Patients with a vitamin D deficiency were four times more likely to be COVID-19 positive than those with a sufficient amount, according to the University of Florida (UF). Also, African American patients with insufficient vitamin D levels were three times more likely to be infected by the coronavirus.
Led by Joseph Katz, DMD, a UF College of Dentistry oral medicine professor, the researchers used the university’s patient database and its Informatics for Integrating Biology and Bedside (i2b2) patient registry platform to review aggregate data of more than 980,000 patients seen at UF Health medical practices from 2015 to 2020.
Funded by the National Institutes of Health, i2b2 is a self-service tool accessible to researchers across the university.
“Research can start out on the bench, where you move from small details and work to create a big picture and discover conclusions about a condition or ailment. In our case, however, we approached the challenge like a jigsaw puzzle in reverse. We were hypothesis-driven,” Katz said.
“We started with the big picture, that oral diseases are linked to COVID-19. But we didn’t know exactly why. We had to break down the puzzle to learn the reasons,” Katz said.
Insufficient vitamin D has been linked with respiratory infections, and research suggests vitamin D treatment may help lessen COVID-19 symptoms, UF said. African Americans are disproportionately affected by COVID-19 and vitamin D deficiency compared to other races for a variety of reasons including skin pigmentation, which reduces vitamin D production.
Vitamin D deficiency also is a key factor in oral health challenges such as periodontal disease, UF said, and its effects on the immune system are well documented. The receptor that acts as a host to the COVID-19 virus, allowing it to enter and infect human cells, is abundant not only in the lungs and other major organs but also in the mouth and oral tissues.
Now that vitamin D deficiency has been linked to COVID-19 susceptibility, the next step, Katz said, is for nutrition experts and others to continue that line of research, looking at individualized patient details for more specific causes and results. For example, studies could be conducted to validate the hypothesis that vitamin D supplementation can help prevent or treat COVID-19.
The researchers used the patient data registry to define cohorts of interest and to drill down to identify commonalities and significant risk factors. They sorted the patient dataset by diagnoses codes, risk factors, and demographic factors and made statistical adjustments for comorbidities and demographic variables.
“I came to UF last year and was not aware of the i2b2 until September, when Dr. Katz suggested we use the aggregated data to study these associations,” said Wei Xue, PhD, a UF research assistant professor of biostatistics in the UF College of Public Health and Health Professions and the UF College of Medicine.
“Without the right data, investigators cannot test and verify their theories. Because of this tool, we could conduct more complicated analyses and not just a summary of statistics,” Xue said.
The i2b2 provides de-identified patient clinical information without individual personal or protected details that is pre-approved for use and bypasses the standard Institutional Review Board process. Use of the i2b2 tool can replace requests for tailored data from the Integrated Data Repository Research (IDR) Services team.
“Traditionally, researchers use i2b2 to determine if a study premise is feasible by asking if enough patients exist within certain criteria for an in-depth study,” said UF Health chief research information officer Chris Harle, PhD, who leads the IDR as a joint program of the UF Clinical and Translational Science Institute and UF Health Information Technology.
“This research team went beyond the norm,” Harle said. “They demonstrated how the i2b2 can be used to conduct cross-sectional analyses and to identify hypothesis-generating associations that stimulate future studies. Using i2b2 in this creative way can lead to more rapid research production by eliminating the need for IRB approval and customized data extractions.”
Katz has published other papers based on i2b2 data and encourages other research teams with strong biostatistics abilities to maximize use of the platform.
“Researchers by nature are skeptical and analytical. We appreciate tools like this that are kept current, and the IDR team has done a great job purifying data and ensuring its quality,” Katz said.
UF Health chief information officer Gigi Lipori, MT, MBA, said UF is committed to providing accessible technology and helpful data resources to faculty across the university.
“It’s exciting when clinicians and researchers pursue innovative ideas with existing technologies,” Lipori said. “In this case, the team conducted rapid research on a timely topic with the tools at their fingertips. Every second counts as we strive to better understand the coronavirus.”
The study, “Increased Risk for COVID-19 in Patients with Vitamin D Deficiency,” was published by Nutrition.
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