Vitamin D and Long COVID Insights: JoAnn E. Manson, MD, MPH, DrPH

An unintended finding arose from the Vitamin D for COVID-19 (VIVID; NCT04536298) trial; although not statistically significant, vitamin D supplementation may reduce long COVID severity and prevalence of symptoms at 8 weeks, according to a recent study published in The Journal of Nutrition.¹

In this Q&A with The American Journal of Managed Care^® (AJMC^®), study author JoAnn E. Manson, MD, MPH, DrPH, Michael and Lee Bell Professor of Women’s Health at Harvard Medical School, and endocrinologist and epidemiologist at Brigham and Women’s Hospital, explained the potential implications of these findings.

This transcript was lightly edited for clarity.

AJMC: To what extent might the timing of vitamin D initiation have influenced the results, and do you think earlier intervention could yield different clinical effects?

Manson: For logistical reasons, it really wasn't possible to start the vitamin D prior to a diagnosis of COVID-19, so the enrollment was that those who were diagnosed with COVID-19 were started on the vitamin D supplements as soon as possible. On average, it was within about 3 days of the diagnosis that they were taking the vitamin D supplements.

There were a lot of challenges doing a trial of this nature, entirely remotely during the pandemic. If it had been possible to treat prior to diagnosis, to have done a much larger trial, and have had the funding for a large-scale trial where vitamin D would be on board in higher amounts than most people take prior to the infection and diagnosis, that would have been optimal. That is the type of trial that we ideally would have done, but with the funding available and the logistics necessary to be treating after the diagnosis of COVID was made, I think that timing was relevant to not being able to see a clear benefit on the acute infection and the development of symptoms from the active infection.

But with 4 weeks of treatment again, there was a promising signal for reduction in long COVID 8 weeks later.

AJMC: Did baseline vitamin D status play a meaningful role in treatment response, and would a more targeted study in patients with significant deficiency be warranted?

Manson: We did have about 40 to 50% of the study population with what would be considered lower levels, and we didn't see a clear difference in results among those with lower levels and those with clearly sufficient levels. But that may be because the trial wasn't large enough. We had about 1700 participants. In this portion of the trial, it was large enough to look at many of the questions, but not really to stratify by lower baseline levels, really low baseline levels of vitamin D, generally for infections. We have seen that those with very low baseline levels tend to do better with vitamin D supplements than those who already have sufficient levels. But overall, in the study population, the vitamin D blood level was only borderline low. It wasn't at the point of profound deficiency in many participants.

AJMC: The study observed a signal toward reduced long COVID that did not reach statistical significance. How should clinicians and researchers interpret this finding?

Manson: I think, in the context of other evidence about vitamin D tamping down inflammation and reduction, we've seen a major biomarker for inflammation. The C-reactive protein, we've seen that in the VITamin D and OmegA3 trial (VITAL; NCT01169259). This effect on tamping down inflammation and also reducing the risk of autoimmune diseases, vitamin D probably does have some benefit for reducing long COVID, but we need a larger randomized and definitive trial to really test this hypothesis. But the results are promising enough, based on the totality of evidence on the benefits of vitamin D supplements, the findings in this trial, although not quite reaching, but very close to reaching statistical significance, and what we know about the safety of vitamin D supplements. This is a very safe supplement to take.

In the VITAL trial, we tested it for 5 years with few, if any, adverse events, and taking everything into account, it would be reasonable to recommend to patients to increase intake of vitamin D, especially during the winter months, when vitamin D blood levels tend to be lower because of less exposure to ultraviolet light and less synthesis of vitamin D in the skin, and also the risk of infections. Upper respiratory infections are more common during the late fall and winter seasons, and that would be a time to encourage patients to get more vitamin D from reading nutrition labels, eating fortified foods, and also very seriously considering taking a supplement of at least 2000 international units (IU) a day because we have long-term data on the safety of 2000 IUs a day and having then a higher vitamin D blood level at the time there may be exposure to these viruses and these infections; likely deriving more benefit than when starting a vitamin D supplement after a diagnosis of a viral infection.

AJMC: How generalizable are these findings across diverse populations and care settings, especially given the study’s inclusion of participants from different geographic regions?

Manson: We did have a diverse study population in terms of geography. We had participants in both the United States, nationwide, as well as in Mongolia, where there tends to be a higher prevalence of vitamin D deficiency—lower blood levels of vitamin D—in that country. We also had racial and ethnic diversity in the cohort.

We think that the findings are likely to be generalizable across countries and races and ethnicities. However, obviously, larger randomized trials would be needed to prove conclusively that all the different groups had similar benefits or similar results from vitamin D in terms of COVID severity of symptoms and long COVID development.

AJMC: Looking ahead, what would an ideal follow-up trial look like to better assess vitamin D’s potential role in preventing long COVID or improving longer-term outcomes?

Manson: The ideal trial would be a vitamin D supplementation prior to infection, looking at whether having vitamin D on board can lead to less severe symptoms of the acute infection, maybe even reduce the incidence of COVID and other viral infections, and also whether the vitamin D supplementation taken prior to the acute illness could also lower the risk of developing long COVID.

That would be the ideal randomized trial. We would like to receive funding for such a large trial. We're looking into various options for funding such a trial. But the next best option would be to do a large trial with vitamin D supplementation started at the very beginning of an infection, right after diagnosis, and then look at the effect of vitamin D supplements and reducing severity of symptoms as well as the development of long COVID. That would be more feasible to do when the trial doesn't have to be done remotely, as in the VIVID trial, which was done during the height of the COVID pandemic, so it had to be done remotely.

But if patients can be immediately given the supplements in these doses right after the diagnosis, that would be earlier treatment, and then again, that would be secondary to having the vitamin D on board prior to the infection. The ideal design is having vitamin D supplementation on board prior to the viral infection starting.

Reference

1. Ganmaa D, Cook KA, Khudyakov P, et al. 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;156(4). doi:10.1016/j.tjnut.2026.101398