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      Vitamin D supplementation for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials

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          Abstract

          Vitamin D supplementation and its impact on immunoregulation are widely investigated. We aimed to assess the prevention and treatment efficiency of vitamin D supplementation in the context of coronavirus disease 2019 (COVID-19) and any disease-related complications. For this systematic review and meta-analysis, we searched databases (PubMed, Embase, Scopus, Web of Science, The Cochrane Library, medRxiv, Cochrane COVID-19 Study Register, and ClinicalTrial.gov) for studies published between 1 November 2019 and 17 September 2021. We considered randomized trials (RCTs) as potentially eligible when patients were tested for SARS-CoV-2 infection and received vitamin D supplementation versus a placebo or standard-of-care control. A random-effects model was implemented to obtain pooled odds ratios for the effect of vitamin D supplementation on the main outcome of mortality as well as clinical outcomes. We identified a total of 5,733 articles, of which eight RCTs (657 patients) met the eligibility criteria. Although no statistically significant effects were reached, the use of vitamin D supplementation showed a trend for reduced mortality [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.32–1.71, p = 0.48] compared with the control group, with even stronger effects, when vitamin D was administered repeatedly (OR 0.33, 95% CI 0.1–1.14). The mean difference for the length of hospitalization was −0.28 (95% CI −0.60 to 0.04), and the ORs were 0.41 (95% CI 0.15–1.12) and 0.52 (95% CI 0.27–1.02) for ICU admission and mechanical ventilation, respectively. In conclusion, vitamin D supplementation did not improve the clinical outcomes in COVID-19 patients, but trends of beneficial effects were observed. Further investigations are required, especially studies focusing on the daily administration of vitamin D.

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          The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

          The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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            Bias in meta-analysis detected by a simple, graphical test

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              RoB 2: a revised tool for assessing risk of bias in randomised trials

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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                31 October 2022
                2022
                31 October 2022
                : 13
                : 1023903
                Affiliations
                [1] 1 Institute of Laboratory Medicine, Universities of Giessen and Marburg Lung Center (UKGMLC), Philipps Universität Marburg, German Center for Lung Research/ Deutsches Zentrum für Lungenforschung (DZL) Marburg , Marburg, Germany
                [2] 2 First Department of Critical Care Medicine and Pulmonary Services, Evangelismos Hospital, Medical School of Athens, National and Kapodistrian University of Athens , Athens, Greece
                [3] 3 Medical School, National and Kapodistrian University of Athens , Athens, Greece
                [4] 4 Institute of Medical Bioinformatics and Biostatistics, Medical Faculty, Philipps University of Marburg , Marburg, Germany
                [5] 5 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School , Boston, MA, United States
                Author notes

                Edited by: Annapurna Vyakarnam, King’s College London, United Kingdom

                Reviewed by: Gill Diamond, University of Louisville, United States; Rob Janssen, Canisius Wilhelmina Hospital, Netherlands

                *Correspondence: Chrysanthi Skevaki, Chrysanthi.Skevaki@ 123456uk-gm.de

                †These authors have contributed equally to this work and share first authorship

                This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.1023903
                9659578
                36389703
                84d7c4bc-6a59-497b-b027-e30cd6a66471
                Copyright © 2022 Kümmel, Krumbein, Fragkou, Hünerbein, Reiter, Papathanasiou, Thölken, Weiss, Renz and Skevaki

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 20 August 2022
                : 10 October 2022
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 48, Pages: 11, Words: 5129
                Funding
                Funded by: Deutsches Zentrum für Lungenforschung , doi 10.13039/501100010564;
                Funded by: Uniklinikum Giessen und Marburg , doi 10.13039/501100009560;
                Funded by: Deutsche Forschungsgemeinschaft , doi 10.13039/501100001659;
                Funded by: Stiftung für Pathobiochemie und Molekulare Diagnostik , doi 10.13039/501100008799;
                Categories
                Immunology
                Original Research

                Immunology
                vitamin d,sars-cov-2,covid-19,systematic review,meta-analysis
                Immunology
                vitamin d, sars-cov-2, covid-19, systematic review, meta-analysis

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