Natural killer (NK) cells, as a part of innate immune system, play an important role during acute viral infection. Before specific immunity develops, NK cells are the first to respond to infected cells.

Previous studies reported that COVID-19 patients have lower than normal NK cell levels. A lower NK cell count correlates with worse survival rate and a longer duration of viral shedding (Bao C. et al 2021).

Witkowski et al. reported that NK cells from healthy individuals can destroy cells infected by SARS-CoV-2, however, this immune-system defense malfunctions in moderate or severe COVID-19 patients. These defective NK cells are impaired in their ability to kill infected cells. Furthermore, people with severe COVID-19 have NK cells with lower ability to produce cytokines and chemokines. These findings provide insights into the factors driving severe COVID-19.

Krämer et al. suggested that reversing the dysfunctional status of COVID-19-associated NK cells might facilitate viral control and tissue protection. Consistent with this finding, several ongoing clinical trials are testing the therapeutic benefit of NK cells against COVID-19 ( NCT04797975, NCT04634370, and NCT04280224).

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1. Bi, J. NK cell dysfunction in patients with COVID-19. Cell Mol Immunol (2022) 19:127–129. doi: 1038/s41423-021-00825-2

2. Narni-Mancinelli E, Vivier E. Clues that natural killer cells help to control COVID. Nature (2021) 600(7888):226-227.doi: 10.1038/d41586-021-02778-y