Relationship Between Plasma Vitamin C and COVID-19 Susceptibility and Severity: A Two-Sample Mendelian Randomization Study

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.

Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies

“…Furthermore, HIVC in combination with other drugs such as giammonium glycyrrhizinate, decreased the incidence rate of ARDS in COVID-19 patients [ 158 ]. Despite the observed benefits of HIVC, conflicting results have been reported in severe COVID-19 patients [ 159 ]. Data from randomized controlled clinical trials are scarce.…”

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“…The analysis did not show reliable evidence of any plausible significant associations of micronutrients’ status and vulnerability to infection or COVID-19 severity [21 ▪▪ ]. This finding was corroborated for vitamin C [22,23], but not for iron, for which higher genetically predicted status had been associated with sepsis [24].…”

The causal effect of oxidative stress on the risk of glaucoma

“…Several rigorous statistical methods were used to investigate the causal relationship between OSIB and glaucoma, including IVW (fixed effects) [ 22 ], IVW (random effects) [ 23 ], MR-Egger regression [ 24 ], weighted median [ 25 ], and MR-PRESSO [ 26 ]. The IVW results were considered unbiased without horizontal pleiotropy [ 27 ].…”

“…IVW (fixed effects) was used when no heterogeneity was found [ 22 ]. Conversely, IVW (random effects) results were considered more reliable when substantial heterogeneity was present [ 23 ]. The MR-Egger regression allowed for pleiotropy in all SNPs and satisfied the instrument strength independent of the direct effect (InSIDE) hypothesis.…”