No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data

Amin, Hasnat A; Drenos, Fotios

doi:10.1136/bmjnph-2020-000151

Cited by 42 publications

(33 citation statements)

References 38 publications

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“…Another Mendelian randomization study failed to find evidence of a linkage between vitamin D deficiency and COVID-19 infection rates or severe disease (45). However, described studies did not consider true vitamin D deficiency in participants, and it can be possible that vitamin D supplementation could benefit insufficient/deficient patients (44,45).…”

Section: Discussionmentioning

confidence: 99%

Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity

et al. 2021

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Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19.Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants.Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course.Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.

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Section: Discussionmentioning

confidence: 99%

Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity

et al. 2021

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“…Results from sensitivity analyses evaluating the effect of genetically predicted vitamin D deficiency or insufficiency on risk of COVID-19 outcomes were similarly null. Our study builds on the findings of a prior MR study of vitamin D and COVID-19, 46 providing replication with genetic BMJ Nutrition, Prevention & Health instruments specifically designed to maximise instrument strength and address MR assumptions, and expanding the scope to include additional COVID-19 outcomes and individuals of non-European ancestry. In summary, our results suggest that long-term usual vitamin D nutritional status does not have a causal effect on susceptibility to COVID-19 infection and its severity.…”

Section: Discussionmentioning

confidence: 99%

“…One prior study used MR to study the vitamin D-COVID-19 association. 46 The present study adds new information by using multiple genetic instruments designed to maximise instrument strength and validity, validating the instruments across population subgroups, and considering additional COVID-19 clinical outcomes.…”

Section: Introductionmentioning

confidence: 96%

Genetically predicted serum vitamin D and COVID-19: a Mendelian randomisation study

Patchen

Clark

Gaddis

et al. 2021

BMJNPH

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ObjectivesTo investigate causality of the association of serum vitamin D with the risk and severity of COVID-19 infection.DesignTwo-sample Mendelian randomisation study.SettingSummary data from genome-wide analyses in the population-based UK Biobank and SUNLIGHT Consortium, applied to meta-analysed results of genome-wide analyses in the COVID-19 Host Genetics Initiative.Participants17 965 COVID-19 cases including 11 085 laboratory or physician-confirmed cases, 7885 hospitalised cases and 4336 severe respiratory cases, and 1 370 547 controls, primarily of European ancestry.ExposuresGenetically predicted variation in serum vitamin D status, instrumented by genome-wide significant single nucleotide polymorphisms (SNPs) associated with serum vitamin D or risk of vitamin D deficiency/insufficiency.Main outcome measuresSusceptibility to and severity of COVID-19 infection, including severe respiratory infection and hospitalisation.ResultsMendelian randomisation analysis, sufficiently powered to detect effects comparable to those seen in observational studies, provided little to no evidence for an effect of genetically predicted serum vitamin D on susceptibility to or severity of COVID-19 infection. Using SNPs in loci related to vitamin D metabolism as genetic instruments for serum vitamin D concentrations, the OR per SD higher serum vitamin D was 1.04 (95% CI 0.92 to 1.18) for any COVID-19 infection versus population controls, 1.05 (0.84 to 1.31) for hospitalised COVID-19 versus population controls, 0.96 (0.64 to 1.43) for severe respiratory COVID-19 versus population controls, 1.15 (0.99 to 1.35) for COVID-19 positive versus COVID-19 negative and 1.44 (0.75 to 2.78) for hospitalised COVID-19 versus non-hospitalised COVID-19. Results were similar in analyses using SNPs with genome-wide significant associations with serum vitamin D (ie, including SNPs in loci with no known relationship to vitamin D metabolism) and in analyses using SNPs with genome-wide significant associations with risk of vitamin D deficiency or insufficiency.ConclusionsThese findings suggest that genetically predicted differences in long-term vitamin D nutritional status do not causally affect susceptibility to and severity of COVID-19 infection, and that associations observed in previous studies may have been driven by confounding. These results do not exclude the possibility of low-magnitude causal effects or causal effects of acute responses to therapeutic doses of vitamin D.

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“…Therefore unlike conventional observational study, Mendelian randomisation analysis is not subject to confounding. Recent Mendelian randomisation studies have clarified that genetically determined Vitamin D exposure is not associated with COVID-19 infection and severity [ 25 – 27 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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No evidence that vitamin D is able to prevent or affect the severity of COVID-19 in individuals with European ancestry: a Mendelian randomisation study of open data

Cited by 42 publications

References 38 publications

Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity

Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity

Genetically predicted serum vitamin D and COVID-19: a Mendelian randomisation study

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

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