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      Post-COVID Syndrome: An Insight on Its Pathogenesis

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          Abstract

          Post-COVID syndrome is increasingly recognized as a new clinical entity in the context of SARS-CoV-2 infection. Symptoms persisting for more than three weeks after the diagnosis of COVID-19 characterize the post-COVID syndrome. Its incidence ranges from 10% to 35%, however, rates as high as 85% have been reported among patients with a history of hospitalization. Currently, there is no consensus on the classification of post-COVID syndrome. We reviewed the published information on post-COVID syndrome, putting emphasis on its pathogenesis. The pathogenesis of post-COVID syndrome is multi-factorial and more than one mechanism may be implicated in several clinical manifestations. Prolonged inflammation has a key role in its pathogenesis and may account for some neurological complications, cognitive dysfunction, and several other symptoms. A multisystem inflammatory syndrome in adults (MIS-A) of all ages has been also described recently, similarly to multisystem inflammatory syndrome in children (MIS-C). The post-infectious inflammatory pathogenetic mechanism of MIS-A is supported by the fact that its diagnosis is established through serology in up to one third of cases. Other pathogenetic mechanisms that are implicated in post-COVID syndrome include immune-mediated vascular dysfunction, thromboembolism, and nervous system dysfunction. Although the current data are indicating that the overwhelming majority of patients with post-COVID syndrome have a good prognosis, registries to actively follow them are needed in order to define the full clinical spectrum and its long-term outcome. A consensus-based classification of post-COVID syndrome is essential to guide clinical, diagnostic, and therapeutic management. Further research is also imperative to elucidate the pathogenesis of post-COVID syndrome.

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          Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review

          The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.
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            6-month consequences of COVID-19 in patients discharged from hospital: a cohort study

            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

              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.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Vaccines (Basel)
                Vaccines (Basel)
                vaccines
                Vaccines
                MDPI
                2076-393X
                12 May 2021
                May 2021
                : 9
                : 5
                : 497
                Affiliations
                [1 ]Directorate of Research, Studies and Documentation, National Public Health Organization, 11523 Athens, Greece
                [2 ]Department of Travel Medicine, National Public Health Organization, 11523 Athens, Greece; androulapavli2017@ 123456gmail.com
                [3 ]Department of Microbiology, Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece; atsakris@ 123456gmail.com
                Author notes
                [* ]Correspondence: helen-maltezou@ 123456ath.forthnet.gr ; Tel.: +30-210-5212173
                Author information
                https://orcid.org/0000-0003-0264-3547
                https://orcid.org/0000-0003-0656-4715
                Article
                vaccines-09-00497
                10.3390/vaccines9050497
                8151752
                34066007
                a32b760d-7e06-4466-a9a7-06d59ee1d8e3
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 25 April 2021
                : 10 May 2021
                Categories
                Review

                covid-19,sars-cov-2,inflammation,post-infectious,complications,long term,pathogenesis

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