A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The Vitamin D for COVID-19 Trial
Journal article, 2026
AbstractBackgroundData from randomized controlled trials of vitamin D3 supplementation in modifying the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are sparse.ObjectivesWe evaluated the effect of vitamin D3 supplementation on healthcare utilization and other clinical outcomes among adults with coronavirus disease 2019 (COVID-19) and their close contacts.MethodsWe conducted a parallel 2-group randomized controlled double-blinded trial targeting free-living adults in the United States and Mongolia. Index participants with newly diagnosed COVID-19 were cluster-randomized with up to one of their cohabiting contacts either to an oral vitamin D3 loading dose of 9600 IU/d for 2 d followed by 3200 IU/d for 4 wk or to placebo. Participants completed weekly questionnaires on healthcare utilization, disease severity, and long COVID (index participants) or new SARS-CoV-2 infection (household contacts). The primary outcome was ≥1 healthcare visits (including hospitalization) or death within 4 wk among the index participants.ResultsIndex participants (n = 1747) were a median of 38.0 y old (IQR: 31.1–47.0), 65.6% female/other sex, 4.2% Black non-Hispanic, 4.8% Hispanic/Latinx, 43.2% Asian, 44.3% non-Hispanic White, and 44.9% vitamin D deficient or insufficient (25-hydroxyvitamin D3 <20 ng/mL). Baseline characteristics for the household contacts (n = 277) were similar. The 4-wk cumulative incidence of healthcare utilization in index participants did not significantly differ between the vitamin D3 (n = 863) and placebo (n = 884) groups [cumulative incidences, 0.28 compared with 0.29; odds ratio (OR), 0.97; 95% confidence interval (CI): 0.75, 1.24]. Similar nonsignificant results were observed for the prespecified secondary treatment and prevention outcomes, though per-protocol analyses showed a nonsignificant trend toward benefit of vitamin D3 on the prevalence of long COVID at 8 wk (OR, 0.78; 95% CI: 0.59, 1.03). No safety concerns were identified.ConclusionsAmong adults with newly diagnosed SARS-CoV-2 infections, vitamin D3 supplementation did not significantly change the 4-wk cumulative incidence of healthcare utilization or COVID-19-related outcomes compared with placebo. Promising results for long COVID warrant further study.This study was registered at clinicaltrials.gov as NCT04536298. First registered on 1 September, 2020.
vitamin D
long COVID
SARS-CoV-2
COVID-19
clinical trial
Author
Davaasambuu Ganmaa
Channing Division of Network Medicine
Harvard School of Public Health
Mongolian Health Initiative
Kaitlyn A. Cook
Smith College
Polyna Khudyakov
Sage Therapeutics, Inc.
Dorjbal Enkhjargal
Mongolian National University of Medical Sciences
Tsolmon Bilegtsaikhan
National Center for Communicable Diseases
Kenneth H. Mayer
Harvard Medical School
Allison Clar
Harvard Medical School
Michael Rueschman
Harvard Medical School
Raji Balasubramanian
University of Massachusetts
Aditi Hazra
Harvard Medical School
Howard D. Sesso
Harvard School of Public Health
Harvard Medical School
Valerie E. Stone
Harvard Medical School
Patricia Copeland
Harvard Medical School
Georgina Friedenberg
Harvard Medical School
Douglas C. Smith
Cedars-Sinai Medical Center
Quanhong Lei
ADARx Pharmaceuticals
Todd Lee
McGill University
Emily G. McDonald
McGill University
Tserenkhuu Enkhtsetseg
Mongolian Health Initiative
Erdenebaatar Sumiya
Mongolian Health Initiative
Yansanjav Narankhuu
Mongolian Health Initiative
Myagmarsuren Erdenetuya
Mongolian National University of Medical Sciences
Dalkh Tserendagva
Mongolian National University of Medical Sciences
Rikard Landberg
Chalmers, Life Sciences, Food and Nutrition Science
Niclas Roxhed
Royal Institute of Technology (KTH)
Susanne Rautiainen Lagerström
Karolinska Institutet
Jo Ann E. Manson
Harvard Medical School
Harvard School of Public Health
Journal of Nutrition
0022-3166 (ISSN) 1541-6100 (eISSN)
Vol. 156 4 101398Subject Categories (SSIF 2025)
Public Health, Global Health and Social Medicine
Health Care Service and Management, Health Policy and Services and Health Economy
Infectious Medicine
DOI
10.1016/j.tjnut.2026.101398
PubMed
41826107