NK cells in COVID-19: protectors or opponents?

Natural killer (NK) cells contribute to early antiviral immunity, and in this preprint, Maucourant et al. report reduced NK cell counts in the peripheral blood of 27 patients hospitalized with moderate or severe COVID-19. In early COVID-19, NK cell activation across distinct subsets was elevated in peripheral blood, mirroring the activation signature of NK cells in the bronchoalveolar lavage fluid of patients with COVID-19. Interestingly, severe hyperinflammation was associated with the proliferation and activation of ‘adaptive’ NK cells, a specialised sub-population with enhanced antibody-dependent cellular cytotoxicity, as well as the arming of CD56bright NK cells with cytotoxic molecules. These results suggest that a distinct NK cell immunophenotype is associated with the severity of COVID-19. Further studies are necessary to define the protective antiviral versus the detrimental pathological roles of NK cells in patients with COVID-19.