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      More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis

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      , MD, PhD 1 , * , , MD, PhD 2 , , BSc 3 , , MD PhD 4 , , MD, MSc 5 , 6 , , MD, Dr. Med 7 , , PhD 8 , 9 , *
      medRxiv
      Cold Spring Harbor Laboratory

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          Abstract

          COVID-19, caused by SARS-CoV-2, can involve sequelae and other medical complications that last weeks to months after initial recovery, which has come to be called Long-COVID or COVID long-haulers. This systematic review and meta-analysis aims to identify studies assessing long-term effects of COVID-19 and estimates the prevalence of each symptom, sign, or laboratory parameter of patients at a post-COVID-19 stage. LitCOVID (PubMed and Medline) and Embase were searched by two independent researchers. All articles with original data for detecting long-term COVID-19 published before 1 st of January 2021 and with a minimum of 100 patients were included. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. Heterogeneity was assessed using I 2 statistics. This systematic review followed Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines, although the study protocol was not registered. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included. The follow-up time ranged from 14 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. It was estimated that 80% (95% CI 65–92) of the patients that were infected with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13). In order to have a better understanding, future studies need to stratify by sex, age, previous comorbidities, severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom. From the clinical perspective, multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.

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          Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

          Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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            Persistent Symptoms in Patients After Acute COVID-19

            This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.
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              Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation.

              Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central's Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols--PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols. © BMJ Publishing Group Ltd 2014.
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                Author and article information

                Journal
                medRxiv
                MEDRXIV
                medRxiv
                Cold Spring Harbor Laboratory
                30 January 2021
                : 2021.01.27.21250617
                Affiliations
                [1 ]Drug Development, Novartis Pharmaceuticals, New Jersey, USA.
                [2 ]Instituto Nacional de Cancerología, Subdirección de Investigación básica, Ciudad de México, México,
                [3 ]National Autonomous University of Mexico, SOMEDICyT, RedMPC, México.
                [4 ]Harvard T.H. Chan School of Public Health Boston, Massachusetts, USA.
                [5 ]Divison of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.
                [6 ]Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
                [7 ]Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
                [8 ]Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, Texas, USA.
                [9 ]Department of Neuroscience in Neurological Surgery, Weill Cornell Medical College, New York, USA.
                Author notes
                [* ]Correspondence to Sonia Villapol, Ph.D., 6670 Bertnet Avenue, Houston, TX, 77030. svillapol@ 123456houstonmethodist.org .
                Author information
                http://orcid.org/0000-0001-7504-3441
                http://orcid.org/0000-0002-3207-6697
                http://orcid.org/0000-0002-0111-1154
                http://orcid.org/0000-0003-1146-9552
                http://orcid.org/0000-0002-9808-063X
                http://orcid.org/0000-0002-9451-1914
                http://orcid.org/0000-0002-6174-4113
                Article
                10.1101/2021.01.27.21250617
                7852236
                33532785
                a0bee10c-3141-4498-8e0e-f24c7587eed5

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.

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