The GNB3 c.825C>T (rs5443) polymorphism and protection against fatal outcome of corona virus disease 2019 (COVID-19)

Abstract

Background and aims: Albeit several factors which influence the outcome of corona virus disease (COVID-19) are already known, genetic markers which may predict the outcome of the disease in hospitalized patients are still very sparse. Thus, in this study, we aimed to analyze whether the single-nucleotide polymorphism (SNP) rs5443 in the gene GNB3, which was associated with higher T cell responses in previous studies, might be a suitable biomarker to predict T cell responses and the outcome of COVID-19 in a comprehensive German cohort.Methods: We analyzed the influence of demographics, pre-existing disorders, laboratory parameters at the time of hospitalization, and GNB3 rs5443 genotype in a comprehensive cohort (N = 1570) on the outcome of COVID-19. In a sub cohort, we analyzed SARS-CoV-2-specific T cell responses and associated GNB3 rs5443 genotypes. We investigated the influence of all factors on COVID-19 fatality in multivariable analysis.Results: We found a younger patient age, normotension or absence of diabetes mellitus or cardiovascular diseases, normal blood cell counts, and low inflammatory markers at hospital admission were protective factors against fatal course of disease. In addition, the rs5443 TT genotype was significantly associated with protection against COVID-19 fatality (OR: 0.60, 95% CI: 0.40–0.92, p = 0.02). We also observed significantly increased SARS-CoV-2-specific T cell responses in rs5443 TT genotype carriers (p = 0.01). Although we observed a significant association of the factors described previously in univariate analysis, only a younger age of the patients, normal blood cell counts, and the GNB3 rs5443 TT genotype remained independent predictors against COVID-19 fatality in multivariable analysis.Conclusion: Immutable predictors for COVID-19 fatality are relatively rare. In this study we could show that the TT genotype of the SNP rs5443 in the gene GNB3 is associated with protection against COVID-19 fatality. It was as well correlated to higher SARS-CoV-2-specific T cell responses, which could result in a milder course of disease in those patients. Based on those observations we hereby provide a further prognostic biomarker, which might be used in routine diagnostics as a predictive factor for COVID-19 mortality already upon hospitalization.

The single nucleotide polymorphism rs4986790 (c.896A>G) in the gene TLR4 as a protective factor in corona virus disease 2019 (COVID-19)

“…The ACE2 rs2285666 GG genotype or G-allele were associated with an almost twofold increased risk of infection and a threefold increased risk of a severe or fatal outcome of COVID-19 (15). We also demonstrated that the GNB3 c.825C>T (rs5443) TT genotype is protective against COVID-19 fatality (16).…”

COVID-19 in der Intensivmedizin

“…Die Variabilität der COVID-19-Verläufe erschwert die klinische Beurteilung, insbesondere wenn es darum geht, Risikopatienten für eine schwere Erkrankung frühzeitig zu erkennen. Eine Vielzahl potenzieller Risikofaktoren für einen schweren COVID-19-Verlauf konnte identifiziert werden [ 3 ]. Dazu gehören insbesondere hohes Patientenalter und Vorerkrankungen wie chronische Nierenerkrankung, Diabetes, arterielle Hypertonie oder Immunsuppression [ 4 , 5 ].…”

Reply to: Comment on “influence of COVID‐19 vaccination on disease activity of rheumatoid arthritis in older patients”

“…Regarding the genetic background, several reports have shown a link between the genetic background and the immunological response following COVID-19 or vaccination. [8][9][10] However, there are no clear data showing a relation between the tendency for RA flares following vaccination and a particular genetic background. Despite differences in the genetic background, at least comparable results have been reported in Japanese 2 and other ethnic groups.…”