A study at the University of Chicago Medicine has found that when it comes to COVID-19, having vitamin D levels above those traditionally considered sufficient may lower the risk of infection, especially for Black people.
The study retrospectively examined the relationship between vitamin D levels and likelihood of testing positive for COVID-19. While levels of 30 ng/ml or more are usually considered "sufficient," the authors found that Black individuals who had levels of 30 to 40 ng/ml had a 2.64 times higher risk of testing positive for COVID-19 than people with levels of 40 ng/ml or greater. Statistically significant associations of vitamin D levels with COVID-19 risk were not found in White people. The study looked at data from over 3,000 patients at UChicago Medicine who had had their vitamin D levels tested within 14 days before a COVID-19 test.
The research team is now recruiting participants for two separate clinical trials testing the efficacy of vitamin D supplements for preventing COVID-19.
This research is an expansion of an earlier study showing that a vitamin D deficiency (less than 20 ng/ml) may raise the risk of testing positive for COVID-19. In the current study, those results were further supported, finding that individuals with a vitamin D deficiency had a 7.2% chance of testing positive for the virus. A separate study recently found that over 80% of patients diagnosed with COVID-19 were vitamin D deficient.
"These new results tell us that having vitamin D levels above those normally considered sufficient is associated with decreased risk of testing positive for COVID-19, at least in Black individuals," said Dr David Meltzer, chief of hospital medicine at UChicago Medicine and lead author of the study. "This supports arguments for designing clinical trials that can test whether or not vitamin D may be a viable intervention to lower the risk of the disease, especially in persons of colour."
Meltzer was inspired to investigate this topic after seeing an article in early 2020 that found people with vitamin D deficiency who had randomly been assigned to receive vitamin D supplementation had much lower rates of viral respiratory infections compared to those who did not receive supplementation. He decided to examine data being collected at UChicago Medicine on COVID-19 to determine the role that vitamin D levels might be playing.
"There's a lot of literature on vitamin D. Most of it has been focused on bone health, which is where the current standards for sufficient vitamin D levels come from," Meltzer explained. "But there's also some evidence that vitamin D might improve immune function and decrease inflammation. So far, the data has been relatively inconclusive.
Based on these results, we think that earlier studies may have given doses that were too low to have much of an effect on the immune system, even if they were sufficient for bone health. It may be that different levels of vitamin D are adequate for different functions."
Vitamin D can be obtained through diet or supplements, or produced by the body in response to exposure of the skin to sunlight. Meltzer noted that most individuals, especially people with darker skin, have lower levels of vitamin D; roughly half of the world's population has levels below 30ng/ml. "Lifeguards, surfers, those are the kinds of folks who tend to have more than sufficient vitamin D levels," he said. "Most folks living in Chicago in the winter are going to have levels that are well below that."
While vitamin D supplements are relatively safe to take, excessive consumption of vitamin D supplements is associated with hypercalcemia, a condition in which calcium builds up in the blood stream and causes nausea, vomiting, weakness, and frequent urination. If left unchecked, it can further lead to bone pain and kidney stones.
"Currently, the adult recommended dietary allowance for vitamin D is 600 to 800 international units (IUs) per day," said Meltzer. "The National Academy of Medicine has said that taking up to 4,000 IUs per day is safe for the vast majority of people, and risk of hypercalcemia increases at levels over 10,000 IUs per day."
One of the challenges of this study is that it is currently difficult to determine exactly how vitamin D may be supporting immune function. "This is an observational study," said Meltzer. "We can see that there's an association between vitamin D levels and likelihood of a COVID-19 diagnosis, but we don't know exactly why that is, or whether these results are due to the vitamin D directly or other related biological factors."
Prompted by the evidence that people with vitamin D deficiency are more likely to test positive for COVID-19 and experience significant symptoms, a team at the University of Chicago and Rush University is conducting two studies to learn whether taking a daily vitamin D supplement can help prevent COVID-19 or decrease the severity of its symptoms.
Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-19 Test Results
David O Meltzer, Thomas J. Best, Hui Zhang, Tamara Vokes, Vineet M Arora, Julian Solway
Published in JAMA Network Open on 19 March 2021
Deficient (ie, <20 ng/mL) or insufficient (ie, 20 to <30 ng/mL) 25-hydroxyvitamin D (also known as calcifediol) levels are more common in Black individuals than White individuals and are associated with increased coronavirus disease 2019 (COVID-19) risk. Whether COVID-19 risk is associated with differences in vitamin D levels of 30 ng/mL or greater is not known.
To examine whether COVID-19 test results are associated with differences in vitamin D levels of 30 ng/mL or greater, including for White individuals and for Black individuals.
Design, Setting, and Participants
This retrospective cohort study was conducted at an academic medical center in Chicago, Illinois. Participants included individuals with data on vitamin D level within 365 days before COVID-19 testing, which was conducted from March 3 to December 30, 2020. Data were analyzed from September 11, 2020, to February 5, 2021.
The last vitamin D level before COVID-19 testing was categorized as less than 20 ng/mL (ie, deficient), 20 to less than 30 ng/mL (ie, insufficient), 30 to less than 40 ng/mL, or 40 ng/mL or greater. Treatment was defined by vitamin D type and dose 14 days before COVID-19 testing and treatment changes after last vitamin D level.
Main Outcomes and Measures
The main outcome was a positive result for COVID-19 in polymerase chain reaction testing. Multivariable analyses tested whether previously measured vitamin D level was associated with having test results positive for COVID-19 in White individuals and in Black individuals, controlling for months and treatment changes since the vitamin D level was measured, as well as demographic characteristics and comorbidity indicators.
A total of 4638 individuals (mean [SD] age 52.8 [19.5] years; 3205 [69%] women) had data for a vitamin D level within 1 year before COVID-19 testing, including 2288 (49%) Black individuals, 1999 (43%) White individuals, and 351 individuals (8%) who were another race/ethnicity (eg, Asian, Mideast Indian, >1 race). Stratified by vitamin D level, 1251 individuals (27%) had less than 20 ng/mL, 1267 individuals (27%) had 20 to less than 30 ng/mL, 1023 individuals (22%) had 30 to less than 40 ng/mL, and 1097 individuals (24%) had 40 ng/mL or greater. Lower vitamin D levels were more common in Black individuals (<20 ng/mL: 829 of 2288 Black individuals [36%]) than White individuals (<20 ng/mL: 315 of 1999 White individuals [16%]). A total of 333 individuals (7%) had test results positive for COVID-19, including 102 White individuals (5%) and 211 Black individuals (9%). 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 = .009; 20 to <30 ng/mL IRR, 1.69 [95% CI, 0.75-3.84]; P = .21; 30 to <40 ng/mL IRR, 2.64 [95% CI, 1.24-5.66]; P = .01). Stratified by vitamin D level, estimated COVID-19 positivity rates in Black individuals were 9.72% (95% CI, 6.74%-13.41%) for individuals with a vitamin D level less than 20 ng/mL, 6.47% (95% CI, 3.33%-10.28%) for individuals with a vitamin D level of 20 to less than 30 ng/mL, 10.10% (95% CI, 6.00%-15.47%) for individuals with a vitamin D level of 30 to less than 40 ng/mL, and 3.82% (95% CI, 1.78%-6.68%) for individuals with a vitamin D level of 40 ng/mL or higher. 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 = .008) per 1-ng/mL increase in vitamin D overall and 0.95 (95% CI, 0.91-0.98; P = .003) per 1-ng/mL increase in vitamin D in Black individuals.
Conclusions and Relevance
In this single-center retrospective cohort study, COVID-19 risk increased among Black individuals with vitamin D level less than 40 ng/mL compared with those with 40 ng/mL or greater and decreased with increasing levels among individuals with levels greater than 30 ng/mL. No significant associations were noted for White individuals. Randomized clinical trials should examine whether increasing vitamin D level to greater than 40 ng/mL affects COVID-19 risk.
[link url="https://www.uchicagomedicine.org/forefront/coronavirus-disease-covid-19/vitamin-d-covid-study"]University of Chicago Medical Centre material [/link]
[link url="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777682"]JAMA Network Open study (Open access)[/link]
See also MedicalBrief archives:
[link url="https://www.medicalbrief.co.za/archives/more-evidence-of-lack-of-vitamin-d-efficacy-for-covid-19-two-studies/"]More evidence of lack of Vitamin D efficacy for COVID-19 — Two studies[/link]
[link url="https://www.medicalbrief.co.za/archives/still-no-definitive-answer-on-vitamin-d3-to-treat-covid-19/"]Still no definitive answer on Vitamin D3 to treat COVID-19[/link]
[link url="https://www.medicalbrief.co.za/archives/covid-19-and-vitamin-d-insufficient-evidence-as-a-treatment-nice-guideline/"]COVID-19 and vitamin D: ‘Insufficient evidence’ as a treatment — NICE Guideline[/link]
[link url="https://www.medicalbrief.co.za/archives/over-80-of-covid-19-patients-have-vitamin-d-deficiency-spain-hospital-study/"]Over 80% of COVID-19 patients have vitamin D deficiency — Spain hospital study[/link]
[link url="https://www.medicalbrief.co.za/archives/low-plasma-vitamin-d-level-has-increased-risk-of-covid-19-infection-israel-population-study/"]Low plasma vitamin D level has increased risk of COVID-19 infection — Israel population study[/link]
[link url="https://www.medicalbrief.co.za/archives/covid-19-and-vitamin-d-sa-experts-say-evidence-is-scant/"]COVID-19 and vitamin D: SA experts say evidence is scant[/link]
[link url="https://www.medicalbrief.co.za/archives/vitamin-d-supplementation-no-benefit-in-preventing-treating-covid-19-consensus-paper/"]Vitamin D supplementation: No benefit in preventing/treating COVID-19 — Consensus paper[/link]
[link url="https://www.medicalbrief.co.za/archives/vitamin-d-levels-may-play-significant-role-in-covid-19-incidence-and-mortality/"]Vitamin D levels may play significant role in COVID-19 incidence and mortality[/link]