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      Extrapulmonary complications of COVID‐19: A multisystem disease?

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          Abstract

          The outbreak of coronavirus disease 2019 (COVID‐19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has been recently declared a pandemic by the World Health Organization. In addition to its acute respiratory manifestations, SARS‐CoV‐2 may also adversely affect other organ systems. To date, however, there is a very limited understanding of the extent and management of COVID‐19‐related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extrapulmonary manifestations of COVID‐19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes the current understanding of the extrapulmonary complications caused by COVID‐19 to improve the management and prognosis of patients with COVID‐19.

          Highlights

          • SARS‐CoV‐2 appears to adversely affect not only the respiratory system but also several other organ systems, including the urinary, cardiovascular, GI, and neurological systems.

          • To date, however, there is very limited understanding of the extent and management of COVID‐19‐related conditions outside of the pulmonary system.

          • Further research is needed to better understand the underlying mechanisms linking SARS‐CoV‐2 with the occurrence of multiple extra‐pulmonary complications.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Wei-jie Guan, Zheng-yi Ni, Yu Hu … (2020)
            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

              Fei Zhou, Ting Yu, Ronghui Du … (2020)
              Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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                Author and article information

                Contributors
                Ming‐Hua Zheng:
                ORCID: http://orcid.org/0000-0003-4984-2631
                zhengmh@wmu.edu.cn
                Journal
                Journal ID (nlm-ta): J Med Virol
                Journal ID (iso-abbrev): J. Med. Virol
                Journal ID (doi): 10.1002/(ISSN)1096-9071
                Journal ID (publisher-id): JMV
                Title: Journal of Medical Virology
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 0146-6615
                ISSN (Electronic): 1096-9071
                Publication date (Electronic): 22 July 2020
                Electronic Location Identifier: 10.1002/jmv.26294
                Affiliations
                [ 1 ] MAFLD Research Center, Department of Hepatology The First Affiliated Hospital of Wenzhou Medical University Wenzhou China
                [ 2 ] Xi'an Medical University Xi'an China
                [ 3 ] Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical University Wenzhou China
                [ 4 ] Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine University and Azienda Ospedaliera Universitaria Integrata of Verona Verona Italy
                [ 5 ] Southampton National Institute for Health Research Biomedical Research Center, Southampton General Hospital University Hospital Southampton Southampton UK
                Author notes
                [*] [* ] Correspondence Ming‐Hua Zheng, MD, PhD, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

                Email: zhengmh@ 123456wmu.edu.cn

                Author information
                https://orcid.org/0000-0002-1726-9298
                https://orcid.org/0000-0002-4325-3900
                https://orcid.org/0000-0001-6322-7753
                http://orcid.org/0000-0003-4984-2631
                Article
                Publisher ID: JMV26294
                DOI: 10.1002/jmv.26294
                PMC ID: 7405144
                PubMed ID: 32648973
                SO-VID: e83b87a8-eb8f-4a87-89d6-c14b124a1065
                Copyright © © 2020 Wiley Periodicals LLC
                License:

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                Date received : 20 April 2020
                Date accepted : 07 July 2020
                Page count
                Figures: 1, Tables: 1, Pages: 13, Words: 8719
                Funding
                Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;
                Award ID: 81500665
                Funded by: Southampton NIHR Biomedical Research Centre
                Award ID: IS‐BRC‐20004
                Categories
                Subject: Review
                Subject: Reviews
                Custom metadata
                source-schema-version-number 2.0
                edited-state corrected-proof
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.6 mode:remove_FC converted:05.08.2020

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: covid‐19,extrapulmonary manifestations,management,sars‐cov‐2
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: covid‐19, extrapulmonary manifestations, management, sars‐cov‐2

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