The coronavirus illness 2019 (COVID-19) pandemic has led to unprecedented adjustments in all features of our lives and has positioned biomedical analysis on the forefront. One of many many urgent questions surrounding extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is figuring out the determinants of the medical spectrum, from individuals with asymptomatic illness to sufferers with extreme COVID-19. As much as 40% of infections could also be asymptomatic, suggesting that a big proportion of individuals could also be protected against illness (1). On the opposite finish of the spectrum is extreme illness, with an total estimated fatality charge close to 1% (2). On pages 422 and 424 of this situation, Zhang et al. (3) and Bastard et al. (4), respectively, report analyses of >1600 sufferers contaminated with SARS-CoV-2 from >15 nations to establish endogenous components that decide susceptibility to extreme COVID-19.