Vitamin D flops in moderate-severe COVID

Among patients with moderate to severe COVID-19, there was no difference in length of hospital stay in those who received a single dose of 200,000 IU of vitamin D₃ versus those who received placebo in a randomized trial in Brazil.

The mean length of hospital stay was approximately 7 days for both groups, with no significant differences in secondary outcomes, including in-hospital mortality, admission to the ICU or the need for mechanical ventilation, reported Rosa Pereira, MD, PhD, of the Universidade de Sao Paulo, and colleagues in an online edition of JAMA.

An accompanying editorial by David Leaf, MD, of Brigham and Women’s Hospital in Boston, and Adit Ginde, MD, MPH, of the University of Colorado School of Medicine at Aurora, noted that previous research showed that lower levels of vitamin D were independently associated with worse outcomes in patients with acute disease, but also that vitamin D supplementation as treatment had no impact on clinical outcomes.

Leaf and Ginde said COVID-19 has sparked renewed interest in vitamin D, adding that this study was “the largest published randomized, double-blind, placebo-controlled trial of vitamin D₃ management among hospitalized patients with COVID-19 to date. “

While the findings taken in isolation “may seem ambiguous” and show no evidence of benefit for patients with moderate to severe disease, they said, perhaps the door shouldn’t be closed completely.

“It is important to keep an open mind to the emerging results of rigorously conducted vitamin D studies (despite smaller sample sizes and significant limitations of some studies),” they wrote, adding that the study did not target outpatients with Mild COVID-19 or the use of vitamin D as prophylaxis against the disease.

Pereira and his colleagues examined data from moderate to severe COVID-19 hospitalized patients at two sites in Sao Paulo from June to August 2020, with the final follow-up in October. Participants were eligible if they were adults who tested positive for SARS-CoV-2 by PCR or had a CT scan finding “consistent with disease” as well as a “diagnosis of influenza syndrome with hospitalization criteria.” The primary outcome was the length of hospital stay, defined as the date of randomization until discharge from hospital.

In total, 240 patients were randomized: 120 to a single oral dose of 200,000 IU of vitamin D and 120 to a placebo. Of these, 237 were included in the primary analysis. The mean age of the participants was 56 years, approximately 44% were women, and the mean reference level of 25-hydroxyvitamin D was 20.9. The intervention was applied after a mean of 10.3 days from the onset of symptoms.

The adjusted hazard ratio for hospital discharge was 0.99 (95% CI 0.71-1.37, P= 0.94). There were also non-significant differences between the intervention and placebo groups in secondary outcomes, including in-hospital mortality (7.6% vs 5.1%, respectively, P= 0.43), ICU admission (16.0% vs 21.2%, P= 0.30) and need for mechanical ventilation (7.6% vs 14.4%, P= 0.09).

In the intervention group, 86.7% achieved 25-hydroxyvitamin D sufficiency versus 10.9% in the placebo group, meaning that “the current null findings cannot be attributed to failure to increase serum levels of 25-hydroxyvitamin D “.

The investigators observed no adverse events, except for a single vomiting episode related to the intervention. They also found no significant differences between the groups in health-related laboratory markers after the intervention.

Data limitations included that a minimal clinically important difference in length of hospital stay between COVID-19 patients has yet to be determined, as well as small and heterogeneous sample size, with different patients with coexisting diseases in different medication regimens.

Leaf and Ginde noted that 30 studies on vitamin D interventions in COVID-19 are currently listed on ClinicalTrials.gov, globally and across the spectrum of diseases. However, they suggested that many of these studies may be “underpowered or not achieving target enrollment,” based on experience during the pandemic.