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      Autoantibodies in COVID-19 survivors with post-COVID symptoms: a systematic review

      systematic-review

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          Abstract

          Objective

          The long-lasting persistence of autoantibodies stands as one of the hypotheses explaining the multisystemic manifestations seen in individuals with post-COVID-19 condition. The current review offers restricted insights into the persistence of autoantibodies in plasma/serum in people with post-COVID symptoms.

          Methods

          PubMed/MEDLINE, CINAHL, EMBASE, and Web of Science databases, as well as on medRxiv and bioRxiv preprint servers were searched up to January 5 th, 2024. Papers investigating the presence of autoantibodies in plasma/serum samples in people with post-COVID symptoms were included. The Newcastle-Ottawa Scale (NOS) was used to assess methodological quality.

          Results

          From 162 identified records, five articles met all inclusion criteria; four studies included infected controls with no post-COVID symptoms whereas all five studies included non-infected controls (410 COVID-19 survivors with post-COVID symptoms, 223 COVID-19 survivors with no post-COVID symptoms as controls and 266 non-infected healthy controls). Four studies concluded that the presence of autoantibodies had a potential (but small) role in post-COVID-19 condition whereas one study concluded that autoantibodies were not associated. Quality assessment showed all studies had high methodological quality.

          Conclusion

          Although evidence suggests that persistent autoantibodies can be associated with post-COVID symptoms, the clinical relevance of their presence seems modest at this stage. Current results highlight further research to clarify the role of autoantibodies in the development of post-COVID symptoms, guiding the development of tailored diagnostic and treatment approaches to enhance patient outcomes.

          Systematic review registration

          https://osf.io/vqz28.

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          Most cited references22

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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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            Long COVID: major findings, mechanisms and recommendations

            Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process. Long COVID is an often debilitating illness of severe symptoms that can develop during or following COVID-19. In this Review, Davis, McCorkell, Vogel and Topol explore our knowledge of long COVID and highlight key findings, including potential mechanisms, the overlap with other conditions and potential treatments. They also discuss challenges and recommendations for long COVID research and care.
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              A clinical case definition of post-COVID-19 condition by a Delphi consensus

              People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1472885Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role: Role:
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                URI : https://loop.frontiersin.org/people/2772957Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2712108Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/291238Role: Role: Role:
                URI : https://loop.frontiersin.org/people/1280287Role: Role: Role:
                URI : https://loop.frontiersin.org/people/813940Role: Role: Role: Role: Role:
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                05 July 2024
                2024
                : 15
                : 1428645
                Affiliations
                [1] 1 Department of Pathology, Johns Hopkins University School of Medicine , Baltimore, MD, United States
                [2] 2 Pamantasan ng Lungsod ng Maynila College of Medicine , Manila, Philippines
                [3] 3 Department of Internal Medicine, Cardinal Santos Medical Center , San Juan, Philippines
                [4] 4 Faculty of Medicine and Surgery, University of Santo Tomas , Manila, Philippines
                [5] 5 College of Medicine, University of the Philippines Manila , Manila, Philippines
                [6] 6 Section of Clinical Biochemistry, University of Verona , Verona, Italy
                [7] 7 Clinical Laboratory, Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center , Madrid, OH, United States
                [8] 8 Department of Physical Therapy, Occupational Therapy, Physical Medicine and Rehabilitation, Universidad Rey Juan Carlos , Madrid, Spain
                Author notes

                Edited by: Jesus Martinez-Barnetche, National Institute of Public Health, Mexico

                Reviewed by: Siriruk Changrob, Cornell University, United States

                Tingting Zhang, Seattle Children’s Research Institute, United States

                *Correspondence: Kin Israel Notarte, kinotarte@ 123456gmail.com ; knotart1@ 123456jhmi.edu ; César Fernández-de-las-Peñas, cesar.fernandez@ 123456urjc.es
                Article
                10.3389/fimmu.2024.1428645
                11257835
                39035011
                196142fd-4847-4e67-a466-fd2ebaf9d53e
                Copyright © 2024 Notarte, Carandang, Velasco, Pastrana, Ver, Manalo, Ng, Grecia, Lippi, Henry and Fernández-de-las-Peñas

                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
                : 06 May 2024
                : 21 June 2024
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 24, Pages: 10, Words: 4414
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Immunology
                Systematic Review
                Custom metadata
                B Cell Biology

                Immunology
                long covid,pasc,post-covid-19,autoantibodies,sars-cov-2 infection (covid-19)
                Immunology
                long covid, pasc, post-covid-19, autoantibodies, sars-cov-2 infection (covid-19)

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