## Materials & experimental systems

<table><thead><tr><th>n/a</th><th>Involved in the study</th></tr></thead><tbody><tr><td>☑</td><td>Antibodies</td></tr><tr><td>☑</td><td>Eukaryotic cell lines</td></tr><tr><td>☑</td><td>Palaeontology and archaeology</td></tr><tr><td>☑</td><td>Animals and other organisms</td></tr><tr><td>☐</td><td>Human research participants</td></tr><tr><td>☑</td><td>Clinical data</td></tr><tr><td>☑</td><td>Dual use research of concern</td></tr></tbody></table>

## Methods

<table><thead><tr><th>n/a</th><th>Involved in the study</th></tr></thead><tbody><tr><td>☑</td><td>ChIP-seq</td></tr><tr><td>☑</td><td>Flow cytometry</td></tr><tr><td>☑</td><td>MRI-based neuroimaging</td></tr></tbody></table>

## Human research participants

Policy information about studies involving human research participants

### Population characteristics

Summary statistics from 46 independent studies were included in consortium meta-analyses. Mean age of cases across studies was 55.3 years. The effective sample size for genetic ancestry populations was: n=11,598 Middle Eastern; n=28,918 South Asian; 43,332 East Asian; 48,714 African; 70,902 Ad-mixed American; 738,538 European. Population characteristics regarding age, sex and exact case and control sample numbers for each contributing study are given in Supplementary Table 1.

### Recruitment

The consortium pre-defined phenotype criteria for cases and controls, but the specific recruitment was carried out independently by each contributing study. COVID-19 disease status (critical illness, hospitalization status) was assessed following the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (PMID: 32358325). The critically ill COVID-19 group included patients who were hospitalized due to symptoms associated with laboratory-confirmed SARS-CoV-2 infection and who required respiratory support or whose cause of death was associated with COVID-19. The hospitalized COVID-19 group included patients who were hospitalized due to symptoms associated with laboratory-confirmed SARS-CoV-2 infection. The reported infection cases group included individuals with laboratory-confirmed SARS-CoV-2 infection or electronic health record, ICD coding or clinically confirmed COVID-19, or self-reported COVID-19 (e.g. by questionnaire), with or without symptoms of any severity. Genetic ancestry-matched controls for the three case definitions were sourced from population-based cohorts, including individuals whose exposure status to SARS-CoV-2 was either unknown or infection- negative for questionnaire/electronic health record based cohorts.

### Ethics oversight

Ethical statements for each contributing study are given in Supplementary Table 1.

Note that full information on the approval of the study protocol must also be provided in the manuscript.