Journal
GENETICS IN MEDICINE
Volume 23, Issue 5, Pages 963-967Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/s41436-020-01077-7
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Funding
- Center for Virology, Medical University of Vienna
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Host genetic variants, particularly KLRC2 deletion and HLA-E*0101, are significantly overrepresented in hospitalized COVID-19 patients, especially those requiring intensive care. These genetic variants are independent risk factors for severe COVID-19.
Purpose Host genetic variants may contribute to severity of COVID-19. NKG2C(+) NK cells are potent antiviral effector cells, potentially limiting the extent of SARS-CoV-2 infections. NKG2C is an activating NK cell receptor encoded by the KLRC2 gene, which binds to HLA-E on infected cells leading to NK cell activation. Heterozygous or homozygous KLRC2 deletion (KLRC2(del)) may naturally occur and is associated with a significantly lower or absent NKG2C expression level. In addition, HLA-E*0101/0103 genetic variants occur, caused by a single-nucleotide polymorphism. We therefore investigated whether the severity of COVID-19 is associated with these genetic variants. Methods We investigated the distribution of KLRC2 deletion and HLA-E*0101/0103 allelic variants in a study cohort of 361 patients with either mild (N = 92) or severe (N = 269) COVID-19. Results Especially the KLRC2(del), and at a lower degree the HLA-E*0101, allele were significantly overrepresented in hospitalized patients (p = 0.0006 and p = 0.01), particularly in patients requiring intensive care (p < 0.0001 and p = 0.01), compared with patients with mild symptoms. Both genetic variants were independent risk factors for severe COVID-19. Conclusion Our data show that these genetic variants in the NKG2C/HLA-E axis have a significant impact on the development of severe SARS-CoV-2 infections, and may help to identify patients at high-risk for severe COVID-19.
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