People with Absence of Natural Killer Cell Receptor Most Likely to Develop Severe COVID-19, Finds Study

People with a partial or total absence of a special, activating receptor in natural killer cells (NK cells) that destroy virus-infected cells are most likely to develop severe COVID-19.

A research group from the Center for Virology at the Medical University of Vienna (Vienna, Austria) has shown that that people who required hospitalization with COVID-19 were significantly more likely to exhibit a genetic variation due to which approximately 4% of the population naturally lack the activation receptor NKG2C, and in 30% of the population this receptor is only partially available.


Normally, the antiviral immune response of NK cells is an important step in combating viral replication in the early phase of the infection. On their surface, these killer cells have special, activating receptors, including the NKG2C receptor, which communicates with an infected cell via one of its specialized surface structures, HLA-E. This interaction results in the destruction of virus-infected cells. The researchers have shown that people who required hospitalization with COVID-19 were significantly more likely to exhibit the genetic variation underlying the lack of the receptor than people who only experienced mild disease. The study indicates the major importance of NK-cell response in the battle against SARS-CoV-2 infection.

"Absence of the receptor was particularly prevalent in COVID-19 patients being treated in intensive care units, irrespective of age or gender. Genetic variations on the HLA-E of the infected cell were also associated with disease severity, albeit to a lesser extent," said Elisabeth Puchhammer-Stöckl who led the research team. "This part of the immune response could therefore also represent an important target for drugs that could help to prevent severe COVID-19 disease."

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Medical University of Vienna