High baseline frequencies of natural killer cells are associated with asymptomatic SARS-CoV-2 infection

This study tested the hypothesis that high frequencies of natural killer (NK) cells are protective against symptomatic SARS-CoV-2 infection. Samples were utilized from the COVID-19 Health Action Response for Marines study, a prospective, observational study of SARS-CoV-2 infection in which participants were enrolled prior to infection and then serially monitored for development of symptomatic or asymptomatic infection. Frequencies and phenotypes of NK cells (CD3^-CD14^-CD19^-CD56⁺) were assessed by flow cytometry. Individuals that developed asymptomatic infections were found to have higher pre-infection frequencies of total NK cells compared to symptomatic individuals (10.61% [SD 4.5] vs 8.33% [SD 4.6], p = 0.011). Circulating total NK cells decreased over the course of infection, reaching a nadir at 4 weeks, while immature NK cells increased, a finding confirmed by multidimensional reduction analysis. These results indicate that NK cells likely play a key role in controlling the severity of clinical illness in individuals infected with SARS-CoV-2.