Abstract: Journal of Steroid Biochemistry and Molecular Biology 211 (2021) 105883 Contents lists available at ScienceDirect Journal of Steroid Biochemistry and Molecular Biology journal homepage: www.elsevier.com/locate/jsbmb Short communication Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies Fausto Petrelli a, *, Andrea Luciani a, Gianluca Perego b, Giuseppina Dognini c, Paolo Luigi Colombelli c, Antonio Ghidini d a Oncology Unit, ASST Bergamo Ovest, Treviglio, BG, Italy Pharmacy Unit, San Raffaele Hospital, Milano, Italy Internal Medicine Unit, ASST Bergamo Ovest, Treviglio, BG, Italy d Oncology Unit, Casa di cura Igea, Milano, Italy b c A R T I C L E I N F O A B S T R A C T Keywords: COVID-19 Infection Vitamin D3 Mortality Meta-analysis Vitamin D modulates the systemic inflammatory response through interaction with immune system. As such, it has a possible protective role against the risk of respiratory tract infections and other diseases. It may be useful in particular, during COVID-19 pandemic. PubMed, the Cochrane Library, and EMBASE were searched from inception until January 31, 2021, for observational or clinical studies reporting the prognosis (and therapeutic effect) of COVID-19 infection in patients with deficient vitamin D levels. The infection rate, severity, and death from COVID-19 infection were pooled to provide an odds ratio with a 95 % confidence interval (OR 95 % CI). An OR > 1 was associated with the worst outcome in deficient compared with nondeficient patients. We assessed the association between vitamin D and risk, severity, and mortality for COVID-19 infection, through a review of 43 observational studies. Among subjects with deficient vitamin D values, risk of COVID-19 infection was higher compared to those with replete values (OR = 1.26; 95 % CI, 1.19–1.34; P < .01). Vitamin D deficiency was also associated with worse severity and higher mortality than in nondeficient patients (OR = 2.6; 95 % CI, 1.84–3.67; P < .01 and OR = 1.22; 95 % CI, 1.04–1.43; P < .01, respectively). Reduced vitamin D values resulted in a higher infection risk, mortality and severity COVID-19 infection. Supplementation may be considered as preventive and therapeutic measure. Vitamin D modulates the systemic inflammatory response through interaction with most cells of the immune system. As such, it has a possible protective role against the risk of respiratory tract infections and other diseases [1]. Vitamin D supplementation resulted in reduced all-cause mortality, according to a recently published meta-analysis [2]. We aimed to assess the association between vitamin D and risk, severity, and mortality for COVID-19 infection. PubMed, the Cochrane Library, and EMBASE were searched from inception until January 31, 2021, for observational or clinical studies reporting the prognosis (and therapeutic effect) of COVID-19 infection in patients with deficient vitamin D levels. The search terms were as follows: ((vitamin D [MeSH Terms]) or (vitamin D) or (25OH vitamin D) OR cholecalciferol OR ergo­ calciferol OR calcitriol)) and (“covid-19”). The infection rate, severity, and death from COVID-19 infection were pooled to provide an odds ratio with a 95 % confidence interval (OR 95 % CI). An OR > 1 was associated with the worst outcome in deficient compared with nondeficient patients. The study adhered to the Meta-analysis of Observational Studies in Epidemiology..