A major randomized trial led by Mass General Brigham found that a four-week course of high-dose vitamin D3 started soon after a positive COVID-19 test did not reduce acute illness severity, healthcare visits or deaths, and did not curb household spread. But in an analysis limited to participants who consistently took the assigned pills, researchers observed a small, borderline statistically significant difference in lingering symptoms reported eight weeks after infection, a finding they say warrants further study.
Findings from a large, randomized trial led by Mass General Brigham suggest vitamin D supplementation is unlikely to meaningfully improve short-term outcomes of COVID-19 when begun shortly after diagnosis, while leaving open the possibility of a modest effect on persistent symptoms in certain analyses.
Trial design and participants
Researchers launched the Vitamin D for COVID-19 (VIVID) Trial to evaluate whether high-dose vitamin D3 could influence outcomes in people recently diagnosed with COVID-19 and in members of their households. The trial enrolled participants in the United States and Mongolia.
In total, 1,747 adults who recently tested positive for COVID-19 and 277 household contacts were randomly assigned to receive either vitamin D3 or placebo daily for four weeks. The dosing protocol was 9,600 IU/day for two days, followed by 3,200 IU/day.
The U.S. portion of the trial ran from December 2020 through September 2022, while the Mongolia portion took place from September 2021 to April 2022. On average, participants began taking vitamin D or placebo about three days after their positive test.
Senior author JoAnn E. Manson, MD, DrPH, is with the Mass General Brigham Department of Medicine. The ScienceDaily release listed Davaasambuu Ganmaa and Kaitlyn A. Cook among the lead authors.
Acute COVID-19 outcomes and household transmission
Over the four-week study period, the researchers reported no meaningful differences between the vitamin D and placebo groups in healthcare utilization or death. In the report, healthcare utilization included hospital stays, clinic visits (in-person or virtual), and emergency room visits. Symptom severity was also described as similar between groups.
The study also found that high-dose vitamin D supplementation did not lower the likelihood that household contacts would become infected with COVID-19.
Long COVID signal in adherence analysis
When the investigators analyzed participants who consistently followed the vitamin D regimen, they observed what they described as a potential signal related to long COVID.
Among those adherent participants, 21% of people taking vitamin D reported at least one lingering symptom eight weeks after infection, compared with 25% in the placebo group. The report characterized this difference as borderline statistically significant.
Manson said: "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." She added that long COVID can include symptoms such as fatigue, shortness of breath, brain fog and other cognitive challenges, and said the team hopes to study whether longer-term vitamin D supplementation may affect long COVID risk and severity in larger populations.
The findings were published in The Journal of Nutrition.
