Figure 1  Hypothesized dual role of NK cells during coronavirus pathogenesis. (A) Healthy Natural Killer (NK) cells in low-risk individuals recognize SARS-CoV-2 infected cells via recognition of viral proteins on the surface of infected cells and through sensing of cytokines and chemokines produced in response to infection. These cells are hypothesized to be able to directly induce apoptosis through death receptor ligation, antibody-dependent cell-mediated cytotoxicity (ADCC), and through the release of cytotoxic granules, in addition to indirectly targeting virally infected cells via modulation of the immune response through cytokine secretion. An effective innate immune response may be able to clear SARS-CoV-2 infection and leave the patient's lungs undamaged. (B) High risk individuals may have dysfunctional NK cells which may not recognize and respond to SARS-CoV-2 infection due to immune evasion strategies employed by the virus. It is hypothesized that an accumulation of infected epithelial cells and innate immune cells, monocyte-macrophages and neutrophils, release cytokines, and chemokines which further recruit immune cells, including NK cells, to the lungs. This may result in the induction of a cytokine storm, led by IFN-γ. This inflammatory state could act as the catalyst for the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), contributing to the significant morbidity, and mortality associated with COVID-19. SARS-CoV-2 infection is associated with reduced NK cell levels and an exhausted phenotype which may impede viral clearance, in addition to severe lung damage.