Association of vitamin B12, folate, and homocysteine with COVID-19 severity and mortality: A systematic review and meta-analysis
Juan R Ulloque-Badaracco, Ali Al-Kassab-Córdova, Esteban A Alarcon-Braga, Enrique A Hernandez-Bustamante, Miguel A Huayta-Cortez, Juan C Cabrera-Guzmán, Pamela Robles-Valcarcel, Vicente A Benites-Zapata
SAGE Open Medicine, doi:10.1177/20503121241253957
Objective: We aimed to review the available evidence on the association between vitamin B12, folate, and homocysteine levels with worse outcomes among COVID-19 patients. Methods: The search was carried out in ten databases simultaneously run on 10 May 2023, without language restrictions. We included cross-sectional, case-control, and cohort studies. The random-effects meta-analysis was performed using the Sidik-Jonkman method and corrected 95% confidence intervals using the truncated Knapp-Hartung standard errors. Standardized mean difference and 95% CI was used as the measure effect size. Results: Thirteen articles were included in this review (n = 2134). Patients with COVID-19 who did not survive had the highest serum vitamin B12 values (SMD: 1.05; 95% CI: 0.31-1.78; p = 0.01, I 2 = 91.22%). In contrast, low serum folate values were associated with patients with severe COVID-19 (SMD: -0.77; 95% CI: -1.35 to -0.19; p = 0.02, I 2 = 59.09%). The remaining tested differences did not yield significant results. Conclusion: Elevated serum levels of vitamin B12 were associated with higher mortality in patients with COVID-19. Severe cases of COVID-19 were associated with low serum folate levels. Future studies should incorporate a larger sample size.
Author contributions
Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethics approval and consent to participate Not applicable.
Informed consent Not applicable.
ORCID iD Vicente A Benites-Zapata https://orcid.org/0000-0002-9158-1108
Supplemental material Supplemental material for this article is available online.
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