Abstract: nutrients Systematic Review Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis Banafsheh Hosseini 1,2, *, Asmae El Abd 1 and Francine M. Ducharme 1,2,3 1 2 3 * Citation: Hosseini, B.; El Abd, A.; Ducharme, F.M. Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis. Nutrients Clinical Research and Knowledge Transfer Unit on Childhood Asthma, Research Centre, Sainte-Justine University Health Centre, Montreal, QC H3T 1C5, Canada; asmae.el.abd.hsj@ssss.gouv.qc.ca (A.E.A.); francine.m.ducharme@umontreal.ca (F.M.D.) Department of Pediatrics, Faculty of Medicine, University of Montreal, Sainte-Justine Hospital, Montreal, QC H3C 3J7, Canada Department of Social and Preventive Medicine, Public Health School, University of Montreal, Montreal, QC H3N 1X9, Canada Correspondence: banafsheh.hosseini@umontreal.ca Abstract: The COVID-19 outbreak has rapidly expanded to a global pandemic; however, our knowledge is limited with regards to the protective factors against this infection. The aim of this systematic literature review and meta-analysis was to evaluate the impact of vitamin D supplementation on COVID-19 related outcomes. A systematic search of relevant papers published until January 2022 was conducted to identify randomized controlled trials (RCTs) and non-randomized studies of intervention (NRISs). The primary outcomes included the risk of COVID-19 infection (primary prevention studies on uninfected individuals), hospital admission (secondary prevention studies on mild COVID-19 cases), and ICU admission and mortality rate (tertiary prevention studies on hospitalized COVID-19 patients). We identified five studies (one RCT, four NRISs) on primary prevention, with five (two RCTs, three NRISs) on secondary prevention, and 13 (six RCTs, seven NRISs) on tertiary prevention. Pooled analysis showed no significant effect on the risk of COVID-19 infection. No meta-analysis was possible on hospitalization risk due to paucity of data. Vitamin D supplementation was significantly associated with a reduced risk of ICU admission (RR = 0.35, 95% CI: 0.20, 0.62) and mortality (RR = 0.46, 95% CI: 0.30, 0.70). Vitamin D supplementation had no significant impact on the risk of COVID-19 infection, whereas it showed protective effects against mortality and ICU admission in COVID-19 patients. 2022, 14, 2134. https://doi.org/ 10.3390/nu14102134 Keywords: vitamin D; COVID-19; hospitalization; mortality; ICU admission Academic Editor: Bruce W. Hollis Received: 20 April 2022 Accepted: 13 May 2022 Published: 20 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).