A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The Vitamin D for COVID-19 Trial, 2026, Ganmaa et al.

[Chandelier]

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

Spoiler: Authors

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

Abstract​

Background​

Data from randomized controlled trials of vitamin D3supplementation in modifying the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are sparse.

Objectives​

We evaluated the effect of vitamin D3supplementation 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 D3loading 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.

Web | DOI | The Journal of Nutrition

 

[Hutan]

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).

An interesting study.

They knew the vitamin D status of the participants at baseline, so they could tell us if baseline deficiency was associated with Long covid at 8 weeks. I don't know if they did, there's a pay wall.

Promising results for long COVID warrant further study.

They do. It would be great if the authors could recognise that Long COVID is a number of different things, and, in any followup study, they report outcomes by different sorts of post-COVID issues.

 

[TiredMathematician]

They knew the vitamin D status of the participants at baseline, so they could tell us if baseline deficiency was associated with Long covid at 8 weeks. I don't know if they did, there's a pay wall.

I have access to the full text, and as far as I can tell, they did not.

 

[Dolphin]

Trial finds vitamin D supplements don’t reduce covid severity but could reduce long COVID risk

Mass General Brigham study results signal a call to do further research into the connection between vitamin D supplementation and long COVID

www.eurekalert.org

News Release 12-Mar-2026

Trial finds vitamin D supplements don’t reduce covid severity but could reduce long COVID risk​

Peer-Reviewed Publication
Mass General Brigham


FacebookXLinkedInWeChatBlueskyMessageWhatsAppEmail

Mass General Brigham study results signal a call to do further research into the connection between vitamin D supplementation and long COVID

In a large, randomized trial, researchers at Mass General Brigham have found that high-dose vitamin D3 did not reduce COVID-19 infection severity, but may impact long COVID outcomes. Results of the study are published in The Journal of Nutrition.

“There’s been tremendous interest in whether vitamin D supplements can be of benefit in COVID, and this is one of the largest and most rigorous randomized trials on the subject,” said senior author JoAnn Manson, MD, DrPH, of the Mass General Brigham Department of Medicine. “While we didn’t find that high-dose vitamin D reduced COVID severity or hospitalizations, we observed a promising signal for long COVID that merits additional research.”

Vitamin D has been hypothesized to boost immune health, but clinical evidence in the context of COVID-19 has been mixed. The Vitamin D for COVID-19 (VIVID) Trial aimed to provide clarity by rigorously evaluating high-dose vitamin D3 supplementation among newly diagnosed COVID-19 patients and their household contacts. Across the United States and Mongolia, 1,747 adults who had recently tested positive for COVID-19 and 277 household contacts were randomized to receive either daily vitamin D3 (9,600 IU/day for two days followed by 3,200 IU/day) or daily placebo for four weeks. The U.S. trial was conducted from December 2020 to September 2022 while the Mongolia trial ran from September 2021 to April 2022. The median time between the participants’ positive COVID-19 tests and the initiation of vitamin D supplementation or placebo was three days.

Alongside Manson, lead authors Davaasambuu Ganmaa, Kaitlyn Cook and team used stratified randomization and statistical weighting to ensure factors that can affect COVID-19 outcomes (including age, sex, body mass index, race/ethnicity and COVID-19 vaccination status) were balanced between the two groups.

The rate of healthcare utilization (including hospitalizations, in-person or virtual clinic visits, and emergency visits) or death did not differ between the vitamin D and placebo groups over a four-week period. Similarly, no significant differences were found in symptom severity. Taking high-dose vitamin D also didn’t reduce the rate at which household contacts contracted COVID-19.

However, an analysis of the participants who adhered to the vitamin D regimen demonstrated a signal that they were less likely to experience long COVID symptoms at eight weeks than those who took placebo pills. In the vitamin D group, 21% reported at least one persistent symptom, compared to 25% in the placebo group, a difference of borderline statistical significance.

“Long COVID, which can include symptoms of fatigue, shortness of breath, brain fog, other cognitive challenges and more, continues to significantly impact people’s lives,” said Manson. “We hope to conduct further research in larger populations on whether long-term vitamin D supplementation reduces the risks and severity of long COVID.”

Authorship: In addition to Manson and Ganmaa, Mass General Brigham authors include Allison Clar, Michael Rueschman, Aditi Hazra, Howard D. Sesso, Valerie E. Stone, Patricia Copeland and Georgina Friedenberg. Additional authors include Cook, Polyna Khudyakov, Dorjbal Enkhjargal, Tsolmon Bilegtsaikhan, Kenneth H. Mayer, Raji Balasubramanian, Douglas C. Smith, Quanhong Lei, Todd Lee, Emily G. McDonald, Tserenkhuu Enkhtsetseg, Erdenebaatar Sumiya, Yansanjav Narankhuu, Myagmarsuren Erdenetuya, Dalkh Tserendagva, Rikard Landberg, Niclas Roxhed and Susanne Rautiainen.

Disclosures: Roxhed is a founder and shareholder of Capitainer AB, a company commercializing the blood collection devices used in this study. All other authors declare no conflicts of interests.

Funding: The study received anonymous foundation support and philanthropic support from Jon Sabes of Minneapolis, Minn. The authors also acknowledge support from the Tishcon Corporation, which donated the vitamin D and placebo study capsules; Takeda; and Capitainer cards. The authors have not declared a specific grant for this research from any funding agency in the public, commercial or nonprofit sectors.

Paper cited: Ganmaa, D., et al. “A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The VIVID Trial.” The Journal of Nutrition. DOI: 10.1016/j.tjnut.2026.101398

###

About Mass General Brigham

Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.

---

Journal​

Journal of Nutrition

DOI​

10.1016/j.tjnut.2026.101398

Method of Research​

Randomized controlled/clinical trial

Subject of Research​

People

Article Title​

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

Article Publication Date​

12-Mar-2026

COI Statement​

Roxhed is a founder and shareholder of Capitainer AB, a company commercializing the blood collection devices used in this study. All other authors declare no conflicts of interests.

 

[rvallee]

4-wk cumulative incidence of healthcare utilization

I don't think I've seen a more bizarre way of assessing anything. Just as bizarre, plenty. More? Nope. Sure, it seems good that it's objective, but that's one way in which an objective endpoint isn't necessarily good.

However, an analysis of the participants who adhered to the vitamin D regimen demonstrated a signal that they were less likely to experience long COVID symptoms at eight weeks than those who took placebo pills. In the vitamin D group, 21% reported at least one persistent symptom, compared to 25% in the placebo group, a difference of borderline statistical significance.

Oddity of "demonstrated a signal" aside, what do we call "borderline statistical significance"? Not significant. Good grief.

 

[rvallee]

This pattern has become too obvious to ignore: whenever a trial is performed on something that is considered benign, it creates too much bias to accept that it doesn't work. It has to be proven to be useless, totally useless beyond any possible doubt, which can't happen, for those involve to not want to hold on to it. Because of the sunk cost, I guess. When people spend years going through such a process, they just can't let go of it if the treatment is assumed to be harmless.

This is the source of the Norwegian government's absurd position that any benign treatment that hasn't been proven to be useless must be tried, just in case. This is completely unsustainable, all it does is pollute the data and cause mass confusion.

And that's considering that the settings in which those things unfold have the gentlest grading curve in history, as long as people aren't offensive or insulting they get a passing grade from participants. So this is two excessive biases acting to create a false blip of "borderline statistical significance". Good grief.

An evidence base made mostly of biasebo. That's just great. The future is so damn weird.