The emergence of novel respiratory viruses such as SARS-CoV-2 results in rapid dissemination through virus-naive populations and an accumulation of critically ill patients in hospitals across the globe. In the absence of an effective vaccine or proven treatment, this accelerating threat to human health must be met with swift deployment of experimental therapeutics. Dozens of prospective drugs and other therapies are being tested in clinical trials or applied via off-label or compassionate use protocols for patients with life-threatening complications of infection with SARS-CoV-2. To date, the potential promise for viral control and disease amelioration with each new approach has been balanced by problematic data concerning possible elevated risk for serious adverse events. This is particularly true for natural killer (NK) cells, whose celebrated antiviral capacity and strong safety profile in the oncology clinic may encourage hasty application of these cells against SARS-CoV-2. Critically, a wealth of data in a variety of respiratory infections reveals a frightening proclivity for NK cells to exacerbate lung damage during viral injury. Here, we weigh evidence supporting and discouraging clinical use of NK cells in the present pandemic, as well as in future outbreaks of respiratory pathogens. This assessment aims to provide insights for clinicians considering application of NK cells in the care of SARS-CoV-2 infected patients.

Numerous cellular and biologic therapies harnessing the antitumor capabilities of NK cells have proven both beneficial and safe in treatment of cancer. These approaches include infusion of allogeneic NK-cell products derived from umbilical cord blood, unrelated blood donors, induced pluripotent stem cells, and established cell lines (eg, NK-92). Adaptive subsets of NK cells, including cytokine-induced memory-like NK cells, exhibit enhanced responsiveness and function in patients (