The role of vitamin D in the age of COVID-19: A systematic review and meta-analysis.

Low vitamin D status may influence whether or not one becomes infected with COVID-19 and may impact outcomes.

• 23 studies were included in the meta‐analysis, all were designed in retrospective nature, except for five studies in prospective nature.
• The studies’ sample size ranged from 19 to 7807 participants, all together they included 11,901 participants across the 23 studies.
• Bias assessment revealed the studies were fair.
• The meta‐analysis of event rates in peer‐reviewed papers showed that 41% of COVID‐19 patients were suffering from vitamin D deficiency, in 42% of patients, levels of vitamin D were lower than the normal range, and only 19% of patients had normal vitamin D levels.
• The meta‐analysis of mean 25(OH)D concentration was 20.3 ng/mL among all COVID‐19 patients, 16.0 ng/mL in severe cases and 24.5 ng/mL in non‐severe cases.
• The meta‐analysis indicated that odds of getting infected with SARS‐CoV‐2 increase by 3.3 times in individuals with vitamin D deficiency.
• The meta‐analysis showed that the probability of developing severe stages of COVID‐19 is 5.1 times higher in patients with vitamin D deficiency.
• The meta‐analysis indicated no significant higher COVID‐19 mortality related to vitamin‐D‐deficient patients.
• Meta‐analysis of available data on comorbidities frequency in COVID‐19 patients was as follows:
  • In non‐severe cases, 13% cancer, 12% chronic kidney disease (CKD), 18% cardiovascular diseases (CVD), 21% diabetes, 29% hypertension (HTN), 12% obesity and 13% respiratory diseases (Figure S1)
  • In severe cases, 13% cancer, 34% CKD, 31% CVD, 35% diabetes, 64% HTN, 33% obesity and 17% respiratory diseases; in overall, 8% cancer, 20% CKD, 26% CVD, 5% dementia, 15% depression/anxiety, 22% obesity, 26% diabetes, 49% HTN and 15% respiratory diseases
• Pooling available data regarding ethnicity distribution among COVID‐19 patients resulted in 2% Afro‐Caribbean, 13% Asian and 87% Caucasian. The results for severe cases were as follows: 2% Asian, 68% Caucasian and 81% Hispanic.

11,901 COVID-19 patients

• Most of studies entered into this meta‐analysis were retrospective in nature.
• There are inevitable challenges with the reliability of data due to different strategies in testing (e.g., vitamin D measurement, COVID‐19 test).
• Other immunomodulatory factors (e.g., levels of vitamin C, zinc, selenium, etc), which might be influential in the outcome of COVID‐19 patients, were not considered in the included studies.

This study found that most of the COVID‐19 patients were suffering from vitamin D deficiency/insufficiency. Also, there is about three times higher chance of getting infected with SARS‐CoV‐2 among vitamin‐D‐deficient individuals and about five times higher probability of developing the severe disease in vitamin‐D‐deficient patients. Vitamin D deficiency showed no significant association with mortality rates in this population.

• A systematic review and meta-analysis was conducted in order to maximize the use of all research that exists about the role of vitamin D in COVID‐19.
• Studies included in the meta‐analysis met the following criteria: 1) comparative or non‐comparative studies both retrospective or prospective in nature; and 2) studies reported the role of vitamin D in confirmed COVID‐19 patients. Studies were excluded if they were in vitro studies, experimental studies, or reviews.
• vitamin D cut‐off points were considered as follows:
  • Vitamin D sufficiency: 25(OH)D concentration greater than 30 ng/mL
  • Vitamin D insufficiency: 25(OH)D concentration of 20‐30 ng/mL
  • Vitamin D deficiency: 25(OH)D level less than 20 ng/mL
• Outcomes included: (a) frequency of vitamin D status in COVID‐19 patients; (b) mean 25(OH)D concentration; (c) association between vitamin D deficiency and SARS‐CoV‐2 infection; (d) association between vitamin D deficiency and COVID‐19 severity; (e) association between vitamin D deficiency and COVID‐19 mortality; (f) comorbidity frequency; and (g) ethnicity frequency.

Ghasemian R, Shamshirian A, Heydari K, Malekan M, Alizadeh-Navaei R, Ebrahimzadeh MA, Ebrahimi Warkiani M, Jafarpour H, Razavi Bazaz S, Rezaei Shahmirzadi A, Khodabandeh M, Seyfari B, Motamedzadeh A, Dadgostar E, Aalinezhad M, Sedaghat M, Razzaghi N, Zarandi B, Asadi A, Yaghoubi Naei V, Beheshti R, Hessami A, Azizi S, Mohseni AR, Shamshirian D. The role of vitamin D in the age of COVID-19: A systematic review and meta-analysis. Int J Clin Pract. 2021 Jul 29:e14675. doi: 10.1111/ijcp.14675. Epub ahead of print. PMID: 34322971; PMCID: PMC8420549.