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Low plasma vitamin D levels emerged as an independent risk factor for COVID-19 infection and hospitalization in a large population-based study.
COVID-19 positive participants were 50% more likely to have low versus normal 25 (OH) D levels in a multivariate analysis controlling for other confounding factors, for example.
The primary message for clinicians is “to assess patients’ vitamin D levels and keep them optimal for overall health as well as for a better immune response to COVID-19,” lead author Milana Frenkel-Morgenstern, PhD, director of El Laboratory of Cancer Genomics and Biocomputing of Complex Diseases at Bar-Ilan University in Ramat Gan, Israel, said Medscape Medical News.
The study was published online July 23 in The FEBS Newspaper.
Previous and ongoing studies are evaluating a potential role for vitamin D in preventing or minimizing the severity of SARS-CoV-2 infection, based on years of research addressing vitamin D for other viral respiratory infections. The evidence to date regarding COVID-19, mainly observational studies, has yielded mixed results.
Multiple experts weigh the controversy in an earlier report. Many point to the limitations of observational data, particularly when it comes to ruling out other factors that could affect the severity of COVID-19 infection. Additionally, in a video report, JoAnn E. Manson, MD, DrPH, of Harvard Medical School in Boston, cites an observational study from three South Asian hospitals that found the most severe COVID-19 patients they had lower vitamin D levels, as well as other “compelling evidence” suggesting an association.
Frenkel-Morgenstern and colleagues studied data from 7,807 people, of whom 10.1% were COVID-19 positive. They evaluated electronic health records for demographic data, possible confounders, and outcomes between February 1 and April 30.
COVID-19 positive participants tended to be younger and more likely to be male and live in a lower socioeconomic area compared to participants who were negative for COVID-19 in a univariate analysis.
Key results
A higher proportion of COVID-19 positive patients had low plasma 25 (OH) D concentrations, about 90%, compared to 85% of participants who were negative for COVID-19. The difference was statistically significant (P <.001).
In addition, the highest likelihood of low vitamin D levels among COVID-19 positives was performed in a multivariate analysis that controlled for demographics, psychiatric and somatic disorders (adjusted odds ratio). [aOR], 1.50). The difference remained statistically significant (P <.001).
Table: Additional risk factors for COVID-19 infection
| Adjusted Odds Ratio | 95% CI | P value | |
|---|---|---|---|
| Male | 1.49 | 1.24 – 1.79 | <.05 |
| Age> 50 years | 1.56 | 1.26 – 1.92 | <.05 |
| Low socioeconomic status | 2.06 | 1.65 – 2.59 | <.001 |
The study was also notable for what did not dot find among participants with COVID-19. For example, the prevalence of dementia, cardiovascular disease, chronic lung disorders, and hypertension were significantly higher among COVID-19 negative participants.
“The severe restrictions on social contacts that were imposed on the entire population and were further emphasized in this highly vulnerable population” could explain these findings, the researchers note.
“We assume that following the instructions of the Israeli Ministry of Health, patients with chronic medical conditions significantly reduced their social contacts,” and thus reduced their risk of infection.
In contrast to previous reports, obesity was not a significant factor associated with an increased likelihood of COVID-19 infection or hospitalization in the current study.
The researchers also linked low plasma 25 (OH) D level with a higher probability of hospitalization for COVID-19 infection (crude OR, 2.09; P <.05).
After controlling for demographics and chronic conditions, the adjusted OR decreased to 1.95 (P = 0.061) in a multivariate analysis. The only factor that remained statistically significant for hospitalization was age over 50 years (aOR, 2.71; P <.001).
Implications and future plans
The large number of participants and the “real-world” population-based design are strengths of the study. Considering potential confounders is another strength, the researchers note. The retrospective design of the database was a limitation.
Going forward, Frenkel-Morgenstern and colleagues “will try to decipher the potential role of vitamin D in the prevention and / or treatment of COVID-19” through three additional studies, he said. Additionally, they would like to perform a meta-analysis to combine data from different countries to further explore the potential role of vitamin D in COVID-19.
“A compelling case”
“This is a large, robust, confounding-adjusted study, consistent with biology and other clinical studies of vitamin D, infections, and COVID-19.”
Wayne Jonas, MD, a practicing family physician and executive director of Samueli’s Integrative Health Programs, said Medscape Medical News.
Because the research was retrospective and observational, the findings cannot interpret a causal link between vitamin D levels and the risk of COVID-19. “That would need a prospective, randomized study,” said Jonas, who was not involved in the current study.
However, “the study presents a compelling argument for possibly detecting vitamin D levels to judge the risk of COVID infection and hospitalization,” Jonas said, “and the compelling need for a large randomized study of vitamin D supplementation to see if it can help prevent infection. “
“Because vitamin D is largely safe, such a study could be done quickly and in healthy people with minimal risk of harm,” he added.
More likelihood of confusion?
“I think the study is of interest,” said Naveed Sattar, PhD, a professor of metabolic medicine at the University of Glasgow, UK, who was also not affiliated with the research. Medscape Medical News.
“While the authors adjusted for some confounding factors, there is great potential for residual confusion,” said Sattar, co-author of a UK Biobank study that found no association between vitamin D stages and COVID-19 infection. in multivariate models.
For example, Sattar said: “Robust adjustment for social class is important since both vitamin D levels and COVID-19 severity are strongly associated with social class.” In addition, it is unknown when and at what time of year vitamin D concentrations were measured in the current study.
“In the end, only a robust randomized trial can tell us whether vitamin D supplementation helps decrease the severity of COVID-19,” added Sattar. “I have no hope that this is the case, but I am glad that some of these trials are [ongoing]”
Frenkel-Morgenstern received a grant from the Institute for Data Sciences COVID-19 to support this work. Frenkel-Morgenstern, Jonas and Sattar have disclosed no relevant financial relationships.
FEBS Journal. Published online July 23, 2020. Full text
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