A prospective, multi-centre, open-label, randomised, controlled trial in hospitalised patients (n = 342) with COVID-19, hypoxia, and signs of a cytokine release syndrome with a 2 × 2 factorial design to evaluate IL-1 blockade (n = 112) versus no IL-1 blockade (n = 230) and IL-6 blockade (n = 227; 114 for tocilizumab and 113 for siltuximab) versus no IL-6 blockade (n = 115) at 16 hospitals in Belgium in 2020 (COV-AID study). This evidence concerns the gene IL1B and COVID-19.