ABSTRACT
BackgroundEvidence recommends that vitamin D might be a crucial supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a systematic review and meta-analysis in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. MethodsA systematic search was performed in PubMed, Scopus, Embase, and Web of Science up to December 18, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. ResultsTwenty-three studies containing 11901participants entered into the meta-analysis. The meta-analysis indicated that 41% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 29%-55%), and in 42% of patients, levels of vitamin D were insufficient (95% CI, 24%-63%). The serum 25-hydroxyvitamin D concentration was 20.3 ng/mL among all COVID-19 patients (95% CI, 12.1-19.8). The odds of getting infected with SARS-CoV-2 is 3.3 times higher among individuals with vitamin D deficiency (95% CI, 2.5-4.3). The chance of developing severe COVID-19 is about five times higher in patients with vitamin D deficiency (OR: 5.1, 95% CI, 2.6-10.3). There is no significant association between vitamin D status and higher mortality rates (OR: 1.6, 95% CI, 0.5-4.4). ConclusionThis 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 5 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.
ABSTRACT
BackgroundCoronavirus Disease 2019 (COVID-19) has become a major global issue with rising the number of infected individuals and mortality in recent months. Among all therapeutic approaches, arguments have raised about hydroxychloroquine (HCQ) efficacy in the treatment of COVID-19. We carried out a systematic review and meta-analysis overcome the controversies regarding the effectiveness of hydroxychloroquine in the treatment of COVID-19. MethodsA systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar and medRxiv pre-print database using all available MeSH terms for COVID-19 and hydroxychloroquine up to July 19, 2020. Studies focused on the effectiveness of HCQ with/without azithromycin (AZM) in confirmed COVID-19 patients were entered into the study. Two researchers have independently evaluated quality assessment of the studies and abstracted data for data extraction. Extracted data were analyzed using CMA v. 2.2.064. Heterogeneity was assessed using the I-squared (I2) test, and fixed/random-effects model was used when appropriate for pooling of studies. ResultsOut of 26 studies entered into our systematic review, 21 studies including 14 comparative studies with control group and seven observational studies containing 103,486 participants have entered into the meta-analysis. The results of the meta-analysis on comparative studies indicated no significant clinical effectiveness (negative in RT-PCR evaluation) for HCQ regimen in the treatment of COVID-19 in comparison to control group (RR: 1.03, 95% CI, 0.79-1.34). The same result was observed for the combination of HCQ+azithromycin (RR: 1.26, 95% CI, 0.91-1.74). No significant differences were found for both HCQ (RR: 0.92, 95% CI, 0.72-1.16) and HCQ+AZM (RR: 1.72, 95% CI, 0.86-3.42) mortality rate; however, mortality was affected by age differences according to meta-regression analysis (P<0.000001). No substantial difference was observed for disease exacerbation (RR: 1.23, 95% CI, 0.65-2.30) between HCQ group and controls. Also, radiological findings significantly improved in the HCQ group (OR: 0.32, 95% CI, 0.11-0.98). Odds of known HCQ adverse effects (diarrhea, vomiting, blurred vision, rash, headache, etc.) occurred in the HCQ regimen group was approximately 3.5 times of control group (OR: 3.40, 95% CI, 1.65-6.98), but no substantial differences were found regarding intubation odds between HCQ group and control group (OR: 2.11, 95% CI, 0.31-14.03). Meta-analysis indicated no significant prophylactic effects for HCQ (OR: 0.40, 95% CI, 0.04-3.65) ConclusionThis systematic review and meta-analysis showed no clinical benefits regarding HCQ treatment with/without azithromycin for COVID-19 patients. Although mortality rate was not significantly different between cases and controls, frequency of adverse effects was substantially higher in HCQ regimen group. However, due to that most of the studies were non-randomized and results were not homogenous, selection bias was unavoidable and further large randomized clinical trials following comprehensive meta-analysis should be taken into account in order to achieve more reliable findings. Also, it is worth mentioning that if this work does not allow to quantify a "value" of the HCQ, it allows at least to know what is not the HCQ and that it would be prudent not to continue investing in this direction.
