The natural killer cell‐associated rs9916629‐C allele is a novel genetic risk factor for fatal COVID‐19. Issue 1 (21st December 2022)

• Record Type: Journal Article
• Authors: Vietzen, Hannes; Furlano, Philippe L.; Traugott, Marianna; Totschnig, David; Hoepler, Wolfgang; Strassl, Robert; Zoufaly, Alexander; Puchhammer‐Stöckl, Elisabeth
• Is Part Of: Journal of medical virology. Volume 95:Issue 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-21
• Subjects: COVID‐19 -- FcγRIIIa -- genetic polymorphism -- HLA‐E -- NK cells -- NKG2C -- rs9916629; Virology -- Periodicals; 616
• DOI: 10.1002/jmv.28404
• Languages: English
• ISSNs: 0146-6615

Abstract

Abstract: The severity of COVID‐19 is associated with individual genetic host factors. Among these, genetic polymorphisms affecting natural killer (NK) cell responses, as variations in the HLA‐E‐ ( HLA‐E *0101/0103), FcγRIIIa‐ ( FcγRIIIa ‐158‐F/V), and NKG2C‐ ( KLRC2 wt/del ) receptor, were associated with severe COVID‐19. Recently, the rs9916629‐C/T genetic polymorphism was identified that indirectly shape the human NK cell repertoire towards highly pro‐inflammatory CD56 bright NK cells. We investigated whether the rs9916629‐C/T variants alone and in comparison to the other risk factors are associated with a fatal course of COVID‐19. We included 1042 hospitalized surviving and 159 nonsurviving COVID‐19 patients as well as 1000 healthy controls. rs9916629‐C/T variants were genotyped by TaqMan assays and were compared between the groups. The patients' age, comorbidities, HLA‐E *0101/0103, FcγRIIIa ‐158‐F/V, and KLRC2 wt/del variants were also determined. The presence of the rs9916629 ‐ C allele was a risk factor for severe and fatal COVID‐19 ( p < 0.0001), independent of the patients' age or comorbidities. Fatal COVID‐19 was more frequent in younger patients (<69.85 years) carrying the FcγRIIIa ‐158‐V/V ( p < 0.006) and in older patients expressing the KLRC2 del variant ( p < 0.003). Thus, patients with the rs9916629 ‐ C allele have a significantly increased risk for fatal COVID‐19 and identification of the genetic variants may be used as prognostic marker for hospitalized COVID‐19 patients.