Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19.

ABSTRACT:

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?ConclusionOur 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.

SUBMITTER: Vietzen H 

PROVIDER: S-EPMC7835668 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature