Abstract: Pharmaceutical Sciences, 2021, 27(Suppl 1), S1-S12 doi:10.34172/PS.2021.13 https://ps.tbzmed.ac.ir/ Review The Impact of Vitamin D Supplementation on Mortality Rate and Clinical Outcomes of COVID-19 Patients: A Systematic Review and Meta-Analysis Leila Nikniaz1 , Mohammad Amin Akbarzadeh2,3,4 , Hossein Hosseinifard5 , Mohammad-Salar Hosseini2,3,4* Tabriz Health Services Management Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 3 Research Center for Evidence-Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 4 Iranian Evidence-Based Medicine (EBM) Centre, Joanna Briggs Institute Affiliated Group, Tabriz, Iran. 5 Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 1 2 Article Info Article History: Received: 26 January 2021 Accepted: 9 March 2021 ePublished: 9 March 2021 Keywords: -COVID-19 -Dietary supplements -SARS-CoV-2 -Treatment outcome -Vitamin D Abstract Background: Several studies have suggested the positive impact of vitamin D on patients infected with SARS-CoV-2. This systematic review aims to evaluate the effects of vitamin D supplementation on clinical outcomes and mortality rate of COVID-19 patients. Methods: A comprehensive search was conducted through the databases of PubMed, Scopus, Web of Knowledge, Embase, Ovid, and The Cochrane Library without time and language limitation, until December 16, 2020. The results were screened, and the outcomes of interest were extracted. Using the Joanna Briggs Institute (JBI) Critical Appraisal Tools, the remaining results were appraised critically. Statistical analysis was performed using the Comprehensive Meta-Analysis (CMA) software version 2.0. Results: Of the 2311 results, four studies and 259 patients were enrolled, including 139 patients in vitamin D intervention groups. The pooled analysis of three studies, reporting the patients’ survival and mortality rate, showed a significantly lower mortality rate among the intervention groups compared with the control groups (OR=0.264, 95% CI=0.099–0.708, p-value=0.008). Two of the studies reported the clinical outcomes based on the World Health Organization’s Ordinal Scale for Clinical Improvement (OSCI) score for COVID-19, where both of them showed a significant decrease in OSCI score in the vitamin D intervention groups. One study reported a lower rate of intensive care unit (ICU) admission, and one study reported a significant decrease in serum levels of Fibrinogen. Conclusion: Prescribing vitamin D supplementation to patients with COVID-19 infection seems to decrease the mortality rate, the severity of the disease, and serum levels of the inflammatory markers. Further studies are needed to determine the ideal type, dosage, and duration of supplementation.