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      Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: A systematic review and meta-analysis

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          Abstract

          Background

          Post-acute COVID-19 Syndrome is now recognized as a complex systemic disease that is associated with substantial morbidity.

          Objectives

          To estimate the prevalence of persistent symptoms and signs at least 12 weeks after acute COVID-19 at different follow-up periods.

          Data sources

          Searches were conducted up to October 2021 in Ovid Embase, Ovid Medline, and PubMed.

          Study eligibility criteria

          Articles in English that reported the prevalence of persistent symptoms among individuals with confirmed SARS-CoV-2 infection and included at least 50 patients with a follow-up of at least 12 weeks after acute illness.

          Methods

          Random-effect meta-analysis was performed to produce pooled prevalence for each symptom at 4 different follow-up time intervals. Between-studies heterogeneity was evaluated using the I 2 statistic and was explored via meta-regression, considering several a priori study level variables. Risk of bias was assessed using the Joanna Briggs Institute (JBI) tool and the Newcastle-Ottawa Scale for prevalence studies and comparative studies, respectively.

          Results

          After screening 3209 studies, a total of 63 studies were eligible, with a total COVID-19 population of 257,348. The most commonly reported symptoms were fatigue, dyspnea, sleep disorder and concentration difficulty (32%, 25%, 24%, and 22% respectively at 3-<6 months follow-up), effort intolerance, fatigue, sleep disorder and dyspnea (45%, 36%, 29% and 25% respectively at 6-<9 months follow-up), fatigue (37%) and dyspnea (21%) at 9-<12 months and fatigue, dyspnea, sleep disorder, myalgia (41%, 31%, 30%, and 22% respectively at >12 months follow-up). There was substantial between-studies heterogeneity for all reported symptoms prevalence.

          Meta-regressions identified statistically significant effect modifiers: world region, male gender, diabetes mellitus, disease severity and overall study quality score. Five of six studies including a comparator group consisting of COVID-19 negative cases observed significant adjusted associations between COVID-19 and several long-term symptoms.

          Conclusions

          This systematic review found that a large proportion of patients experience PACS 3 to 12 months after recovery from the acute phase of COVD-19. However, available studies of PACS are highly heterogeneous. Future studies need to have appropriate comparator groups, standardized symptoms definitions and measurements and longer follow-up.

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

          David Moher, Larissa Shamseer, Mike Clarke … (2017)
          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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            6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

            Chaolin Huang, Lixue Huang, Yeming Wang … (2021)
            Background The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity. Methods We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences. Findings In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up. Interpretation At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery. Funding National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.
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              Post-acute COVID-19 syndrome

              Ani Nalbandian, Kartik Sehgal, Aakriti Gupta … (2021)
              Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.
              Article 0 comments Cited 1888 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Microbiol Infect
                Journal ID (iso-abbrev): Clin Microbiol Infect
                Title: Clinical Microbiology and Infection
                Publisher: European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd.
                ISSN (Print): 1198-743X
                ISSN (Electronic): 1469-0691
                Publication date PMC-release: 3 February 2022
                Publication date (Electronic): 3 February 2022
                Affiliations
                [1 ]Department of Family & Community Medicine, Alfaisal University, Riyadh, Saudi Arabia
                [2 ]The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom
                [3 ]Barts and the London School of Medicine and Dentistry, Queen Mary University, London, United Kingdom
                [4 ]College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
                [5 ]Center for Clinical Trial Research, School of Medicine, Cardiff University, United Kingdom
                [6 ]UMass chan medical school, Baystate, MA, USA
                [7 ]Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA
                [8 ]Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh Saudi Arabia
                [9 ]Infectious Diseases Section, Department of Medical Specialties King Fahad Medical City, Riyadh, Saudi Arabia
                [10 ]Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
                [11 ]Department of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
                Author notes
                [∗ ]Corresponding author. Professor of Medicine and Epidemiology, Section of Infectious Diseases, King Fahd Medical City, PO Box 59046, Riyadh 11525, Saudi Arabia. Tel.: +966112889999.
                [∗∗]

                These 2 authors contributed equally as first authors.

                [#]

                These 4 authors contributed equally as second authors.

                Article
                Publisher Item ID: S1198-743X(22)00038-6
                DOI: 10.1016/j.cmi.2022.01.014
                PMC ID: 8812092
                PubMed ID: 35124265
                SO-VID: 10b21e06-bc31-4ec2-af3b-89509377fcf3
                Copyright © © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 2 July 2021
                Date revision received : 13 January 2022
                Date accepted : 17 January 2022
                Categories
                Subject: Systematic Review

                ScienceOpen disciplines: Microbiology & Virology
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology

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