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      Cytokines (IL1β, IL6, TNFα) and serum cortisol levels may not constitute reliable biomarkers to identify individuals with post-acute sequelae of COVID-19

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          Abstract

          Background:

          Post-acute sequelae of COVID-19 (PASC) comprise a broad spectrum of symptoms such as fatigue, general weakness, compromised attention and sleep or anxiety disorders. PASC represents a medical and socio-economic challenge.

          Objectives:

          Our study evaluated cytokines (IL-1β, IL-6 and TNFα) and cortisol levels in a cohort of typical patients with PASC, suffering concentration problems, fatigue and difficulties finding words.

          Design:

          This was a prospective cohort study. Four groups were analysed and compared: those who had never contracted SARS-CoV-2 ( n = 13), infected but had no PASC ( n = 34), infected with former PASC that resolved ( n = 40) and patients with ongoing PASC after infection ( n = 91).

          Methods:

          Cytokine and cortisol serum levels were determined in patients’ blood samples.

          Results:

          Cytokine levels of IL-1β, IL-6, TNFα and cortisol levels did not differ between groups analysed.

          Conclusion:

          This may indicate a non-organic/psychosomatic genesis of PASC; further studies are needed to elucidate the underlying causes of PACS, and non-organic causes should not be overlooked.

          Plain language summary

          Without clear biological markers for people who will continue to present with post-acute sequelae of COVID-19 (PASC) should we now focus on psychological factors?

          Many people across the globe are still suffering from post-acute sequelae of COVID-19 (PASC), commonly called post-COVID. Typical symptoms of PASC include severe tiredness (fatigue), concentration deficits (brain fog) or difficulty finding words. We need a better understanding of how these symptoms arise to find ways to help patients. Our team of researchers set out to explore this. We posed the question: could measurements of immune system activity provide an identifier for people who are susceptible to post-COVID?

          The participants in our study were divided into four groups: 1. A group of 13 people who had never contracted SARS-CoV-2. 2. A group of 34 people who had been infected with SARS-CoV-2 but had no PASC. 3. A group of 40 people who had been infected with SARS-CoV-2 and had already suffered from PASC that had now resolved. 4. A group of 91 people who were no longer sick with COVID-19 but were still suffering from PASC.

          Serum samples from all participants were taken to measure cytokine and cortisol levels. People with PASC could not be identified by testing their blood samples for cytokines (IL-1β, IL-6, TNFα) or cortisol. No difference between the four groups was found on any marker. Measuring these cytokines or cortisol is, therefore, unlikely to be useful in predicting which patients will suffer from PASC. Continuation of symptoms long after COVID-19 has passed is distressing for many people worldwide. Psychological factors may play a role and need to be studied further in order to help this patient population.

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          Most cited references21

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          Attributes and predictors of long COVID

          Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called 'long COVID', are rising but little is known about prevalence, risk factors or whether it is possible to predict a protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app1. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.
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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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              Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae

              Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Writing – original draft
                Role: Formal analysisRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: Data curation
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Writing – review & editing
                Journal
                Ther Adv Neurol Disord
                Ther Adv Neurol Disord
                TAN
                sptan
                Therapeutic Advances in Neurological Disorders
                SAGE Publications (Sage UK: London, England )
                1756-2856
                1756-2864
                12 February 2024
                2024
                : 17
                : 17562864241229567
                Affiliations
                [1-17562864241229567]Department of Neurology and Center for Translational and Behavioral Neurosciences, University Medicine Essen, University Duisburg-Essen, Essen, Germany
                [2-17562864241229567]Department of Neurology and Center for Translational and Behavioral Neurosciences, University Medicine Essen, University Duisburg-Essen, Essen, Germany
                [3-17562864241229567]Department of Neurology and Center for Translational and Behavioral Neurosciences, University Medicine Essen, University Duisburg-Essen, Essen, Germany
                [4-17562864241229567]Department of Neurology and Center for Translational and Behavioral Neurosciences, University Medicine Essen, University Duisburg-Essen, Essen, Germany
                [5-17562864241229567]Department of Neurology and Center for Translational and Behavioral Neurosciences, University Medicine Essen, University Duisburg-Essen, Essen, Germany
                [6-17562864241229567]Department of Endocrinology, Diabetes and Metabolism, Clinical Chemistry – Division of Laboratory Research, University Medicine Essen, University Duisburg-Essen, Essen, Germany
                [7-17562864241229567]Central Laboratory, University Medicine Essen, University Duisburg-Essen, Essen, Germany
                [8-17562864241229567]Department of Neurology and Center for Translational and Behavioral Neurosciences, University Medicine Essen, University Duisburg-Essen, Essen, Germany
                [9-17562864241229567]Department of Neurology and Center for Translational and Behavioral Neurosciences, University Medicine Essen, Hufelandstr. 55, Essen 45147, Germany
                Author notes
                Author information
                https://orcid.org/0000-0002-5720-8393
                https://orcid.org/0000-0001-5813-3242
                https://orcid.org/0000-0002-8836-0443
                Article
                10.1177_17562864241229567
                10.1177/17562864241229567
                10860378
                38348267
                50e2db3e-b9b1-4bd4-b39b-eeae80b2f401
                © The Author(s), 2024

                This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 6 November 2023
                : 15 January 2024
                Categories
                Brief Report
                Custom metadata
                January-December 2024
                ts1

                biomarker,immuno-profile,post-acute sequela of covid-19,sars-cov-2

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