RT Journal Article
T1 Micronutrients, Vitamin D, and Inflammatory Biomarkers in COVID-19: A Systematic Review and Meta-analysis of Causal Inference Studies.
A1 Alcala-Santiago, Angela
A1 Rodriguez-Barranco, Miguel
A1 Sanchez-Perez, Maria-Jose
A1 Gil, Angel
A1 Garcia-Villanova, Belen
A1 Molina-Montes, Esther
K1 Mendelian randomization
K1 Causal inference
K1 Inflammatory markers
K1 Micronutrients
K1 Vitamin D
AB Context: Experimental 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.Objectives: The 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.Results: There 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.Conclusion: MR 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.
PB Oxford University Press
YR 2024
FD 2024-10-24
LK https://hdl.handle.net/10668/24319
UL https://hdl.handle.net/10668/24319
NO Alcalá-Santiago Á, Rodriguez-Barranco M, Sánchez MJ, Gil Á, García-Villanova B, Molina-Montes E. Micronutrients, Vitamin D, and Inflammatory Biomarkers in COVID-19: A Systematic Review and Meta-analysis of Causal Inference Studies. Nutr Rev. 2024 Oct 24:nuae152.
NO This research was funded by Project PECOVID-0200– 2020, funded by Con-sejer�ıa de Salud y Consumo de la Junta de Andaluc�ıa and co-funded by the European Regional Development Fund (ERDF-FEDER).
DS RISalud
RD Apr 10, 2025