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

Blood Adv. 2020 Oct 27;4(20):5035-5039. doi: 10.1182/bloodadvances.2020002650.


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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Betacoronavirus / immunology
  • COVID-19
  • Coronavirus Infections / blood
  • Coronavirus Infections / immunology*
  • Cytotoxicity, Immunologic*
  • Female
  • Humans
  • Inflammation / blood
  • Inflammation / immunology
  • Interleukin-2 Receptor alpha Subunit / blood
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukins / blood
  • Interleukins / immunology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / blood
  • Pneumonia, Viral / immunology*
  • SARS-CoV-2
  • Severity of Illness Index
  • Young Adult


  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Interleukins