The severe COVID-19 3p21.31 risk locus harbors several common variants and contains 17 known protein-coding genes including LC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, CCR1, CCR3, CCR2, and CCR5. However, so far, causative variants and genes at this risk locus, influencing COVID-19 pathogenesis, remain to be investigated. The gene discussed is XCR1; the disease is COVID-19.