Lack of association between HLA and asymptomatic SARS-CoV-2 infection

Abstract

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B*15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B*15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the US (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B*15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified. These findings suggest that memory T-cell immunity to seasonal coronaviruses does not strongly influence the outcome of SARS-CoV-2 infection in unvaccinated individuals.

Introduction

Primary infection with SARS-CoV-2 underlies a broad spectrum of clinical manifestations in unvaccinated individuals, ranging from silent infection to lethal COVID-19 pneumonia. Rare and common human genetic variants have been associated with hypoxemic COVID-19 pneumonia ^1–5. Inborn errors of TLR3- and/or TLR7-dependent type I IFN immunity in respiratory epithelial cells and plasmacytoid dendritic cells underlie critical COVID-19 pneumonia in 1–5% of cases ^1,6–8. Moreover, autoantibodies neutralizing type I interferon (IFN) underlie at least another 15% of cases ^9–11, further highlighting the key role of type I IFNs in protective immunity to SARS-CoV-2 infection in the respiratory tract. Inborn errors of the OAS-RNase L pathway underlie MIS-C in about 1% of cases ¹², but the other manifestations of SARS-CoV-2 infection remain unexplained (COVID toes, long COVID etc.). In the large sample study from the COVID-19 Host Genetics Initiative, only one human leukocyte antigen (HLA) class II allele, HLA-DRB1*04:01, has been found to confer a small decrease in the risk of critical COVID-19 (OR = 0.8) ². By contrast, we have documented a stronger association between HLA-A*03:01 and side effects following inoculation with the Pfizer-BioNTech COVID-19 mRNA vaccine ¹³, which was subsequently replicated ¹⁴.

In this context, in July 2023, an association was reported between the HLA-B*15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals ¹⁵. The OR was 2.40 (95%CI: 1.54–3.64) for heterozygotes, reaching 8.58 (95%CI: 1.74–34.43) in homozygotes. Silent SARS-CoV-2 infection had not hitherto been explicitly studied as a phenotype in large genetic studies. This study further showed that T-cells from HLA-B*15:01 individuals who had not been infected with SARS-CoV-2 recognized a SARS-CoV-2 T-cell epitope by cross-reactivity due to prior exposure to one of two common cold coronaviruses: OC43-CoV or HKU1-CoV¹⁵. Moreover, more than 100 immunogenic SARS-CoV-2 peptides are highly similar to peptides from at least one human coronavirus (hCoV) presented by a wide range of classical HLA molecules ¹⁶. We, therefore, tested the hypothesis of an association between HLA alleles and asymptomatic SARS-CoV-2 infection in two large independent cohorts. We aimed: (i) to test the association with HLA-B*15:01 and (ii) to identify additional HLA alleles potentially associated with asymptomatic COVID-19.

Material and methods

Cohorts and phenotype information

US prospective cohort

Participants in the US prospective cohort came from two studies: the Helix DNA Discovery Project and the Healthy Nevada Project. All the enrolled participants provided written informed consent for participation and were recruited through protocols conforming to local ethics requirements. The Helix DNA Discovery Project was reviewed and approved by the Western Institutional Review Board. For the Healthy Nevada Project (HNP), the University of Nevada, Reno Institutional Review Board approved the study (project 956068–12). The procedures followed were in accordance with ethical standards, and appropriate informed consent was obtained. We performed an online survey that we sent a few times in 2021. The survey takes about 15 minutes to complete and has been published in the past ¹³. We received responses from 8,125 unique Helix DNA Discovery Project participants and 9,315 unique Healthy Nevada Project participants. The participants in this cohort were 18 to 89+ years old, 65% were female, and 85% were of European genetic ancestry. The respondents indicated whether they had been infected and whether they had been vaccinated, as well as information on exposure, reasons for testing, and comorbidities. They rated the severity and duration of their symptoms and disease. They answered questions about 24 specific symptoms known to occur after SARS-CoV-2 infection.

CHGE cohort

Since the beginning of the pandemic, the COVID Human Genetic Effort (CHGE) has enrolled more than 10,000 individuals with SARS-CoV-2 infection and broad clinical manifestations from all over the world. All the enrolled participants provided written informed consent for participation and were recruited through protocols conforming to local ethics requirements. For patients enrolled in the French COVID cohort (ClinicalTrials.gov NCT04262921), ethics approval was obtained from the Comité de Protection des Personnes Ile De France VI (ID RCB, 2020-A00256–33) or the Ethics Committee of Erasme Hospital (P2020/203). For participants enrolled in the COV-Contact study (ClinicalTrials.gov NCT04259892), ethics approval was obtained from the CPP IDF VI (ID RCB, 2020-A00280–39). For patients enrolled in the Italian cohort, ethics approval was obtained from the University of Milano-Bicocca School of Medicine, San Gerardo Hospital, Monza–Ethics Committee of the National Institute of Infectious Diseases Lazzaro Spallanzani (84/2020) (Italy), and the Comitato Etico Provinciale (NP 4000–Studio CORONAlab). STORM-Health care workers were enrolled in the STudio OsseRvazionale sullo screening dei lavoratori ospedalieri per COVID-19 (STORM-HCW) study, with approval from the local institutional review board (IRB) obtained on June 18, 2020. Patients and relatives from San Raffaele Hospital (Milan) were enrolled in COVID-BioB/Gene-COVID protocols and, for additional studies, TIGET-06, with the approval of the local ethics committee. Patients and relatives from Rome were enrolled in Protocol no. 50/20 (Tor Vergata University Hospital). Informed consent was obtained from each patient. For the patients enrolled in the COVIDeF Study Group (ClinicalTrials.gov NCT04352348), ethics approval was obtained from the Comité de Protection des Personnes Ile de France XI (ID RCB, 2020-A00754–35). For patients enrolled in Spain, the study was approved by the Committee for Ethical Research of the Infanta Leonor University Hospital, code 008–20; the Committee for Ethical Research of the 12 de Octubre University Hospital, code 16/368; the Bellvitge University Hospital, code PR127/20; the University Hospital of Gran Canaria Dr. Negrín, code 2020–200–1 COVID-19; and the Vall d’Hebron University Hospital, code PR(AMI)388/2016. Anonymized samples were sequenced at the National Institute of Allergy and Infectious Diseases (NIAID) through the Uniformed Services University of the Health Sciences (USUHS)/the American Genome Center (TAGC) under nonhuman subject research conditions; no additional IRB consent was required at the National Institutes of Health (NIH). For patients enrolled in the Swedish COVID cohort, ethics approval was obtained from the Swedish Ethical Review Agency (2020–01911 05).

The physicians classified the patients as follows: i) Critical cases were defined as patients with pneumonia requiring high-flow oxygen (> 6 L/min) and/or requiring admission to the intensive care unit; ii) Severe cases were defined as patients with pneumonia requiring low-flow oxygen (< 6 L/min); iii) Moderate cases were defined as patients with ambulatory pneumonia; iv) Mild cases were defined as pauci-symptomatic patients, with the presence of mild, self-healing symptoms such as cough, fever, body aches, anosmia; and v) Asymptomatic cases were defined as infected individuals with no symptoms. The presence of infection was assessed on the basis of a positive PCR test and/or serological test and/or the presence of typical symptoms such as anosmia or ageusia after exposure to a confirmed COVID-19 case.

SARS-CoV-2 Human Challenge Characterisation Study

34 participants seronegative to spike protein were challenged with D614G-containing pre-Alpha SARS-CoV-2, of whom 33 consented for genetic analysis. Additional details on the study design and participants were previously published ¹⁷. Ethics approval was obtained from the UK Health Research Authority Ad Hoc Specialist Ethics Committee (reference: 20/UK/0002). Written informed consent was obtained from participants before screening and enrollment.

Sequencing

US prospective cohort

DNA samples were sequenced and analyzed at Helix with the Exome+^® assay as previously described ¹⁸. Genotype processing was performed in Hail ¹⁹.

CHGE cohort

Whole-exome (WES) or whole-genome sequencing (WGS) was performed at several sequencing centers, including the Genomics Core Facility of the Imagine Institute (Paris, France), the Yale Center for Genome Analysis (USA), Macrogen (USA), Psomagen (USA), the New-York Genome Center (NY, USA), TAGC (USUHS, Bethesda, USA), MNM Bioscience (Poland), Invitae (San Francisco, USA), the Genomic Sequencing Platform Seqoia (France), the Centre National de Recherche en Génomique Humaine (CNRGH, Evry, France), the Genomics Division-ITER of the Canarian Health System sequencing hub (Canary Islands, Spain), and the AlJalila Genomics Center (Dubai). Libraries for WES were generated with the Twist and Twist Plus Human Core Exome Kit, the xGen Exome Research Panel from Integrated DNA Technologies (IDT; xGen V1 and V2), Agilent SureSelect (Human All Exon V6 and V7) panels, the SeqCap EZ MedExome Kit from Roche, the Nextera Flex for Enrichment-Exome kit, the Illumina TruSeq Exome panel and WES custom target enrichment probes. Massively parallel sequencing was performed on HiSeq 4000, HiSeq 2500, NextSeq 550 or NovaSeq 6000 systems (Illumina).

For principal component analysis (PCA), common variants from the gnomAD v2.1 Exome dataset were jointly genotyped with GATK GenotypeGVCFs. PCA was performed with PLINK v1.9 software on a pruned set of ~14,600 SNPs not in linkage disequilibrium (maximum r2 value for linkage disequilibrium of 0.4 between pairs of SNPs), with a minor allele frequency (MAF) > 1%, a call rate > 99%, and P value for departure from Hardy–Weinberg equilibrium > 10e−5, as previously described ²⁰. The ancestral origin of the patients was further inferred from the PCA, as previously described ²⁰.

SARS-CoV-2 Human Challenge Characterisation Study

Whole-genome sequencing was performed on Illumina NovaSeq (Novogene Ltd., IK), yielding 150bp paired-end reads. The average depth of coverage was > 50x with a minimum of 31x. PCA and global ancestry inference were performed using Hail according to the protocol described by the gnomAD project ²¹.

HLA calls / imputation

US prospective cohort

HLA types for A, B, C, DPB1, DQA1, DQB1, and DRB1 were imputed with HIBAG using the default recommendations ²². Individual genotypes were imputed with the model for the most appropriate genetic ancestry for each individual. Probabilities greater than 0.5 were used for genotype calling.

CHGE cohort

Classical class I and class II HLA alleles were typed from the raw WES or WGS reads with HLA*LA software [10], which uses a linear projection method to align reads to a population reference graph and enables high HLA typing accuracy from WES or WGS data.

SARS-CoV-2 Human Challenge Characterisation Study

HLA alleles were typed from raw WGS reads with HLA*LA software at G group resolution. Only HLA calls with a posterior probability of 100% and a minimum coverage of 20x were retained in the analysis. At the B locus, all individual calls fulfilled these filtering criteria at 2-field resolution.

These tools have been validated for their accuracy to call HLA alleles at 2-field resolution, particularly in populations of European ancestry. For example, the HIBAG HLA calls made at Helix for 7 genes in 7 European ancestry Coriell samples showed 99% concordance with the known HLA calls for these individuals. Differences caused by HLA allele calling should mostly be limited to rare HLA types and populations with poor imputation references.

HLA-WAS

We used Regenie ²³ for the genetic analysis. In brief, this method builds a whole-genome regression model based on common variants to account for the effects of relatedness and population stratification; it also accounts for situations in which there is an extreme case-control imbalance likely to lead to test statistic inflation with other analysis methods. We used the approximate Firth p value when the logistic regression p value was below 0.01. The covariates included were age group, sex and the first five principal components.

For the US prospective cohort, a representative set of 184,445 coding and noncoding LD-pruned, high-quality common variants were identified for the construction of PCs and the whole-genome regression model, as previously described ¹⁸. PCs were calculated within the European group. For CHGE, the set of ~14,600 SNPs used for PCA within the European group was used for the whole-genome regression model.

Meta-analysis

Results were combined by inverse variance-weighted fixed-effects meta-analysis with METAL ²⁴. Effect was provided as the BETA value and the STDERR was provided as the SE.

Power calculation

We estimated the power required to detect an effect similar to that reported by Augusto, Murdolo & Chatzileontiadou et al. with the Genetic Association Study (GAS) Power Calculator, which uses a method derived from the CaTS power calculator for two-stage association studies ²⁵. The parameters used were: HLA-B*15:01 frequency: 0.05; prevalence of asymptomatic infection: 0.1; Dominant inheritance model; p-value threshold = 0.05; numbers of cases and controls according to the third definition in both cohorts.

Serology

Plasma IgG titres were determined using MesoScale Discovery Coronavirus panel 2 plates on a SQ120 instrument. Binding titres given as arbitrary units per milliliter (AU/ml) based on a kit-provided human plasma standard curve.

Results

US prospective cohort description

We first conducted an HLA-wide association study (HLA-WAS) in a prospective population-based US cohort (Figure 1). Participants were either part of the Helix DNA Discovery Project or the Healthy Nevada project, and were recruited before the start of the COVID-19 pandemic. All participants underwent Exome+^® sequencing, which targets the exome and a few hundred thousand non-exonic common SNPs, providing a backbone for imputation of the most common SNPs in the genome. HLA alleles were called for seven genes (HLA -A, -B, -C, -DPB1, -DQA1, -DQB1, and -DRB1) with HIBAG ²². The 17,434 adults who responded to at least one of the COVID-19 infection and vaccination surveys sent in 2021 included 1,680 participants reporting SARS-CoV-2 infection while unvaccinated. A continuous spectrum of symptoms, duration of illness was reported following SARS-CoV-2 infection (Figure S1). The most common symptoms were muscle and body aches, and a cough (Figure S1A). No symptoms at all were reported by 5.1% of individuals (n=86), whereas 5.3% of the infected participants required hospitalization with or without oxygen therapy (n=58) or were admitted to the intensive care unit (n=31) (Figure S1B).

Figure 1: Study design.

A: Description of the two cohorts and definitions of asymptomatic and symptomatic cases. B: List of HLA-wide association studies and meta-analyses performed.

HLA-wide association in the US prospective cohort

We tested the hypothesis that HLA alleles play an important role in the early response to SARS-CoV-2 by considering three case definitions for the asymptomatic cases (Figure 1A): 1) ‘0 symptoms’ was a stringent definition of asymptomatic as a total absence of symptoms (n=86); 2) ‘Max 1 day’ was a definition of asymptomatic in which the presence of one symptom for no more than one day was tolerated (n=111). This definition was used to increase the power for detection of an association by enlarging the ‘asymptomatic’ group whilst still identifying individuals who cleared the virus quickly and efficiently; 3) ‘Max 2 days’ was a definition as close as possible to that used by Augusto, Murdolo & Chatzileontiadou et al., considering participants to be asymptomatic if none of their symptoms lasted three days or more, and if the reason for testing was unrelated to symptoms (n=286) ¹⁵. We used only one definition for controls (individuals with symptoms lasting at least three days). The control group included all individuals admitted to the ICU or the hospital and anyone reporting symptoms of at least three days’ duration with some impact on their daily routine (n=1,247). For the HLA-WAS, we restricted the analysis to individuals with a genetically inferred European ancestry (Figure S1C–D), leading to a total of 59 to 191 asymptomatic cases and of 945 symptomatic controls (Figure 1A). Age and sex distribution are shown in Table S1. The association test was performed with Regenie ²³ under a dominant inheritance model, with age, sex and the first five principal components as covariates (see Supplemental methods). The risk of detecting false positive associations was decreased by limiting the analysis to the 105 HLA alleles with an allele frequency of at least 1% in this cohort. No statistically significant associations (at a corrected threshold of p<0.00047) were found with any of the three phenotype definitions (Table 1, Tables S2–4). The top-ranked HLA allele was DRB1*16:01, which was depleted in asymptomatic individuals, with the strongest effect being observed in the ‘Max 2 days’ group of asymptomatic patients (OR [95%CI] = 0.06 [0 – 1.5], p=0.004, Table 1).

Table 1:

Top-ranked alleles in the HLA-WAS on the US prospective cohort.

Allele	OR [95% CI]a	p value	AFb	Asymptomatic definitionc
DRB1*16:01	0.06 [0.002–1.5]	0.004	0.012	Max 2 days
A*32:01	2.19 [1.3–3.8]	0.008	0.035	Max 2 days
B*07:02	1.58 [1.1–2.3]	0.016	0.13	Max 2 days
C*07:02	1.53 [1.1–2.2]	0.020	0.14	Max 2 days
DQB1*06:02	1.52 [1.1–2.2]	0.025	0.14	Max 2 days
DQB1*05:02	0.29 [0.1–1.1]	0.037	0.015	Max 2 days

^aOdds ratio (OR) of being asymptomatic, i.e. OR>1 indicates that the allele is more frequent in asymptomatic individuals. CI: confidence interval.

^bAllele frequency (AF) is based on the frequency of the allele in the US prospective cohort ‘Max 2 days’ analysis because this analysis included the largest numbers of cases and controls.

^cFor each allele, the top-ranked result across the three asymptomatic definitions in the US prospective cohort is given.

HLA-wide association in the CHGE cohort

We next studied patients recruited by the physicians of the international CHGE consortium. These physicians classified participants with SARS-CoV-2 infections according to acute disease severity: asymptomatic, mild, moderate, severe, or critical (Figure S2A). Whole-exome or whole-genome sequencing data were available for 7,229 participants and HLA alleles were typed with HLA*LA ²⁶. In this HLA-WAS, we compared the patients classified as ‘asymptomatic’ by the clinicians (n=311) with those in three sets of symptomatic controls: 1) the patients with the most extreme symptoms requiring hospitalization and oxygen supplementation (i.e. those with a severe or critical form of the disease, n=4,451); 2) all symptomatic patients, whatever their acute disease severity (i.e. mild, moderate, severe or critical, n=5,682); and 3) symptomatic patients not requiring oxygen supplementation (i.e. mild and moderate patients only, n=1,231); this last group of symptomatic patients is the most similar to the symptomatic patients groups of the US prospective cohort and the study by Augusto, Murdolo & Chatzileontiadou et al. (Figure 1). We restricted the analysis to individuals of European genetic ancestry and the final study population comprised 206 asymptomatic cases, 1,625 patients with severe or critical disease and 574 patients with mild or moderate disease (Figure S2B–C). Age and sex distribution are shown in Table S1. Analyses were also performed under a dominant inheritance model with age group, sex and the first five principal components as covariates. This analysis was performed with Regenie and was limited to the 117 HLA alleles with an allele frequency of at least 1% in this cohort. No statistically significant association (at a corrected threshold of p<0.00043) was identified in the HLA-WAS, regardless of the definition of symptomatic patients used (Tables S5–S7). The top-ranked HLA allele found to be enriched in asymptomatic individuals was HLA-B*40:02, for which the strongest effect was observed in comparison with the group of symptomatic patients with severe or critical disease (OR [95%CI] = 3.4 [1.5 – 7.7], p=0.005, Table 2).

Table 2:

Top-ranked alleles in the HLA-WAS on the CHGE European cohort.

Allele	OR [95% CI]a	p value	AFb	Controls usedc
B*40:02	3.42 [1.5–7.7]	0.005	0.016	Severe + Critical
DPB1*01:01	0.28 [0.1–0.8]	0.007	0.042	Severe + Critical
A*23:01	2.5 [1.2–5.0]	0.010	0.023	Mild + Moderate
B*49:01	2.26 [1.2–4.3]	0.014	0.031	Mild + Moderate
A*03:01	1.66 [1.1–2.5]	0.019	0.12	Severe + Critical
DQA1*01:02	1.54 [1.1–2.2]	0.022	0.18	Mild + Moderate
A*30:02	2.46 [1.1–5.6]	0.031	0.019	Mild + Moderate
B*57:01	0.47 [0.2–1.0]	0.047	0.027	Mild + Moderate
A*68:02	3.53 [1.0–12.2]	0.047	0.01	Mild + Moderate
DPB1*03:01	0.65 [0.4–1.0]	0.049	0.093	Mild + Moderate

^aOdds ratio (OR) of being asymptomatic, i.e. OR>1 indicates that the allele is more frequent in asymptomatic individuals. CI: confidence interval.

^bAllele frequency (AF) is based on the frequency of the allele in the CHGE European cohort ‘All’ analysis, which included the largest numbers of cases and controls.

^cFor each allele, the top-ranked result across three sets of symptomatic patients in the CHGE European sample is given.

HLA-wide meta-analysis

We then performed three meta-analyses, denoted M1, M2, M3 (Figure 1B), combining the results from our two independent cohorts with METAL ²⁴. The first used the strictest definitions for the groups: the HLA-WAS with the ‘0 symptoms’ group of asymptomatic patients in the US prospective cohort and the HLA-WAS limited to patients with severe and critical disease only in the CHGE cohort (Table S8). The second meta-analysis combined the HLA-WAS with the ‘Max 1 day’ definition of asymptomatic patients for the US prospective cohort (0 symptoms or 1 symptom for 1 day) with the HLA-WAS with all symptomatic cases from the CHGE (Table S9). The final meta-analysis used the results for the asymptomatic and symptomatic groups most closely resembling those of the study by Augusto, Murdolo & Chatzileontiadou et al. (Table S10). The meta-analyses detected no statistically significant associations (at a corrected threshold of p<0.00047) between HLA alleles and asymptomatic SARS-CoV-2 infection (Table 3, Tables S8–10). The top-ranked HLA allele was HLA-B*40:02 (p-value = 0.0008), for which enrichment was observed in asymptomatic individuals relative to symptomatic individuals in both cohorts and in the meta-analysis based on the strictest definitions.

Table 3:

Top-ranked alleles in the meta-analyses and corresponding results in the US prospective and CHGE cohorts.

Allele	Meta-analysis			US Prospective Cohortb		CHGE Cohortb
	Meta-analysis number	OR [95% CI]a	p value	OR [95% CI]a	p value	OR [95% CI]a	p value
B*40:02	M1	3.51 [1.7–7.3]	0.0008	4.05 [0.7–24.6]	0.128	3.42 [1.5–7.7]	0.005
DPB1*01:01	M2	0.43 [0.3–0.7]	0.0015	0.43 [0.2–1.0]	0.058	0.43 [0.2–0.8]	0.010
DQA1*01:02	M3	1.41 [1.1–1.8]	0.007	1.31 [0.9–1.8]	0.119	1.54 [1.1–2.2]	0.022
A*23:01	M2	2.22 [1.2–4.0]	0.007	2.14 [0.7–6.6]	0.186	2.25 [1.1–4.4]	0.019
DQB1*06:02	M3	1.46 [1.1–2.0]	0.013	1.52 [1.1–2.2]	0.025	1.33 [0.8–2.2]	0.276
C*03:03	M1	0.52 [0.3–0.9]	0.015	0.48 [0.2–1.2]	0.132	0.54 [0.3–1.0]	0.055
B*49:01	M3	1.96 [1.1–3.4]	0.019	1.29 [0.4–3.9]	0.657	2.26 [1.2–4.3]	0.014
B*07:02	M3	1.42 [1.1–1.9]	0.021	1.58 [1.1–2.3]	0.016	1.16 [0.7–1.9]	0.554
DRB1*15:01	M3	1.38 [1.0–1.9]	0.037	1.42 [1–2.1]	0.075	1.32 [0.8–2.2]	0.264

^aOdds ratio (OR) of being asymptomatic, i.e. OR>1 indicates that the allele is more frequent in asymptomatic individuals. CI: confidence interval.

^bFor each allele, ORs and p values obtained in the US prospective and CHGE cohorts with asymptomatic or controls definitions used in the corresponding meta-analysis are given.

Lack of replication for HLA-B*15:01

An analysis focusing on HLA-B*15:01 did not replicate the association between HLA-B*15:01 and asymptomatic SARS-CoV-2 infection (Figure 2A–C) despite being well powered (>95%) to detect an effect similar to that reported by Augusto, Murdolo & Chatzileontiadou et al. (OR of 2.40 for enrichment in asymptomatic vs. symptomatic patients, p=5.67×10⁻⁵) (Figure S3). We further estimated the frequency of HLA-B*15:01 in various groups of patients of the CHGE consortium, including children with SARS-CoV-2 infection complicated by multisystem inflammatory syndrome (classified as MIS-C) and individuals with high levels of exposure who never tested positive (classified as ‘resistors’) ^12,27. This frequency ranged from 2.4% in asymptomatic individuals to 6.0% in resistors (Figure 2C–D). We also looked at individuals from non-European genetic ancestries. Similarly, we found no difference in frequency between asymptomatic and symptomatic individuals (Figure 2E and Table S11). Overall, no enrichment in the HLA-B*15:01 allele was observed among asymptomatic individuals in our US population-based prospective cohort, or in the international CHGE cohort.

Figure 2: HLA-B*15:01 is not enriched in asymptomatic cases.

A: Odds Ratio (OR) and 95% confidence intervals (CI) for the association of HLA-B*15:01 with asymptomatic SARS-CoV-2 infection in both cohorts and in the meta-analysis.

B: Allele frequency and 95% confidence intervals in the US prospective cohort subgroups.</p/>C: Allele frequency and 95% CI in the CHGE European sample.</p/>D: Allele frequency and 95% CI in individuals highly exposed to SARS-CoV-2 who never tested positive (‘Resistors’, n=291) and children with SARS-CoV-2 infection complicated by multisystem inflammatory syndrome (‘MIS-C’, n=235) from the European CHGE sample.

E: Allele frequency and 95% CI in Middle Eastern (ME) individuals from the CHGE cohort (Symptomatic, n=895; Asymptomatic, n=37).

Symptoms and serology for participants with HLA-B*15:01 in the SARS-CoV-2 Human Challenge Characterisation Study

The mechanism proposed as an explanation for the association between HLA-B*15:01 and asymptomatic SARS-CoV-2 infection was pre-existing immunity, probably due to prior infection with OC43-CoV or HKU1-CoV ¹⁵. Unfortunately, no serological data were available for the HLA-B*15:01 carriers in the US prospective and the CHGE cohorts. We tested the hypothesis that the lack of association in our study was due to an absence of prior infection with OC43-CoV or HKU1-CoV by examining the data for the SARS-CoV-2 Human Challenge Characterisation Study (ClinicalTrials.gov identifier NCT04865237; funder, UK Vaccine Taskforce), in which 34 participants seronegative to spike protein were challenged with D614G-containing pre-Alpha SARS-CoV-2, of whom 33 consented for genetic analysis ¹⁷. Serological data, history of prior infections with other coronaviruses and genetic data were available, together with infection status and data concerning the recorded symptoms. HLA alleles were called with HLA*LA from whole-genome sequences obtained from the participants. Three of the 17 infected participants (positive test result) carried an HLA-B*15:01 allele, as well as three of the 16 who stayed uninfected. Only one of the 17 infected participants was fully asymptomatic and this participant did not carry the HLA-B*15:01 allele. The three infected participants with an HLA-B*15:01 allele were symptomatic (Figure 3), despite evidence of prior exposure to OC43-CoV and HKU1-CoV (Figure S4). Thus, prior exposure to a coronavirus did not prevent the HLA-B*15:01 carriers from developing symptoms following SARS-CoV-2 infection.

Figure 3: HLA-B*15:01 in the SARS-CoV-2 Human Challenge Characterisation Study.

Symptoms and HLA-B genotypes for 18 infected participants. Daily total symptom score was calculated using self-reported symptom diaries three times daily. Daily total symptom scores are displayed in the heatmap, ranging from green (no symptoms) to red (highest symptom score). The heatmap is derived from figure 2 in Zhou J. et al, Lancet Microbe (2023)

Discussion

Our analyses identified no associations between classical HLA alleles and asymptomatic SARS-CoV-2 infection. In particular, we did not replicate the previously reported association between HLA-B*15:01 and asymptomatic SARS-CoV-2 infection. Another recent study in a Spanish cohort found no associations between classical HLA alleles and asymptomatic SARS-CoV-2 infection ²⁸. One possible explanation for the difference in results regarding HLA-B*15:01 is that the studies analyzed different groups of individuals living in different environments. However, the US prospective cohort we analyzed has many features in common with the cohort analyzed by Augusto, Murdolo & Chatzileontiadou et al.: specifically, the participants were from the US, with a slight bias towards women, the phenotype was assessed on the basis of self-reported surveys at multiple time points during the pandemic before summer 2021 (before the SARS-CoV-2 Delta variant became dominant in the US ²⁹). The percentage of individuals self-reporting asymptomatic infection were similar between the two, as were the rates of each symptom. Alternatively, the difference in results may reflect differences in the handling of potential population stratification. Augusto, Murdolo & Chatzileontiadou et al. did not consider population structure in their study on bone marrow donors, probably because no genetic information outside of the HLA region was available, whereas we accounted for population structure by restricting our analysis to those of European ancestry and including the first five principal components as covariates in our regression model. The highly polymorphic nature of the HLA region and the differences in allele frequencies between human sub-populations contribute to a high risk of false-positive results in association analyses. The frequency of HLA-B*15:01 is known to vary across continents, between continental populations within the US (Figure S5A) and even between European countries (Figure S5B). Population stratification may, thus, have played a confounding role in the study by Augusto, Murdolo & Chatzileontiadou et al.

Overall, the absence of an association between classical HLA alleles and asymptomatic SARS-CoV-2 infection is consistent with the modest impact of HLA variation on severe or critical COVID-19 ³⁰. Most genetic and immunological studies of severe or critical COVID-19 pneumonia in unvaccinated individuals have implicated type I IFNs, suggesting that intrinsic and innate immunity play a more crucial role than adaptive immunity in the early response to SARS-CoV-2. Pre-existing immunity due to prior infections with common cold coronaviruses may help to prevent the development of symptoms following SARS-CoV-2 infection, but our results suggest that either (i) pre-existing CD4 and CD8 T-cell immunity may not play an important role, or (ii) pre-existing immunity is not stronger for individuals with a particular HLA allele than for those with any other HLA allele. This result is also consistent with the absence of any strong association between HLA alleles and clinical outcomes during the acute phase for the other primary viral infections studied to date ^31–33. By contrast, HLA alleles have been associated with multiple clinical or laboratory outcomes during chronic infections, including viral (e.g., HIV, HBV, HCV), mycobacterial (e.g., leprosy) and protozoan infections ^33–36. HLA alleles are also known to be associated with adaptive immune responses to vaccinations ^13,37,38. Our findings suggest that memory T-cell immunity to seasonal coronaviruses does not strongly influence the outcome of SARS-CoV-2 infection in unvaccinated individuals.

Members of COVID Human Genetic Effort:

Laurent Abel¹, Alessandro Aiuti², Saleh Al-Muhsen³, Fahd Al-Mulla⁴, Ali Amara⁵, Mark S. Anderson⁶, Evangelos Andreakos⁷, Andrés A. Arias⁸, Lisa M. Arkin⁹, Hagit Baris Feldman¹⁰, Paul Bastard¹, Alexandre Belot¹¹, Catherine M. Biggs¹², Dusan Bogunovic¹³, Alexandre Bolze¹⁴, Anastasiia Bondarenko¹⁵, Alessandro Borghesi¹⁶, Ahmed A. Bousfiha¹⁷, Petter Brodin¹⁸, Yenan Bryceson¹⁹, Manish J. Butte²⁰, Jean-Laurent Casanova²¹, Giorgio Casari²², John Christodoulou²³, Aurélie Cobat¹, Roger Colobran²⁴, Antonio Condino-Neto²⁵, Stefan N. Constantinescu²⁶, Megan A. Cooper²⁷, Clifton L. Dalgard²⁸, Murkesh Desai²⁹, Beth A. Drolet³⁰, Xavier Duval³¹, Jamila El Baghdadi³², Philippine Eloy³³, Sara Espinosa-Padilla³⁴, Jacques Fellay³⁵, Carlos Flores³⁶, José Luis Franco³⁷, Antoine Froidure³⁸, Guy Gorochov³⁹, Peter K. Gregersen⁴⁰, Bodo Grimbacher⁴¹, Filomeen Haerynck⁴², David Hagin⁴³, Rabih Halwani⁴⁴, Lennart Hammarström⁴⁵, James R. Heath⁴⁶, Elena W.Y. Hsieh⁴⁷, Eystein Husebye⁴⁸, Kohsuke Imai⁴⁹, Yuval Itan⁵⁰, Emmanuelle Jouanguy¹, Elżbieta Kaja⁵¹, Timokratis Karamitros⁵², Kai Kisand⁵³, Cheng-Lung Ku⁵⁴, Yu-Lung Lau⁵⁵, Yun Ling⁵⁶, Carrie L. Lucas⁵⁷, Tom Maniatis⁵⁸, Davood Mansouri⁵⁹, László Maródi⁶⁰, France Mentré³², Isabelle Meyts⁶¹, Joshua D. Milner⁶², Kristina Mironska⁶³, Trine H. Mogensen⁶⁴, Tomohiro Morio⁶⁵, Lisa F.P. Ng⁶⁶, Luigi D. Notarangelo⁶⁷, Antonio Novelli⁶⁸, Giuseppe Novelli⁶⁹, Cliona O’Farrelly⁷⁰, Satoshi Okada⁷¹, Keisuke Okamoto⁷², Tayfun Ozcelik⁷³, Qiang Pan-Hammarström⁴⁵, Jean W. Pape⁷⁴, Rebeca Perez de Diego⁷⁵, Jordi Perez-Tur⁷⁶, David S. Perlin⁷⁷, Graziano Pesole⁷⁸, Anna M. Planas⁷⁹, Carolina Prando⁸⁰, Aurora Pujol⁸¹, Anne Puel¹, Lluis Quintana-Murci⁸², Sathishkumar Ramaswamy⁸³, Laurent Renia⁶⁶, Igor Resnick⁸⁴, Carlos Rodríguez-Gallego⁸⁵, Vanessa Sancho-Shimizu⁸⁶, Anna Sediva⁸⁷, Mikko R.J. Seppänen⁸⁸, Mohammad Shahrooei⁸⁹, Anna Shcherbina⁹⁰, Ondrej Slaby⁹¹, Andrew L. Snow⁹², Pere Soler-Palacín⁹³, Vassili Soumelis⁹⁴, András N. Spaan⁹⁵, Ivan Tancevski⁹⁶, Stuart G. Tangye⁹⁷, Ahmad Abou Tayoun⁸³, Şehime Gülsün Temel⁹⁸, Christian Thorball⁹⁹, Pierre Tiberghien¹⁰⁰, Sophie Trouillet-Assant¹⁰¹, Stuart E. Turvey¹⁰², K M Furkan Uddin¹⁰³, Mohammed J. Uddin¹⁰⁴, Diederik van de Beek¹⁰⁵, Donald C. Vinh¹⁰⁶, Horst von Bernuth¹⁰⁷, Joost Wauters¹⁰⁸, Mayana Zatz¹⁰⁹, Pawel Zawadzki¹¹⁰, Qian Zhang¹, Shen-Ying Zhang¹

¹Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; Paris Cité University, Imagine Institute, Paris, France; St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA, ²San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, and Vita Salute San Raffaele University, Milan, Italy, ³Immunology Research Lab, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia, ⁴Dasman Diabetes Institute, Department of Genetics and Bioinformatics, Dasman, Kuwait, ⁵Laboratory of Genomes & Cell Biology of Disease, INSERM U944, CNRS UMR 7212, Université de Paris, Institut de Recherche Saint-Louis, Hôpital Saint-Louis, Paris, France, ⁶Diabetes Center, University of California San Francisco, San Francisco, CA, USA, ⁷Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece, ⁸St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Primary Immunodeficiencies Group, Department of Microbiology and Parasitology, School of Medicine, University of Antioquia, Medellín, Colombia; School of Microbiology, University of Antioquia UdeA, Medellín, Colombia, ⁹Department of Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA, ¹⁰The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, ¹¹Pediatric Nephrology, Rheumatology, Dermatology, HFME, Hospices Civils de Lyon, National Referee Centre RAISE, and INSERM U1111, Université de Lyon, Lyon, France, ¹²Department of Pediatrics, BC Children’s and St Paul’s Hospitals, University of British Columbia, Vancouver, BC, Canada, ¹³Icahn School of Medicine at Mount Sinai, New York, NY, USA, ¹⁴Helix, San Mateo, CA, USA, ¹⁵International European University, Kyiv, Ukraine, ¹⁶Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, ¹⁷Clinical Immunology Unit, Department of Pediatric Infectious Disease, CHU Ibn Rushd and LICIA, Laboratoire d’Immunologie Clinique, Inflammation et Allergie, Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco, ¹⁸SciLifeLab, Department Of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden, ¹⁹Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden, ²⁰Division of Immunology, Allergy, and Rheumatology, Department of Pediatrics and the Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, USA, ²¹The Rockefeller University & Howard Hughes Medical Institute, New York, NY, USA; Necker Hospital for Sick Children & INSERM, Paris, France, ²²Clinical Genomics, IRCCS San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan, Italy, ²³Murdoch Children’s Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia, ²⁴Immunology Division, Genetics Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus, UAB, Barcelona, Catalonia, Spain, ²⁵Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil, ²⁶de Duve Institute and Ludwig Cancer Research, Brussels, Belgium, ²⁷Washington University School of Medicine, St Louis, MO, USA, ²⁸Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA, ²⁹Bai Jerbai Wadia Hospital for Children, Mumbai, India, ³⁰School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA, ³¹Université de Paris, IAME UMR-S 1137, INSERM, Paris, France; Inserm CIC 1425, Paris, France, ³²Genetics Unit, Military Hospital Mohamed V, Rabat, Morocco, ³³Hôpital Bichat, Paris, France, ³⁴Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico, ³⁵School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, ³⁶Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife; CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid; Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain; Faculty of Health Sciences, University of Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain, ³⁷Group of Primary Immunodeficiencies, University of Antioquia UDEA, Medellin, Colombia, ³⁸Pulmonology Department, Cliniques Universitaires Saint-Luc ; Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium, ³⁹Sorbonne Université, Inserm, Centre d’Immunologie et des Maladies Infectieuses-Paris (CIMI PARIS), Assistance Publique-Hôpitaux de Paris (AP-HP) Hôpital Pitié-Salpêtrière, Paris, France, ⁴⁰Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA, ⁴¹Center for Chronic Immunodeficiency & Institute for Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany, ⁴²Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Laboratory, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium, ⁴³The Genetics Institute Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, ⁴⁴Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE, Prince Naif center for Immunology Research, King Saud University, Riyadh, SA, ⁴⁵Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden, ⁴⁶Institute for Systems Biology, Seattle, WA, USA, ⁴⁷Departments of Pediatrics, Immunology and Microbiology, University of Colorado, School of Medicine, Aurora, CO, USA, ⁴⁸Department of Medicine, Haukeland University Hospital, Bergen, Norway, ⁴⁹Department of Community Pediatrics, Perinatal and Maternal Medicine, Tokyo Medical and Dental University (TMDU), Tokyo, Japan, ⁵⁰Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA, ⁵¹Department of Medical Chemistry and Laboratory Medicine, Poznan University of Medical Sciences, Poznan, Poland, ⁵²Bioinformatics and Applied Genomics Unit, Hellenic Pasteur Institute, Athens, Greece, ⁵³Molecular Pathology, Department of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu Estonia, ⁵⁴Chang Gung University, Taoyuan County, Taiwan, ⁵⁵Department of Paediatrics & Adolescent Medicine, The University of Hong Kong, Hong Kong, China, ⁵⁶Shanghai Public Health Clinical Center, Fudan University, Shanghai, China, ⁵⁷Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA, ⁵⁸Zukerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA, ⁵⁹Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, The Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Masih Daneshvari Hospital, Shahid Beheshti, University of Medical Sciences, Tehran, Iran, ⁶⁰Primary Immunodeficiency Clinical Unit and Laboratory, Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, Budapest, Hungary, ⁶¹Department of Pediatrics, University Hospitals Leuven; KU Leuven, Department of Microbiology, Immunology and Transplantation; Laboratory for Inborn Errors of Immunity, KU Leuven, Leuven, Belgium, ⁶²Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA, ⁶³University Clinic for Children’s Diseases, Department of Pediatric Immunology, Medical Faculty, University “ StCyril and Methodij” Skopje, North Macedonia, ⁶⁴Department of Biomedicine, Aarhus University, Aarhus, Denmark, ⁶⁵Tokyo Medical & Dental University Hospital, Tokyo, Japan, ⁶⁶A*STAR Infectious Disease Labs, Agency for Science, Technology and Research, Singapore; Lee Kong Chian School of Medicine, Nanyang Technology University, Singapore, ⁶⁷National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA, ⁶⁸Laboratory of Medical Genetics, IRCCS Bambino Gesù Children’s Hospital, Rome, Italy, ⁶⁹Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy, ⁷⁰Comparative Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland, ⁷¹Department of Pediatrics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan, ⁷²Tokyo Medical and Dental University, Tokyo, Japan, ⁷³Department of Molecular Biology and Genetics, Bilkent University, Bilkent - Ankara, Turkey, ⁷⁴Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti, ⁷⁵Institute of Biomedical Research of IdiPAZ, University Hospital “La Paz”, Madrid, Spain, ⁷⁶Institut de Biomedicina de València-CSIC, CIBERNED-ISCIII, Unitat Mixta de Neurologia i Genètica, IIS La Fe, Vallencia, Spain, ⁷⁷Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA, ⁷⁸Department of Biosciences, Biotechnology and Environment, University of Bari A. Moro, Bari, Italy, ⁷⁹IIBB-CSIC, IDIBAPS, Barcelona, Spain, ⁸⁰Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil, ⁸¹Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain; Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain; Center for Biomedical Research on Rare Diseases (CIBERER), ISCIII, Barcelona, Spain, ⁸²Human Evolutionary Genetics Unit, CNRS U2000, Institut Pasteur, Paris, France; Human Genomics and Evolution, Collège de France, Paris, France, ⁸³Al Jalila Children’s Hospital, Dubai, UAE, ⁸⁴University Hospital St Marina, Varna, Bulgaria, ⁸⁵Department of Immunology, University Hospital of Gran Canaria Dr Negrín, Canarian Health System, Las Palmas de Gran Canaria; Department of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain; Department of Medical and Surgical Sciences, School of Medicine, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain, ⁸⁶Department of Paediatric Infectious Diseases and Virology, Imperial College London, London, UK; Centre for Paediatrics and Child Health, Faculty of Medicine, Imperial College London, London, UK, ⁸⁷Department of Immunology, Second Faculty of Medicine Charles University, V Uvalu, University Hospital in Motol, Prague, Czech Republic, ⁸⁸Adult Immunodeficiency Unit, Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Rare Diseases Center and Pediatric Research Center, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, ⁸⁹Dr. Shahrooei Lab, 22 Bahman St., Ashrafi Esfahani Blvd, Tehran, Iran; Clinical and Diagnostic Immunology lab, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium, ⁹⁰Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia, ⁹¹Central European Institute of Technology & Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic, ⁹²Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA, ⁹³Pediatric 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, Catalonia, Spain, ⁹⁴Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, Paris, France; AP-HP, Hôpital Saint-Louis, Laboratoire d’Immunologie, Paris, France, ⁹⁵St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands, ⁹⁶Department of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria, ⁹⁷Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent’s Clinical School, Faculty of Medicine, UNSW Sydney, NSW, Australia, ⁹⁸Departments of Medical Genetics & Histology and Embryology, Faculty of Medicine; Department of Translational Medicine, Health Sciences Institude, Bursa Uludağ University, Bursa, Turkey, ⁹⁹Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, ¹⁰⁰Etablissement Francais Du Sang, La Plaine-Saint Denis, Saint-Denis, France, ¹⁰¹Hospices Civils de Lyon, Lyon, France; International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France, ¹⁰²BC Children’s Hospital, The University of British Columbia, Vancouver, Canada, ¹⁰³Centre for Precision Therapeutics, Genetics & Genomic Medicine Centre, NeuroGen Children’s Healthcare and Lecturer, Holy Family Red Crescent Medical College Dhaka, Bangladesh, ¹⁰⁴College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE; Cellular Intelligence (Ci) Lab, GenomeArc Inc, Toronto, ON, Canada, ¹⁰⁵Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands, ¹⁰⁶Department of Medicine, Division of Infectious Diseases, McGill University Health Centre, Montréal, Québec, Canada; Infectious Disease Susceptibility Program, Research Institute, McGill University Health Centre, Montréal, Québec, Canada, ¹⁰⁷Department of Pediatric Pneumology, Immunology and Intensive Care, Charité Universitätsmedizin, Berlin University Hospital Center, Berlin, Germany; Labor Berlin GmbH, Department of Immunology, Berlin, Germany; Berlin Institutes of Health (BIH), Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany, ¹⁰⁸Department of General Internal Medicine, Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium, ¹⁰⁹Biosciences Institute, University of São Paulo, São Paulo, Brazil, ¹¹⁰Molecular Biophysics Division, Faculty of Physics, A Mickiewicz University, Poznań, Poland.

Members of COVID-STORM Clinicians:

Giuseppe Foti¹, Giuseppe Citerio¹, Ernesto Contro¹, Alberto Pesci², Maria Grazia Valsecchi³, Marina Cazzaniga⁴, Giacomo Bellani⁵.

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. ⁵Interdepartmental Centre for Medical Sciences (CISMed), University of Trento, Trento, Italy.

Members of COVID Clinicians:

Jorge Abad¹, Giulia Accordino², Micol Angelini³, Sergio Aguilera-Albesa⁴, Aina Aguiló-Cucurull⁵, Alessandro Aiuti⁶, Esra Akyüz Özkan⁷, Ilad Alavi Darazam⁸, Jonathan Antonio Roblero Albisures⁹, Juan C. Aldave¹⁰, Miquel Alfonso Ramos¹¹, Taj Ali Khan¹², Anna Aliberti¹³, Seyed Alireza Nadji¹⁴, Gulsum Alkan¹⁵, Suzan A. AlKhater¹⁶, Jerome Allardet-Servent¹⁷, Luis M. Allende¹⁸, Rebeca Alonso-Arias¹⁹, Mohammed S. Alshahrani²⁰, Laia Alsina²¹, Marie-Alexandra Alyanakian²², Blanca Amador Borrero²³, Zahir Amoura²⁴, Arnau Antolí²⁵, Romain Arrestier²⁶, Mélodie Aubart²⁷, Teresa Auguet²⁸, Iryna Avramenko²⁹, Gökhan Aytekin³⁰, Axelle Azot³¹, Seiamak Bahram³², Fanny Bajolle³³, Fausto Baldanti³⁴, Aurélie Baldolli³⁵, Maite Ballester³⁶, Hagit Baris Feldman³⁷, Benoit Barrou³⁸, Federica Barzaghi⁶, Sabrina Basso³⁹, Gulsum Iclal Bayhan⁴⁰, Alexandre Belot⁴¹, Liliana Bezrodnik⁴², Agurtzane Bilbao⁴³, Geraldine Blanchard-Rohner⁴⁴, Ignacio Blanco⁴⁵, Adeline Blandinières⁴⁶, Daniel Blázquez-Gamero⁴⁷, Alexandre Bleibtreu⁴⁸, Marketa Bloomfield⁴⁹, Mireia Bolivar-Prados⁵⁰, Anastasiia Bondarenko⁵¹, Alessandro Borghesi³, Raphael Borie⁵², Elisabeth Botdhlo-Nevers⁵³, Ahmed A. Bousfiha⁵⁴, Aurore Bousquet⁵⁵, David Boutolleau⁵⁶, Claire Bouvattier⁵⁷, Oksana Boyarchuk⁵⁸, Juliette Bravais⁵⁹, M. Luisa Briones⁶⁰, Marie-Eve Brunner⁶¹, Raffaele Bruno⁶², Maria Rita P. Bueno⁶³, Huda Bukhari⁶⁴, Jacinta Bustamante³³, Juan José Cáceres Agra⁶⁵, Ruggero Capra⁶⁶, Raphael Carapito⁶⁷, Maria Carrabba⁶⁸, Giorgio Casari⁶, Carlos Casasnovas⁶⁹, Marion Caseris⁷⁰, Irene Cassaniti³⁴, Martin Castelle⁷¹, Francesco Castelli⁷², Martín Castillo de Vera⁷³, Mateus V. Castro⁶³, Emilie Catherinot⁷⁴, Jale Bengi Celik⁷⁵, Alessandro Ceschi⁷⁶, Martin Chalumeau⁷⁷, Bruno Charbit⁷⁸, Cécile Boulanger⁷⁹, Père Clavé⁵⁰, Bonaventura Clotet⁸⁰, Anna Codina⁸¹, Yves Cohen⁸², Roger Colobran⁸³, Cloé Comarmond⁸⁴, Alain Combes⁸⁵, Patrizia Comoli³⁹, Angelo G. Corsico², Taner Coşkuner⁸⁶, Aleksandar Cvetkovski⁸⁷, Cyril Cyrus⁸⁸, David Dalmau⁸⁹, François Danion⁹⁰, David Ross Darley⁹¹, Vincent Das⁹², Nicolas Dauby⁹³, Stéphane Dauger⁹⁴, Paul De Munter⁹⁵, Loic de Pontual⁹⁶, Amin Dehban⁹⁷, Geoffroy Delplancq⁹⁸, Alexandre Demoule⁹⁹, Isabelle Desguerre¹⁰⁰, Antonio Di Sabatino¹⁰¹, Jean-Luc Diehl¹⁰², Stephanie Dobbelaere¹⁰³, Elena Domínguez-Garrido¹⁰⁴, Clément Dubost¹⁰⁵, Olov Ekwall¹⁰⁶, Şefika Elmas Bozdemir¹⁰⁷, Marwa H. Elnagdy¹⁰⁸, Melike Emiroglu¹⁵, Akifumi Endo¹⁰⁹, Emine Hafize Erdeniz¹¹⁰, Selma Erol Aytekin¹¹¹, Maria Pilar Etxart Lasa¹¹², Romain Euvrard¹¹³, Giovanna Fabio⁶⁸, Laurence Faivre¹¹⁴, Antonin Falck¹¹⁵, Muriel Fartoukh¹¹⁶, Morgane Faure¹¹⁷, Miguel Fernandez Arquero¹¹⁸, Ricard Ferrer¹¹⁹, Jose Ferreres¹²⁰, Carlos Flores¹²¹, Bruno Francois¹²², Victoria Fumadó¹²³, Kitty S. C. Fung¹²⁴, Francesca Fusco¹²⁵, Alenka Gagro¹²⁶, Blanca Garcia Solis¹²⁷, Pierre Garçon³⁴³, Pascale Gaussem¹²⁸, Zeynep Gayretli¹²⁹, Juana Gil-Herrera¹³⁰, Laurent Gilardin¹³¹, Audrey Giraud Gatineau¹³², Mònica Girona-Alarcón¹³³, Karen Alejandra Cifuentes Godínez¹³⁴, Jean-Christophe Goffard¹³⁵, Nacho Gonzales¹³⁶, Luis I. Gonzalez-Granado¹³⁷, Rafaela González-Montelongo¹³⁸, Antoine Guerder¹³⁹, Belgin Gülhan¹⁴⁰, Victor Daniel Gumucio¹⁴¹, Leif Gunnar Hanitsch¹⁴², Jan Gunst¹⁴³, Marta Gut¹⁴⁴, Jérôme Hadjadj¹⁴⁵, Filomeen Haerynck¹⁴⁶, Rabih Halwani¹⁴⁷, Lennart Hammarström¹⁴⁸, Selda Hancerli¹⁴⁹, Tetyana Hariyan¹⁵⁰, Nevin Hatipoglu¹⁵¹, Deniz Heppekcan¹⁵², Elisa Hernandez-Brito¹⁵³, Po-ki Ho¹⁵⁴, María Soledad Holanda-Peña¹⁵⁵, Juan P. Horcajada¹⁵⁶, Sami Hraiech¹⁵⁷, Linda Humbert¹⁵⁸, Ivan F. N. Hung¹⁵⁹, Alejandro D. Iglesias¹⁶⁰, Antonio Íñigo-Campos¹³⁸, Matthieu Jamme¹⁶¹, María Jesús Arranz⁸⁹, Marie-Thérèse Jimeno¹⁶², Iolanda Jordan¹³³, Saliha Kanık-Yüksek¹⁶³, Yalcin Kara¹⁶⁴, Aydın Karahan¹⁶⁵, Adem Karbuz¹⁶⁶, Kadriye Kart Yasar¹⁶⁷, Ozgur Kasapcopur¹⁶⁸, Kenichi Kashimada¹⁶⁹, Sevgi Keles¹¹¹, Yasemin Kendir Demirkol¹⁷⁰, Yasutoshi Kido¹⁷¹, Can Kizil¹⁷², Ahmet Osman Kılıç¹⁷³, Adam Klocperk¹⁷⁴, Antonia Koutsoukou¹⁷⁵, Zbigniew J. Król¹⁷⁶, Hatem Ksouri¹⁷⁷, Paul Kuentz¹⁷⁸, Arthur M. C. Kwan¹⁷⁹, Yat Wah M. Kwan¹⁸⁰, Janette S. Y. Kwok¹⁸¹, Jean-Christophe Lagier¹⁸², David S. Y. Lam¹⁸³, Vicky Lampropoulou¹⁸⁴, Fanny Lanternier¹⁸⁵, Yu-Lung Lau¹⁸⁶, Fleur Le Bourgeois⁹⁴, Yee-Sin Leo¹⁸⁷, Rafael Leon Lopez¹⁸⁸, Daniel Leung¹⁸⁶, Michael Levin¹⁸⁹, Michael Levy⁹⁴, Romain Lévy³³, Zhi Li⁷⁸, Daniele Lilleri³⁴, Edson Jose Adrian Bolanos Lima¹⁹⁰, Agnes Linglart¹⁹¹, Eduardo López-Collazo¹⁹², José M. Lorenzo-Salazar¹³⁸, Céline Louapre¹⁹³, Catherine Lubetzki¹⁹³, Kwok-Cheung Lung¹⁹⁴, Charles-Edouard Luyt¹⁹⁵, David C. Lye¹⁹⁶, Cinthia Magnone¹⁹⁷, Davood Mansouri¹⁹⁸, Enrico Marchioni¹⁹⁹, Carola Marioli², Majid Marjani²⁰⁰, Laura Marques²⁰¹, Jesus Marquez Pereira²⁰², Andrea Martín-Nalda²⁰³, David Martínez Pueyo²⁰⁴, Javier Martinez-Picado²⁰⁵, Iciar Marzana²⁰⁶, Carmen Mata-Martínez²⁰⁷, Alexis Mathian²⁴, Larissa R. B. Matos⁶³, Gail V. Matthews²⁰⁸, Julien Mayaux²⁰⁹, Raquel McLaughlin-Garcia²¹⁰, Philippe Meersseman²¹¹, Jean-Louis Mège²¹², Armand Mekontso-Dessap²¹³, Isabelle Melki¹¹⁵, Federica Meloni³⁴⁶, Jean-François Meritet²¹⁴, Paolo Merlani²¹⁵, Özge Metin Akcan²¹⁶, Isabelle Meyts²¹⁷, Mehdi Mezidi²¹⁸, Isabelle Migeotte²¹⁹, Maude Millereux²²⁰, Matthieu Million²²¹, Tristan Mirault²²², Clotilde Mircher²²³, Mehdi Mirsaeidi²²⁴, Yoko Mizoguchi²²⁵, Bhavi P. Modi²²⁶, Francesco Mojoli¹³, Elsa Moncomble²²⁷, Abián Montesdeoca Melián²²⁸, Antonio Morales Martinez²²⁹, Francisco Morandeira²³⁰, Pierre-Emmanuel Morange²³¹, Clémence Mordacq¹⁵⁸, Guillaume Morelle²³², Stéphane J. Mouly²³³, Adrián Muñoz-Barrera¹³⁸, Cyril Nafati²³⁴, Shintaro Nagashima²³⁵, Yu Nakagama¹⁷¹, Bénédicte Neven²³⁶, João Farela Neves²³⁷, Lisa F. P. Ng²³⁸, Yuk-Yung Ng²³⁹, hubert Nielly¹⁰⁵, Yeray Novoa Medina²¹⁰, Esmeralda Nuñez Cuadros²⁴⁰, Semsi Nur Karabela¹⁶⁷, J. Gonzalo Ocejo-Vinyals²⁴¹, Keisuke Okamoto¹⁰⁹, Mehdi Oualha³³, Amani Ouedrani²², Tayfun Özçelik²⁴², Aslinur Ozkaya-Parlakay¹⁴⁰, Michele Pagani¹³, Qiang Pan-Hammarström¹⁴⁸, Maria Papadaki²⁴³, Christophe Parizot²⁰⁹, Philippe Parola²⁴⁴, Tiffany Pascreau²⁴⁵, Stéphane Paul²⁴⁶, Estela Paz-Artal²⁴⁷, Sigifredo Pedraza²⁴⁸, Nancy Carolina González Pellecer¹³⁴, Silvia Pellegrini²⁴⁹, Rebeca Pérez de Diego¹²⁷, Xosé Luis Pérez-Fernández¹⁴¹, Aurélien Philippe²⁵⁰, Quentin Philippot¹¹⁶, Adrien Picod²⁵¹, Marc Pineton de Chambrun⁸⁵, Antonio Piralla³⁴, Laura Planas-Serra²⁵², Dominique Ploin²⁵³, Julien Poissy²⁵⁴, Géraldine Poncelet⁷⁰, Garyphallia Poulakou¹⁷⁵, Marie S. Pouletty²⁵⁵, Persia Pourshahnazari²⁵⁶, Jia Li Qiu-Chen²⁵⁷, Paul Quentric²⁰⁹, Thomas Rambaud²⁵⁸, Didier Raoult²¹², Violette Raoult²⁵⁹, Anne-Sophie Rebillat²²³, Claire Redin²⁶⁰, Léa Resmini²⁶¹, Pilar Ricart²⁶², Jean-Christophe Richard²⁶³, Raúl Rigo-Bonnin²⁶⁴, Nadia rivet⁴⁶, Jacques G. Rivière²⁶⁵, Gemma Rocamora-Blanch²⁵, Mathieu P. Rodero²⁶⁶, Carlos Rodrigo²⁶⁷, Luis Antonio Rodriguez¹⁹⁰, Carlos Rodriguez-Gallego²⁶⁸, Agustí Rodriguez-Palmero²⁶⁹, Carolina Soledad Romero²⁷⁰, Anya Rothenbuhler²⁷¹, Damien Roux²⁷², Nikoletta Rovina¹⁷⁵, Flore Rozenberg²⁷³, Yvon Ruch⁹⁰, Montse Ruiz²⁷⁴, Maria Yolanda Ruiz del Prado²⁷⁵, Juan Carlos Ruiz-Rodriguez¹¹⁹, Joan Sabater-Riera¹⁴¹, Kai Saks²⁷⁶, Maria Salagianni¹⁸⁴, Oliver Sanchez²⁷⁷, Adrián Sánchez-Montalvá²⁷⁸, Silvia Sánchez-Ramón²⁷⁹, Laire Schidlowski²⁸⁰, Agatha Schluter²⁵², Julien Schmidt²⁸¹, Matthieu Schmidt²⁸², Catharina Schuetz²⁸³, Cyril E. Schweitzer²⁸⁴, Francesco Scolari²⁸⁵, Anna Sediva²⁸⁶, Luis Seijo²⁸⁷, Analia Gisela Seminario⁴², Damien Sene²³, Piseth Seng²²¹, Sevtap Senoglu¹⁶⁷, Mikko Seppänen²⁸⁸, Alex Serra Llovich²⁸⁹, Mohammad Shahrooei⁹⁷, Anna Shcherbina²⁹⁰, Virginie Siguret²⁹¹, Eleni Siouti²⁹², David M. Smadja²⁹³, Nikaia Smith⁷⁸, Ali Sobh²⁹⁴, Xavier Solanich²⁵, Jordi Solé-Violán²⁹⁵, Catherine Soler²⁹⁶, Pere Soler-Palacín²⁹⁷, Betül Sözeri⁸⁶, Giulia Maria Stella², Yuriy Stepanovskiy²⁹⁸, Annabelle Stoclin²⁹⁹, Fabio Taccone²¹⁹, Yacine Tandjaoui-Lambiotte³⁰⁰, Jean-Luc Taupin³⁰¹, Simon J. Tavernier³⁰², Loreto Vidaur Tello¹¹², Benjamin Terrier³⁰³, Guillaume Thiery³⁰⁴, Christian Thorball²⁶⁰, Karolina Thorn³⁰⁵, Caroline Thumerelle¹⁵⁸, Imran Tipu³⁰⁶, Martin Tolstrup³⁰⁷, Gabriele Tomasoni³⁰⁸, Julie Toubiana⁷⁷, Josep Trenado Alvarez³⁰⁹, Vasiliki Triantafyllia³¹⁰, Sophie Trouillet-Assant³¹¹, Jesús Troya³¹², Owen T. Y. Tsang³¹³, Liina Tserel³¹⁴, Eugene Y. K. Tso³¹⁵, Alessandra Tucci³¹⁶, Şadiye Kübra Tüter Öz¹⁵, Matilde Valeria Ursini¹²⁵, Takanori Utsumi²²⁵, Yurdagul Uzunhan³¹⁷, Pierre Vabres³¹⁸, Juan Valencia-Ramos³¹⁹, Ana Maria Van Den Rym¹²⁷, Isabelle Vandernoot³²⁰, Valentina Velez-Santamaria³²¹, Silvia Patricia Zuniga Veliz¹³⁴, Mateus C. Vidigal³²², Sébastien Viel²⁵³, Cédric Villain³²³, Marie E. Vilaire-Meunier²²³, udit Villar-García³²⁴, Audrey Vincent⁵⁷, Dimitri Van der Linden³²⁵, Guillaume Voiriot³²⁶, Alla Volokha³²⁷, Fanny Vuotto¹⁵⁸, Els Wauters³²⁸, Joost Wauters³²⁹, Alan K. L. Wu³³⁰, Tak-Chiu Wu³³¹, Aysun Yahşi³³², Osman Yesilbas³³³, Mehmet Yildiz¹⁶⁸, Barnaby E. Young¹⁸⁷, Ufuk Yükselmiş³³⁴, Mayana Zatz⁶³, Marco Zecca³⁹, Valentina Zuccaro⁶², Jens Van Praet³³⁵, Bart N. Lambrecht³³⁶, Eva Van Braeckel³³⁶, Cédric Bosteels³³⁶, Levi Hoste³³⁷, Eric Hoste³³⁸, Fré Bauters³³⁶, Jozefien De Clercq³³⁶, Catherine Heijmans³³⁹, Hans Slabbynck³⁴⁰, Leslie Naesens³⁴¹, Benoit Florkin³⁴², Mary-Anne Young³⁴⁴, Amanda Willis³⁴⁴, Paloma Lapuente-Suanzes³⁴⁵, Ana de Andrés-Martín³⁴⁵.

¹Germans Trias i Pujol University Hospital and Research Institute, Badalona, Barcelona, Spain. ²Respiratory Diseases Division, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy. ³Neonatal Intensive Care Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. ⁴Navarra Health Service Hospital, Pamplona, Spain. ⁵Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain; Immunology Division, Genetics Department, Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona (UAB), Barcelona, Catalonia, Spain. ⁶Immunohematology Unit, San Raffaele Hospital, Milan, Italy. ⁷Ondokuz Mayıs University Medical Faculty Pediatrics, Samsun, Turkey. ⁸Department of Infectious Diseases, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ⁹Hospital Regional de Huehuetenango, “Dr. Jorge Vides de Molina,” Huehuetenango, Guatemala. ¹⁰Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru. ¹¹Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat Spain. ¹²Khyber Medical University, Khyber Pakhtunkhwa, Pakistan. ¹³Anesthesia and Intensive Care, Rianimazione I, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. ¹⁴Virology Research Center, National Institutes of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ¹⁵Department of Pediatrics, Division of Pediatric Infectious Diseases, Selcuk University Faculty of Medicine, Konya, Turkey. ¹⁶College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; Department of Pediatrics, King Fahad Hospital of the University, Al-Khobar, Saudi Arabia. ¹⁷Intensive Care Unit, Hôpital Européen, Marseille, France. ¹⁸Immunology Department, Hospital 12 de Octubre, Research Institute imas12, Complutense University, Madrid, Spain. ¹⁹Immunology Department, Asturias Central University Hospital, Biosanitary Research Institute of the Principality of Asturias (ISPA), Oviedo, Spain. ²⁰Emergency and Critical Care Medicine Departments, College of Medicine, Imam AbdulRahman Ben Faisal University, Dammam, Saudi Arabia. ²¹Clinical Immunology and Primary Immunodeficiencias Unit, Hospital Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Barcelona, Spain; Universitat de Barcelona, Barcelona, Spain. ²²Department of Biological Immunology, Necker Hospital for Sick Children, AP-HP and INEM, Paris, France. ²³Internal Medicine Department, Hôpital Lariboisière, AP-HP, Paris, France; Université de Paris, Paris, France. ²⁴Internal Medicine Department, Pitié-Salpétrière Hospital, Paris, France. ²⁵Department of Internal Medicine, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain. ²⁶Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, AP-HP, Créteil, France; Groupe de Recherche Clinique CARMAS, Faculté de Santé de Créteil, Université Paris Est Créteil, Créteil, France. ²⁷INSERM U1163, University of Paris, Imagine Institute, Paris, France and Pediatric Neurology Department, Necker-Enfants malades Hospital, AP-HP, Paris, France. ²⁸Hospital U. de Tarragona Joan XXIII. Universitat Rovira i Virgili (URV). IISPV, Tarragona, Spain. ²⁹Department of Propedeutics of Pediatrics and Medical Genetics, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine. ³⁰Department of Immunology and Allergy, Konya City Hospital, Konya, Turkey. ³¹Private Practice, Paris, France. ³²INSERM U1109, University of Strasbourg, Strasbourg, France. ³³Necker Hospital for Sick Children, AP-HP, Paris, France. ³⁴Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. ³⁵Department of Infectious Diseases, CHU de Caen, Caen, France. ³⁶Consorcio Hospital General Universitario, Valencia, Spain. ³⁷Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. ³⁸Department of Urology, Nephrology, Transplantation, APHP-SU, Sorbonne Université, INSERM U 1082, Paris, France. ³⁹Cell Factory and Pediatric Hematology-Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. ⁴⁰Yildirim Beyazit University, Faculty of Medicine, Ankara City Hospital, Children’s Hospital, Ankara, Turkey. ⁴¹University of Lyon, CIRI, INSERM U1111, National Referee Centre RAISE, Pediatric Rheumatology, HFME, Hospices Civils de Lyon, Lyon, France. ⁴²Center for Clinical Immunology, CABA, Buenos Aires, Argentina. ⁴³Cruces University Hospital, Bizkaia, Spain. ⁴⁴Paediatric Immunology and Vaccinology Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. ⁴⁵University Hospital and Research Institute “Germans Trias i Pujol,” Badalona, Spain. ⁴⁶Hematology, Georges Pompidou Hospital, AP-HP, Paris, France. ⁴⁷Pediatric Infectious Diseases Unit, Instituto de Investigación Hospital 12 de Octubre (imas12), Hospital Universitario 12 de Octubre, Universidad Complutense, Madrid, Spain. ⁴⁸Infectious disease Unit, Pitié-Salpêtrière Hospital, AP-AP, Paris, France. ⁴⁹Department of Pediatrics, Thomayer’s Hospital, first Faculty of Medicine, Charles University, Prague, Czech Republic; Department of Immunology, Motol University Hospital, Second Faculty of Medicine, Charles University, Prague, Czech Republic. ⁵⁰Centro de Investigación Biomédica en Red de Enfermedades Hepàticas y Digestivas (Ciberehd), Hospital de Mataró, Consorci Sanitari del Maresme, Mataró, Spain. ⁵¹Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine. ⁵²Service de Pneumologie, Hopital Bichat, AP-HP, Paris, France. ⁵³Department of Infectious Diseases, CIC1408, GIMAP CIRI INSERM U1111, University Hospital of Saint-Etienne, Saint-Etienne, France. ⁵⁴Clinical 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. ⁵⁵Bégin Military Hospital, St Mandé, France. ⁵⁶Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié Salpêtrière, Service de Virologie, Paris, France. ⁵⁷Endocrinology Unit, AP-HP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. ⁵⁸Department of Children’s Diseases and Pediatric Surgery, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. ⁵⁹Pneumology Unit, Tenon Hospital, AP-HP, Paris, France. ⁶⁰Department of Respiratory Diseases, Hospital Clínico y Universitario de Valencia, Valencia, Spain. ⁶¹Intensive Care Unit, Réseau Hospitalier Neuchâtelois, Neuchâtel, Switzerland. ⁶²Infectious Diseases Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. ⁶³Human Genome and Stem Cell Research Center, University of São Paulo, São Paulo, Brazil. ⁶⁴Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. ⁶⁵Hospital Insular, Las Palmas de Gran Canaria, Spain. ⁶⁶MS Center, Spedali Civili, Brescia, Italy. ⁶⁷Laboratoire d’ImmunoRhumatologie Moléculaire, plateforme GENOMAX, INSERM UMR_S 1109, Faculté de Médecine, ITI TRANSPLANTEX NG, Université de Strasbourg, Strasbourg, France. ⁶⁸Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Milan, Italy. ⁶⁹Neuromuscular Unit, Neurology Department, Hospital Universitari de Bellvitge–IDIBELL and CIBERER, Barcelona, Spain. ⁷⁰Hopital Robert Debré, Paris, France. ⁷¹Pediatric Immunohematology Unit, Necker Enfants Malades Hospital, AP-HP, Paris, France. ⁷²Department of Infectious and Tropical Diseases, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. ⁷³Doctoral Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. ⁷⁴Hôpital Foch, Suresnes, France. ⁷⁵Selcuk University Faculty of Medicine, Department of Anesthesiology and Reanimation, Intensive Care Medicine Unit, Konya, Turkey. ⁷⁶Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale and Faculty of Biomedical Sciences, Università della Svizzera italiana, Lugano, Switzerland. ⁷⁷Necker Hospital for Sick Children, Paris University, AP-HP, Paris, France. ⁷⁸Pasteur Institute, Paris, France. ⁷⁹Department of Pediatric Hemato-oncology, UCL Louvain, Brussels, Belgium. ⁸⁰University Hospital and Research Institute “Germans Trias i Pujol,” IrsiCaixa AIDS Research Institute, UVic-UCC, Badalona, Spain. ⁸¹Clinical Biochemistry, Pathology, Paediatric Neurology and Molecular Medicine Departments and Biobank, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Esplugues, Spain. ⁸²AP-HP, Avicenne Hospital, Intensive Care Unit, Bobigny, France; University Sorbonne Paris Nord, Bobigny, France; INSERM, U942, F-75010, Paris, France. ⁸³Hospital Universitari Vall d’Hebron, Barcelona, Spain. ⁸⁴Pitié-Salpêtrière Hospital, Paris, France. ⁸⁵Service de médecine Intensive Réanimation, Groupe Hospitalier Pitié-Salpêtrière, Sorbonne Université, Paris, France. ⁸⁶Umraniye Training and Research Hospital, Istanbul, Turkey. ⁸⁷Faculty of Medical Sciences at University “Goce Delcev,” Shtip, North Macedonia. ⁸⁸Department of Biochemistry, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. ⁸⁹Fundació Docencia i Recerca Mutua Terrassa, Barcelona, Spain. ⁹⁰Maladies Infectieuses et Tropicales, Nouvel Hôpital Civil, CHU Strasbourg, Strasbourg, France. ⁹¹UNSW Medicine, St Vincent’s Clinical School, Sydney, NSW, Australia; Department of Thoracic Medicine, St Vincent’s Hospital Darlinghurst, Sydney, NSW, Australia. ⁹²Intensive Care Unit, Montreuil Hospital, Montreuil, France. ⁹³CHU Saint-Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium. ⁹⁴Pediatric Intensive Care Unit, Robert-Debré University Hospital, AP-HP, Paris, France. ⁹⁵General Internal Medicine, University Hospitals Leuven, Leuven, Belgium. ⁹⁶Hôpital Jean Verdier, AP-HP, Bondy, France. ⁹⁷Dr. Shahrooei Lab, 22 Bahman St., Ashrafi Esfahani Blvd, Tehran, Iran; Clinical and Diagnostic Immunology lab, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium. ⁹⁸Centre de génétique humaine, CHU Besançon, Besançon, France. ⁹⁹Sorbonne Université médecine and AP-HP Sorbonne université site Pitié-Salpêtrière, Paris, France. ¹⁰⁰Pediatric Neurology Department, Necker-Enfants Malades Hospital, AP-HP, Paris, France. ¹⁰¹Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. ¹⁰²Intensive Care Unit, Georges Pompidou Hospital, AP-HP, Paris, France. ¹⁰³Department of Pneumology, AZ Delta, Roeselare, Belgium. ¹⁰⁴Molecular Diagnostic Unit, Fundación Rioja Salud, Logroño, La Rioja, Spain. ¹⁰⁵Bégin Military Hospital, Saint Mandé, France. ¹⁰⁶Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ¹⁰⁷Bursa City Hospital, Bursa, Turkey. ¹⁰⁸Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. ¹⁰⁹Tokyo Medical and Dental University, Tokyo, Japan. ¹¹⁰Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey. ¹¹¹Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Konya, Turkey. ¹¹²Intensive Care Medicine, Donostia University Hospital, Biodonostia Institute of Donostia, CIBER Enfermedades Respiratorias ISCIII, Donostia, Spain. ¹¹³Internal Medicine, University Hospital Edouard Herriot, Hospices Civils de Lyon, Lyon, France. ¹¹⁴Centre de Génétique, CHU Dijon, Dijon, France. ¹¹⁵Robert Debré Hospital, Paris, France. ¹¹⁶AP-HP Tenon Hospital, Paris, France. ¹¹⁷Sorbonne Universités, UPMC University of Paris, Paris, France. ¹¹⁸Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain. ¹¹⁹Intensive Care Department, Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain; Shock, Organ Dysfunction and Resuscitation Research Group, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain. ¹²⁰Intensive Care Unit, Hospital Clínico y Universitario de Valencia, Valencia, Spain. ¹²¹Genomics 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; Faculty of Health Sciences, University of Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. ¹²²CHU Limoges and INSERM CIC 1435 and UMR 1092, Limoges, France. ¹²³Infectious 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. ¹²⁴Department of Pathology, United Christian Hospital, Hong Kong, China. ¹²⁵Institute of Genetics and Biophysics “Adriano Buzzati-Traverso,” IGB-CNR, Naples, Italy. ¹²⁶Department of Pediatrics, Children’s Hospital Zagreb, University of Zagreb School of Medicine, Zagreb, Josip Juraj Strossmayer University of Osijek, Medical Faculty Osijek, Osijek, Croatia. ¹²⁷Laboratory of Immunogenetics of Human Diseases, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. ¹²⁸Hematology, AP-HP, Hopital Européen Georges Pompidou and INSERM UMR-S1140, Paris, France. ¹²⁹Faculty of Medicine, Department of Pediatrics, Division of Pediatric Infectious Diseases, Karadeniz Technical University, Trabzon, Turkey. ¹³⁰Division of Immunology, Hospital General Universitario and Instituto de Investigación Sanitaria “Gregorio Marañón,” Madrid, Spain. ¹³¹Bégin Military Hospital, Bégin, France. ¹³²Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, IHU Méditerranée Infection, Marseille, France, French Armed Forces Center for Epidemiology and Public Health (CESPA), Marseille, France. ¹³³Pediatric Intensive Care Unit, Hospital Sant Joan de Déu, Barcelona, Spain. ¹³⁴Gestion Integral en Salud, Guatemala. ¹³⁵Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. ¹³⁶Immunodeficiencies Unit, Research Institute Hospital, Madrid, Spain. ¹³⁷Primary Immunodeficiencies Unit, Pediatrics, University Hospital 12 de Octubre, Madrid, Spain; School of Medicine Complutense University of Madrid, Madrid, Spain. ¹³⁸Genomics Division, Instituto Tecnológico y de Energías Renovables (ITER), Santa Cruz de Tenerife, Spain. ¹³⁹Assistance Publique Hôpitaux de Paris, Paris, France. ¹⁴⁰Ankara City Hospital, Ankara, Turkey. ¹⁴¹Department of Intensive Care, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain. ¹⁴²Immunodeficiency Outpatient Clinic, Institute for Medical Immunology, FOCIS Center of Excellence, Charité Universitätsmedizin Berlin, Germany. ¹⁴³Surgical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium. ¹⁴⁴CNAG-CRG, Barcelona Institute of Science and Technology, Barcelona, Spain. ¹⁴⁵Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Paris, France. ¹⁴⁶Department of Paediatric Immunology and Pulmonology, Center for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Center, PID Research Lab, Ghent University Hospital, Ghent, Belgium. ¹⁴⁷Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE, Prince Naif center for Immunology Research, King Saud University, Riyadh, SA. ¹⁴⁸Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. ¹⁴⁹Department of Pediatrics (Infectious Diseases), Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. ¹⁵⁰I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. ¹⁵¹Pediatric Infectious Diseases Unit, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. ¹⁵²Health Sciences University, Darıca Farabi Education and Research Hospital, Kocaeli, Turkey. ¹⁵³Department of Immunology, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. ¹⁵⁴Department of Paediatrics, Queen Elizabeth Hospital, Hong Kong, China. ¹⁵⁵Intensive Care Unit. Marqués de Valdecilla Hospital, Santander, Spain. ¹⁵⁶Hospital del Mar, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), UAB, UPF, Barcelona, Spain. ¹⁵⁷Intensive Care Unit, APHM, Marseille, France. ¹⁵⁸CHU Lille, Lille, France. ¹⁵⁹Department of Medicine, University of Hong Kong, Hong Kong, China. ¹⁶⁰Department of Pediatrics, Columbia University, New York, NY, USA. ¹⁶¹Centre hospitalier intercommunal Poissy Saint Germain en Laye, Poissy, France. ¹⁶²IHU Méditerranée Infection, Service de l’Information Médicale, Hôpital de la Timone, Marseille, France. ¹⁶³Health Science University Ankara City Hospital, Ankara, Turkey. ¹⁶⁴Eskişehir Osmangazi University, Pediatric Infectious Diseases, Eskişehir, Turkey. ¹⁶⁵Mersin City Education and Research Hospital, Mersin, Turkey. ¹⁶⁶Division of Pediatric Infectious Diseases, Prof. Dr. Cemil Tascıoglu City Hospital, Istanbul, Turkey. ¹⁶⁷Departments of Infectious Diseases and Clinical Microbiology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. ¹⁶⁸Department of Pediatric Rheumatology, Istanbul University-Cerrahpasa, Istanbul, Turkey. ¹⁶⁹Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan. ¹⁷⁰Health Sciences University, Umraniye Education and Research Hospital, Istanbul, Turkey. ¹⁷¹Department of Parasitology and Research Center for Infectious Disease Sciences, Graduate School of Medicine, Osaka City University, Osaka, Japan. ¹⁷²Pediatric Infectious Diseases Unit of Osman Gazi University Medical School in Eskişehir, Turkey. ¹⁷³Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey. ¹⁷⁴Department of Immunology, Second Faculty of Medicine, Charles University and University Hospital in Motol, Prague, Czech Republic. ¹⁷⁵ICU, First Department of Respiratory Medicine, National and Kapodistrian University of Athens, Medical School, “Sotiria” General Hospital of Chest Diseases, Athens, Greece. ¹⁷⁶Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw, Poland. ¹⁷⁷Clinique des soins intensifs, HFR Fribourg, Fribourg, Switzerland. ¹⁷⁸Oncobiologie Génétique Bioinformatique, PC Bio, CHU Besançon, Besançon, France. ¹⁷⁹Department of Intensive Care, Tuen Mun Hospital, Hong Kong, China. ¹⁸⁰Paediatric Infectious Disease Unit, Hospital Authority Infectious Disease Center, Princess Margaret Hospital, Hong Kong (Special Administrative Region), China. ¹⁸¹Department of Pathology, Queen Mary Hospital, Hong Kong, China. ¹⁸²Aix Marseille Univ, IRD, MEPHI, IHU Méditerranée Infection, Marseille, France. ¹⁸³Department of Paediatrics, Tuen Mun Hospital, Hong Kong, China. ¹⁸⁴Biomedical Research Foundation of the Academy of Athens, Athens, Greece. ¹⁸⁵Necker Hospital, Paris, France. ¹⁸⁶Department of Paediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong, China. ¹⁸⁷National Centre for Infectious Diseases, Singapore, Singapore. ¹⁸⁸Hospital Universitario Reina Sofía, Cordoba, Spain. ¹⁸⁹Imperial College, London, England. ¹⁹⁰Hospital General San Juan de Dios, Ciudad de Guatemala, Guatemala. ¹⁹¹Endocrinology and Diabetes for Children, AP-HP, Bicêtre Paris-saclay hospital, Le Kremlin-Bicêtre, France. ¹⁹²Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. ¹⁹³Neurology Unit, AP-HP Pitié-Salpêtrière Hospital, Paris University, Paris, France. ¹⁹⁴Department of Medicine, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China. ¹⁹⁵Intensive Care Unit, AP-HP Pitié-Salpêtrière Hospital, Paris University, Paris, France. ¹⁹⁶National Centre for Infectious Diseases, Singapore, Singapore; Tan Tock Seng Hospital, Singapore, Singapore; Yong Loo Lin School of Medicine, Singapore, Singapore; Lee Kong Chian School of Medicine, Singapore, Singapore. ¹⁹⁷Hospital de Niños Dr. Ricardo Gutierrez, Buenos Aires, Argentina. ¹⁹⁸Department of Clinical Immunology and Infectious Diseases, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ¹⁹⁹Neurooncology and Neuroinflammation Unit, IRCCS Mondino Foundation, Pavia, Italy. ²⁰⁰Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. ²⁰¹Coordenadora da Unidade de Infeciologia e Imunodeficiências do Serviço de Pediatria, Centro Materno-Infantil do Norte, Porto, Portugal. ²⁰²Hospital Sant Joan de Déu and University of Barcelona, Barcelona, Spain. ²⁰³Pediatric 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, Catalonia, Spain. ²⁰⁴Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona, Spain. ²⁰⁵IrsiCaixa AIDS Research Institute, ICREA, UVic-UCC, Research Institute “Germans Trias i Pujol,” Badalona, Spain. ²⁰⁶Department of Laboratory, Cruces University Hospital, Barakaldo, Bizkaia, Spain, Bizkaia, Spain. ²⁰⁷Intensive Care Unit, Hospital General Universitario “Gregorio Marañón,” Madrid, Spain. ²⁰⁸University of New South Wales, Sydney, NSW, Australia. ²⁰⁹AP-HP Pitié-Salpêtrière Hospital, Paris, France. ²¹⁰Department of Pediatrics, Complejo Hospitalario Universitario Insular-Materno Infantil, Canarian Health System, Las Palmas de Gran Canaria, Spain. ²¹¹Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium. ²¹²Aix-Marseille University, APHM, Marseille, France. ²¹³Service de Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, Assistance Publique–Hôpitaux de Paris (AP-HP), Groupe de Recherche Clinique CARMAS, Faculté de Santé de Créteil, Université Paris Est Créteil, France. ²¹⁴AP-HP Cohin Hospital, Paris, France. ²¹⁵Department of Critical Care Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland. ²¹⁶Necmettin Erbakan University, Meram Medical Faculty, Division of Pediatric Infectious Diseases, Konya, Turke4y. ²¹⁷Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium; KU Leuven, Department of Microbiology, Immunology and Transplantation; Laboratory for Inborn Errors of Immunity, KU Leuven, Leuven, Belgium. ²¹⁸Hospices Civils de Lyon, Hôpital de la Croix-Rousse, Lyon, France. ²¹⁹Hôpital Erasme, Brussels, Belgium. ²²⁰Centre hospitalier de gonesse, Gonesse, France. ²²¹Aix Marseille Univ, IRD, AP-HM, MEPHI, IHU Méditerranée Infection, Marseille, France. ²²²Vascular Medicine, Georges Pompidou Hospital, AP-HP, Paris, France. ²²³Institut Jérôme Lejeune, Paris, France. ²²⁴Division of Pulmonary and Critical Care, College of Medicine-Jacksonville, University of Florida, Jacksonville, FL, USA. ²²⁵Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan. ²²⁶BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada. ²²⁷Médecine Intensive Réanimation, Hôpitaux Universitaires Henri Mondor, Assistance Publique–Hôpitaux de Paris (AP-HP), Créteil, France. ²²⁸Guanarteme Health Care Center, Canarian Health System, Las Palmas de Gran Canaria, Spain. ²²⁹Regional University Hospital of Malaga, Malaga, Spain. ²³⁰Department of Immunology, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain. ²³¹Aix Marseille Univ, INSERM, INRAE, C2VN, Marseille, France. ²³²Department of General Paediatrics, Hôpital Bicêtre, AP-HP, University of Paris Saclay, Le Kremlin-Bicêtre, France. ²³³INSERM U1144, Université de Paris, DMU INVICTUS, AP-HP.Nord, Département de Médecine Interne, Lariboisière Hospital, Paris, France. ²³⁴CHU de La Timone, Marseille, France. ²³⁵Department of Epidemiology, Infectious Disease Control and Prevention, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. ²³⁶Pediatric Immunology and Rheumatology Department, Necker Hospital, AP-HP, Paris, France. ²³⁷Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal. ²³⁸Infectious Disease Horizontal Technology Centre, A*STAR, Singapore, Singapore; Singapore Immunology Network, A*STAR, Singapore. ²³⁹Department of Medicine and Geriatrics, Tuen Mun Hospital, Hong Kong, China. ²⁴⁰Regional Universitary Hospital of Malaga, Málaga, Spain. ²⁴¹Department of Immunology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. ²⁴²Bilkent University, Department of Molecular Biology and Genetics, Ankara, Turkey. ²⁴³BRFAA, Athens, Greece. ²⁴⁴IHU Méditerranée Infection, Aix Marseille Univ, IRD, AP-HM, SSA, VITROME, IHU Méditerranée Infection, Marseille, France. ²⁴⁵L’Hôpital Foch, Suresnes, France. ²⁴⁶Department of Immunology, CIC1408, GIMAP CIRI INSERM U1111, University Hospital of Saint-Etienne, Saint-Etienne, France. ²⁴⁷Department of Immunology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain. ²⁴⁸Unit of Biochemistry, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico. ²⁴⁹Diabetes Research Institute, IRCCS San Raffaele Hospital, Milan, Italy. ²⁵⁰AP-HP Hôpitaux Universitaires Paris-Sud, Le Kremlin-Bicêtre, France. ²⁵¹AP-HP, Avicenne Hospital, Intensive Care Unit, Bobigny, France; INSERM UMR-S 942, Cardiovascular Markers in Stress Conditions (MASCOT), University of Paris, Paris, France. ²⁵²Neurometabolic Diseases Laboratory, IDIBELL-Hospital Duran i Reynals, Barcelona; CIBERER U759, ISCiii Madrid, Spain. ²⁵³Hospices Civils de Lyon, Lyon, France. ²⁵⁴Univ. Lille, INSERM U1285, CHU Lille, Pôle de médecine intensive-réanimation, CNRS, UMR 8576–Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France. ²⁵⁵Department of General pediatrics, Robert Debre Hospital, Paris, France. ²⁵⁶University of British Columbia, Vancouver, BC, Canada. ²⁵⁷Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Barcelona, Catalonia, Spain; Diagnostic Immunology Research Group, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Catalonia, Spain. ²⁵⁸AP-HP, Avicenne Hospital, Intensive Care Unit, Bobigny, France; University Sorbonne Paris Nord, Bobigny, France. ²⁵⁹Centre Hospitalier de Saint-Denis, St Denis, France. ²⁶⁰Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. ²⁶¹Paris Cardiovascular Center, PARCC, INSERM, Université de Paris, Paris, France. ²⁶²Germans Trias i Pujol Hospital, Badalona, Spain. ²⁶³Medical Intensive Care Unit, Hopital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France. ²⁶⁴Department of Clinical Laboratory, Hospital Universitari de Bellvitge, IDIBELL, Barcelona, Spain. ²⁶⁵Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron, Vall d’Hebron Research Institute, Vall d’Hebron Barcelona Hospital Campus., Barcelona, Spain. ²⁶⁶Université de Paris, CNRS UMR-8601, Paris, France; Team Chemistry and Biology, Modeling and Immunology for Therapy, CBMIT, Paris, France. ²⁶⁷Germans Trias i Pujol University Hospital and Research Institute, Badalona, Spain. ²⁶⁸Department of Immunology, University Hospital of Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain; Department of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain. ²⁶⁹Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), 08908 L’Hospitalet de Llobregat, Barcelona, Spain; University Hospital Germansn Trias i Pujol, Badalona, Barcelona, Catalonia, Spain. ²⁷⁰Consorcio Hospital General Universitario, Valencia, Spain. ²⁷¹AP-HP Hôpitaux Universitaires Paris-Sud, Paris, France. ²⁷²Intensive Care Unit, Louis-Mourier Hospital, Colombes, France. ²⁷³Virology Unit, Université de Paris, Cohin Hospital, AP-HP, Paris, France. ²⁷⁴Neurometabolic Diseases Laboratory and CIBERER U759, Barcelona, Spain. ²⁷⁵Hospital San Pedro, Logroño, Spain. ²⁷⁶University of Tartu, Institute of Biomedicine and Translational Medicine, Tartu, Estonia. ²⁷⁷Respiratory Medicine, Georges Pompidou Hospital, AP-HP, Paris, France. ²⁷⁸Infectious Diseases Department, International Health Program of the Catalan Institute of Health (PROSICS), Vall d’Hebron University Hospital (HUVH), Vall d’Hebron Barcelona Hospital Campus, Universitat Autónoma de Barcelona, Barcelona, Spain. ²⁷⁹Hospital Clínico San Carlos and IdSSC, Madrid, Spain. ²⁸⁰Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. ²⁸¹AP-HP, Avicenne Hospital, Intensive Care Unit, Bobigny, France. ²⁸²Service de Médecine Intensive Réanimation, Institut de Cardiologie, Hopital Pitié-Salpêtrière, Paris, France. ²⁸³Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. ²⁸⁴CHRU de Nancy, Hôpital d’Enfants, Vandoeuvre, France. ²⁸⁵Chair of Nephrology, University of Brescia, Brescia, Italy. ²⁸⁶Department of Immunology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic. ²⁸⁷Clínica Universidad de Navarra and Ciberes, Madrid, Spain. ²⁸⁸HUS Helsinki University Hospital, Children and Adolescents, Rare Disease Center, and Inflammation Center, Adult Immunodeficiency Unit, Majakka, Helsinki, Finland. ²⁸⁹Fundació Docencia I Recerca Mutua Terrassa, Terrassa, Spain. ²⁹⁰D. Rogachev National Medical and Research Center of Pediatric Hematology, Oncology, Immunoogy, Moscow, Russia. ²⁹¹Haematology Laboratory, Lariboisière Hospital, University of Paris, Paris, France. ²⁹²Biomedical Research Foundation of the Academy of Athens, Athens, Greece. ²⁹³INSERM U1140, University of Paris, European Georges Pompidou Hospital, Paris, France. ²⁹⁴Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt. ²⁹⁵Intensive Care Medicine, Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Las Palmas de Gran Canaria, Spain. ²⁹⁶CHU de Saint Etienne, Saint-Priest-en-Jarez, France. ²⁹⁷Pediatric 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, Catalonia, Spain. ²⁹⁸Department of Pediatric Infectious Diseases and Pediatric Immunology, Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine. ²⁹⁹Gustave Roussy Cancer Campus, Villejuif, France. ³⁰⁰Intensive Care Unit, Avicenne Hospital, AP-HP, Bobigny, France. ³⁰¹Laboratory of Immunology and Histocompatibility, Saint-Louis Hospital, Paris University, Paris, France. ³⁰²Center for Inflammation Research, Laboratory of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium. ³⁰³Department of Internal Medicine, Université de Paris, INSERM, U970, PARCC, F-75015, Paris, France. ³⁰⁴Service de médecine intensive réanimation, CHU de Saint-Etienne, France. ³⁰⁵Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. ³⁰⁶University of Management and Technology, Lahore, Pakistan. ³⁰⁷Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark. ³⁰⁸First Division of Anesthesiology and Critical Care Medicine, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy. ³⁰⁹Intensive Care Department, Hospital Universitari MutuaTerrassa, Universitat Barcelona, Terrassa, Spain. ³¹⁰Laboratory of Immunobiology, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece. ³¹¹International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France; Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France. ³¹²Infanta Leonor University Hospital, Madrid, Spain. ³¹³Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, China. ³¹⁴University of Tartu, Institute of Clinical Medicine, Tartu, Estonia. ³¹⁵Department of Medicine, United Christian Hospital, Hong Kong, China. ³¹⁶Hematology Department, ASST Spedali Civili di Brescia, Brescia, Italy. ³¹⁷Pneumologie, Hôpital Avicenne, AP-HP, INSERM U1272, Université Sorbonne Paris Nord, Bobigny, France. ³¹⁸Dermatology Unit, Laboratoire GAD, INSERM UMR1231 LNC, Université de Bourgogne, Dijon, France. ³¹⁹University Hospital of Burgos, Burgos, Spain. ³²⁰Center of Human Genetics, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. ³²¹Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain. ³²²University of São Paulo, São Paulo, Brazil. ³²³CHU de Caen, Caen, France. ³²⁴Hospital del Mar–IMIM Biomedical Research Institute, Barcelona, Catalonia, Spain. ³²⁵Pediatric Infectious Diseases, Pediatric Department, Cliniques universitaires Saint-Luc, UCL Louvain, Brussels Belgium. ³²⁶Sorbonne Université, Service de Médecine Intensive Réanimation, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. ³²⁷Pediatric Infectious Disease and Pediatric Immunology Department, Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine. ³²⁸Department of Pneumology, University Hospitals Leuven, Leuven, Belgium. ³²⁹Laboratory for Clinical Infectious and Inflammatory Disorders, Department of Microbiology, Immunology, and Transplantation, Leuven, Belgium. ³³⁰Department of Clinical Pathology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China. ³³¹Department of Medicine, Queen Elizabeth Hospital, Hong Kong, China. ³³²Ankara City Hospital, Children’s Hospital, Ankara, Turkey. ³³³Division of Pediatric Infectious Disease, Department of Pediatrics, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. ³³⁴Health Sciences University, Lütfi Kırdar Kartal Education and Research Hospital, İstanbul, Turkey. ³³⁵Department of Nephrology and Infectiology, AZ Sint-Jan, Bruges, Belgium. ³³⁶Department of Respiratory Medicine, Ghent University Hospital, Belgium. ³³⁷Department of Pediatric Pulmonology and Immunology, Ghent University Hospital, Ghent, Belgium. ³³⁸Department of Intensive Care Unit, Ghent University Hospital, Ghent, Belgium. ³³⁹Department of Pediatric Hemato-oncology, Jolimont Hospital, La louvière, Belgium. ³⁴⁰Department of Pulmonology, ZNA Middelheim, Antwerp, Belgium. ³⁴¹Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium. ³⁴²Department of Pediatric Immuno-hémato-rheumatology, CHR Citadelle, Liége, Belgium. ³⁴³Intensive Care Unit, Grand Hôpital de l’Est Francilien Site de Marne-La-Vallée, Jossigny, France. ³⁴⁴Clinical Translational and Engagement Platform, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; School of Clinical Medicine, UNSW Medicine & Health, St Vincent’s Healthcare Clinical Campus, Faculty of Medicine and Health, UNSW Sydney, Kensington, NSW, Australia. ³⁴⁵Department of Immunology, University Hospital Ramón y Cajal, Madrid, Spain. ³⁴⁶Respiratory Diseases Division, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy.

Members of Orchestra Working Group:

Laurent Abel¹, Matilda Berkell², Valerio Carelli³, Alessia Fiorentino³, Surbhi Malhotra², Alessandro Mattiaccio³, Tommaso Pippucci³, Marco Seri³, Evelina Tacconelli⁴

¹Inserm, University Paris cité, Imagine Institute, Paris, France, ²University of Antwerp, Antwerp, Belgium, ³University of Bologna, Bologna, 40138, Italy, ⁴University of Verona, 37129 Verona, Italy

Members of French COVID Cohort Study Group:

Laurent Abel¹, Claire Andrejak², François Angoulvant³, Delphine Bachelet⁴, Marie Bartoli⁵, Romain Basmaci⁶, Sylvie Behillil⁷, Marine Beluze⁸, Dehbia Benkerrou⁹, Krishna Bhavsar⁴, Lila Bouadma⁴, Sabelline Bouchez¹⁰, Maude Bouscambert¹¹, Minerva Cervantes-Gonzalez⁴, Anissa Chair⁴, Catherine Chirouze¹², Alexandra Coelho¹³, Camille Couffignal⁴, Sandrine Couffin-Cadiergues¹⁴, Eric d’Ortenzio⁵, Marie-Pierre Debray⁴, Laurene Deconinck⁴, Dominique Deplanque¹⁵, Diane Descamps⁴, Mathilde Desvallée¹⁶, Alpha Diallo⁵, Alphonsine Diouf¹³, Céline Dorival⁹, François Dubos¹⁷, Xavier Duval⁴, Brigitte Elharrar¹⁸, Philippine Eloy⁴, Vincent Enouf⁷, Hélène Esperou¹⁴, Marina Esposito-Farese⁴, Manuel Etienne¹⁹, Eglantine Ferrand Devouge¹⁹, Nathalie Gault⁴, Alexandre Gaymard¹¹, Jade Ghosn⁴, Tristan Gigante²⁰, Morgane Gilg²⁰, Jérémie Guedj²¹, Alexandre Hoctin¹³, Isabelle Hoffmann⁴, Ikram Houas¹⁴, Jean-Sébastien Hulot²², Salma Jaafoura¹⁴, Ouifiya Kafif⁴, Florentia Kaguelidou²³, Sabrina Kali⁴, Antoine Khalil⁴, Coralie Khan¹⁶, Cédric Laouénan⁴, Samira Laribi⁴, Minh Le⁴, Quentin Le Hingrat⁴, Soizic Le Mestre⁵, Hervé Le Nagard²⁴, François-Xavier Lescure⁴, Sophie Letrou⁴, Yves Levy²⁵, Bruno Lina¹¹, Guillaume Lingas²⁴, Jean Christophe Lucet⁴, Denis Malvy²⁶, Marina Mambert¹³, France Mentré⁴, Amina Meziane⁹, Hugo Mouquet⁷, Jimmy Mullaert⁴, Nadège Neant²⁴, Duc Nguyen²⁶, Marion Noret²⁷, Saad Nseir¹⁷, Aurélie Papadopoulos¹⁴, Christelle Paul⁵, Nathan Peiffer-Smadja⁴, Thomas Perpoint²⁸, Ventzislava Petrov-Sanchez⁵, Gilles Peytavin⁴, Huong Pham⁴, Olivier Picone⁶, Valentine Piquard⁴, Oriane Puéchal²⁹, Christian Rabaud³⁰, Manuel Rosa-Calatrava¹¹, Bénédicte Rossignol²⁰, Patrick Rossignol³⁰, Carine Roy⁴, Marion Schneider⁴, Richa Su⁴, Coralie Tardivon⁴, Marie-Capucine Tellier⁴, François Téoulé⁹, Olivier Terrier¹¹, Jean-François Timsit⁴, Christelle Tual³¹, Sarah Tubiana⁴, Sylvie Van Der Werf⁷, Noémie Vanel³², Aurélie Veislinger³¹, Benoit Visseaux⁴, Aurélie Wiedemann²⁵, Yazdan Yazdanpanah⁴

¹INSERM UMR 1163, Paris, France. ²CHU Amiens, Amiens, France. ³Hôpital Necker, Paris, France. ⁴Hôpital Bichat, Paris, France. ⁵ANRS, Paris, France. ⁶Hôpital Louis Mourier, Colombes, France. ⁷Pasteur Institute, Paris, France. ⁸F-CRIN Partners Platform, Paris, France. ⁹INSERM UMR 1136, Paris, France. ¹⁰CHU Nantes, France. ¹¹INSERM UMR 1111, Lyon, France. ¹²CHRU Jean Minjoz, Besançon, France. ¹³INSERM UMR 1018, Paris, France. ¹⁴INSERM Sponsor, Paris, France. ¹⁵Centre d’Investigation Clinique, INSERM CIC 1403, Centre Hospitalo universitaire de Lille, Lille, France. ¹⁶INSERM UMR 1219, Bordeaux, France. ¹⁷CHU Lille, Lille, France. ¹⁸CHI de Créteil, Créteil, France. ¹⁹CHU Rouen, Rouen, France. ²⁰F-CRIN INI-CRCT, Nancy, France. ²¹Université de Paris, INSERM, IAME, F-75018 Paris, France. ²²Hôpital Européen Georges Pompidou, Paris, France. ²³Hôpital Robert Debré, Paris, France. ²⁴INSERM UMR 1137, Paris, France. ²⁵Vaccine Research Institute (VRI), INSERM UMR 955, Créteil, France. ²⁶CHU Bordeaux, Bordeaux, France. ²⁷RENARCI, Annecy, France. ²⁸CHU Lyon, Lyon, France. ²⁹REACTing, Paris, France. ³⁰CHU Nancy, Nancy, France. ³¹INSERM CIC-1414, Rennes, France. ³²Hôpital la Timone, Marseille, France.

Members of CoV-Contact Cohort:

Loubna Alavoine¹, Sylvie Behillil², Charles Burdet³, Charlotte Charpentier⁴, Aline Dechanet⁵, Diane Descamps⁶, Xavier Duval⁷, Jean-Luc Ecobichon¹, Vincent Enouf⁸, Wahiba Frezouls¹, Nadhira Houhou⁵, Ouifiya Kafif⁵, Jonathan Lehacaut¹, Sophie Letrou¹, Bruno Lina⁹, Jean-Christophe Lucet¹⁰, Pauline Manchon⁵, Mariama Nouroudine¹, Valentine Piquard⁵, Caroline Quintin¹, Michael Thy¹¹, Sarah Tubiana¹, Sylvie van der Werf⁸, Valérie Vignali¹, Benoit Visseaux¹⁰, Yazdan Yazdanpanah¹⁰, Abir Chahine¹², Nawal Waucquier¹², Maria-Claire Migaud¹², Dominique Deplanque¹², Félix Djossou¹³, Mayka Mergeay-Fabre¹⁴, Aude Lucarelli¹⁵, Magalie Demar¹³, Léa Bruneau¹⁶, Patrick Gérardin¹⁷, Adrien Maillot¹⁶, Christine Payet¹⁸, Bruno Laviolle¹⁹, Fabrice Laine¹⁹, Christophe Paris¹⁹, Mireille Desille-Dugast¹⁹, Julie Fouchard¹⁹, Denis Malvy²⁰, Duc Nguyen²⁰, Thierry Pistone²⁰, Pauline Perreau²⁰, Valérie Gissot²¹, Carole L. E. Goas²¹, Samatha Montagne²², Lucie Richard²³, Catherine Chirouze²⁴, Kévin Bouiller²⁴, Maxime Desmarets²⁵, Alexandre Meunier²⁶, Marilou Bourgeon²⁶, Benjamin Lefévre²⁷, Hélène Jeulin²⁸, Karine Legrand²⁹, Sandra Lomazzi³⁰, Bernard Tardy³¹, Amandine Gagneux-Brunon³², Frédérique Bertholon³³, Elisabeth Botelho-Nevers³², Christelle Kouakam³⁴, Leturque Nicolas³⁴, Layidé Roufai³⁴, Karine Amat³⁵, Sandrine Couffin-Cadiergues³⁴, Hélène Espérou³⁶, Samia Hendou³⁴

¹Centre d’Investigation Clinique, INSERM CIC 1425, Hôpital Bichat Claude Bernard, AP-HP, Paris, France. ²Institut Pasteur, Paris, France. ³Université de Paris, IAME, INSERM U1137, Paris, France; Hôpital Bichat Claude Bernard, AP-HP, Paris, France. ⁴Service de Virologie, Université de Paris, INSERM, IAME, UMR 1137, Hôpital Bichat Claude Bernard, AP-HP, Paris, France. ⁵Hôpital Bichat Claude Bernard, AP-HP, Paris, France. ⁶IAME INSERM U1140, Hôpital Bichat Claude Bernard, AP-HP, Paris, France. ⁷Centre d’Investigation Clinique, INSERM CIC 1425, AP-HP, IAME, Paris University, Paris, France. ⁸Institut Pasteur, U3569 CNRS, Université de Paris, Paris, France. ⁹Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS U5308, ENS, UCBL, Lyon, France. ¹⁰IAME INSERM U1138, Hôpital Bichat Claude Bernard, AP-HP, Paris, France. ¹¹Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France. ¹²Centre d’Investigation Clinique, INSERM CIC 1403, Centre Hospitalo universitaire de Lille, Lille, France. ¹³Service des maladies infectieuses, Centre Hospitalo universitaire de Cayenne, Guyane, France. ¹⁴Centre d’Investigation Clinique, INSERM CIC 1424, Centre Hospitalier de Cayenne, Cayenne, Guyane Française. ¹⁵Service Hôpital de jour Adulte, Centre Hospitalier de Cayenne, Guyane, France. ¹⁶Centre d’Investigation Clinique, INSERM CIC 1410, Centre Hospitalo universitaire de la Réunion, La Réunion, France. ¹⁷Centre d’Investigation Clinique, INSERM CIC 1410, CHU Reunion, Saint-Pierre, Reunion Island. ¹⁸Centre d’Investigation Clinique, INSERM CIC 1410, Centre de Ressources Biologiques, Centre Hospitalo universitaire de la Réunion, La Réunion, France. ¹⁹Centre d’Investigation Clinique, INSERM CIC 1414, Centre Hospitalo universitaire de Rennes, Rennes, France; Centre de Ressources Biologiques, CRB Santé, Centre Hospitalo universitaire de Rennes, Rennes, France. ²⁰Service des maladies infectieuses, Centre Hospitalo universitaire de Bordeaux, Bordeaux, France. ²¹Centre d’Investigation Clinique, INSERM CIC 1415, CHRU Tours, Tours, France. ²²CRBT, Centre Hospitalo universitaire de Tours, Tours, France. ²³Pole de Biologie Médicale, Centre Hospitalo universitaire de Tours, Tours, France. ²⁴Service des maladies infectieuses, Centre Hospitalo universitaire de Besançon, Besançon, France. ²⁵Service des maladies infectieuses, Centre d’investigation clinique, INSERM CIC1431, Centre Hospitalier Universitaire de Besançon, Besançon, France. ²⁶Centre de Ressources Biologiques–Filière Microbiologique de Besançon, Centre Hospitalier Universitaire, Besançon, France. ²⁷Université de Lorraine, CHRU-Nancy and APEMAC, Infectious and Tropical Diseases, Nancy, France. ²⁸Laboratoire de Virologie, CHRU de Nancy Brabois, Vandoeuvre-lès-Nancy, France. ²⁹INSERM CIC-EC 1433, Centre Hospitalo universitaire de Nancy, Nancy, France. ³⁰Centre de ressources Biologiques, Centre Hospitalo universitaire de Nancy, Nancy, France. ³¹Centre d’Investigation Clinique, INSERM CIC 1408, Centre Hospitalo universitaire de Saint Etienne, Saint Etienne, France. ³²Service des maladies infectieuses, Centre Hospitalo universitaire de Saint Etienne, Saint Etienne, France. ³³Service des maladies infectieuses, CRB⁴²-BTK, Centre Hospitalo Universitaire de Saint Etienne, Saint Etienne, France. ³⁴Pole Recherche Clinique, INSERM, Paris, France. ³⁵IMEA Fondation Léon M’Ba, Paris, France. ³⁶INSERM Clinical Research Department, Paris, France.

Members of the COVIDeF study group:

Serge Bureau¹, Yannick Vacher¹, Anne Gysembergh-Houal¹, Lauren Demerville¹, Abla Chachoua¹, Sebastien Abad², Radhiya Abassi³, Abdelrafie Abdellaoui³, Abdelkrim Abdelmalek⁴, Hendy Abdoul⁵, Helene Abergel⁶, Fariza Abeud⁷, Sophie Abgrall⁸, Noemie Abisror⁴, Marylise Adechian⁹, Nordine Aderdour⁹, Hakeem Farid Admane⁴, Frederic Adnet², Sara Afritt⁵, Helene Agostini¹⁰, Claire Aguilar¹¹, Sophie Agut¹², Tommaso Francesco Aiello¹³, Marc Ait Kaci¹⁴, Hafid Ait Oufella⁴, Gokula Ajeenthiravasan¹⁵, Virginie Alauzy³, Fanny Alby-Laurent¹¹, Lucie Allard², Marie-Alexandra Alyanakian¹¹, Blanca Amador Borrero⁷, Sabrina Amam⁶, Lucile Amrouche¹¹, Marc Andronikof¹⁶, Dany Anglicheau¹¹, Nadia Anguel⁹, Djillali Annane¹⁵, Mohammed Aounzou³, Caroline Aparicio⁷, Gladys Aratus⁴, Jean-Benoit Arlet¹⁴, Jeremy Arzoine³, Elisabeth Aslangul¹³, Mona Assefi³, Adeline Aubry³, Laetitia Audiffred⁴, Etienne Audureau¹⁷, Christelle Nathalie Auger⁵, Jean-Charles Auregan⁸, Celine Awotar¹¹, Sonia Ayllon Milla⁵, Delphine Azan⁵, Laurene Azemar⁷, Billal Azzouguen⁷, Marwa Bachir Elrufaai¹², Aïda Badsi⁷, Prissile Bakouboula¹¹, Coline Balcerowiak³, Fanta Balde¹², Elodie Baldivia¹⁷, Eliane-Flore Bangamingo¹⁸, Amandine Baptiste³, Fanny Baran-Marszak², Caroline Barau¹⁷, Nathalie Barget¹⁹, Flore Baronnet³, Romain Barthelemy⁷, Jean-Luc Baudel⁴, Camille Baudry², Elodie Baudry⁹, Laurent Beaugerie⁴, Adel Belamri³, Nicolas Belaube¹², Rhida Belilita³, Pierre Bellassen³, Rawan Belmokhtar², Isabel Beltran⁶, Ruben Benainous², Mourad Benallaoua², Robert Benamouzig², Amélie Benbara¹⁹, Jaouad Benhida³, Anis Benkhelouf³, Jihene Benlagha¹⁸, Chahinez Benmostafa¹⁴, Skander Benothmane¹⁸, Miassa Bentifraouine², Laurence Berard⁴, Quentin Bernier³, Enora Berti¹⁷, Astrid Bertier⁹, Laure Berton⁷, Simon Bessis¹⁵, Alexandra Beurton²⁰, Celine Bianco⁴, Clara Bianquis³, Frank Bidar³, Philippe Blanche⁵, Clarisse Blayau¹², Alexandre Bleibtreu³, Emmanuelle Blin¹², Coralie Bloch-Queyrat², Marie-Christophe Boissier², Diane Bollens⁴, Marion Bolzoni⁴, Rudy pierre Bompard¹², Nicolas Bonnet², Justine Bonnouvrier⁴, Shirmonecrystal Botha³, Wissam Boucenna⁴, Fatiha Bouchama³, Olivier Bouchaud², Hanane Bouchghoul⁹, Taoueslylia Boudjebla¹², Noel Boudjema¹⁷, Catherine Bouffard⁶, Adrien Bougle³, Meriem Bouguerra³, Leila Bouras⁷, Agnes Bourcier³, Anne Bourgarit Durand¹⁹, Anne Bourrier⁴, Fabrice Bouscarat⁶, Diane Bouvry², Nesrine Bouziri³, Ons Bouzrara³, Sarah Bribier⁹, Delphine Brugier³, Melanie Brunel¹¹, Eida Bui⁴, Anne Buisson²¹, Iryna Bukreyeva⁹, Côme Bureau²⁰, Jacques Cadranel¹², Johann Cailhol², Ruxandra Calin¹², Clara Campos Vega¹¹, Pauline Canavaggio³, Marta Cancella³, Delphine Cantin²², Albert Cao³, Lionel Carbillon¹⁹, Nicolas Carlier⁵, Clementine Cassard³, Guylaine Castor⁷, Marion Cauchy⁷, Olivier Cha⁴, Benjamin Chaigne⁵, Salima Challal², Karine Champion⁷, Patrick Chariot¹⁹, Julie Chas¹², Simon Chauveau², Anthony Chauvin⁷, Clement Chauvin¹⁸, Nathalie Chavarot¹¹, Kamélia Chebbout³, Mustapha Cherai³, Ilaria Cherubini³, Amelie Chevalier⁵, Thibault Chiarabini⁴, Thierry Chinet¹⁰, Richard Chocron¹⁴, Pascaline Choinier¹², Juliette Chommeloux³, Christophe Choquet⁶, Laure Choupeaux¹¹, Benjamin Chousterman⁷, Dragosmarius Ciocan⁸, Ada Clarke⁵, Gaëlle Clavere²³, Florian Clavier³, Karine Clement³, Sebastien Clerc¹⁴, Yves Cohen², Fleur Cohen³, Adrien Cohen²³, Audrey Coilly²⁴, Hester Colboc²⁵, Pauline Colin³, Magalie Collet⁷, Chloé Comarmond⁷, Emeline Combacon⁵, Alain Combes³, Celine Comparon², Jean-Michel Constantin³, Hugues Cordel², Anne-Gael Cordier⁹, Adrien Costantini¹⁰, Nathalie Costedoat Chalumeau⁵, Camille Couffignal⁶, Doriane Coupeau⁴, Alain Creange¹⁷, Yannie Cuvillier Lamarre²², Charlène Da Silveira⁶, Sandrine Dautheville Guibal El Kayani¹², Nathalie De Castro¹⁸, Yann De Rycke³, Lucie Del Pozo¹⁹, Quentin Delannoy³, Mathieu Delay¹², Robin Deleris³, Juliette Delforge¹³, Laëtitia Delphine³, Noemie Demare², Sophie Demeret³, Alexandre Demoule³, Aurore Deniau², François Depret¹⁸, Sophie Derolez², Ouda Derradji⁹, Nawal Derridj¹⁰, Vincent Descamps⁶, Lydia Deschamps⁶, Celine Desconclois⁸, Cyrielle Desnos³, Karine Desongins¹⁸, Robin Dhote², Benjamin Diallo¹², Morgane Didier², Myriam Diemer⁷, Stephane Diez⁹, Juliette Djadi-Prat¹⁴, Fatima-Zohra Djamouri Monnory¹², Siham Djebara³, Naoual Djebra², Minette Djietcheu¹⁸, Hadjer Djillali⁴, Nouara Djouadi⁴, Severine Donneger¹⁹, Catarina Dos Santos⁵, Nathalie Dournon², Martin Dres²⁰, Laura Droctove³, Marie Drogrey³, Margot Dropy³, Elodie Drouet⁴, Valérie Dubosq¹², Evelyne Dubreucq¹², Estelle Dubus⁷, Boris Duchemann², Thibault Duchenoy⁵, Emmanuel Dudoignon¹⁸, Romain Dufau¹⁹, Florence Dumas⁵, Clara Duran¹⁰, Emmanuelle Duron²⁴, Antoine Durrbach¹⁷, Claudine Duvivier¹¹, Nathan Ebstein², Jihane El Khalifa⁶, Alexandre Elabbadi¹², Caroline Elie¹¹, Gabriel Ernotte³, Anne Esling¹¹, Martin Etienne⁹, Xavier Eyer⁷, Muriel sarah Fartoukh¹², Takoua Fayali³, Marion Fermaut¹⁹, Arianna Fiorentino⁴, Souha Fliss², Marie-Céline Fournier⁷, Benjamin Fournier¹¹, Hélène Francois¹², Olivia Freynet², Yvann Frigout¹⁴, Isaure Fromont⁷, Axelle Fuentes⁶, Thomas Furet³, Joris Galand⁷, Marc Garnier⁴, Agnes Gaubert³, Stéphane Gaudry², Samuel Gaugain⁷, Damien Gauthier³, Maxime Gautier⁷, Sophie Georgin-Lavialle¹², Daniela Geromin¹⁴, Mohamed Ghalayini², Bijan Ghaleh¹⁷, Myriam Ghezal²¹, Aude Gibelin¹², Linda Gimeno³, Benoit Girard⁵, Bénédicte Giroux Leprieur², Doryan Gomes¹⁸, Elisabete Gomes-Pires¹¹, Guy Gorochov³, Anne Gouge¹⁸, Amel Gouja¹⁷, Helene Goulet¹², Sylvain Goupil¹¹, Jeanne Goupil De Bouille², Julien Gras⁷, Segolene Greffe¹⁰, Lamiae Grimaldi⁹, Paul Guedeney³, Bertrand Guidet⁴, Matthias Guillo¹⁸, Mariechristelle Gulczynski²⁶, Tassadit Hadjam⁷, Didier Haguenauer¹³, Soumeya Hammal³, Nadjib Hammoudi³, Olivier Hanon²³, Anarole Harrois⁹, Pierre Hausfater³, Coraline Hautem¹⁴, Guillaume Hekimian³, Nicholas Heming¹⁵, Olivier Hermine¹¹, Sylvie Ho³, Marie Houllier⁹, Benjamin Huot⁷, Tessa Huscenot⁷, Wafa Ibn Saied¹², Ghilas Ikherbane³, Meriem Imarazene¹¹, Patrick Ingiliz⁴, Lina Iratni¹⁷, Stephane Jaureguiberry⁹, Jean-Francois Jean-Marc¹⁰, Deleena Jeyarajasingham¹⁸, Pauline Jouany¹⁴, Veronique Jouis⁷, Clement Jourdaine⁷, Ouifiya Kafif⁶, Rim Kallala²⁴, Sandrine Katsahian¹⁴, Lilit Kelesyan²⁷, Vixra Keo³, Flora Ketz²¹, Warda Khamis², Enfel Khelili³, Mehdi Khellaf¹⁷, Christy Gaëlla Kotokpo Youkou¹⁰, Ilias Kounis²⁴, Gaelle Kpalma³, Jessica Krause⁴, Vincent Labbe¹², Karine Lacombe⁴, Jean-Marc Lacorte³, Anne Gaelle Lafont⁴, Emmanuel Lafont¹¹, Lynda Lagha²⁷, Lionel Lamhaut¹¹, Aymeric Lancelot³, Cecilia Landman⁴, Fanny Lanternier¹¹, Cecile Larcheveque³, Caroline Lascoux Combe¹⁸, Ludovic Lassel¹², Benjamin Laverdant¹², Christophe Lavergne¹⁸, Jean-Rémi Lavillegrand⁴, Pompilia Lazureanu⁷, Loïc Le Guennec³, Lamia Leberre⁴, Claire Leblanc¹⁹, Marion Leboyer²⁸, Francois Lecomte⁵, Marine Lecorre³, Romain Leenhardt⁴, Marylou Lefebvre⁴, Bénédicte Lefebvre⁴, Paul Legendre⁵, Anne Leger³, Laurence Legros²⁴, Justyna Legrosse³, Sébastien Lehuunghia⁵, Julien Lemarec³, Jeremie Leporrier-Ext¹¹, Manon Lesein⁵, Hubert Lesur²⁴, Vincent Levy², Albert Levy¹⁴, Edwige Lopes⁷, Amanda Lopes⁷, Vanessa Lopez¹¹, Julien Lopinto¹², Olivier Lortholary¹¹, Badr Louadah⁷, Bénédicte Loze¹⁸, Marie-Laure Lucas²², Axelle Lucasamichi⁸, Liem Binh Luong⁵, Arouna Magazimama-Ext⁷, David Maingret⁷, Lakhdar Mameri¹⁸, Philippe Manivet⁷, Cylia Mansouri⁴, Estelle Marcault⁶, Jonathan Marey⁵, Nathalie Marin⁵, Clémence Marois³, Olivier Martin², Lou Martineau³, Cannelle Martinez-Lopez¹⁵, Pierre Martyniuck⁴, Pauline Mary De Farcy²⁹, Nessrine Marzouk¹², Rafik Masmoudi¹⁴, Alexandre Mebazaa⁷, Frédéric Mechai², Fabio Mecozzi¹¹, Chamseddine Mediouni¹⁰, Bruno Megarbane⁷, Mohamed Meghadecha²², Élodie Mejean¹², Arsene Mekinian⁴, Nour Mekki Abdelhadi⁶, Rania Mekni³, Thinhinan Sabrina Meliti³, Breno Melo Lima¹⁸, Paris Meng¹², Soraya Merbah³, Fadhila Messani², Yasmine Messaoudi³, Baboo-Irwinsingh Mewasing¹², Lydia Meziane³, Carole Michelot-Burger¹¹, Françoise Mignot¹⁸, Fadi Hillary Minka⁷, Makoto Miyara³, Pierre Moine¹⁵, Jean-Michel Molina¹⁸, Anaïs Montegnies-Boulet⁵, Alexandra Monti²¹, Claire Montlahuc¹⁸, Anne-Lise Montout³, Alexandre Moores⁵, Caroline Morbieu⁵, Helene Mortelette¹⁴, Stéphane Mouly⁷, Rosita Muzaffar¹⁸, Cherifa Iness Nacerddine³, Marine Nadal¹², Hajer Nadif³, Kladoum Nassarmadji⁷, Pierre Natella¹⁷, Sandrine Ndingamondze³, Stefan Neraal⁵, Caroline Nguyen⁶, Bao N’Guyen³, Isabelle Nion Larmurier⁴, Luc Nlomenyengue¹⁴, Nicolas Noel⁹, Hilario Nunes², Edris Omar³, Zineb Ouazene⁴, Elise Ouedraogo², Wassila Ouelaa³, Anissa Oukhedouma³, Yasmina Ould Amara³, Herve Oya³, Johanna Oziel², Thomas Padilla³, Elena Paillaud²⁶, Solenne Paiva³, Beatrice Parfait⁵, Perrine Parize¹¹, Christophe Parizot³, Antoine Parrot¹², Arthur Pavot⁹, Laetitia Peaudecerf⁵, Frédéric Pene⁵, Marion Pepin¹⁰, Julie Pernet³, Claire Pernin⁷, Mylène Petit², Olivier Peyrony¹⁸, Marie-Pierre Pietri²², Olivia Pietri⁴, Marc Pineton De Chambrun³, Michelle Pinson¹³, Claire Pintado¹⁸, Valentine Piquard⁶, Christine Pires³, Benjamin Planquette¹⁴, Sandrine Poirier⁸, Anne-Laure Pomel⁸, Stéphanie Pons³, Diane Ponscarme¹⁸, Annegaelle Pourcelot⁹, Valérie Pourcher³, Anne Pouvaret¹¹, Florian Prever⁴, Miresta Previlon¹⁸, Margot Prevost³, Marie-Julie Provoost⁷, Cyril Quemeneur³, Cédric Rafat¹², Agathe Rami⁷, Brigitte Ranque¹⁴, Maurice Raphael⁹, Jean Herle Raphalen¹¹, Anna Rastoin⁷, Mathieu Raux³, Amani Rebai², Michael Reby²⁵, Alexis Regent⁵, Asma Regrag¹⁴, Matthieu Resche-Rigon¹⁸, Quentin Ressaire¹⁸, Christian Richard⁹, Mariecaroline Richard³, Maxence Robert³, Benjamin Rohaut³, Camille Rolland-Debord¹², Jacques Ropers³, Anne-Marie Roque-Afonso²⁴, Charlotte Rosso³⁰, Mélanie Rousseaux⁴, Nabila Rousseaux³, Swasti Roux²⁶, Lorène Roux⁴, Claire Rouzaud¹¹, Antoine Rozes³, Emma Rubenstein⁷, Jean-Marc Sabate², Sheila Sabet¹², Sophie-Caroline Sacleux²⁴, Nathalie Saidenberg Kermanach², Faouzi Saliba²⁴, Dominique Salmon²², Laurent Savale³¹, Guillaume Savary³, Rebecca Sberro¹¹, Anne Scemla¹¹, Frederic Schlemmer¹⁷, Mathieu Schwartz⁷, Saïd Sedfi³, Samia Sefir-Kribel⁵, Philippe Seksik⁴, Pierre Sellier⁷, Agathe Selves³, Nicole Sembach¹⁴, Luca Semerano², Marie-Victoire Senat⁹, Damien Sene⁷, Alexandra Serris¹¹, Lucile Sese², Naima Sghiouar¹⁵, Johanna Sigaux², Martin Siguier¹², Johanne Silvain³, Noémie Simon³, Tabassome Simon⁴, Lina Innes Skandri², Miassa Slimani², Aurélie Snauwaert⁶, Harry Sokol⁴, Heithem Soliman⁴, Nisrine Soltani⁹, Benjamin Soyer⁷, Gabriel Steg⁶, Lydia Suarez⁷, Tali-Anne Szwebel⁵, Kossi Taffame³, Yacine Tandjaoui-Lambiotte², Claire Tantet², Mariagrazia Tateo¹⁸, Igor Theodose¹⁸, Pierre clement Thiebaud⁴, Caroline Thomas⁴, Kelly Tiercelet¹⁸, Julie Tisserand⁹, Carole Tomczak¹⁸, Krystel Torelino³, Fatima Touam-Ext¹¹, Lilia Toumi¹¹, Gustave Toury¹⁴, Mireille Toy-Miou³, Olivia Tran Dinh Thanh Lien⁷, Alexy Trandinh⁶, Jean-Marc Treluyer⁵, Baptiste Trinque⁷, Jennifer Truchot⁵, Florence Tubach³, Sarah Tubiana⁶, Simone Tunesi¹⁹, Matthieu Turpin¹², Agathe Turpin³, Tomas Urbina⁴, Rafael Usubillaga Narvaez²², Yurdagul Uzunhan², Prabakar Vaittinadaayar²⁷, Arnaud Valent¹⁸, Maelle Valentian¹², Nadia Valin⁴, Hélène Vallet⁴, Marina Vaz³, Miguel-Alejandro Vazquezibarra⁷, Benoit Vedie¹⁴, Laetitia Velly³, Celine Verstuyft⁹, Cedric Viallette³, Eric Vicaut⁷, Dorothee Vignes⁸, Damien Vimpere¹¹, Myriam Virlouvet⁹, Guillaume Voiriot¹², Lena Voisot²¹, Emmanuel Weiss²⁷, Nicolas Weiss³, Anaïs Winchenne², Youri Yordanov⁴, Lara Zafrani¹⁸, Mohamad Zaidan⁹, Wissem Zaidi⁴, Cathia Zak¹², Aida Zarhrate-Ghoul³, Ouassila Zatout⁶, Suzanne Zeino⁹, Michel Zeitouni³, Naïma Zemirli³, Lorene Zerah³, Ounsa Zia³, Marianne Ziol¹⁹, Oceane Zolario⁴, Julien Zuber¹¹

¹DRCI-APHP, Paris, France, ²Hôpital Avicenne, Bobigny, France, ³Hôpital Pitié-Salpêtrière, Paris, France, ⁴Hôpital Saint-Antoine, Paris, France, ⁵Hôpital Cochin, Paris, France, ⁶Hôpital Bichat, Paris, France, ⁷Hôpital Lariboisière, Paris, France, ⁸Hôpital Antoine Béclère, Clamart, France, ⁹Hôpital Kremlin Bicêtre, Le Kremlin-Bicêtre, France, ¹⁰Hôpital Ambroise-Paré, Boulogne Billancourt, France, ¹¹Hopital Necker Enfants malades, Paris, France, ¹²Hôpital Tenon, Paris, France, ¹³Hôpital Louis Mourier, Colombes, France, ¹⁴Hôpital Européen Georges Pompidou, Paris, France, ¹⁵Hôpital Raymond Poincaré, Garches, France, ¹⁶Hôpital Antoine Béclère, Calmart, France, ¹⁷Hôpital Henri Mondor, Créteil, France, ¹⁸Hôpital Saint Louis, Paris, France, ¹⁹Hôpital Jean Verdier, Bondy, France, ²⁰Université Paris-Sorbonne, Hôpital Pitié-Salpêtrière, INSERM, Paris, France, ²¹Hôpital Charles Foix, Ivry-sur-Seine, France, ²²Hôpital Hôtel Dieu, Paris, France, ²³Hôpital Broca, Paris, France, ²⁴Hôpital Paul-Brousse, Villejuif, France, ²⁵Hôpital Rothschild, Paris, France, ²⁶Hôpital Corentin Celton, Issy-les-Moulineaux, France, ²⁷Hôpital Beaujon, Clichy, France, ²⁸Hôpital Albert Chenevier, Créteil, France, ²⁹Hôpital Sainte-Périne, Paris, France, ³⁰Université Paris-Sorbonne, Hôpital Pitié-Salpêtrière, INSERM, CNRS, Paris, France, ³¹Université Paris-Saclay, Hôpital Kremlin Bicêtre, INSERM, Le Kremlin-Bicêtre, France

Members of Amsterdam UMC Covid-19 Biobank:

Michiel van Agtmael², Anne Geke Algera¹, Brent Appelman², Frank van Baarle¹, Diane Bax³, Martijn Beudel⁴, Harm Jan Bogaard⁵, Marije Bomers², Peter Bonta⁵, Lieuwe Bos¹, Michela Botta¹, Justin de Brabander², Godelieve de Bree², Sanne de Bruin¹, David T. P. Buis¹, Marianna Bugiani⁵, Esther Bulle¹, Osoul Chouchane², Alex Cloherty³, Mirjam Dijkstra¹², Dave A. Dongelmans¹, Romein W. G. Dujardin¹, Paul Elbers¹, Lucas Fleuren¹, Suzanne Geerlings², Theo Geijtenbeek³, Armand Girbes¹, Bram Goorhuis², Martin P. Grobusch², Florianne Hafkamp³, Laura Hagens¹, Jorg Hamann⁷, Vanessa Harris², Robert Hemke⁸, Sabine M. Hermans², Leo Heunks¹, Markus Hollmann⁶, Janneke Horn¹, Joppe W. Hovius², Menno D. de Jong⁹, Rutger Koning⁴, Endry H. T. Lim¹, Niels van Mourik¹, Jeaninne Nellen², Esther J. Nossent⁵, Frederique Paulus¹, Edgar Peters², Dan A. I. Pina-Fuentes⁴, Tom van der Poll², Bennedikt Preckel⁶, Jan M. Prins², Jorinde Raasveld¹, Tom Reijnders², Maurits C. F. J. de Rotte¹², Michiel Schinkel², Marcus J. Schultz¹, Femke A. P. Schrauwen¹², Alex Schuurmans¹⁰, Jaap Schuurmans¹, Kim Sigaloff¹, Marleen A. Slim^1,2, Patrick Smeele⁵, Marry Smit¹, Cornelis S. Stijnis², Willemke Stilma¹, Charlotte Teunissen¹¹, Patrick Thoral¹, Anissa M. Tsonas¹, Pieter R. Tuinman², Marc van der Valk², Denise P. Veelo⁶, Carolien Volleman¹, Heder de Vries¹, Lonneke A. Vught^1,2, Michèle van Vugt², Dorien Wouters¹², A. H. (Koos) Zwinderman¹³, Matthijs C. Brouwer⁴, W. Joost Wiersinga², Alexander P. J. Vlaar¹, Diederik van de Beek⁴

¹Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. ²Department of Infectious Diseases, 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 Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. ⁷Amsterdam UMC Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. ⁸Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. ⁹Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. ¹⁰Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. ¹¹Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. ¹²Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. ¹³Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands.

Members of NIAID-USUHS COVID Study Group:

Miranda F. Tompkins¹, Camille Alba¹, Andrew L. Snow², Daniel N. Hupalo¹, John Rosenberger¹, Gauthaman Sukumar¹, Matthew D. Wilkerson¹, Xijun Zhang¹, Justin Lack³, Andrew J. Oler⁴, Kerry Dobbs⁵, Ottavia M. Delmonte⁵, Jeffrey J. Danielson⁵, Andrea Biondi⁶, Laura Rachele Bettini⁶, Mariella D’Angiò⁶, Ilaria Beretta⁷, Luisa Imberti⁸, Alessandra Sottini⁸, Virginia Quaresima⁸, Eugenia Quiros-Roldan⁹, Camillo Rossi¹⁰, Riccardo Castagnoli¹¹, Daniela Montagna¹², Luigi D. Notarangelo¹³.

¹American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. ²Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. ³NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD, USA. ⁴Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. ⁵Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. ⁶Pediatric Departement and Centro Tettamanti-European Reference Network PaedCan, EuroBloodNet, MetabERN-University of Milano-Bicocca-Fondazione MBBM-Ospedale, San Gerardo, Monza, Italy. ⁷Department of Infectious Diseases, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. ⁸CREA Laboratory, Diagnostic Department, ASST Spedali Civili di Brescia, Brescia, Italy. ⁹Department of Infectious and Tropical Diseases, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy. ¹⁰Chief Medical Officer, ASST Spedali Civili di Brescia, Brescia, Italy. ¹¹Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. ¹²Laboratory of Immunology and Transplantation, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy. ¹³National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Data availability

Data supporting the findings of this study are available within the manuscript and supplemental files. The whole-genome sequencing data of anonymized patients recruited through the National Institutes of Health (NIH) and sequenced at the National Institute of Allergy and Infectious Diseases (NIAID) through the Uniformed Services University of the Health Sciences (USUHS)/the American Genome Center (TAGC) are available under dbGaP submission phs002245.v1. Other patients were not consented to share the raw WES/WGS data files beyond the research and clinical teams.