Is Vit D over 40 ng/mL protective against Covid?

Covid-19 infection was significantly linked with vitamin D levels among Black patients, with risk increasing as vitamin D levels decreased — however, the same was not true for White patients, according to results from a retrospective cohort study from Chicago.

While vitamin D supplementation has struck out as treatment for conditions such as atrial fibrillation and asthma, previous evidence suggests that vitamin D may play a role in Covid-19 severity.

“Evidence on whether vitamin D levels above the deficient range are associated with Covid-19 risk, and whether such associations differ between White individuals and individuals of other races, could inform the design of randomized clinical trials to test whether vitamin D supplementation reduces Covid-19 risk and clinical decision-making before completion of such trials,” David O. Meltzer, MD, PhD, of the University of Chicago, and colleagues explained in JAMA Network Open.

In order to determine whether this association impacted Black and White individuals, Meltzer and colleagues conducted an analysis of electronic health records at the University of Chicago Medicine (UCM) to examine whether positive Covid-19 tests were associated with a person’s most recent vitamin D level within 365 days before Covid-19 testing.

“[The] findings of this cohort study reinforce prior findings by ourselves and others that lower vitamin D levels (e.g., <20 ng/mL) are associated with increased risk of having test results positive for Covid-19 and provides evidence that Covid-19 risk is also increased for Black individuals with a vitamin D level of 30 to less than 40 ng/mL compared with individuals with a vitamin D level of 40 ng/mL or greater,” they found. “Risk of positive Covid-19 test results decreased significantly with increased vitamin D level of 30 ng/mL or greater when measured as a continuous variable.”

For their analysis, Meltzer and colleagues looked at data for all 106,635 individuals tested for Covid-19 using polymerase chain reaction (PCR) testing at UCM from March 3 through Dec. 30, 2020 — of these, 4,941 had data on vitamin D level from within 365 days prior to being tested for Covid-19 and 4,638 had complete data and were included in the study. Data were analyzed from Sept. 11, 2020, through Feb. 5, 2021.

The most recent recorded vitamin D levels prior to PCR testing were split into four categories — <20 ng/mL (i.e., deficient), 20 to <30 ng/mL (i.e., insufficient), 30 to <40 ng/mL, or ≥40 ng/mL. “Because more distant level may be less informative of level at the time of Covid-19 testing, analyses controlled for the timing of the most recent measurement and changes in vitamin D treatment after that level and before Covid-19 testing,” the study authors noted.

Mean (SD) participant age was 52.8 (19.5) years, and 3,205 (69%) were women — 2,288 (49%) were Black, 1,999 (43%) were White, and 351 (8%) were Asian, Mideast Indian, or more than one race/ethnicity. In terms of vitamin D level, 1,251 (27%) had <20 ng/mL, 1,267 (27%) had 20 to <30 ng/mL, 1,023 (22%) had 30 to <40 ng/mL, and 1,097 (24%) had 40 ng/mL.

Black patients were more likely to have lower vitamin D levels (<20 ng/mL: 829 of 2,288 Black individuals [36%]) than White patients (<20 ng/mL: 315 of 1,999 White individuals [16%]), the study authors added.

“A total of 333 individuals (7%) had test results positive for Covid-19, including 102 White individuals (5%) and 211 Black individuals (9%),” Meltzer and colleagues wrote. “Multivariate analysis controlling for time since last vitamin D level measurement was used to estimate the outcomes associated with levels 14 days before Covid-19 testing. A positive test result for Covid-19 was not significantly associated with vitamin D levels in White individuals but was associated with vitamin D levels in Black individuals (compared with ≥40 ng/mL: <20 ng/mL incidence rate ratio [IRR], 2.55 [95% CI, 1.26-5.15]; P= 0.009; 20 to <30 ng/mL IRR, 1.69 [95% CI, 0.75-3.84]; P=0.21; 30 to <40 ng/mL IRR, 2.64 [95% CI, 1.24-5.66]; P=0.01).”

When stratified by vitamin D level, Covid-19 positivity rates for Black individuals were as follows:

  • <20 ng/mL: 9.72% (95% CI, 6.74%-13.41%).
  • 20 to <30 ng/mL: 6.47% (95% CI, 3.33%-10.28%).
  • 30 to <40 ng/mL: 10.10% (95% CI, 6.00%-15.47%).
  • 40 ng/mL or higher: 3.82% (95% CI, 1.78%-6.68%).

“Multivariate analysis in individuals with a vitamin D level of 30 ng/mL or greater found that the IRR of a positive Covid-19 test result was 0.97 (95% CI, 0.94-0.99; P=0.008) per 1-ng/mL increase in vitamin D overall and 0.95 (95% CI, 0.91-0.98; P=0.003) per 1-ng/mL increase in vitamin D in Black individuals,” they added.

Meltzer and colleagues acknowledged that the fact that this association was strong among patients who were Black, but not White, may reflect the already substantially heightened risk for Covid-19 infection among the Black community, which has been linked to socioeconomic factors and structural inequality. However, they also noted that Black patients may me more susceptible to vitamin D deficiencies, seeing as lighter skin increases vitamin D production in response to sunlight and “vitamin D binding proteins may vary by race and affect vitamin D bioavailability.”

The study authors argued that their findings “increase the urgency” for public health experts to consider whether increase sun exposure and vitamin D supplementation may have a protective effect against Covid-19, particularly among Black patients.

“While the increasing availability of Covid-19 vaccines is likely to reduce the spread of Covid-19 and hence any potential benefits of vitamin D supplementation, the presence of new strains resistant to existing vaccines may increase the potential benefits of vitamin D supplementation, and vitamin D supplementation may be useful in populations not receiving the vaccine,” they wrote. “Weakened host responses may also enhance the conditions for development of viral mutation, so supplementation might have benefits at the population level in reducing the risk of mutant strains.”

Study limitations included the potential for omitted confounders other than vitamin D that may have impacted infection risk, limiting the data to UCM electronic health records, and that electronic health records may not capture use of over-the-counter vitamin D supplements. Also, the study authors noted that their study population was centered in a single northern U.S. city that contains many Black patients, older adults with chronic illnesses, and health care workers, meaning their results might not be representative of other populations.

  1. Results from a retrospective cohort study found that Black patients with lower vitamin D levels were at increased risk for Covid-19 infection, but the same association did not hold true for White patients.
  2. These findings support past research suggesting that vitamin D supplementation may have a protective effect against Covid-19.

John McKenna, Associate Editor, BreakingMED™

Meltzer and coauthors Best and Zhang were supported by the Learning Health Care System Core of the University of Chicago/Rush University Institute for Translational Medicine (ITM) Clinical and Translational Science Award (ITM 2.0: Advancing Translational Science in Metropolitan Chicago; grant No. UL1TR002389, principal investigator: Dr. Solway) and the African American Cardiovascular pharmacogenetic Consortium (grant No. U54-MD010723, Drs Perera and Meltzer).


Cat ID: 190

Topic ID: 79,190,730,933,190,926,192,927,151,928,925,934