Genetically proxied concentrations of soluble intercellular adhesion molecule 1 (sICAM) were inversely associated with the risk of SARS-CoV-2 infection (OR: 0.96, 95%CI: 0.94 to 0.98, p = 3.0 × 10−4), very severe respiratory confirmed COVID-19 (OR: 0.82, 95%CI: 0.73 to 0.91, p = 1.0 × 10−4) and hospitalization due to COVID-19 (OR: 0.89, 95%CI: 0.82 to 0.95, p = 8.0 × 10−4); hospitalization due to COVID-19 was also inversely associated with soluble vascular cell adhesion molecule 1 (sVCAM) (OR: 0.65, 95%CI: 0.48 to 0.88, p = 4.5 × 10−3). This evidence concerns the gene ICAM1 and COVID-19.