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      Unraveling the Mystery Surrounding Post-Acute Sequelae of COVID-19

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          Abstract

          More than one year since its emergence, corona virus disease 2019 (COVID-19) is still looming large with a paucity of treatment options. To add to this burden, a sizeable subset of patients who have recovered from acute COVID-19 infection have reported lingering symptoms, leading to significant disability and impairment of their daily life activities. These patients are considered to suffer from what has been termed as “chronic” or “long” COVID-19 or a form of post-acute sequelae of COVID-19, and patients experiencing this syndrome have been termed COVID-19 long-haulers. Despite recovery from infection, the persistence of atypical chronic symptoms, including extreme fatigue, shortness of breath, joint pains, brain fogs, anxiety and depression, that could last for months implies an underlying disease pathology that persist beyond the acute presentation of the disease. As opposed to the direct effects of the virus itself, the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be largely responsible for the appearance of these lasting symptoms, possibly through facilitating an ongoing inflammatory process. In this review, we hypothesize potential immunological mechanisms underlying these persistent and prolonged effects, and describe the multi-organ long-term manifestations of COVID-19.

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          A pneumonia outbreak associated with a new coronavirus of probable bat origin

          Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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            Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

            Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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              Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

              The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                30 June 2021
                2021
                30 June 2021
                : 12
                : 686029
                Affiliations
                [1] 1 College of Medicine, University of Sharjah , Sharjah, United Arab Emirates
                [2] 2 Sharjah Institute for Medical Research, University of Sharjah , Sharjah, United Arab Emirates
                [3] 3 Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, King Saud University , Riyadh, Saudi Arabia
                [4] 4 Meakins-Christie Laboratories, Research Institute of the McGill University Healthy Center, McGill University , Montreal, QC, Canada
                [5] 5 Prince Abdullah Ben Khaled Celiac Disease Chair, Department of Pediatrics, Faculty of Medicine, King Saud University , Riyadh, Saudi Arabia
                [6] 6 Infectious Diseases Section, Department of Medical Specialties, King Fahad Medical City , Riyadh, Saudi Arabia
                [7] 7 College of Medicine, Alfaisal University , Riyadh, Saudi Arabia
                [8] 8 Division of Infectious Diseases, Mayo Clinic College of Medicine and Science , Rochester, MN, United States
                [9] 9 Division of Epidemiology, Mayo Clinic College of Medicine and Science , Rochester, MN, United States
                Author notes

                Edited by: Gennady Bocharov, Institute of Numerical Mathematics (RAS), Russia

                Reviewed by: Vito Salvador Hernandez, National Autonomous University of Mexico, Mexico; Venkata Bollimpelli, Emory University, United States

                *Correspondence: Imad M. Tleyjeh, Tleyjeh.Imad@ 123456mayo.edu ; Rabih Halwani, rhalwani@ 123456sharjah.ac.ae

                This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology

                †These authors share senior authorship

                Article
                10.3389/fimmu.2021.686029
                8278217
                34276671
                ae167f81-49eb-4f37-80b9-85ddb8617c69
                Copyright © 2021 Ramakrishnan, Kashour, Hamid, Halwani and Tleyjeh

                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
                : 26 March 2021
                : 14 June 2021
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 153, Pages: 16, Words: 8572
                Categories
                Immunology
                Review

                Immunology
                long covid-19,chronic covid-19,long-haulers,sars-cov-2,clinical manifestations,immunopathology,post-acute covid-19 syndrome,post-acute sequelae of covid-19

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