Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies

Front Immunol. 2020 Jun 23;11:1512. doi: 10.3389/fimmu.2020.01512. eCollection 2020.


Natural Killer (NK) cells are innate immune responders critical for viral clearance and immunomodulation. Despite their vital role in viral infection, the contribution of NK cells in fighting SARS-CoV-2 has not yet been directly investigated. Insights into pathophysiology and therapeutic opportunities can therefore be inferred from studies assessing NK cell phenotype and function during SARS, MERS, and COVID-19. These studies suggest a reduction in circulating NK cell numbers and/or an exhausted phenotype following infection and hint toward the dampening of NK cell responses by coronaviruses. Reduced circulating NK cell levels and exhaustion may be directly responsible for the progression and severity of COVID-19. Conversely, in light of data linking inflammation with coronavirus disease severity, it is necessary to examine NK cell potential in mediating immunopathology. A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. In this review, we summarize the current understanding of how NK cells respond in both early and late coronavirus infections, and the implication for ongoing COVID-19 clinical trials. Using this immunological lens, we outline recommendations for therapeutic strategies against COVID-19 in clearing the virus while preventing the harm of immunopathological responses.

Keywords: COVID-19; NK cells; immunotherapy; innate immunity; interferon.

Publication types

  • Review

MeSH terms

  • Adoptive Transfer / methods*
  • Adrenal Cortex Hormones / therapeutic use
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Ascorbic Acid / therapeutic use
  • Betacoronavirus / drug effects
  • Betacoronavirus / immunology*
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / mortality
  • Coronavirus Infections / virology
  • Cytokines / antagonists & inhibitors
  • Cytokines / metabolism
  • Disease Susceptibility / immunology
  • Humans
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology
  • Immunologic Memory
  • Interferon Type I / metabolism
  • Interferon Type I / therapeutic use
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • Mice
  • Pandemics
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / mortality
  • Pneumonia, Viral / virology
  • SARS-CoV-2


  • Adrenal Cortex Hormones
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Interferon Type I
  • Ascorbic Acid