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      ACE-2 down-regulation may act as a transient molecular disease causing RAAS dysregulation and tissue damage in the microcirculatory environment among COVID-19 patients

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          Abstract

          SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the etiological agent of COVID-19 (coronavirus disease 2019) and the cause of the current pandemic, produces multiform manifestations throughout the body, causing indiscriminate damage to multiple organ systems, particularly the lungs, heart, brain, kidney, and vasculature. The aim of this review is to provide a new look at the data already available for COVID-19, exploring it as a transient molecular disease that causes negative regulation of ACE-2 (angiotensin-converting enzyme 2) and, consequently, deregulates the renin-angiotensin-aldosterone system (RAAS), promoting important changes in the microcirculatory environment. In addition, the authors seek to demonstrate how these microcirculatory changes may be responsible for the wide variety of injury mechanisms observed in different organs in this disease. This new proposed concept of COVID-19 provides a unifying pathophysiological picture of this infection and offers new insights for a rational treatment strategy to combat this new pandemic.

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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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              Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

              Zunyou Wu, Jennifer M. McGoogan (2020)
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                Author and article information

                Journal
                Journal ID (nlm-ta): Am J Pathol
                Journal ID (iso-abbrev): Am J Pathol
                Title: The American Journal of Pathology
                Publisher: Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology.
                ISSN (Print): 0002-9440
                ISSN (Electronic): 1525-2191
                Publication date PMC-release: 6 May 2021
                Publication date (Electronic): 6 May 2021
                Affiliations
                [1 ]Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
                [2 ]Centro di Ricerca Lino Rossi, Anatomic Pathology MED-08, Università degli Studi di Milano, Milan, Italy
                [3 ]Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goias, Goiania, Goias, Brazil
                [4 ]Department of Pathology, Faculty of Medicine, Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil
                Author notes
                [∗ ] Correspondence should be addressed to: Simone G. Ramos, Associate Professor of Pathology, Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, 14049-900, Ribeirão Preto, São Paulo, Brazil. Tel: +55 16 3315-3341
                Article
                Publisher Item ID: S0002-9440(21)00194-2
                DOI: 10.1016/j.ajpath.2021.04.010
                PMC ID: 8099789
                PubMed ID: 33964216
                SO-VID: 1d285ca8-2b25-46bb-bffe-253c09a5ed81
                Copyright © © 2021 Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 6 January 2021
                Date revision received : 5 April 2021
                Date accepted : 22 April 2021
                Categories
                Subject: Review

                ScienceOpen disciplines: Pathology
                Keywords: covid-19,ace-2,ang ii,microcirculation,immunothrombosis,thromboinflammation,pathogenesis,molecular disease
                Data availability:
                ScienceOpen disciplines: Pathology
                Keywords: covid-19, ace-2, ang ii, microcirculation, immunothrombosis, thromboinflammation, pathogenesis, molecular disease

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