Less than a week later Open JAMA network published a small study showing that zinc and vitamin C were not associated with improvement in mild COVID-19 infections in 240 people JAMA The study also found that a single dose of vitamin D had no significant effect on moderate to severe COVID-19 infections.
The study, published yesterday by Igor Murai, PhD, a rheumatologist from São Paulo, and colleagues, reported that hospital stay was a median of 7.0 days for both the intervention and placebo groups, and although there were differences of up to 8, 4 percentage points between hospital mortality, admission to the intensive care unit (ICU) and the need for mechanical ventilation, all were not statistically significant.
“When this clinical trial is conducted [in] isolation, the findings may appear ambiguous; that is, the results do not exclude clinically important benefits (or harm) from high doses of vitamin D3 administration in hospitalized patients with moderate to severe COVID-19, “American doctors David Leaf, MD, MMSc and Adit Ginde, MD, MPH, write in a related article JAMA comment.
“However, in conjunction with existing randomized clinical trials of vitamin D administration in patients hospitalized with respiratory infection and critical illness, the results reported by Murai et al do not support routine administration of vitamin D in patients hospitalized with COVID-19 moderate to severe. “
Safe but ineffective supplement
The researchers recruited adult patients in São Paulo who were hospitalized with COVID-19, but did not require mechanical ventilation or ICU admission at the time of registration. From June 2 to August 27, 2020, half of the 240 patients randomly received a single dose of 200,000 international units (IU) of 25-hydroxyvitamin D (25[OH]D) in addition to the standard of care, and the other half received a placebo. Three people were excluded from the final results because they withdrew consent.
The patients were on average 56.2 years old and were randomized at a median of 10.3 days after the onset of symptoms and a median of 1.4 days after hospitalization. The most common comorbidities were obesity (57.8% in the intervention group vs 53.7% in the placebo group), hypertension (56.3% vs 49.2%) and diabetes (41.2% vs 29.7% ).
None of the primary or secondary outcomes reached statistical significance. Hospital mortality was 7.6% in the treatment group and 5.1% in the placebo group (95% confidence interval [CI], -4.1% to 9.2%; FOR = 0.43), admission to the ICU after enrollment was 16.0% vs 21.2% (95% CI, -15.1% to 4.7%; FOR = 0.30), and 7.6% vs 14.4% required mechanical ventilation (95% CI, -15.1% to 1.2%; FOR = 0.09).
For patients requiring mechanical ventilation, there was no significant difference between duration (average of 15.0 days vs 12.8; 95% CI, -8.4 to 12.8; FOR = 0.69).
Before vitamin D doses were administered, the patients’ average vitamin D level was 21.2 nanograms per milliliter (ng / mL) in the intervention group and 20.6 ng / mL in the placebo group – 20 ng / mL is considered healthy. And only about a quarter of all participants were severely disabled (less than 12 ng / mL). While 25 (OH) D levels increased significantly to an average of 44.4 ng / mL in the vitamin D group, Leaf and Ginde point out that this does not measure how much the body was actually able to convert.
The only adverse effect reported was a case of vomiting.
The biggest RCT so far, but still underpowered
At the JAMA Comment, Leaf and Ginde say that while the results appear to show the insignificance of vitamin D for treatment with COVID-19 and is the largest randomized, double-blind, placebo-controlled trial that has evaluated the vitamin published so far, the study had notable design limits, including being insufficient.
“With 208 participants, they would have 80% power to detect a 50% difference in hospital stay, which is a highly unlikely result,” they wrote.
In addition, they write, not only does the study’s focus on moderate to severe patients limit its generalization, but other COVID anti-inflammatory studies have had results highly dependent on the severity of the disease. The lack of vitamin D deficiency may also have impacted the results.
While this does not detract from the researchers’ final conclusions, they write: “Given the lack of highly effective therapies against COVID-19, except perhaps for corticosteroids, it is important to keep an open mind for the results emerging from rigorously conducted vitamin D studies (despite smaller sample sizes and important limitations of some studies). “