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      Hepatotropic Properties of SARS-CoV-2—Preliminary Results of Cross-Sectional Observational Study from the First Wave COVID-19 Pandemic

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          Abstract

          Liver injury—expressed as elevated liver enzymes—is common in patients with COVID-19. Little is known about the potential mechanisms of liver damage by SARS-CoV-2. A direct cytopathic effect on hepatocytes as well as injury related to hypoxia or hepatotoxicity are being considered. The aim of the study was to compare the clinical characteristic of COVID-19 disease in patients with normal and abnormal liver enzymes activity. A group of 150 patients with COVID-19, hospitalized in our center, was analyzed. Patients with the known liver comorbidities were excluded ( n = 15). Clinical features and laboratory parameters were compared between patients with normal and abnormal aminotransferase values. Liver injury expressed as any alanine aminotransferase (ALT) elevation was noted in 45.6% of patients hospitalized due to COVID-19. The frequencies of aspartate aminotransferase (AST) elevation were lower. It was noted that elevated ALT/AST unfavorably affected other parameters related to liver function such as albumin level; gamma-glutamyl transpeptidase (GGTP); and partly, ALP activity and influenced inflammation-related parameters. The most probable cause of mild hepatitis during COVID-19 was anoxia and immune-mediated damage due to the inflammatory response following SARS-CoV-2 infection. A direct cytopathic effect of SARS-CoV-2 on hepatocytes, albeit less probable, can be considered as well. The use of potentially hepatotoxic drugs may contribute to liver damage.

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          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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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            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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              SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

              Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                09 February 2021
                February 2021
                : 10
                : 4
                : 672
                Affiliations
                [1 ]Department of Infectious Diseases, Hepatology and Liver Transplantation, Pomeranian Medical University, 71-455 Szczecin, Poland; hankaaa.wisniewska@ 123456gmail.com (H.W.); ewakarpinska@ 123456interia.pl (E.K.); monika.a.hornung@ 123456gmail.com (M.H.); jurczykkrzysztof@ 123456interia.pl (K.J.); asklepiada@ 123456wp.pl (Ł.L.); theville@ 123456wp.pl (Ł.S.); dbander@ 123456interia.pl (D.B.)
                [2 ]Department of Biochemical Sciences, Pomeranian Medical University, 71-460 Szczecin, Poland; karzyd@ 123456pum.edu.pl
                [3 ]Department of Infectious, Tropical Diseases, and Immune Deficiency, Pomeranian Medical University, 71-455 Szczecin, Poland; milosz.parczewski@ 123456pum.edu.pl (M.P.); j.niscigorska-olsen@ 123456wp.pl (J.N.-O.); magdalenka86.mwj@ 123456gmail.com (M.W.-J.); kasiamaciejewsk@ 123456gmail.com (K.M.); celina.aga@ 123456gmail.com (A.L.); malwina_k_cieslak@ 123456tlen.pl (M.K.-C.); bogusz.aw@ 123456gmail.com (B.A.-W.)
                Author notes
                [* ]Correspondence: martaws@ 123456wp.pl or hepatologia@ 123456spwsz.szczecin.pl ; Tel./Fax: +48-91-813-9456
                Author information
                https://orcid.org/0000-0002-3430-9079
                https://orcid.org/0000-0003-1869-1084
                https://orcid.org/0000-0003-2092-3737
                Article
                jcm-10-00672
                10.3390/jcm10040672
                7916209
                33572429
                9dfc3e94-64ee-408a-bd49-4d639f3087b4
                © 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 ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 December 2020
                : 04 February 2021
                Categories
                Article

                covid-19,sars-cov-2 infection,liver enzyme abnormality,liver dysfunction

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