SynthesisNutrition reviews2025
Micronutrients, Vitamin D, and Inflammatory Biomarkers in COVID-19: A Systematic Review and Meta-analysis of Causal Inference Studies.
Synthesis in Nutrition reviews, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Vitamin D and Health Outcomes: State-of-the-Art Review of Triangulated Evidence and Ongoing Controversies.Current nutrition reports · 2026Review
- Causal Effect of Fatty Fish Consumption on Influenza: Evidence From Two-Sample Mendelian Randomization.Journal of multidisciplinary healthcare · 2025Article
- The development of a therapeutic strategy for post-acute sequelae of COVID-19 should be based on an efficient classification of pathogenesis.Frontiers in medicine · 2025Article
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Authors and funding
6 authors.
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Abstract
contextExperimental and observational studies suggest that circulating micronutrients, including vitamin D (VD), may increase COVID-19 risk and its associated outcomes. Mendelian randomization (MR) studies provide valuable insight into the causal relationship between an exposure and disease outcomes.
objectivesThe aim was to conduct a systematic review and meta-analysis of causal inference studies that apply MR approaches to assess the role of these micronutrients, particularly VD, in COVID-19 risk, infection severity, and related inflammatory markers. DATA SOURCES: Searches (up to July 2023) were conducted in 4 databases. DATA EXTRACTION AND ANALYSIS: The quality of the studies was evaluated based on the MR-STROBE guidelines. Random-effects meta-analyses were conducted where possible.
resultsThere were 28 studies (2 overlapped) including 12 on micronutrients (8 on VD) and COVID-19, 4 on micronutrients (all on VD) and inflammation, and 12 on inflammatory markers and COVID-19. Some of these studies reported significant causal associations between VD or other micronutrients (vitamin C, vitamin B6, iron, zinc, copper, selenium, and magnesium) and COVID-19 outcomes. Associations in terms of causality were also nonsignificant with regard to inflammation-related markers, except for VD levels below 25 nmol/L and C-reactive protein (CRP). Some studies reported causal associations between cytokines, angiotensin-converting enzyme 2 (ACE2), and other inflammatory markers and COVID-19. Pooled MR estimates showed that VD was not significantly associated with COVID-19 outcomes, whereas ACE2 increased COVID-19 risk (MR odds ratio = 1.10; 95% CI: 1.01-1.19) but did not affect hospitalization or severity of the disease. The methodological quality of the studies was high in 13 studies, despite the majority (n = 24) utilizing 2-sample MR and evaluated pleiotropy.
conclusionMR studies exhibited diversity in their approaches but do not support a causal link between VD/micronutrients and COVID-19 outcomes. Whether inflammation mediates the VD-COVID-19 relationship remains uncertain, and highlights the need to address this aspect in future MR studies exploring micronutrient associations with COVID-19 outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022328224.
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