Increased IFNAR2 expression was protective in individuals with symptoms of COVID-19 without PCR-confirmed SARS-CoV-2 against severe COVID-19, or individuals who were negative for or had perhaps not yet tested positive for COVID-19 (OR = 0.75, 95% CI 0.66–0.86; adjusted p = 3.0 × 10–3) with insufficient evidence to suggest protection for individuals who did test positive (adjusted p = 0.04) where it failed weighted mode MR sensitivity testing but colocalized. This evidence concerns the gene IFNAR2 and COVID-19.