Zhang, A. Pizzorno, L. Miorin, P., 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 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, 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 (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and, Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Europe', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University., ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), and ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021)