High-dose vitamin D3 does not reduce COVID-19 severity, but may impact long COVID outcomes

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. 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."

JoAnn Manson, MD, DrPH, senior author, Mass General Brigham Department of Medicine

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."