Association of Vitamin D Deficiency With COVID-19 Infection Severity

Systematic Review and Meta-Analysis

Zhen Wang; Avni Joshi; Kaitlin Leopold; Sarah Jackson; Stephanie Christensen; Tarek Nayfeh; Khaled Mohammed; Ana Creo; Peter Tebben; Seema Kumar


Clin Endocrinol. 2022;96(3):287-287. 

In This Article

Abstract and Introduction


Background: We sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID-19) infection.

Methods: Multiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID-19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission.

Results: Seventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50–4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40–7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48–3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25–0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut-offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends.

Conclusions: Vitamin D deficiency is associated with greater severity of COVID-19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID-19.


Coronavirus disease 2019 (COVID-19) was initially identified in Wuhan, China in late 2019 and subsequently became a global pandemic.[1] The illness varies widely in severity with affected individuals being asymptomatic or developing mild, moderate or severe illness, which can be fatal. The case fatality rates have been different between geographic regions and countries.[2] The specific risk factors for a severe illness identified so far include older age, male sex, obesity, cardiovascular disease, chronic lung disease, diabetes mellitus and cancer.[1,3] Additionally, race is an important factor as several studies have shown that Black, Hispanic and Asian individuals accounted for a disproportionately higher number of hospitalisations and deaths due to COVID-19 in the United Kingdom and the United States.[4] Many of the abovementioned risk factors are not modifiable, hence it is important to identify modifiable factors that might contribute to COVID-19 infection severity. Diet and nutrition have important implications in immune functioning and infection risk, especially vitamin D level.[5] Vitamin D may be one potentially modifiable risk factor postulated to modulate COVID-19 infection severity.[6]

Vitamin D, in addition to its role in skeletal health, may modulate immune regulation.[7] The vitamin D receptor is present in a variety of cells involved in immune regulation, including monocytes, activated T and B lymphocytes and dendritic cells. Vitamin D has been shown to impact cytokine synthesis, lymphocyte proliferation, antibody production, monocyte activation and cell-mediated immunity.[7] A systematic review and meta-analysis of 25 randomised, double-blind placebo-controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration found that vitamin D supplementation was beneficial in reducing the risk of acute respiratory tract infection.[8] There is a conflicting opinion on the role of vitamin D in impacting the risk of COVID-19, with some studies suggesting that vitamin D deficiency increases the risk of COVID-19 infection[9,10] while others did not find a significant association.[11] Similarly, there is conflicting evidence on whether vitamin D deficiency is associated with greater severity of COVID-19 infection.[12–17]

To further investigate this relationship and obtain greater clarity on this issue, we conducted this systematic review and meta-analysis to evaluate the association between vitamin D deficiency and the severity of COVID-19 infection.