Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19

 Elevated plasma IFN-α levels are correlated with COVID-19 disease severity. NK cells in the severe COVID-19 patients showed increased expression of IFN-stimulated genes and genes involved in IFN-α signaling. In contrast, up-regulation of TNF-induced genes in the NK cells was observed in moderate diseases. Although NK cells exert anti-SARS-CoV-2 activity, this was impaired in severe COVID-19. Moreover, NK cells exhibited impaired anti-fibrotic activity, which was likely correlated with the development of fibrotic lung disease in severe COVID-19.