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

We first tested the specific hypothesis that inborn errors of Toll-like receptor 3 (TLR3)– and interferon regulatory factor 7 (IRF7)–dependent type I interferon (IFN) immunity, which underlie life-threatening influenza pneumonia, may also underlie life-threatening COVID-19 pneumonia (5) (Fig. 2). We considered three loci previously shown to be mutated in patients with critical influenza pneumonia: TLR3 (6), IRF7 (7), and IRF9 (8). We also considered 10 loci mutated in patients with other viral illnesses but directly connected to the three core genes conferring influenza susceptibility: TICAM1/TRIF (9), UNC93B1 (10), TRAF3 (11), TBK1 (12), IRF3 (13), and NEMO/IKBKG (14) in the TLR3-dependent type I IFN induction pathway, and IFNAR1 (15), IFNAR2 (16), STAT1 (17), and STAT2 (18) in the IRF7- and IRF9-dependent type I IFN amplification pathway. We collected both monoallelic and biallelic nonsynonymous variants with a minor allele frequency (MAF) <0.001 at all 13 loci. Twelve of the 13 candidate loci are autosomal, whereas NEMO is X-linked. For the latter gene, we considered only a recessive model (19). Autosomal-dominant (AD) inheritance has not been proven for six of the 12 autosomal loci (UNC93B1, IRF7, IFNAR1, IFNAR2, STAT2, and IRF9). Nevertheless, we considered heterozygous variants because none of the patients enrolled had been hospitalized for critical viral infections before COVID-19, raising the possibility that any underlying genetic defects that they might have display a lower penetrance for influenza and other viral illnesses than for COVID-19, which is triggered by a more virulent virus.

We found four unrelated patients with biallelic variants of IRF7 or IFNAR1 (Table 1 and table S1). We also found 113 patients carrying 113 monoallelic variants at 12 loci: TLR3 (N = 7 patients/7 variants), UNC93B1 (N = 10/9), TICAM1 (N = 17/15), TRAF3 (N = 6/6), TBK1 (N = 12/11), IRF3 (N = 5/5), IRF7 (N = 20/13), IFNAR1 (N = 14/13), IFNAR2 (N = 17/15), STAT1 (N = 4/4), STAT2 (N = 11/11), and IRF9 (N = 4/4). We detected no copy number variation for these 13 genes. Unexpectedly, one of these variants has been reported in patients with life-threatening influenza pneumonia (TLR3 p.Pro554Ser) (6, 20) and another was shown to be both deleterious and dominant-negative (IFNAR1 p.Pro335del) (21). Nine of the 118 biallelic or monoallelic variants were predicted to be LOF (pLOF), whereas the remaining 109 were missense or in-frame indels (table S1). In a sample of 534 controls with asymptomatic or mild SARS-CoV-2 infection, we found only one heterozygous pLOF variation with a MAF <0.001 at the 13 loci (IRF7 p.Leu99fs). A PCA-adjusted burden test on the 12 autosomal loci revealed significant enrichment in pLOF variants in patients relative to controls [P = 0.01; odds ratio (OR) = 8.28; 95% confidence interval (CI) = 1.04 to 65.64] under an AD mode of inheritance. The same analysis performed on synonymous variants with a MAF <0.001 was not significant (P = 0.19), indicating that our ethnicity-adjusted burden test was well calibrated.

We tested these 118 variants experimentally in ad hoc overexpression systems. We found that 24 variants of eight genes were deleterious (including all the pLOF variants) because they were loss-of-expression, LOF, or severely hypomorphic: TLR3 (N = 4 variants), UNC93B1 (N = 1), TICAM1 (N = 3), TBK1 (N = 2), IRF3 (N = 2), IRF7 (N = 8), IFNAR1 (N = 3), and IFNAR2 (N = 1) (table S1, Fig. 3, and figs. S1 to S8). Consistently, heterozygous LOF variants of IRF3 and IRF7 were reported in single patients with life-threatening influenza pneumonia (22, 23). The remaining 94 variants were biochemically neutral. Twenty-three patients carried these 24 deleterious variants, resulting in four autosomal-recessive (AR) deficiencies (homozygosity or compound heterozygosity for IRF7; homozygosity for IFNAR1) and 19 AD deficiencies. These 23 patients did not carry candidate variants at the other 417 loci known to underlie inborn errors of immunity (table S2) (24–26). These findings suggest that at least 23 (3.5%) unrelated patients of the 659 patients tested suffered from a deficiency at one of eight loci among the 13 tested: four patients with a known AR disorder (IRF7 or IFNAR1) (7, 15), 11 with a known AD disorder (TLR3, TICAM1, TBK1, or IRF3) (6, 9, 12, 13, 20), and eight with a previously unknown AD genetic disorder (UNC93B1, IRF7, IFNAR1, or IFNAR2).

We tested cells from patients with selected genotypes and showed that PHA-driven T cell blasts (PHA-T cells) from patients with AR or AD IRF7 deficiency had low levels of IRF7 expression (Fig. 4A). We then isolated circulating plasmacytoid dendritic cells (pDCs) from a patient with AR IRF7 deficiency (fig. S9A) (7). These cells were present in normal proportions (fig. S9B), but they did not produce any detectable type I or III IFNs in response to SARS-CoV-2, as analyzed by cytometric bead array (CBA), enzyme-linked immunosorbent assay (ELISA), and RNA sequencing (RNA-seq) (Fig. 4, B and C). We also showed that PHA-T cells from a patient with AR IFN-α/β receptor 1 (IFNAR1) deficiency had impaired IFNAR1 expression and responses to IFN-α2 or IFN-β, and that the patient’s SV40-transformed fibroblast (SV40-Fib) cells did not respond to IFN-α2 or IFN-β (Fig. 5). We then infected TLR3^−/−, TLR3^+/−, IRF7^−/− SV40-Fib cells, and IRF7^−/− SV40-Fib cells rescued with wild-type (WT) IRF7; IFNAR1^−/− SV40-Fib cells, and IFNAR1^−/− SV40-Fib cells rescued with WT IFNAR1, all of which were previously transduced with angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2). SARS-CoV-2 infection levels were higher in mutant cells than in cells from healthy donors, and transduction of WT IRF7 or IFNAR1 rescued their defects (Fig. 6). Collectively, these findings showed that AR IRF7 deficiency impaired the production of type I IFN by pDCs stimulated with SARS-CoV-2, whereas AR and AD deficiencies of TLR3 or AR deficiency of IFNAR1 impaired fibroblast-intrinsic type I IFN immunity to SARS-CoV2. They also suggest that heterozygosity for LOF variations at the other five mutated loci also underlie life-threatening COVID-19.

We tested whether these genotypes impaired the production of type I IFN in vivo during the course of SARS-CoV-2 infection. We measured the levels of the 13 types of IFN-α in the blood of patients during the acute phase of COVID-19. We found that 10 of the 23 patients with mutations for whom samples were available (one with AR IRF7 deficiency, four with AD IRF7 deficiency, one with AD TLR3 deficiency, two with AD TBK1 deficiency, one with AR IFNAR1 deficiency, and one with AD TICAM1 deficiency) had serum IFN-α levels <1 pg/ml (Fig. 7). By contrast, previously published cohorts of patients hospitalized with unexplained, severe COVID-19 had various serum IFN-α levels, significantly higher than our 10 patients [one-way analysis of variance (ANOVA), P = 1.4 × 10⁻⁷; Fig. 7] (27, 28). Another 29 patients from our cohort displaying auto-antibodies (auto-Abs) against type I IFNs, reported in an accompanying paper, had undetectable levels of serum IFN-α (29). Moreover, none of the 23 patients with LOF mutations of the eight genes had detectable auto-Abs against type I IFNs (29), strongly suggesting that the two mechanisms of disease are similar but independent. Excluding patients with auto-Abs against type I IFN from the burden test of pLOF variants at the 12 autosomal loci strengthened the association signal (P = 0.007; OR = 8.97; 95% CI = 1.13 to 71.09).

Collectively, our data suggest that at least 23 of the 659 patients with life-threatening COVID-19 pneumonia studied had known (six disorders) or new (four disorders) genetic defects at eight loci involved in the TLR3- and IRF7-dependent induction and amplification of type I IFNs. This discovery reveals the essential role of both the double-stranded RNA sensor TLR3 and type I IFN cell-intrinsic immunity in the control of SARS-CoV-2 infection in the lungs, consistent with their previously documented roles in pulmonary immunity to influenza virus (5–8). These genotypes were silent until infection with SARS-CoV-2. The most thought-provoking examples are the AR deficiencies of IRF7 and IFNAR1. AR IRF7 deficiency was diagnosed in two individuals aged 49 and 50 years, and AR IFNAR1 deficiency was diagnosed in two individuals aged 26 and 38 years, and none of the four patients had a prior history of life-threatening infections (Table 1). One patient with IRF7 deficiency was tested and was seropositive for several common viruses, including various influenza A and B viruses (figs. S10 and S11). These genetic defects therefore display incomplete penetrance for influenza respiratory distress and only manifested clinically upon infection with the more virulent SARS-CoV-2.

The AR form of IFNAR1 deficiency highlights the importance of type I IFN production relative to type III IFN production, which is also impaired by defects of TLR3, IRF7, and IRF9 (5). This conclusion is also supported by our accompanying report of neutralizing auto-Abs against type I IFNs, but not type III IFNs, in other patients with life-threatening COVID-19 pneumonia (29). Inborn errors of TLR3- and IRF7-dependent type I IFN immunity at eight loci were found in as many as 23 patients (3.5%) of various ages (17 to 77 years) and ancestries (various nationalities from Asia, Europe, Latin America, and the Middle East) and in patients of both sexes (Table 1). Our findings suggest that there may be mutations in other type I IFN–related genes in other patients with life-threatening COVID-19 pneumonia. They also suggest that the administration of type I IFN may be of therapeutic benefit in selected patients, at least early in the course of SARS-CoV-2 infection.

We thank the patients, their families, and healthy donors for placing their trust in us; Y. Nemirowskaya, D. Papandrea, M. Woollet, D. Liu, C. Rivalain, and C. Patissier for administrative assistance; A. Adeleye, D. Bacikova, E. McGrath Martinez, A. R. Soltis, K. Dobbs, J. Danielson, H. Matthews, and S. Weber for technical and other assistance; M. M. A. Ata and F. Al Ali for their contribution to VirScan experiments; S. Elledge (Brigham and Women’s Hospital and Harvard Medical School, Boston, MA) for kindly providing the VirScan phage library used in this study; A. W. Ashbrook, the BSL3 manager of the Rice laboratory assistance; M. Lazzaro, Director of Immigration and Academic Appointments, for assistance; W. Chung, K. Kiryluk, S. O'Byrne, D. Pendrick, J. Williamson, C. Andrews, and M. Disco in the J.M. lab for assistance; M. Andreoni (Tor Vergata, Italy) for his clinical contribution; and A. Novelli (Bambino Gesù Hospital, Italy) for his collaboration. We thank the GEN-COVID Multicenter study (https://sites.google.com/dbm.unisi.it/gen-covid). This study used the high-performance computational resources of the National Institutes of Health (NIH) HPC Biowulf cluster (http://hpc.nih.gov) and the Office of Cyber Infrastructure and Computational Biology (OCICB) High Performance Computing (HPC) cluster at the National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD. The opinions and assertions expressed herein are those of the authors and are not to be construed as reflecting the views of the Uniformed Services University of the Health Sciences (USUHS) or the U.S. Department of Defense (DoD). Funding: This work was supported by a generous donation from the Fisher Center for Alzheimer’s Research Foundation. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the NIH (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), the 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). I.M. is a senior clinical investigator with the FWO Vlaanderen; I.M. and L.M. 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”. L.K. was supported by a fellowship from the French Ministry of Research. V.S.-S. is supported by a UKRI Future Leaders Fellowship (MR/S032304/1). S.Z.A.-M. is supported by the Elite Journals Program at King Saud University through grant no. PEJP-16-107. The J.M. laboratory is supported by Columbia University COVID biobank and grant no. 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. J.L.P. 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 no. 824110 (EasiGenomics grant no. COVID-19/PID12342) to A.P., and Roche and Illumina Covid Match Funds to M.G.. C.R.G. and colleagues are supported by Instituto 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. H.S. 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 A.G.-S. laboratory 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. J.R.H. is supported by Biomedical Advanced Research and Development Authority under Contract (HHSO10201600031C). Author contributions: A.G., A.A., A.A.A., A.L.S., A.-L.N., A.C., A.C., A.P., B.B., B.S.R., C.A., C.M., C.K., C.L., C.M.R., C.L.D., D.D., E.M., E.J., F.A., F.A-M., F.O., F.A., F.K., G.N., G.S., G.G., H.-H.H., H.K.A.S., H.S., I.K.D.S., I.M., J.L.P., J.R., J.E.H., J.C., J.M., J.Y., K.D., K.B., L.A., L.L.-D., L.K., L.M., L.B-M., L.B., L.D.N., M.M-V., M.C., M.O., M.C., M.N., M.F.T., M.S., M.F.A., N.M., N.S., P.B., P.M., Q.Z., Q.Z., Q.P., R.L., R.Y., S.A.T., S.Z.A-M., S.H., S.K., S.H., S.B.-D., T.K., T.M., T.H.M., V.S.-S., V.S., V.B., W.S., X.D., Y.S., and Z.L. either performed or supervised experiments, generated and analyzed data, and contributed to the manuscript. A.S., A.C.U., A.B., A.O., A.P., B.B., D.V.D.B., F.R., G.K., J.M., P.Z., S-Y.Z., T.L.-V., Y.S., and Y.Z. performed computational analysis. A.S., A.N.S., A.M.-N., A.B., C.R., D.M., D.C.V., E.Q.-R., F.H., I.M., I.V., J.B., J.-C.G., L.R.B., L.R., L.I., M.D., P.B., P.S.-P., P.-E.M., R.H., R.C., S.K., S.P., T.O., Y.T.-L., K.K., S.S., J.F., and S.N.K. evaluated and recruited patients to COVID and/or control cohorts. Q.Z. and J.-L.C. wrote the manuscript. All authors edited the manuscript. J.-L.C. supervised the project. Competing interests: The authors declare no competing financial interests. J.-L.C. is listed as an inventor on patent application US63/055,155 filed by The Rockefeller University that encompasses aspects of this publication. R.L. is a non-executive director of Roche and its subsidiary Genentech. Data and materials availability: Plasma, cells, and genomic DNA are available from J.-L.C. or D.V. under a material transfer agreement with Rockfeller University/Research Institute-McGill University Health Centre. pSCRPSY_TMPRSS2-2A-NeoR_ACE2 and Huh-7.5 cells are available upon request from C.R. under a material transfer agreement with The Rockefeller University, or The Rockefeller University and Apath, LLC, respectively. Clinical data, DNA, and other patient samples are available from the Amsterdam UMC Covid-19 Biobank (D.v.d.B.) under a material transfer agreement with Amsterdam UMC. Material and reagents used are almost exclusively commercially available and nonproprietary. Requests for materals derived from human samples may be made available, subject to any underlying restrictions on such samples. J.-L.C. can make material transfer agreements available through The Rockefeller University. Detailed genotype counts for all coding variants in the genes investigated in this manuscript are available at Dryad (41). The whole-genome sequencing datasets used for the analyses, including critical patients and asymptomatic controls described in this manuscript, were deposited in dbGaP under accession number phs002245.v1.p1. All other data are available in the manuscript or the supplementary material. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.

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, 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, Italy.

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*

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, and Complutense University, Madrid, Spain. ¹¹Clinical Immuology and Primary Immunodeficiencies Unit, Hospital 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. ²⁴Department of Urology, Nephrology, and 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, and 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. ³³Department of Pulmonology, Ghent University Hospital, Ghent, Belgium. ³⁴Clinical 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. ³⁵Endocrinology Unit, APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. ³⁶Department of Children’s Diseases and Pediatric Surgery, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. ³⁷Human Genome and Stem-Cell Research Center, University of São Paulo, São Paulo, Brazil. ³⁸Hospital Insular, Las Palmas de Gran Canaria, Spain. ³⁹Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Konya State Hospital, Konya, Turkey. ⁴⁰MS Center, Spedali Civili, Brescia, Italy. ⁴¹Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy. ⁴²Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain. ⁴³Hopital Robert Debré, Paris, France. ⁴⁴Pediatric Immuno-hematology Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France. ⁴⁵Department of Infectious and Tropical Diseases, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. ⁴⁶Doctoral Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. ⁴⁷Hôpital Foch, Suresnes, France. ⁴⁸Necker Hospital for Sick Children, Paris University, AP-HP, Paris, France. ⁴⁹Pasteur Institute, Paris, France. ⁵⁰McGill University Health Centre, Montreal, Canada. ⁵¹University Hospital and Research Institute “Germans Trias i Pujol,” IrsiCaixa AIDS Research Institute, UVic-UCC, Badalona, Spain. ⁵²Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Esplugues, Spain. ⁵³Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. ⁵⁴Department of Infectious Diseases and Clinical Microbiology, Konya Training and Research Hospital, Konya, Turkey. ⁵⁵Hospital Universitari Vall d’Hebron, Barcelona, Spain. ⁵⁶Pitié-Salpêtrière Hospital, Paris, France. ⁵⁷Fundació Docència i Recerca Mútua Terrassa, Barcelona, Spain; Hospital Universitari Mutua Terrassa, Universitat de Barcelona, Terrassa, Catalonia, Spain. ⁵⁸UNSW Medicine, St. Vincent’s Clinical School, and Department of Thoracic Medicine, St. Vincent’s Hospital Darlinghurst, Sidney, Australia. ⁵⁹CHU Saint-Pierre, Université Libre de Bruxelles, 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. ⁶⁵Intensive Care Unit, Georges Pompidou Hospital, APHP, Paris, France. ⁶⁶Department of Pneumology, AZ Delta, Roeselare, Belgium. ⁶⁷Institut Jérôme Lejeune, Paris, France. ⁶⁸Department of Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. ⁶⁹Department of Chest, Faculty of Medicine, Mansoura University, Mansoura, Egypt. ⁷⁰Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. ⁷¹Faculty of Medicine, Division of Pediatric Infectious Diseases, Selcuk University, Konya, Turkey. ⁷²Division of Pediatric Infectious Diseases, Ondokuz Mayıs University, Samsun, Turkey. ⁷³Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, Turkey. ⁷⁴Centre Hospitalier Fleyriat, Bourg-en-Bresse, France. ⁷⁵Division of Clinical Immunology and Allergy, Department of Internal Medicine, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. ⁷⁶Centre de Génétique, CHU Dijon, Dijon, France. ⁷⁷APHP Tenon Hospital, Paris, France. ⁷⁸Sorbonne Universités, UPMC University of Paris, Paris, France. ⁷⁹Department of Clinical Immunology , Hospital Clínico San Carlos, Madrid, Spain. ⁸⁰Genomics 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. ⁸¹CHU Limoges and Inserm CIC 1435 and UMR 1092, Limoges, France. ⁸²Infectious 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. ⁸³Institute of Genetics and Biophysics “Adriano Buzzati-Traverso,” IGB-CNR, Naples, Italy. ⁸⁴Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. ⁸⁵Hematology, APHP, Hopital Européen Georges Pompidou and Inserm UMR-S1140, Paris, France. ⁸⁶Hospital General Universitario and Instituto de Investigación Sanitaria “Gregorio Marañón,” Madrid, Spain. ⁸⁷Bégin military Hospital, Bégin, France. ⁸⁸Pediatric Intensive Care Unit, Hospital Sant Joan de Déu, Barcelona, Spain. ⁸⁹Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. ⁹⁰Division of Critical Care Medicine, Department of Anesthesiology and Reanimation, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. ⁹¹Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain. ⁹²Assistance Publique Hôpitaux de Paris, Paris, France. ⁹³Division of Allergy and Immunology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. ⁹⁴CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST); Universitat Pompeu Fabra (UPF), Barcelona, Spain. ⁹⁵Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Paris, France. ⁹⁶Ghent University Hospital, Ghent, Belgium. ⁹⁷Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. ⁹⁸Department of Laboratory Medicine, SE14186, Huddinge, Karolinska Institutet, Stockholm, Sweden. ⁹⁹Pediatric Infectious Diseases Unit, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. ¹⁰⁰Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. ¹⁰¹Department of Pediatric Hemato-Oncology, Jolimont Hospital; Department of Pediatric Hemato-Oncology, HUDERF, Brussels, Belgium. ¹⁰²Intensive Care Unit, Marqués de Valdecilla Hospital, Santander, Spain. ¹⁰³Hospital del Mar, Parc de Salut Mar, Barcelona, Spain. ¹⁰⁴Department of Pediatric Pulmonology and Immunology, Ghent University Hospital, Ghent, Belgium. ¹⁰⁵Department of Intensive Care Unit, Ghent University Hospital, Ghent, Belgium. ¹⁰⁶Intensive Care Unit, APHM, Marseille, France. ¹⁰⁷CHU Lille, Lille, France. ¹⁰⁸Department of Pediatrics, Columbia University, New York, NY, USA. ¹⁰⁹Centre Hospitalier Intercommunal Poissy Saint Germain en Laye, Poissy, France. ¹¹⁰Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain. ¹¹¹Hospital Sant Joan de Déu, Kids Corona Platfform, Barcelona, Spain. ¹¹²Department of Intensive Care Unit, University Hospital Antwerp, Antwerp, Belgium. ¹¹³Selcuk University, Faculty of Medicine, Chest Diseases Department, Konya, Turkey. ¹¹⁴Division of Allergy and Immunology, Balikesir Ataturk City Hospital, Balikesir, Turkey. ¹¹⁵Division of Critical Care Medicine, Selcuk University, Faculty of Medicine, Konya, Turkey. ¹¹⁶Division of Pediatric Infectious Diseases, Prof. Dr. Cemil Tascıoglu City Hospital, Istanbul, Turkey. ¹¹⁷Departments of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. ¹¹⁸Meram Medical Faculty, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. ¹¹⁹Health Sciences University, Umraniye Education and Research Hospital, Istanbul, Turkey. ¹²⁰Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic. ¹²¹Central Clinical Hospital of Ministry of the Interior and Administration in Warsaw, Warsaw, Poland. ¹²²Oncobiologie Génétique Bioinformatique, PC Bio, CHU Besançon, Besançon, France. ¹²³Paediatric Infectious Disease Unit, Hospital Authority Infectious Disease Center, Princess Margaret Hospital, Hong Kong (Special Administrative Region), China. ¹²⁴Aix Marseille University, IRD, MEPHI, IHU Méditerranée Infection, Marseille, France. ¹²⁵Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China. ¹²⁶National Centre for Infectious Diseases, Singapore. ¹²⁷Hospital Universitario Reina Sofía, Cordoba, Spain. ¹²⁸Imperial College, London, UK. ¹²⁹Endocrinology and Diabetes for Children, AP-HP, Bicêtre Paris-Saclay Hospital, Le Kremlin-Bicêtre, France. ¹³⁰Department of Medical Genetics, University Hospital Antwerp, Antwerp, Belgium. ¹³¹Neurology Unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. ¹³²Intensive Care Unit, APHP Pitié-Salpêtrière Hospital, Paris University, Paris, France. ¹³³National Centre for Infectious Diseases; Tan Tock Seng Hospital; Yong Loo Lin School of Medicine; Lee Kong Chian School of Medicine, Singapore. ¹³⁴Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ¹³⁵Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. ¹³⁶Hospital Sant Joan de Déu and University of Barcelona, Barcelona, Spain. ¹³⁷Pediatric 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. ¹³⁸Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona, Spain. ¹³⁹IrsiCaixa AIDS Research Institute, ICREA, UVic-UCC, Research Institute “Germans Trias i Pujol,” Badalona, Spain. ¹⁴⁰Department of Laboratory, Cruces University Hospital, Barakaldo, Bizkaia, Spain. ¹⁴¹University of New South Wales, New South Wales, Australia. ¹⁴²APHP Pitié-Salpêtrière Hospital, Paris, France. ¹⁴³Aix-Marseille University, APHM, Marseille, France. ¹⁴⁴Robert Debré Hospital, Paris, France. ¹⁴⁵APHP Cohin Hospital, Paris, France. ¹⁴⁶Necmettin Erbakan University Meram Faculty of Medicine Department of Pediatric Infectious Diseases, Konya, Turkey. ¹⁴⁷University Hospitals Leuven, Leuven, Belgium. ¹⁴⁸Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France. ¹⁴⁹Hôpital Erasme, Brussels, Belgium. ¹⁵⁰CH Gonesse, Gonesse, France. ¹⁵¹Vascular Medicine, Georges Pompidou Hospital, APHP, Paris, France. ¹⁵²Division of Pulmonary and Critical Care, University of Miami, Miami, FL, USA. ¹⁵³Guanarteme Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. ¹⁵⁴Regional University Hospital of Malaga, Malaga, Spain. ¹⁵⁵Aix-Marseille Université, Marseille, France. ¹⁵⁶Department of General Paediatrics, Hôpital Bicêtre, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France. ¹⁵⁷Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium. ¹⁵⁸CHU de La Timone, Marseille, France. ¹⁵⁹Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal. ¹⁶⁰Infectious Diseases Horizontal Technlogy Centre, A*STAR; Singapore Immunology Network, A*STAR, Singapore. ¹⁶¹Department of Pediatrics, Complejo Hospitalario Universitario Insular-Materno Infantil, Canarian Health System, Las Palmas de Gran Canaria, Spain. ¹⁶²Regional Universitary Hospital of Málaga, Málaga, Spain. ¹⁶³Hospital Universitario Marqués de Valdecilla, Santander, Spain. ¹⁶⁴Faculty of Medicine, Ataturk University, Erzurum, Turkey. ¹⁶⁵Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey. ¹⁶⁶Department of Biosciences and Nutrition, Karolinska Institutet, SE14183, Stockholm, Sweden. ¹⁶⁷L’Hôpital Foch, Suresnes, France. ¹⁶⁸Department of Immunology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre imas12, Madrid, Spain. ¹⁶⁹APHP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. ¹⁷⁰Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona; CIBERER U759, ISCiii, Madrid, Spain. ¹⁷¹Hospices Civils de Lyon, Lyon, France. ¹⁷²Université de Lille, Inserm U1285, CHU Lille, Paris, France. ¹⁷³Departement of General Pediatrics, University Hospital Robert Debré, APHP, Paris, France. ¹⁷⁴Necmettin Erbakan University, Konya, Turkey. ¹⁷⁵Germans Trias i Pujol Hospital, Badalona, Spain. ¹⁷⁶Medical Intensive Care Unit, Hopital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France. ¹⁷⁷Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus., Barcelona, Spain. ¹⁷⁸Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. ¹⁷⁹Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona, Spain. ¹⁸⁰Consorcio Hospital General Universitario, Valencia, Spain. ¹⁸¹APHP Hôpitaux Universitaires Paris-Sud, Paris, France. ¹⁸²Virology Unit, Université de Paris, Cohin Hospital, APHP, Paris, France. ¹⁸³Hospital San Pedro, Logroño, Spain. ¹⁸⁴Respiratory Medicine, Georges Pompidou Hospital, APHP, Paris, France. ¹⁸⁵Department of Immunology, Hospital Clínico San Carlos, Madrid, Spain. ¹⁸⁶Service de Médecine Intensive Réanimation, Institut de Cardiologie, Hopital Pitié-Salpêtrière, Paris, France. ¹⁸⁷CHRU de Nancy, Hôpital d’Enfants, Vandoeuvre, France. ¹⁸⁸Chair of Nephrology, University of Brescia, Brescia, Italy. ¹⁸⁹Department of Immunology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic. ¹⁹⁰Clínica Universidad de Navarra, Madrid, Spain. ¹⁹¹HUS Helsinki University Hospital, Children and Adolescents, Rare Disease Center, and Inflammation Center, Adult Immunodeficiency Unit, Majakka, Helsinki, Finland. ¹⁹²Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain. ¹⁹³Department of Pulmonology, ZNA Middelheim, Antwerp, Belgium. ¹⁹⁴INSERM UMR-S 1140, Biosurgical Research Lab (Carpentier Foundation), Paris University and Hopital Européen Georges Pompidou, Paris, France. ¹⁹⁵Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt. ¹⁹⁶Critical Care Unit, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. ¹⁹⁷CHU de Saint Etienne, Saint-Priest-en-Jarez, France. ¹⁹⁸Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. ¹⁹⁹Gustave Roussy Cancer Campus, Villejuif, France. ²⁰⁰Intensive Care Unit, Avicenne Hospital, APHP, Bobigny, France. ²⁰¹Laboratory of Immunology and Histocompatibility, Saint-Louis Hospital, Paris University, Paris, France. ²⁰²Department 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. ²⁰³Department of Internal Medicine, Université de Paris, INSERM, U970, PARCC, F-75015, Paris, France. ²⁰⁴First Division of Anesthesiology and Critical Care Medicine, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. ²⁰⁵Intensive Care Department, Hospital Universitari Mutua Terrassa, Universitat Barcelona, Terrassa, Spain. ²⁰⁶Hospices Civils de Lyon, Lyon Sud Hospital, Lyon, France. ²⁰⁷Infanta Leonor University Hospital, Madrid, Spain. ²⁰⁸Hematology Department, ASST Spedali Civili di Brescia, Brescia, Italy. ²⁰⁹Pneumologie, Hôpital Avicenne, APHP, INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France. ²¹⁰Dermatology Unit, Laboratoire GAD, INSERM UMR1231 LNC, Université de Bourgogne, Dijon, France. ²¹¹University Hospital of Burgos, Burgos, Spain. ²¹²Intensive Care Unit, M. Middelares Ghent, Ghent, Belgium. ²¹³Department of Nephrology and Infectiology, AZ Sint-Jan Brugge-Oostende AV, Bruges, Belgium. ²¹⁴Center of Human Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. ²¹⁵Department of Chest Diseases, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey. ²¹⁶CHU de Caen, Caen, France. ²¹⁷Sorbonne Université, Service de Médecine Intensive Réanimation, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. ²¹⁸General Intensive Care Unit, Konya Training and Research Hospital, Konya, Turkey. ²¹⁹CHU de Nancy, Nancy, France. ²²⁰University of Lyon, CIRI, INSERM U1111, National Referee Centre RAISE, Pediatric Rheumatology, HFME, Hospices Civils de Lyon, Lyon, France.

*Leader of COVID Clinicians.

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.

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.

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.

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.

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 Halwani​³², 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.

Huie Jing^1,2, Wesley Tung^1,2, Christopher R. Luthers³, Bradly M. Bauman³, Samantha Shafer^2,4, Lixin Zheng^2,4, Zinan Zhang^2,4, Satoshi Kubo^2,4, Samuel D. Chauvin^2,4, Kazuyuki Meguro^1,2, Elana Shaw^1,2, Michael Lenardo^2,4, 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.