Impaired natural killer cell counts and cytolytic activity in patients with severe COVID-19

Abstract

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–driven coronavirus disease 2019 (COVID-19) has caused unprecedented human death and has seriously threatened the global economy. Early data suggest a surge in proinflammatory cytokines in patients with severe COVID-19, which has been associated with poor outcomes. We recently postulated that the inflammatory response in patients with severe COVID-19 disease is not inhibited by natural killer (NK) cells, resulting in a “cytokine storm.” Here, we assessed the NK-cell functional activity and the associated cytokines and soluble mediators in hospitalized COVID-19 patients. Significantly impaired NK-cell counts and cytolytic activity were observed in COVID-19 patients when compared with healthy controls. Also, cytokines like interleukin 12 (IL12), IL15, and IL21 that are important for NK-cell activity were not detected systematically. Serum concentrations of soluble CD25 (sCD25)/soluble IL2 receptor α (sIL2-Rα) were significantly elevated and were inversely correlated with the percentage of NK cells. Impaired NK-cell cytolytic activity together with other laboratory trends including elevated sCD25 were consistent with a hyperinflammatory state in keeping with macrophage-activation syndrome. Our findings suggest that impaired counts and cytolytic activity of NK cells are important characteristics of severe COVID-19 and can potentially facilitate strategies for immunomodulatory therapies.

Immune responses to SARS-CoV-2 infection in Humans and ACE2 humanized mice

“…These questions remain unanswered. Stefania Varchetta et al 11 and Mohammed Osman et al 12 both observed a reduction of immature NK cells and a parallel enrichment in the mature subset. Of note, a significant reduction of IFN-γ secretion and degranulation activity, related to cytolytic activity, was observed in NK cells, which could be associated with exhaustion of NK cells.…”

“…Among the studies on NK cells, many 11 , 12 , 13 , 14 focus on the significantly impaired NK cell counts but not the NK cell frequency observed in COVID-19 patients. They believe NK cells are hyperactivated in the acute phase of COVID-19, but return to the normal level after clinical recovery from COVID-19.…”

COVID-19 vaccines: The status and perspectives in delivery points of view

“…A previous study showed that migration of NK cells and macrophages helped clear SARS-CoV [ 176 ], and NK cells from COVID-19 patients showed increased perforin levels, providing a basis for understanding the role of NK cells in COVID-19 infections [ 177 ]. Given the importance of NK cells in acute viral infection, recent studies have demonstrated potential strategies for NK cell-based immunotherapy for COVID-19 [ 178 ]. An ongoing clinical trial in China investigates the use of NK cells for viral clearance in severe COVID-19-associated pneumonia patients (NCT04280224).…”

COVID-19, rheumatic diseases and immune dysregulation—a perspective

“…Natural killer (NK) cells normally counteract these inflammatory signals by killing viral-infected cells, activated monocytes and T cells, thereby acting to reduce the inflammatory response [ 34 , 35 ]. In COVID-19, however, NK cell number and function are reduced in patients with severe disease, thereby potentiating the CRS [ 36 ].…”