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 < 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.
【초록키워드】 COVID-19, intensive care, severe COVID-19, Antiviral, polymorphism, NK cell, NK cells, hospitalized patients, infections, severity of COVID-19, Patient, Mild, genetic variants, Genetic variant, receptor, distribution, SARS-CoV-2 infections, mild symptoms, single-nucleotide polymorphism, HLA-E, Activation, expression level, infected cells, independent risk factors, help, severe SARS, allele, independent risk factor, study cohort, infected cell, effector cells, homozygous, allelic variants, significantly lower, severe SARS-CoV-2, bind, KLRC2, identify, caused, significantly, addition, investigated, contribute, occur, hospitalized patient, activating, allelic variant, single-nucleotide, 【제목키워드】 variant, risk factor, Deletion, receptor,