Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics
Authors: De Smet D. , De Smet K. , Herroelen P. , Gryspeerdt S. , Martens G.A. 
Published: May 2020

Structured abstractImportanceVitamin D deficiency increases the incidence of respiratory virus infections. More than 1 billion people worldwide are vitamin D deficient. If vitamin D deficiency is associated to incidence or severity of SARS-CoV-2 infection, a global call could be made for vitamin D supplementation to mitigate the pandemic.Objectiveto determine if lower serum 25-hydroxyvitamin D (25(OH)D) levels are correlated to the risk for COVID-19 and its severity as measured by CTDesignsingle-center observational studySettingAZ Delta general hospitalParticipants186 consecutive patients with PCR-confirmed SARS-CoV-2 infection hospitalized for COVID-19 from March 1, 2020 to April 7, 2020Main outcome and measurescomparative analysis of 25(OH)D levels in patients hospitalized for COVID-19 at various radiological stages and a season/age/sex-matched diseased control populationResultswe report on 186 SARS-CoV-2 infected patients requiring hospitalization for severe COVID-19: 109 males (median age 68 years, IQR 53–79 years) and 77 females (median age 71 years, IQR 65–74 years). At admission patients were screened by CT to determine temporal changes of COVID-19 lung disease and classified as stage 1 (ground glass opacities), 2 (crazy paving pattern) and 3 (consolidation). At intake, 25(OH)D levels were measured and compared to a season-matched population of 2717 diseased controls, consisting of 999 males (median age 69 years, IQR 53–81 years) and 1718 females (median age 68 years, IQR 43–83 years). Male and female COVID-19 patients combined showed lower median 25(OH)D than controls (18.6 ng/mL, IQR 12.6–25.3, versus 21.5 ng/mL, IQR 13.9–30.8; P=0.0016) and a higher fraction of vitamin D deficiency (58.6% versus 45.2%, P=0.0005). A strong sexual dimorphism was found: female patients had comparable vitamin D status as control females. Male COVID-19 patients, however, showed markedly higher percentage of vitamin D deficiency than controls (67.0% versus 49.2%, P=0.0006) and this effect was more pronounced with advanced radiological stage ranging from 55.2% in stage 1 to 74% in stage 3.Conclusions and relevancevitamin D deficiency is a possible risk factor for severe SARS-CoV-2 infection in males. Vitamin D supplementation might be an inexpensive, accessible and safe mitigation for the SARS-CoV-2 pandemic.Key pointsQuestion: does vitamin D deficiency predispose to severity of SARS-CoV-2 infection?Findings: in this observational study on 186 consecutive patients hospitalized with PCR-confirmed SARS-CoV-2 infection, we find that patients with severe COVID-19 show lower median serum 25(OH)D and a higher percentage of vitamin D deficiency at intake than a season/age-matched reference population. The correlation between vitamin D deficiency and the need for hospitalization due to COVID-19 was only seen in male patients. In males but not females, the percentage of vitamin D deficient patients also increased with more advanced COVID-19 disease stage as measured by CT.Meaning: our data indicate a strong statistical correlation between the degree of vitamin D deficiency and severity of COVID-19 lung disease. With more than 1 billion people worldwide affected by vitamin D deficiency, vitamin D supplementation might be a lifesaving, inexpensive, accessible and safe component of primary prevention during the SARS-CoV-2 pandemic and beyond