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      The role of vitamin D in outcomes of critical care in COVID-19 patients: evidence from an umbrella meta-analysis of interventional and observational studies

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          Abstract

          Objectives:

          Several meta-analyses have suggested the beneficial effect of vitamin D on patients infected with severe acute respiratory syndrome coronavirus-2. This umbrella meta-analysis aims to evaluate influence of vitamin D supplementation on clinical outcomes and the mortality rate of COVID-19 patients.

          Design:

          Present study was designed as an umbrella meta-analysis. The following international databases were systematically searched till March 2023: Web of Science, PubMed, Scopus, and Embase.

          Settings:

          Random-effects model was employed to perform meta-analysis. Using AMSTAR critical evaluation tools, the methodological quality of the included meta-analyses was evaluated.

          Participants:

          Adult patients suffering from COVID-19 were studied.

          Results:

          Overall, 13 meta-analyses summarising data from 4 randomised controlled trial and 9 observational studies were identified in this umbrella review. Our findings revealed that vitamin D supplementation and status significantly reduced mortality of COVID-19 [Interventional studies: (ES = 0·42; 95 % CI: 0·10, 0·75, P < 0·001; I 2 = 20·4 %, P = 0·285) and observational studies (ES = 1·99; 95 % CI: 1·37, 2·62, P < 0·001; I 2 = 00·0 %, P = 0·944). Also, vitamin D deficiency increased the risk of infection and disease severity among patients.

          Conclusion:

          Overall, vitamin D status is a critical factor influencing the mortality rate, disease severity, admission to intensive care unit and being detached from mechanical ventilation. It is vital to monitor the vitamin D status in all patients with critical conditions including COVID patients.

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          Most cited references28

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          Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

          William Grant, Henry Lahore, Sharon McDonnell … (2020)
          The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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            Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews

            Beverley Shea, Jeremy M. Grimshaw, George A Wells … (2007)
            Background Our objective was to develop an instrument to assess the methodological quality of systematic reviews, building upon previous tools, empirical evidence and expert consensus. Methods A 37-item assessment tool was formed by combining 1) the enhanced Overview Quality Assessment Questionnaire (OQAQ), 2) a checklist created by Sacks, and 3) three additional items recently judged to be of methodological importance. This tool was applied to 99 paper-based and 52 electronic systematic reviews. Exploratory factor analysis was used to identify underlying components. The results were considered by methodological experts using a nominal group technique aimed at item reduction and design of an assessment tool with face and content validity. Results The factor analysis identified 11 components. From each component, one item was selected by the nominal group. The resulting instrument was judged to have face and content validity. Conclusion A measurement tool for the 'assessment of multiple systematic reviews' (AMSTAR) was developed. The tool consists of 11 items and has good face and content validity for measuring the methodological quality of systematic reviews. Additional studies are needed with a focus on the reproducibility and construct validity of AMSTAR, before strong recommendations can be made on its use.
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              Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

              Adrian Martineau, David A. Jolliffe, Richard Hooper … (2017)
              Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration PROSPERO CRD42014013953.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Public Health Nutr
                Journal ID (iso-abbrev): Public Health Nutr
                Journal ID (publisher-id): PHN
                Title: Public Health Nutrition
                Publisher: Cambridge University Press (Cambridge, UK )
                ISSN (Print): 1368-9800
                ISSN (Electronic): 1475-2727
                Publication date (Electronic, collection): 2024
                Publication date (Electronic, pub): 24 April 2024
                Volume: 27
                Issue: 1
                Electronic Location Identifier: e127
                Affiliations
                [ 1 ]City of London Dental School, University of Bolton , London, UK
                [ 2 ]Orthodontic Department, Dental School, Tehran Medical Sciences, Islamic Azad University , Tehran, Iran
                [ 3 ]Student Research Committee, Tabriz University of Medical Sciences , Tabriz, Iran
                [ 4 ]Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences , Tabriz, Iran
                [ 5 ]School of Medicine, Guilan University of Medical Sciences , Rasht, Iran
                [ 6 ]Nutrition Research Center, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences , Attar-Neishaburi St., Golgasht Alley, Azadi Blvd., Tabriz, Iran
                Author notes
                Author information
                https://orcid.org/0000-0002-9353-8066
                Article
                Publisher Item ID: S1368980024000934
                DOI: 10.1017/S1368980024000934
                PMC ID: 11112434
                PubMed ID: 38654693
                SO-VID: 319f8a86-9c07-46ee-9a1e-f8d89c11a29d
                Copyright © © The Authors 2024
                License:

                This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.

                History
                Date received : 26 April 2023
                Date revision received : 10 November 2023
                Date accepted : 08 February 2024
                Page count
                Figures: 5, Tables: 2, References: 28, Pages: 12
                Categories
                Subject: Systematic Review and Meta-Analysis
                Subject: Nutritional Epidemiology

                ScienceOpen disciplines: Public health
                Keywords: vitamin d,mortality,intensive care unit,critical illness,covid-19,umbrella meta-analysis
                Data availability:
                ScienceOpen disciplines: Public health
                Keywords: vitamin d, mortality, intensive care unit, critical illness, covid-19, umbrella meta-analysis

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