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

Plasma 25(OH)D levels < 75 nmol/L appear to be an independent risk factor for COVID-19 infection and hospitalization in an Israeli population.

• The proportion of infected individuals was 10.02% (782/7807) for COVID-19-positive and 7025 (89.98%) for COVID-19-negative. The COVID-19-positive group was younger  and more male (mean age, 35.58 years; 49.23% male) than the COVID-19-negative     group (47.35 years; 40.56% male; P <0.001 for both).
• The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 (47.4 nmol/L vs. 51.3 nmol/L).
• Single variable analysis of the data showed an association between a low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (P < 0.001), and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (P < 0.05).
• When this 25(OH)D data was reanalyzed to control for demographic variables, and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (P < 0.001)] and of hospitalization due to the SARS-CoV-2 virus [1.95 (P = 0.061)] were preserved.
• Age over 50 years, male gender and low–medium socioeconomic status were

associated with the risk of COVID-19 infection; age over 50 years was also associated       with the likelihood of hospitalization due to COVID-19.

The study population included the 14,022 members of Leumit Health Services (Israel), aged 2 months to 103 years who were tested for COVID-19 infection during the study period and who had at least one previous blood test for the plasma 25(OH)D level. After excluding individuals without data on plasma 25(OH)D levels, the study sample was composed of 7807 individuals.

• The major weakness of the study is its retrospective database design. A retrospective study’s inherent limitation makes it impossible to infer causality in the association between vitamin D status and the risk of COVID-19.
• A possible selection bias arises in that vitamin D levels were not tested population-wide but instead testing depended on the symptoms or health conditions of individual subjects.
• More studies are required to assess the effects of vitamin D3 supplements on the risk of hospitalizations due to COVID-19 infection.

Plasma 25(OH)D levels < 75 nmol/L are associated with COVID-19 hospitalization as a risk factor, particularly, for patients testing positive for COVID-19, after adjusting for age, gender, socioeconomic factors and chronic, mental and physical disorders. A serum 25(OH)D level < 75 nmol/L was also identified as independently associated with the likelihood of COVID-19 infection.

• This was a population-based study utilizing data from the Leumit Health Services database, a large health maintenance organization in Israel that provides services to around 730,000 members nationwide. The comprehensive computerized database is continuously updated with regard to demographics, medical visits, laboratory tests and hospitalizations.
• Data of each subject were collected from the database and included age, gender, socioeconomic status, weight, height, BMI, current smoking status, psychiatric and somatic comorbidities, and hospitalizations as a result of the COVID-19 infection.
• All the somatic and psychiatric diagnoses were based on the International Classification of Disease, Tenth Revision codes and included, chronic lung disorders (asthma, chronic obstructive pulmonary disease), diabetes, hypertension, depressive and anxiety disorders, schizophrenia and dementia.
• Obesity was considered as BMI ³ 30m²/kg.
• Optimal 25(OH)D levels defined by the Endocrine Society, National Osteoporosis

Foundation and International Osteoporosis Foundation were used. Plasma 25(OH)D levels < 75 nmol/L were considered as suboptimal and referred as ‘low’ in this study.

Merzon E, Tworowski D, Gorohovski A, Vinker S, Golan Cohen A, Green I, Frenkel-Morgenstern M. Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study. FEBS J. 2020 Sep;287(17):3693-3702. doi: 10.1111/febs.15495. Epub 2020 Aug 28. PMID: 32700398; PMCID: PMC7404739.