Serum 25(OH)D Level on Hospital Admission Associated With COVID-19 Stage and Mortality

Dieter De Smet, MD; Kristof De Smet, MD; Pauline Herroelen, MSc; Stefaan Gryspeerdt, MD; Geert A. Martens, MD, PhD


Am J Clin Pathol. 2021;155(3):381-388. 

In This Article

Abstract and Introduction


Objectives: Vitamin D deficiency was previously correlated with incidence and severity of coronavirus disease 2019 (COVID-19). We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) level on admission and radiologic stage and outcome of COVID-19 pneumonia.

Methods: A retrospective observational trial was done on 186 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–infected individuals hospitalized from March 1, 2020, to April 7, 2020, with combined chest computed tomography (CT) and 25(OH)D measurement on admission. Multivariate regression analysis was performed to study if vitamin D deficiency (25(OH)D <20 ng/mL) correlates with survival independently of confounding comorbidities.

Results: Of the patients with COVID-19, 59% were vitamin D deficient on admission: 47% of females and 67% of males. In particular, male patients with COVID-19 showed progressively lower 25(OH)D with advancing radiologic stage, with deficiency rates increasing from 55% in stage 1 to 74% in stage 3. Vitamin D deficiency on admission was not confounded by age, ethnicity, chronic lung disease, coronary artery disease/hypertension, or diabetes and was associated with mortality (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.30–11.55), independent of age (OR, 1.09; 95% CI, 1.03–1.14), chronic lung disease (OR, 3.61; 95% CI, 1.18–11.09), and extent of lung damage expressed by chest CT severity score (OR, 1.12; 95% CI, 1.01–1.25).

Conclusions: Low 25(OH)D levels on admission are associated with COVID-19 disease stage and mortality.


In a subset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, excessive recruitment of proinflammatory cells and cytokine release contribute to alveolar and endothelial damage, triggering a vicious cycle that evolves toward severe coronavirus disease 2019 (COVID-19).[1,2] Beside its role in calcium metabolism, 1,25-dihydroxyvitamin D is a pleiotropic regulator of the immune system.[3–5] It stimulates the expression of cathelicidins and β-defensins in respiratory epithelia as a barrier to pathogen invasion.[6,7] It acts as a protolerogenic and anti-inflammatory cytokine by inhibiting T helper 1 (Th1) proliferation and switching Th1 CD4 T cells and M1-polarized macrophages toward a type II immunity. Vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] <20 ng/mL) has been associated with increased incidence of acute viral respiratory infections and asthma exacerbations.[8,9] Data are rapidly emerging that vitamin D–deficient individuals have a higher relative risk of testing positive for SARS-CoV-2 infection[10–13] than vitamin D–sufficient people or that indicate an association between low 25(OH)D levels and clinical severity of COVID-19 pneumonia.[11,14–18] More than a billion people worldwide are vitamin D deficient,[19] with variations between sexes, ethnicities, social groups, and geographies that appear to correlate with differences in incidence and outcome of COVID-19 lung disease. Here, we investigated serum 25(OH)D levels in 186 consecutive individuals hospitalized for severe SARS-CoV-2 infection as function of radiologic stage of COVID-19 pneumonia. We studied the association between 25(OH)D status on admission and COVID-19 mortality and its possible confounding by age, sex, and known vitamin D–impacted comorbidities such as diabetes, chronic lung disease, and coronary artery disease.