Evanston, IL—COVID-19 patients who are severely deficient in vitamin D are twice as likely to experience severe complications, including death, according to research led by Northwestern University. The study, titled The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients, is available on medRxiv, a preprint server for health sciences.

The researchers conducted a statistical analysis of data from hospitals and clinics across China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the UK and the U.S., according to a press release from Northwestern. The analysis revealed that in countries with high COVID-19 mortality rates, including Italy, Spain and the UK, patients had lower vitamin D levels than patients in countries that were not as severely affected by the pandemic.

That said, lead researcher Vadim Backman of Northwestern noted, “While I think it is important for people to know that vitamin D deficiency might play a role in mortality, we don’t need to push vitamin D on everybody. This needs further study, and I hope our work will stimulate interest in this area. The data also may illuminate the mechanism of mortality, which, if proven, could lead to new therapeutic targets.”

According to the release, the researchers decided to study vitamin D levels after observing differences in COVID-19 mortality rates from country to country. There were a variety of hypotheses for the unexplained differences, including differing levels of healthcare quality, age distributions in population, testing rates, or different strains of the coronavirus.

“None of these factors appears to play a significant role,” Backman said in the release. “The healthcare system in northern Italy is one of the best in the world. Differences in mortality exist even if one looks across the same age group. And, while the restrictions on testing do indeed vary, the disparities in mortality still exist even when we looked at countries or populations for which similar testing rates apply. Instead, we saw a significant correlation with vitamin D deficiency.”

In addition to the correlation between vitamin D deficiency and mortality, the research revealed a strong correlation between vitamin D levels and cytokine storm, a hyperinflammatory condition caused by an overactive immune system. “Cytokine storm can severely damage lungs and lead to acute respiratory distress syndrome and death in patients,” explained Ali Daneshkhah, the paper’s first author. “This is what seems to kill a majority of COVID-19 patients, not the destruction of the lungs by the virus itself. It is the complications from the misdirected fire from the immune system.”

Vitamin D enhances the innate immune systems, and also prevents the immune system from becoming dangerously overactive, which is why the researchers believe the vitamin plays a “major role.” According to the release, having healthy levels of vitamin D could protect patients against severe complications, including death, from COVID-19.

“Our analysis shows that it might be as high as cutting the mortality rate in half,” Backman said. “It will not prevent a patient from contracting the virus, but it may reduce complications and prevent death in those who are infected.”

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Backman also, according to the release, said this correlation might help explain “the many mysteries” surrounding COVID-19, including why children are less likely to die; children don’t have a fully developed acquired immune system, which is the immune system’s second line of defense and more likely to overreact.

“Children primarily rely on their innate immune system,” Backman explained in the release. “This may explain why their mortality rate is lower.”

More research is needed, and Backman stressed that people should not take excessive doses of vitamin D, which might come with negative side effects. “It is hard to say which dose is most beneficial for COVID-19,” he noted in the release. “However, it is clear that vitamin D deficiency is harmful, and it can be easily addressed with appropriate supplementation. This might be another key to helping protect vulnerable populations, such as African-American and elderly patients, who have a prevalence of vitamin D deficiency.”

A second study, released May 7, 2020, also looks at Vitamin D. This research, titled The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, is published in the journal Aging Clinical and Experimental Research. Led by Dr. Lee Smith of Anglia Ruskin University (ARU) and Petre Cristian Ilie, lead urologist of Queen Elizabeth Hospital King’s Lynn NHS Foundation Trust, this study found an association between low average levels of vitamin D and high numbers of COVID-19 cases and mortality rates across 20 European countries.

“We found a significant crude relationship between average vitamin D levels and the number COVID-19 cases, and particularly COVID-19 mortality rates, per head of population across the 20 European countries,” Dr. Smith said in a release from ARU. “Vitamin D has been shown to protect against acute respiratory infections, and older adults, the group most deficient in vitamin D, are also the ones most seriously affected by COVID-19. A previous study found that 75% of people in institutions, such as hospitals and care homes, were severely deficient in vitamin D. We suggest it would be advisable to perform dedicated studies looking at vitamin D levels in COVID-19 patients with different degrees of disease severity.”

It was noted that the study does have limitations: the number of cases in each country is affected by the number of tests performed, as well as the different measures taken by each country to prevent the spread of infection, according to the release. Also, the researchers said, it is important to remember that correlation does not necessarily mean causation.

 

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