The role of vitamin C in pneumonia and COVID-19 infection in adults with European ancestry: a Mendelian randomisation study

Abstract

Background High dose vitamin C infusion has been proposed to treat critically ill patients, including patients with pneumonia and severe COVID-19. However, trials have shown mixed findings. Here we assessed the unconfounded associations of vitamin C with COVID-19 and pneumonia using the Mendelian randomisation approach. Methods This is a separate-sample Mendelian randomisation study using publicly available data. We applied single nucleotide polymorphisms (SNPs) that were associated with plasma vitamin C, in a recent genome-wide association study (GWAS) as genetic instruments to the GWAS of severe COVID-19, COVID-19 hospitalisation and any infection in the COVID-19 host genetics initiative and the GWAS of pneumonia in the UK Biobank, to assess whether people with genetically predicted higher levels of plasma vitamin C had lower risk of severe COVID-19 and pneumonia. Results Genetically predicted circulating levels of vitamin C was not associated with susceptibility to severe COVID-19, COVID-19 hospitalisation, any COVID-19 infection nor pneumonia. Similar results were obtained when a weighted median and MR-Egger methods were used. Conclusions Mendelian randomisation analysis provided little evidence for an association of genetically predicted circulating levels of vitamin C with COVID-19 or pneumonia and thus our findings provided little support to the use of vitamin C in prevention and treatment in these patients, unless high dose vitamin C infusion has therapeutic effects via different biological pathways.

Assessment of vitamin C effects on pneumonia and COVID-19 using Mendelian randomization: analysis may be misleading

“…Based on their Mendelian randomization study, Hui et al concluded that there is no support for the use of vitamin C in the prevention and treatment of pneumonia or COVID-19 [1]. However, their study has limitations.…”

“…Hui et al [1] used single nucleotide polymorphisms (SNPs) that were associated with plasma vitamin C level in the genome-wide association study in 52,018 people of European ancestry [2]. However, the cited study states "the variance of plasma vitamin C explained by the 11 lead SNPs was 1.87% on average" [2].…”

“…Although it is fundamentally essential in a vitamin C study to know which levels of the vitamin are being compared, Hui et al did not state what they considered to be low and high vitamin C levels [1]. We estimate the average difference in plasma vitamin C levels explained by the selected SNPs as follows.…”

COVID-19-Associated acute respiratory distress syndrome (CARDS): Mechanistic insights on therapeutic intervention and emerging trends

“…An in vitro study revealed that surplus Zinc supplementation can decrease IFN-γ expression in younger subject whereas in elderly persons increased interferon-alpha (IFN-α) production by leukocytes. However award-risk ratio is in favor of Zinc supplementation in COVID-19 [190] , [191] . There are less preclinical and clinical data on this aspect and results from currently ongoing trials employing Zinc in COVID-19 will throw light on the efficacy against viral infections in vivo.…”

Bias against Vitamin C in Mainstream Medicine: Examples from Trials of Vitamin C for Infections

“…The goal of this paper is to demonstrate the bias against vitamin C by using examples primarily from the trials on vitamin C for infections. Some reviews and studies on vitamin C and respiratory infections [10][11][12][13][14][15] have been flawed [16][17][18][19][20][21][22][23], but this paper does not systematically review the effect of vitamin C on infections, since this is covered in other publications [4][5][6][7][8][9][24][25][26][27][28][29][30][31][32].…”