Furthermore, in this study we observed the differential role of human SP-A variants in lung and systemic immune response to SARS-CoV-2 infection, and different effect of human SP-A variants on the direct antiviral function and the immune modulation after viral infection in the humanized murine COVID-19 model, which can explain the observation, i.e. the lower viral load in the lung and higher levels of proinflammatory cytokines with severe morbidity and mortality in the SP-A2 (1A0) mice. This evidence concerns the gene SFTPA1 and viral infectious disease.