The impact of vitamin D supplementation on mortality rate and clinical outcomes of COVID-19 patients: A systematic review and meta-analysis
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Abstract
Background: Several studies have suggested the positive impact of vitamin D on patients infected with SARS-CoV-2. This systematic review aims to evaluate the effects of vitamin D supplementation on clinical outcomes and mortality rate of COVID-19 patients. Methods: A comprehensive search was conducted through the databases of PubMed, Scopus, Web of Knowledge, Embase, Ovid, and The Cochrane Library without time and language limitation, until December 16, 2020. The results were screened, and the outcomes of interest were extracted. Using the Joanna Briggs Institute (JBI) Critical Appraisal Tools, the remaining results were appraised critically. Statistical analysis was performed using the Comprehensive Meta-Analysis (CMA) software version 2.0. Results: Of the 2311 results, four studies and 259 patients were enrolled, including 139 patients in vitamin D intervention groups. The pooled analysis of three studies, reporting the patients’ survival and mortality rate, showed a significantly lower mortality rate among the intervention groups compared with the control groups (OR=0.264, 95% CI=0.099–0.708, p-value=0.008). Two of the studies reported the clinical outcomes based on the World Health Organization’s Ordinal Scale for Clinical Improvement (OSCI) score for COVID-19, where both of them showed a significant decrease in OSCI score in the vitamin D intervention groups. One study reported a lower rate of intensive care unit (ICU) admission, and one study reported a significant decrease in serum levels of Fibrinogen. Conclusion: Prescribing vitamin D supplementation to patients with COVID-19 infection seems to decrease the mortality rate, the severity of the disease, and serum levels of the inflammatory markers. Further studies are needed to determine the ideal type, dosage, and duration of supplementation.
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SciScore for 10.1101/2021.01.04.21249219: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved by the Ethics Committee of Tabriz University of Medical Sciences, Tabriz, Iran. Search Strategy: The current systematic review was designed and conducted in 2020. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources A comprehensive search was conducted among the databases of PubMed, Scopus, Web of Knowledge, Embase, Ovid, and The Cochrane Library, using a combination of the following free keywords and related MeSH (Medical Subject Headings) Terms: vitamin D, vitamin D3, vit d, cholecalciferol, ergocalciferol, … SciScore for 10.1101/2021.01.04.21249219: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: The study was approved by the Ethics Committee of Tabriz University of Medical Sciences, Tabriz, Iran. Search Strategy: The current systematic review was designed and conducted in 2020. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources A comprehensive search was conducted among the databases of PubMed, Scopus, Web of Knowledge, Embase, Ovid, and The Cochrane Library, using a combination of the following free keywords and related MeSH (Medical Subject Headings) Terms: vitamin D, vitamin D3, vit d, cholecalciferol, ergocalciferol, 25-hydroxyvitamin, dihydrotachysterol, calcidiol, 25-hydroxycholecalciferol, covid, covid-19, sars-cov-2, 2019-ncov, coronavirus. Embasesuggested: (EMBASE, RRID:SCR_001650)Cochrane Librarysuggested: (Cochrane Library, RRID:SCR_013000)MeSHsuggested: (MeSH, RRID:SCR_004750)The search strategy for PubMed was as follows: (“Vitamin D”[Mesh] OR Vitamin D OR vitamin D3 OR Vit D OR Cholecalciferol OR Ergocalciferol OR 25-Hydroxyvitamin OR Dihydrotachysterol OR calcidiol OR 25-hydroxycholecalciferol) AND ((“COVID-19” [Supplementary Concept]) OR “severe acute respiratory syndrome coronavirus 2” [Supplementary Concept] OR covid OR covid-19 OR sars-cov-2 OR 2019-ncov OR coronavirus). PubMedsuggested: (PubMed, RRID:SCR_004846)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:However, our review had some limitations. Prominently, the number of publications in the topic is low to draw precise conclusions. Moreover, although the reported heterogenicity was low, the results of the meta-analysis on mortality rate might still be affected by the low number of the included studies. Also, due to the lack of studies reporting the ICU admission and clinical outcomes, performing a quantitative analysis (meta-analysis) on these outcomes was impossible. Also, the difference in the dose of the administered supplementations might have affected the results. We strongly recommend performing further studies, especially clinical trials, on the current topic and among different patients’ groups. Although some population-based studies have already shown the higher prevalence of severe outcomes among the vitamin D-deficient patients, still, we have insufficient evidence-based knowledge about the specific effects of vitamin D supplementation of COVID-19 patients, the impact on the infected patients’ survival, mortality rate and disease progression, the possible side-effects, the proper dosage and route of prescription, the duration of the prescription course, and the potential prophylactic effects; which may be the most beneficial and practical application of vitamin D during this medical state of emergency.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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SciScore for 10.1101/2021.01.04.21249219: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement The study was approved by the Ethics Committee of Tabriz University of Medical Sciences, Tabriz, Iran. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable A total of 259 individuals (140 females and 119 males) were present in the included studies, 139 of which were allocated to the intervention groups. Table 2: Resources
Software and Algorithms Sentences Resources Methods: A comprehensive search was conducted through the databases of PubMed, Scopus, Web of Knowledge, Embase, Ovid, and The Cochrane Library with no limitation in time and language, until December 16, 2020. P…SciScore for 10.1101/2021.01.04.21249219: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement The study was approved by the Ethics Committee of Tabriz University of Medical Sciences, Tabriz, Iran. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable A total of 259 individuals (140 females and 119 males) were present in the included studies, 139 of which were allocated to the intervention groups. Table 2: Resources
Software and Algorithms Sentences Resources Methods: A comprehensive search was conducted through the databases of PubMed, Scopus, Web of Knowledge, Embase, Ovid, and The Cochrane Library with no limitation in time and language, until December 16, 2020. PubMedsuggested: (PubMed, RRID:SCR_004846)Embasesuggested: (EMBASE, RRID:SCR_001650)Cochrane Librarysuggested: (Cochrane Library, RRID:SCR_013000)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
However, our review had some limitations. Prominently, the number of publications in the topic is low to draw precise conclusions. Moreover, although the reported heterogenicity was low, the results of the metaanalysis on mortality rate might still be affected by the low number of the included studies. Also, due to the lack of studies reporting the ICU admission and clinical outcomes, performing a quantitative analysis (meta-analysis) on these outcomes was impossible. Also, the difference in the dose of the administered supplementations might have affected the results. We strongly recommend performing further studies, especially clinical trials, on the current topic and among different patients' groups. Although some population-based studies have already shown the higher prevalence of severe outcomes among the vitamin D-deficient patients, still, we have insufficient evidence-based knowledge about the specific effects of vitamin D supplementation of COVID-19 patients, the impact on the infected patients’ survival, mortality rate and disease progression, the possible side-effects, the proper dosage and route of prescription, the duration of the prescription course, and the potential prophylactic effects; which may be the most beneficial and practical application of vitamin D during this medical state of emergency.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
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