We postulate, based on the available literature, that the SP-A genotype contributes to the relative risk and/or severity of COVID-19 in the presence or absence of co-infection with non-SARS-CoV-2 pathogens and that the macrophage-mediated signaling mechanisms may differentially regulate the “hyperinflammatory response” as a function of the SP-A genotype. The gene discussed is SFTPA2; the disease is coinfection.