Monaz: Hello, I'm Monaz Mehta, editor in the Cochrane Editorial and Methods department. Cochrane is producing a series of reviews to help decision makers respond to the COVID-19 pandemic. In May 2021, we published the first version of a living systematic review on the effects of vitamin D supplementation and, in this podcast, Vanessa Piechotta talks to the first author and her colleague at the University Hospital in Cologne Germany, Julia Stroehlein, about the potential effects of vitamin D and the evidence they've found. 

Vanessa: Hi Julia, thanks for being here with us today. Could you begin by telling us about the background to your review, and why people think that vitamin D supplementation might have a positive effect for people with COVID-19?

Julia: Hi Vanessa, it's good to be here. Vitamin D is important for several mechanisms in our body that are often affected by COVID-19, including our heart and blood vessels, lungs and airways and, perhaps most importantly, our immune system. Over the last year, several studies have suggested that many patients with severe COVID-19 had vitamin D deficiency, which led to the question of whether vitamin D has a role in the disease. However, risk factors for developing severe COVID-19 also strongly overlap with those for vitamin D deficiency, such as obesity. This makes it difficult to tell if vitamin D deficiency itself is actually a risk factor for severe COVID-19, and means that we need studies in which vitamin D supplementation is given to patients to see if this would prevent progression to severe disease or support their recovery. 

Vanessa: That sounds great in theory, so why is it important to review its effectiveness and why are you using a living systematic review approach to do this?

Julia: Yes, you're right, in theory it sounds great, but it has to be proven by evidence from randomised trials, which is what we're looking for. The review is also important because although vitamin D is thought to be generally safe, excess supplementation can lead to toxic levels, which, in rare cases, can cause kidney failure or, even, death.
We're using this living approach in the review to keep up with the currency of the evidence, because in the context of the pandemic, new evidence is continuously emerging.

Vanessa: So, let's move to that evidence, what were you able to include in the May 2021 version of the review?

Julia: At the moment, we're able to include 3 randomised trials, reporting on 356 participants, not all of whom were vitamin D deficient at baseline. Two of the studies looked at patients with moderate or severe disease, requiring hospitalization, and one study looked at patients with mild disease. 
All the studies compared vitamin D supplementation to placebo or standard care alone, but each used different forms and doses of vitamin D. 

Vanessa: Now, what can these studies tell us about its effectiveness for people with COVID-19?

Julia: For patients with moderate to severe COVID-19, we included data from two studies and 313 participants and the evidence was inconclusive on whether or whether not vitamin D supplementation has any effect on all-cause mortality by the time of hospital discharge or whether it prevents clinical worsening considering the need for invasive mechanical ventilation.
In regard to mild disease, the single study that we identified did not report any of our outcomes of interest. 

Vanessa: What about the safety aspects? What evidence could you find about any unwanted events?

Julia: Only one study, which was the largest we included with nearly 240 participants, reported adverse events. This found that one person in the vitamin D group experienced an event (which was vomiting), and there were no adverse events in the control group. However, this sample is far too small to draw any reliable conclusions so, on the basis of the current evidence, we do not know whether vitamin D supplementation is associated with a higher risk of harms.

Vanessa: Thanks. In summary, what's your conclusion and what are your next steps?

Julia: The take home message for the moment needs to be that the information from the currently available studies is inconclusive and we are uncertain about whether vitamin D supplementation is an effective and safe treatment for people with COVID-19. Looking to the future, we know of at least 21 ongoing studies, and three more have completed but not yet published their results. These studies might resolve some of the uncertainties and we plan to update the review when the cumulating evidence will allow us to derive more certain conclusions. 

Vanessa: Finally, Julia, if people would like to read the review, how can they get hold of it?

Julia: It's available online from www Cochrane Library dot com. Typing 'vitamin D and COVID-19' in the search box will bring up a link to the review.