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      ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma

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          Abstract

          ACE2 is the primary receptor for SARS‐CoV‐2. We demonstrate that lower airway expression of ACE2 is increased in older adults and males. Lower ACE2 expression in epithelial cells also occurs in people with asthma and is associated with reduced furin and increased ADAM‐17 expression. This may partly explain the relative sparing of people with asthma from severe COVID‐19.

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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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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Na Zhu, Dingyu Zhang, Wenling Wang … (2020)
            Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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              Is Open Access

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

              Peng Zhou, Xing-Lou Yang, Xian-Guang Wang … (2020)
              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.
              Article 0 comments Cited 10123 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Peter A.B. Wark: (View ORCID Profile)
                Mathew S. Eapen: (View ORCID Profile)
                Thomas Iosifidis: (View ORCID Profile)
                Journal
                Title: Respirology
                Abbreviated Title: Respirology
                Publisher: Wiley
                ISSN (Print): 1323-7799
                ISSN (Electronic): 1440-1843
                Publication date (Electronic): January 17 2021
                Affiliations
                [1 ]Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health University of Newcastle Newcastle NSW Australia
                [2 ]Department of Respiratory and Sleep Medicine John Hunter Hospital Newcastle NSW Australia
                [3 ]Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy University of Newcastle Newcastle NSW Australia
                [4 ]Telethon Kids Institute University of Western Australia Perth WA Australia
                [5 ]School of Public Health Curtin University Perth WA Australia
                [6 ]Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine University of Tasmania Launceston TAS Australia
                [7 ]Clinical Research Design and Statistics Hunter Medical Research Institute Newcastle NSW Australia
                [8 ]Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology University of Western Australia Perth WA Australia
                [9 ]Department of Respiratory and Sleep Medicine Perth Children's Hospital Perth WA Australia
                [10 ]Centre for Inflammation, Centenary Institute, and Faculty of Science University of Technology Sydney Sydney NSW Australia
                Article
                DOI: 10.1111/resp.14003
                SO-VID: 2564240d-0288-403a-bf7b-047902cec530
                Copyright © © 2021
                License:

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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