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Certain genetic conditions in people significantly influence their immune response against the SARS-CoV-2 virus and can influence the severity of the COVID-19 disease. A research group led by MedUni Vienna was able to show that certain genetic variants of the CD16a antibody receptor are associated with the risk of severe COVID-19. Around 15 percent of the population is affected. The results were recently published in the journal Genetics in Medicine.

Natural killer (NK) cells play an important role in fighting virus replication from the early stages of viral infections. NK cells have special receptors on their surface that bind to some of the antibodies that are formed specifically against viruses. This enables antibody-dependent activation of the killer cells (ADCC), which leads to the destruction of the virus-infected cells and triggers the release of pro-inflammatory factors.

This interaction between antibody and NK cell surface receptor is influenced by certain genetic factors, resulting in either strong (high affinity) or weak (low affinity) binding genetic receptor variants.
A research group from the Center for Virology at the Medical University of Vienna, led by Hannes Vietzen and Elisabeth Puchhammer-Stöckl, in cooperation with Alexander Zoufaly from the Klinik Favoriten, has now shown that certain genetic variants of the CD16a antibody receptor are associated with the risk of severe COVID-19 .

In their study, which was recently published in the journal “Genetics in Medicine”, the authors show that people who had to be hospitalized due to a severe SARS-CoV-2 infection had the high-affinity variant of the CD16a receptor significantly more frequently . This high-affinity variant only occurs in about 15 percent of the population, and carriers of this variant have a significantly increased risk of severe COVID-19 courses. This high-affinity variant was particularly common in patients who had to be treated with COVID-19 in intensive care units or who died with COVID-19.

In subsequent cell culture experiments, the research team was able to show that this high-affinity variant of the antibody receptor leads to a significantly increased antibody-dependent activation of NK cells and to a particularly high release of pro-inflammatory factors.

Hannes Vietzen: “The antibody-dependent activation of NK cells is a relatively late immune response. This late immune response no longer seems to control the SARS-CoV-2 virus replication, but rather contributes to a worsening of the COVID-19 disease through an excessive immune response.”

The tests are special scientific investigations. Routine laboratory testing for these parameters is not planned, as there are currently no therapeutic and preventive options targeting this genetic predisposition to reduce the risk of severe COVID-19. The genetic predisposition is only one of several factors that influence the severity of the disease.

Publication: Genetics in Medicine
High-affinity FcγRIIIa genetic variants and potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) responses contributing to severe COVID-19
Hannes Vietzen, Vera Danklmaier, Alexander Zoufaly, Elisabeth Puchhammer-Stöckl;
2022 Apr 30;S1098-3600(22)00722-5. doi: 10.1016/j.gim.2022.04.005

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