Update publication information. Update information. The COVID-19 pandemic is spreading globally with high disparity in the susceptibility of the disease severity. Identification of the key underlying factors for this disparity is highly warranted. Here we describe constructing a proteomic risk score based on 20 blood proteomic biomarkers which predict the progression to severe COVID-19. We demonstrate that in our own cohort without infection, this proteomic risk score is positively associated with proinflammatory cytokines mainly among older, but not younger, individuals. We further discovered that a core set of gut microbiota could accurately predict the above proteomic biomarkers using a machine learning model, and that these gut microbiota features are highly correlated with proinflammatory cytokines.