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      Characterising long COVID: a living systematic review

      systematic-review

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          Abstract

          Background

          While it is now apparent clinical sequelae (long COVID) may persist after acute COVID-19, their nature, frequency and aetiology are poorly characterised. This study aims to regularly synthesise evidence on long COVID characteristics, to help inform clinical management, rehabilitation strategies and interventional studies to improve long-term outcomes.

          Methods

          A living systematic review. Medline, CINAHL (EBSCO), Global Health (Ovid), WHO Global Research on COVID-19 database, LitCovid and Google Scholar were searched till 17 March 2021. Studies including at least 100 people with confirmed or clinically suspected COVID-19 at 12 weeks or more post onset were included. Risk of bias was assessed using the tool produced by Hoy et al. Results were analysed using descriptive statistics and meta-analyses to estimate prevalence.

          Results

          A total of 39 studies were included: 32 cohort, 6 cross-sectional and 1 case–control. Most showed high or moderate risk of bias. None were set in low-income countries and few included children. Studies reported on 10 951 people (48% female) in 12 countries. Most included previously hospitalised people (78%, 8520/10 951). The longest mean follow-up time was 221.7 (SD: 10.9) days post COVID-19 onset. Over 60 physical and psychological signs and symptoms with wide prevalence were reported, most commonly weakness (41%; 95% CI 25% to 59%), general malaise (33%; 95% CI 15% to 57%), fatigue (31%; 95% CI 24% to 39%), concentration impairment (26%; 95% CI 21% to 32%) and breathlessness (25%; 95% CI 18% to 34%). 37% (95% CI 18% to 60%) of patients reported reduced quality of life; 26% (10/39) of studies presented evidence of reduced pulmonary function.

          Conclusion

          Long COVID is a complex condition with prolonged heterogeneous symptoms. The nature of studies precludes a precise case definition or risk evaluation. There is an urgent need for prospective, robust, standardised, controlled studies into aetiology, risk factors and biomarkers to characterise long COVID in different at-risk populations and settings.

          PROSPERO registration number

          CRD42020211131.

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          Most cited references64

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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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            Quantifying heterogeneity in a meta-analysis.

            The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.
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              Rayyan—a web and mobile app for systematic reviews

              Background Synthesis of multiple randomized controlled trials (RCTs) in a systematic review can summarize the effects of individual outcomes and provide numerical answers about the effectiveness of interventions. Filtering of searches is time consuming, and no single method fulfills the principal requirements of speed with accuracy. Automation of systematic reviews is driven by a necessity to expedite the availability of current best evidence for policy and clinical decision-making. We developed Rayyan (http://rayyan.qcri.org), a free web and mobile app, that helps expedite the initial screening of abstracts and titles using a process of semi-automation while incorporating a high level of usability. For the beta testing phase, we used two published Cochrane reviews in which included studies had been selected manually. Their searches, with 1030 records and 273 records, were uploaded to Rayyan. Different features of Rayyan were tested using these two reviews. We also conducted a survey of Rayyan’s users and collected feedback through a built-in feature. Results Pilot testing of Rayyan focused on usability, accuracy against manual methods, and the added value of the prediction feature. The “taster” review (273 records) allowed a quick overview of Rayyan for early comments on usability. The second review (1030 records) required several iterations to identify the previously identified 11 trials. The “suggestions” and “hints,” based on the “prediction model,” appeared as testing progressed beyond five included studies. Post rollout user experiences and a reflexive response by the developers enabled real-time modifications and improvements. The survey respondents reported 40% average time savings when using Rayyan compared to others tools, with 34% of the respondents reporting more than 50% time savings. In addition, around 75% of the respondents mentioned that screening and labeling studies as well as collaborating on reviews to be the two most important features of Rayyan. As of November 2016, Rayyan users exceed 2000 from over 60 countries conducting hundreds of reviews totaling more than 1.6M citations. Feedback from users, obtained mostly through the app web site and a recent survey, has highlighted the ease in exploration of searches, the time saved, and simplicity in sharing and comparing include-exclude decisions. The strongest features of the app, identified and reported in user feedback, were its ability to help in screening and collaboration as well as the time savings it affords to users. Conclusions Rayyan is responsive and intuitive in use with significant potential to lighten the load of reviewers.
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                Author and article information

                Journal
                BMJ Glob Health
                BMJ Glob Health
                bmjgh
                bmjgh
                BMJ Global Health
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2059-7908
                2021
                27 September 2021
                27 September 2021
                : 6
                : 9
                : e005427
                Affiliations
                [1 ]departmentSchool of Health Sciences , City University of London , London, UK
                [2 ]departmentISARIC Global Support Centre, Centre for Tropical Medicine and Global Health , University of Oxford , Oxford, UK
                [3 ]departmentDepartment of Clinical Research, Faculty of Infectious and Tropical Diseases , London School of Hygiene and Tropical Medicine , London, UK
                [4 ]departmentBristol Medical School , University of Bristol , Bristol, UK
                [5 ]Long Covid Support , Birmingham, UK
                [6 ]departmentAnaesthetic Department , Queen Elizabeth Hospital , Kings Lynn, UK
                [7 ]Julius-Maximilians-Universität Würzburg , Würzburg, Bayern, Germany
                [8 ]departmentDepartment of Paediatrics and Paediatric Infectious Diseases, Institute of Child’s Health , Sechenov First Moscow State Medical University (Sechenov University) , Moscow, Russia
                [9 ]departmentInflammation, Repair and Development Section, National Heart and Lung Institute, Faculty of Medicine , Imperial College London , London, UK
                [10 ]Research and Clinical Center for Neuropsychiatry , Moscow, Russia
                [11 ]departmentBodleian Health Care Libraries , University of Oxford , Oxford, UK
                [12 ]Freelance , Soquel, California, USA
                [13 ]departmentMRC-University of Glasgow Centre for Virus Research , University of Glasgow , Glasgow, UK
                Author notes
                [Correspondence to ] Dr Charitini Stavropoulou; C.Stavropoulou@ 123456city.ac.uk

                LS and CS are joint senior authors.

                Author information
                http://orcid.org/0000-0003-3659-7788
                http://orcid.org/0000-0002-1786-8530
                http://orcid.org/0000-0002-6162-4146
                http://orcid.org/0000-0003-2075-2130
                http://orcid.org/0000-0001-8568-9107
                http://orcid.org/0000-0001-8439-9933
                http://orcid.org/0000-0003-4307-1848
                Article
                bmjgh-2021-005427
                10.1136/bmjgh-2021-005427
                8478580
                34580069
                d08b7080-044c-4505-b8bf-8407708a667f
                © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                History
                : 17 February 2021
                : 19 August 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 215091/Z/18/Z
                Funded by: FundRef http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: OPP1209135
                Funded by: FundRef http://dx.doi.org/10.13039/100011272, FP7 Health;
                Award ID: 602525
                Categories
                Original Research
                1506
                2474
                Custom metadata
                unlocked

                covid-19,public health,systematic review
                covid-19, public health, systematic review

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