In this study, using SARS-CoV-2-infected air–liquid interface (ALI) cultures of human primary bronchial epithelial cells and monocytes, we established that PROS1 reduces the epithelial and myeloid inflammation, promotes basal cell regeneration, and enhances antigen presentation, which may determine milder lung pathologies in viral diseases like COVID-19. This evidence concerns the gene PROS1 and viral infectious disease.