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Over 200,000 people have died in the U.S. from COVID-19, mostly older Americans and those with preexisting conditions. However, acute SARS-CoV-2 infections in children are mostly mild, with low hospitalization rates and few deaths, a pattern that also emerged in previous coronavirus outbreaks. Recent reports demonstrate that asymptomatic children have similar or higher SARS-CoV-2 RNA levels in nasopharyngeal swabs compared to infected adults, which suggests that the distinct pathogenesis of SARS-CoV-2 infection in children and adults is not driven by the virus but by differences in age-related host factors. Understanding the disease mitigating host factors of airway epithelial cells in children and adults will advance our knowledge on the cellular responses that are critical for protecting against severe COVID-19. This project will use single cell RNA-sequencing technology to define host cellular factors in airway epithelium that mediate differential SARS-CoV-2 responses in infants and adults.