The results of a study by researchers at Tehran University of Medical Sciences, and Boston University Medical Center, suggest that improving vitamin D status in the general population, and in particular in patients hospitalized with COVID-19, could help to reduce the severity of COVID-19 disease and associated deaths. The study, reported in PLOS ONE, found that hospitalized COVID-19 patients who had sufficient vitamin D—i.e., they had blood levels of 25-hydroxyvitamin D of at least 30 ng/mL—had a significantly lower risk of adverse clinical outcomes, including becoming unconscious, hypoxia, and death, than patients who were vitamin D deficient.

In addition, patients who were vitamin D sufficient had lower blood levels of the inflammatory marker C-reactive protein, and higher blood lymphocyte levels. “This study provides direct evidence that vitamin D sufficiency can reduce the complications, including the cytokine storm (release of too many proteins into the blood too quickly) and ultimately death from COVID-19,” commented Michael F. Holick, PhD, MD, professor of medicine, physiology and biophysics and molecular medicine at Boston University School of Medicine.

Holick is corresponding author of the investigators’ published paper, which is titled “Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection.”

The SARS-CoV-2 coronavirus causes respiratory and systemic disease that ranges in severity from mild respiratory symptoms to severe lung injury, multi-organ failure, and death. The total number of confirmed cases in Iran, by May 20, 2020, was 126,949, with 7,183 deaths, equivalent to 86 deaths per 1M population, the authors wrote.

Vitamin D [1,25-dihydroxyvitamin D; 1,25(OH)2D] has been shown to have immunomodulatory activity, and it has previously been suggested that the vitamin could have a protective effect against COVID-19, the authors noted. Vitamin D interaction with its receptor in immune cells modulates the innate and acquired immune systems in response to invasion of bacterial and viral pathogens. Vitamin D also modulates the renin-angiotensin pathway and downregulates ACE2. “Therefore, vitamin D might help in treatment of COVID-19 by preventing the cytokine storm and subsequent ARDS [acute respiratory distress syndrome] which is commonly the cause of mortality,” the authors commented.

The team noted that while Iran is a sunny country, the prevalence of vitamin D deficiency is high, especially in older people who present with more severe clinical manifestations after exposure to SARS-CoV-2. The researchers hypothesized that vitamin D sufficiency might reduce the risk of severe COVID-19 and adverse clinical outcomes, including death associated with COVID-19 infection.

For their study, they analyzed data from 235 hospitalized patients with COVID-19. Vitamin D status was assessed by taking a blood test to measure serum levels of 25-hydroxyvitamin D. The patients were followed for clinical outcomes, including clinical severity of infection, becoming unconscious, difficulty in breathing resulting in hypoxia, and death. Patient blood was also analyzed for C-reactive protein and for lymphocyte count.

The researchers compared all of these parameters in patients who were vitamin D deficient, to those who were vitamin D sufficient. The results found that among patients who were older than 40 years, those who were vitamin D sufficient were 51.5% less likely to die from the infection compared with patients who were vitamin D deficient, or insufficient, with a 25-hydroxyvitamin D blood level of less than 30 ng/mL. “Only 9.7% of patients older than 40 years who were vitamin D sufficient succumbed to the infection compared to 20% who had a circulating level of 25(OH)D< 30 ng/mL,” the scientists noted. Vitamin D sufficiency was also linked with much lower serum CRP levels, and increased lymphocyte numbers.

“The present study revealed an independent association between vitamin D sufficiency [25(OH)D ≥30 ng/mL] and decreased risk of adverse clinical outcomes from COVID-19,” they further stated. “After adjusting for confounding factors, there was a significant association between vitamin D sufficiency and reduction in clinical severity, inpatient mortality serum levels of C-reactive protein (CRP), and an increase in lymphocyte percentage.”

The team suggested that the significant reduction in serum CRP, together with increased lymphocytes percentage, indicate that vitamin D sufficiency also may help to modulate the immune response, possibly by reducing risk for cytokine storm in response to the SARS-CoV-2 viral infection. “This beneficial effect on the immune system may also reduce the risk of acquiring this insidious potentially life-threatening viral infection,” they wrote.

Holick previously published a study suggesting that a sufficient amount of vitamin D can reduce the risk of catching coronavirus by 54%, and he believes that being vitamin D sufficient helps to fight the consequences from being infected not only with the coronavirus, but also other viruses that cause upper respiratory tract illnesses, including influenza. “There is great concern that the combination of influenza infection and a coronal viral infection could substantially increase hospitalizations and death due to complications from these viral infections,” he said.

The investigators are recommending that additional, controlled studies should be carried out to evaluate the role of vitamin D status on the risk of developing COVID-19 infection and mitigating complications and mortality in those with SARS-CoV-2 infection. They acknowledge that just how high a blood level of vitamin D is needed for optimum immune system effects isn’t known—“it remains debatable as to what the optimum serum level of 25(OH)D should be for maximizing its effect on the immune system.” Nevertheless, they concluded, “… based on the available literature and results from this study it is reasonable to recommend vitamin D supplementation, along the guidelines recommended by the Endocrine Society to achieve a blood level of 25(OH)D of at least 30/mL, to children and adults to potentially reduce risk of acquiring the infection and for all COVID-19 patients especially those being admitted into the hospital.”

According to Holick, the newly reported study provides a simple and cost-effective strategy to improve the body’s ability to fight the coronavirus and reduce the adverse clinical outcomes of COVID-19, including requiring ventilator support, and overactive immune response leading to cytokine storm and death. “Because vitamin D deficiency and insufficiency is so widespread in children and adults in the United States and worldwide, especially in the winter months, it is prudent for everyone to take a vitamin D supplement to reduce the risk of being infected and having complications from COVID-19,” he stated.

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