A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The Vitamin D for COVID-19 Trial
et al., The Journal of Nutrition, doi:10.1016/j.tjnut.2026.101398, VIVID, NCT04536298, Mar 2026
Vitamin D for COVID-19
8th treatment shown to reduce risk in
October 2020, now with p < 0.00000000001 from 136 studies, recognized in 18 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,400+ studies for
210+ treatments. c19early.org
|
VIVID trial - results were withheld without explanation for over 3 years, until long after the end of the pandemic. There is no scientific or ethical justification for withholding results this long. There are many serious anomolies in the design and analysis:
A combination of insufficient dosage, poorly chosen form for late treatment (cholecalciferol), very poor adherence, (and potentially inferior medication) resulted in minimal increase in vitamin D levels. Supp. Table 7 shows an increase of only 3.7 and 5.1 ng/mL in the treatment groups (and 2.3 ng/mL in the Mongolia placebo group). These increases are over 4 weeks, suggesting very minimal increase in the first few days where treatment could potentially be more beneficial. The trial dosage and form is more typical of a prophylaxis trial, but here is used for very late treatment.
Supp. Figure 3 shows no increase in vitamin D levels over the first two weeks, the minimal increase is all during the last two weeks (US cohort, no weekly data is reported for Mongolia).
Treatment was very late: authors do not report treatment delay but we estimate 5-7 days with the upper quartile likely reaching 8-10+ days. The reported 3-day median (IQR 3-5) from diagnostic test to treatment is a survivor-biased estimate - measured only among the subset who received pills by the day 3 survey, and this excludes the delay from symptoms to testing.
Inclusion was initially only patients within 5 days from the onset of COVID-19 symptoms. This was changed mid-trial to diagnosis within 7 days, i.e., unlimited treatment delay. Further, the trial was changed to enroll asymptomatic patients, include even younger and lower-risk patients, and remove comorbidity/risk factor-related eligibility criteria. Time from symptom onset is the most important factor in COVID-19 treatment. Authors provide breakdowns by 8 different subgroups in Supp. Table 9, yet provide no breakdown by treatment delay, and do not even report the average treatment delay.
Authors frame the changes as required to increase enrollment, however the US trial enrolled its first patient on January 6, 2021, and the change to drop the <5-days from symptoms requirement was submitted on January 15, 2021. It is not possible to know how enrollment would vary, and there are many ways to increase enrollment that do not involve changing the inclusion to make the trial of very limited value. Moreover, testing early intervention in higher risk patients with a smaller trial is many times more valuable than a larger trial testing late intervention with lower risk patients.
Extreme and unwarranted changes to the outcomes were made during the trial - on April 2, 20211, and April 8, 20222. Several original outcomes are not reported at all.
ICU admission - completely missing
Ventilator/ventilation support - completely missing
Time to hospitalization/death - completely missing
Hospitalization or death (original primary endpoint) - only appears in adverse events, and not COVID-19 specific.
Ventilator/ventilation support - completely missing
Time to hospitalization/death - completely missing
Hospitalization or death (original primary endpoint) - only appears in adverse events, and not COVID-19 specific.
Subgroup analysis points to potential benefit for:
- higher risk patients ≥40 - OR 0.82 [0.57-1.18]
- patients not already on vitamin D treatment - OR 0.86 [0.64-1.15]
- Mongolia (higher adherence) - OR 0.93 [0.67-1.29]
- patients not already on vitamin D treatment - OR 0.86 [0.64-1.15]
- Mongolia (higher adherence) - OR 0.93 [0.67-1.29]
The authors' insitutions - Mass General Brigham (MGB) and Harvard-affiliated hospitals did not administer vitamin D for their COVID-19 patients, providing an incentive for results to not show significant benefit, which would confirm moral and reputational liability for harm. Organizations typically do not admit to their decisions resulting in significantly higher mortality.
Patients were very low-risk patients (zero mortality).
Health care utilization included virtual visits and routine care which may have very limited relation to COVID-19 severity.
There was an 8-fold higher hospitalization rate in Mongolia compared with the US despite the US cohort having higher baseline symptom severity, suggesting that "hospitalization" is measuring something fundamentally different between the countries.
Funding for the trial was anonymous. ICMJE guidelines state that authors should disclose all sources of support. Anonymous funding of clinical trials is unusual and raises questions because it prevents readers from assessing potential financial conflicts. Funding may have been affiliated with pharmaceutical interests (which would likely prefer to be anonymous).
Adherence was extremely low in the US - 67% compared with 95% in Mongolia.
Adherence was significantly higher for patients already on vitamin D treatment - OR 1.63 [1.26-2.10], Supp. Table 6.
Patients already on vitamin D treatment were significantly more likely to contribute results - OR 2.01 [1.49-2.70], Supp. Table 4.
Patients in Mongolia were much more likely to contribute results - OR 40.8 [19-87], Supp. Table 4.
Vitamin D patients had higher adherence and reporting in all breakdowns (4 independent groups for adherence, Supp. Table 5 and 1 for reporting, Supp. Table 4). While not statistically significant, there is the possibility that placebo blinding was imperfect.
Cholecalciferol was used in this study.
Meta-analysis shows that late stage treatment with calcitriol / calcifediol (or
paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 66% [47‑78%] lower risk vs. 43% [32‑52%] lower risk.
Cholecalciferol requires two hydroxylation steps to become activated - first
in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol,
paricalcitol, and alfacalcidol are active vitamin D analogs that do not
require conversion. This allows them to have more rapid onset of action
compared to cholecalciferol. The time delay for cholecalciferol to increase
serum calcifediol levels can be 2-3 days, and the delay for converting
calcifediol to active calcitriol can be up to 7 days.
This is the 41st COVID-19 RCT for vitamin D, which collectively show efficacy with p=0.00000049.
This is the 136th COVID-19 controlled study for vitamin D, which collectively show efficacy with p<0.0000000001.
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HCU, 4.0% lower, OR 0.96, p = 0.76, treatment 863, control 884, COVID-19 related HCU, RR approximated with OR.
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HCU, 3.0% lower, OR 0.97, p = 0.79, treatment 863, control 884, all-cause HCU, RR approximated with OR.
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risk of long COVID, 17.0% lower, OR 0.83, p = 0.24, treatment 863, control 884, RR approximated with OR.
|
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risk of transmission, 71.0% higher, OR 1.71, p = 0.21, treatment 139, control 138, RR approximated with OR.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Ganmaa et al., 12 Mar 2026, Double Blind Randomized Controlled Trial, placebo-controlled, multiple countries, peer-reviewed, 27 authors, study period 29 December, 2020 - 1 July, 2022, trial NCT04536298 (history) (VIVID).
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