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The Immunomodulatory Activity of High Doses of Vitamin D in Critical Care Patients with Severe SARS-CoV-2 Pneumonia—A Randomized Controlled Trial

A. Gonçalves, Sónia Velho, B. Rodrigues, Maria Lobo Antunes, Miguel Cardoso, Ana Godinho-Santos, João Gonçalves, António Marinho

Nutrients, 2025

207 participants · 4 citations

Abstract

Vitamin D receptor [VDR] expression promotes LL37 expression, possibly contributing to host defense. The hypothesis was that an increase in 25 hydroxyvitamin D [25vitD] could lead to enhanced VDR expression and increased LL-37 production, thereby contributing to improved prognosis in critically ill patients. Methods: A nonblinded, randomized controlled trial was conducted. A total of 207 patients admitted to ICU with severe SARS-CoV-2 pneumonia were included and received different doses of cholecalciferol (500 MU, 3 MU/day, no cholecalciferol) during their ICU and hospital stay. 25vitD levels as well as LL37 and monocytes’ VDR gene expression were evaluated on admission and after. Clinical evolution, ICU mortality, hospital mortality, and 60-day mortality were evaluated. Results: The median age was 57.7 years and the majority of patients were Caucasian [87.4%] and male [70.5%]. There was a significant difference in 25vitD levels between groups on the third [p = 0.002] and seventh [p < 0.001] days. Patients supplemented with 500 MU of cholecalciferol had a very significant increase in monocytes’ VDR gene expression and showed a better clinical evolution in the ICU, with a significant correlation to evolution factors. Higher LL37 on admission had a significant negative association with hospital and ICU mortality, lost after adjustment for comorbidities to a nearly significant association with ICU, hospital, and 60-day mortality. Conclusion: Supplementation with higher doses of…

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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 207 participants or records.

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