A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The Vitamin D for COVID-19 Trial

Davaasambuu Ganmaa; Kaitlyn A Cook; Polyna Khudyakov; Dorjbal Enkhjargal; Tsolmon Bilegtsaikhan; Kenneth H Mayer; Allison Clar; Michael Rueschman; Raji Balasubramanian; Aditi Hazra; Howard D Sesso; Valerie E Stone; Patricia Copeland; Georgina Friedenberg; Douglas C Smith; Quanhong Lei; Todd Lee; Emily G McDonald; Tserenkhuu Enkhtsetseg; Erdenebaatar Sumiya; Yansanjav Narankhuu; Myagmarsuren Erdenetuya; Dalkh Tserendagva; Rikard Landberg; Niclas Roxhed; Susanne Rautiainen Lagerström; JoAnn E Manson

doi:10.1016/j.tjnut.2026.101398

A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The Vitamin D for COVID-19 Trial

J Nutr. 2026 Apr;156(4):101398. doi: 10.1016/j.tjnut.2026.101398. Epub 2026 Mar 12.

Authors

Davaasambuu Ganmaa¹, Kaitlyn A Cook², Polyna Khudyakov³, Dorjbal Enkhjargal⁴, Tsolmon Bilegtsaikhan⁵, Kenneth H Mayer⁶, Allison Clar⁷, Michael Rueschman⁸, Raji Balasubramanian⁹, Aditi Hazra⁷, Howard D Sesso¹⁰, Valerie E Stone¹¹, Patricia Copeland⁷, Georgina Friedenberg⁷, Douglas C Smith¹², Quanhong Lei¹³, Todd Lee¹⁴, Emily G McDonald¹⁴, Tserenkhuu Enkhtsetseg¹⁵, Erdenebaatar Sumiya¹⁵, Yansanjav Narankhuu¹⁵, Myagmarsuren Erdenetuya¹⁶, Dalkh Tserendagva¹⁷, Rikard Landberg¹⁸, Niclas Roxhed¹⁹, Susanne Rautiainen Lagerström²⁰, JoAnn E Manson²¹

Affiliations

¹ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Mongolian Health Initiative, Ulaanbaatar, Mongolia.
² Program in Statistical and Data Sciences, Smith College, Northampton, MA, USA.
³ Sage Therapeutics, Cambridge, MA, USA.
⁴ Department of Pharmaceutical Chemistry and Pharmacognosy, School of Pharmacy, Mongolian National University of Medical Science, Ulaanbaatar, Mongolia.
⁵ National Center for Communicable Disease, Ulaanbaatar, Mongolia.
⁶ The Fenway Institute, Fenway Health and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
⁷ Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Department of Biostatistics and Epidemiology, University of Massachusetts, School of Public Health, Amherst, MA, USA.
¹⁰ Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹² Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹³ ADARx Pharmaceuticals Inc., San Diego, CA, USA.
¹⁴ Department of Medicine, McGill University, Montreal, Canada.
¹⁵ Mongolian Health Initiative, Ulaanbaatar, Mongolia.
¹⁶ Department of Clinical Pharmacy and Management, School of Pharmacy, Mongolian National University of Medical Science, Ulaanbaatar, Mongolia.
¹⁷ Department of Internal Medicine, International School of Mongolian Medicine, Mongolian National University of Medical Science, Ulaanbaatar, Mongolia.
¹⁸ Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
¹⁹ Department of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden.
²⁰ Department of Global Public Health, Karolinska Institute, Stockholm, Sweden.
²¹ Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: jmanson@bwh.harvard.edu.

PMID: 41826107
DOI: 10.1016/j.tjnut.2026.101398

Abstract

Background: Data 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.

Objectives: We 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.

Methods: We 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.

Results: Index 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.

Conclusions: Among 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.

Keywords: COVID-19; SARS-CoV-2; clinical trial; long COVID; vitamin D.

Publication types

Randomized Controlled Trial

MeSH terms

Adult
Aged
COVID-19 Drug Treatment*
COVID-19* / epidemiology
COVID-19* / mortality
Cholecalciferol* / administration & dosage
Cholecalciferol* / therapeutic use
Dietary Supplements*
Double-Blind Method
Female
Humans
Male
Middle Aged
SARS-CoV-2
Treatment Outcome
United States / epidemiology
Vitamin D* / administration & dosage
Vitamins / administration & dosage
Vitamins / therapeutic use

Substances

Cholecalciferol
Vitamin D
Vitamins

Associated data

ClinicalTrials.gov/NCT04536298