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

Song Chen; Changhua Zheng; Tianlai Chen; Dianhua Huang; Yuancheng Pan; Shunyou Chen

doi:10.3389/fmed.2022.844228

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

Front Med (Lausanne). 2022 Mar 9:9:844228. doi: 10.3389/fmed.2022.844228. eCollection 2022.

Authors

Song Chen¹, Changhua Zheng², Tianlai Chen³, Dianhua Huang¹, Yuancheng Pan¹, Shunyou Chen¹

Affiliations

¹ Department of Orthopedics, Fuzhou Second Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
² Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, China.
³ The Third Department of Clinical Medicine, Fujian Medical University, Fuzhou, China.

Abstract

Background: Considering 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.

Methods: The 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.

Results: In 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.

Conclusion: According 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.

Keywords: COVID-19; Mendelian randomization study; SNP; Vitamin C; cause effect.