In this section, we will briefly review the role of SP-A genetics on the regulation of the alveolar macrophage, alveolar microenvironment, survival outcomes, and pulmonary disease susceptibility, and discuss how this knowledge may apply to COVID-19 and/or how SP-A variants, by providing the first line of defense, may contribute to COVID-19 outcomes. The gene discussed is SFTPA1; the disease is lung disorder.