Abstract: Internal and Emergency Medicine https://doi.org/10.1007/s11739-021-02902-w IM - ORIGINAL Vitamin D deficiency is associated with higher risks for SARS‑CoV‑2 infection and COVID‑19 severity: a retrospective case–control study Ariel Israel1 · Assi Cicurel1,2 · Ilan Feldhamer1 · Felicia Stern3 · Yosef Dror3 · Shmuel M. Giveon4 · David Gillis5 · David Strich6 · Gil Lavie1,7 Received: 17 September 2021 / Accepted: 20 November 2021 © The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI) 2021 Abstract Robust evidence of whether vitamin D deficiency is associated with COVID-19 infection and its severity is still lacking. The aim of the study was to evaluate the association between vitamin D levels and the risks of SARS-CoV-2 infection and severe disease in those infected. A retrospective study was carried out among members of Clalit Health Services (CHS), the largest healthcare organization in Israel, between March 1 and October 31, 2020. We created two matched case–control groups of individuals for which vitamin D levels and body mass index (BMI) were available before the pandemic: group (A), in which 41,757 individuals with positive SARS-CoV-2 PCR tests were matched with 417,570 control individuals without evidence of infection, and group (B), in which 2533 patients hospitalized in severe condition for COVID-19 were matched with 2533 patients who were tested positive for SARS-CoV-2, but were not hospitalized. Conditional logistic models were fitted in each of the groups to assess the association between vitamin D levels and outcome. An inverse correlation was demonstrated between the level of vitamin D and the risks of SARS-CoV-2 infection and of severe disease in those infected. Patients with very low vitamin D levels (< 30 nmol/L) had the highest risks for SARS-CoV-2 infection and also for severe COVID-19 when infected—OR 1.246 [95% CI 1.210–1.304] and 1.513 [95% CI 1.230–1.861], respectively. In this large observational population study, we show a significant association between vitamin D deficiency and the risks of SARS-CoV-2 infection and of severe disease in those infected. Keywords COVID-19 · SARS-CoV-2 · Vitamin D · Large population · Retrospective study