Abstract
BackgroundConsidering the antioxidant function of Vitamin C, also called ascorbic acid, it is widely used against viral infections such as coronavirus disease (COVID-19) based on in vitro, observational, and ecological studies. Many confounding factors that can affect Vitamin C levels. Thus, the association described to date may not be causal. To determine the causal relationship between genetically predicted plasma Vitamin C and COVID-19 susceptibility and severity, we performed two-sample Mendelian randomization (MR) based on large samples.MethodsThe summary-level data for Vitamin C was obtained from a GWAS meta-analysis, which included 52,018 individuals from four studies of European ancestry. Data for COVID-19 HGI results were obtained from the meta-analysis of 35 GWASs with more than 1,000,000 subjects of European ancestry, including 32,494 cases with COVID-19 susceptibility and 1,316,207 controls, 9,986 cases with COVID-19 hospitalization and 1,877,672 controls, and 5,101 cases with COVID-19 severe disease and 1,383,241 controls. Mendelian randomization (MR) analysis was conducted to examine the effect of selected single nucleotide polymorphisms and COVID-19 susceptibility, hospitalization, disease severity. Several sensitivity analyses were performed with inverse-variance weighted (random-effect model), inverse variance weighted (fixed-effect model), weighted median, and maximum likelihood methods for estimating the causal effects.ResultsIn this MR study, genetic predisposition to the levels of plasma Vitamin C was not associated with COVID-19 susceptibility (OR: 0.99, 95% CI: 0.84–1.17, P = 0.91), hospitalization (OR: 1.10, 95% CI: 0.71–1.71, P = 0.67) and severity (OR: 0.83, 95% CI: 0.43–1.59, P = 0.58). The association was consistent in complementary analyses. No potential heterogeneities and directional pleiotropies were observed for the analysis results.ConclusionAccording to our study, no correlation was observed between plasma Vitamin C levels and COVID-19 susceptibility and severity. Further studies in different ethnics are necessary to explore the potential role and mechanisms of circulating serum Vitamin C levels on COVID-19.
Highlights
Coronavirus disease (COVID-19) is characterized by cytokine storms that result in immunogenic damage, especially to the endothelium and alveolar membrane [1, 2]
All instrumental variables were associated with the Vitamin C at a genome-wide significance levels (P < 5 × 10−8) and linkage disequilibrium (LD) r2 < 0.001 at a 10, 000 kb window, which confirmed the independence for the selected genetic variants [20]
Eleven independent single-nucleotide polymorphism (SNP) were associated with three COVID19 phenotypes with linkage disequilibrium (LD) r2 < 0.001 at a 10,000 kb window, which confirmed the independence for the selected genetic variants
Summary
Coronavirus disease (COVID-19) is characterized by cytokine storms that result in immunogenic damage, especially to the endothelium and alveolar membrane [1, 2]. Vitamin C, otherwise known as ascorbic acid, is a an essential nutrient It boosts immunity and acts as a potent antioxidant [5], promote the synthesis of vasopressin and cortisol, enhance the neutrophil extracellular trap (NET) function, and improve the body’s resistance to viruses [6, 7]. A meta-analysis showed that the use of vitamin C was not associated with the decreased risk of COVID19 [10]. These studies included limited sample sizes with potential confounders. Considering the antioxidant function of Vitamin C, called ascorbic acid, it is widely used against viral infections such as coronavirus disease (COVID-19) based on in vitro, observational, and ecological studies. To determine the causal relationship between genetically predicted plasma Vitamin C and COVID-19 susceptibility and severity, we performed two-sample Mendelian randomization (MR) based on large samples
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