ISG15, MX1, ZBP1 and IFNL1 were the top four proteins most contributing to the accuracy of random forest models for discriminating all COVID-19 cases from controls, and these proteins were also among the top ones for prediction of severe and critical COVID-19 (Fig. 8d), moderate COVID-19 (Supplementary Fig. 3), and for mild or asymptomatic cases (Supplementary Fig. 4). This evidence concerns the gene ISG15 and COVID-19.