Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study

Aim To evaluate associations of plasma 25(OH)D status with the likelihood of coronavirus disease (COVID-19) infection and hospitalization. Methods The study population included the 14,000 members of Leumit Health Services who were tested for COVID-19 infection from February 1st to April 30th 2020, and who had at least one previous blood test for plasma 25(OH)D level. “Suboptimal” or “low” plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below 30 ng/mL. Results Of 7,807 individuals, 782 (10.1%) were COVID-19-positive, and 7,025 (89.9%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval [CI] 18.41-19.59) vs . 20.55 (95% CI 20.32-20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24-2.01, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI 1.01-4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI 1.08-1.95, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI 0.98-4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19. Conclusion Low plasma 25(OH)D level appears to be an independent risk factor for COVID-19 infection and hospitalization. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Funding Source: COVID-19 Data Sciences Institute (DSI) grant (for M.F-M.). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical considerations: This is a data-based study, and as such, has no clinical trial registration number. The study received approval from the Leumit Health Services research committee and the Shamir Medical Centre IRB. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes This is a data-based study, and as such, has no clinical trial registration number. The study received approval from the Leumit Health Services research committee and the Shamir Medical Centre IRB.