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      COVID-19 and the liver-related deaths to come

      brief-report
      Author(s): 1 , 2 ,
      Publication date (Electronic):
      Journal: Nature Reviews. Gastroenterology & Hepatology
      Publisher: Nature Publishing Group UK
      Keywords: Microbiology, SARS-CoV-2

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          Abstract

          Coronavirus disease 2019 (COVID-19) itself and/or the use of hepatotoxic drugs might negatively affect the course and management of patients with pre-existing chronic liver diseases. However, the greatest effect of COVID-19 on liver diseases will be indirect and delayed, resulting from the impending global economic crisis.

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          Autopsy Findings and Venous Thromboembolism in Patients With COVID-19

          Dominic Wichmann, Jan-Peter Sperhake, Marc Lütgehetmann … (2020)
          Background: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. Objective: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. Design: Prospective cohort study. Setting: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19. Patients: The first 12 consecutive COVID-19–positive deaths. Measurements: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS–CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. Limitation: Limited sample size. Conclusion: The high incidence of thromboembolic events suggests an important role of COVID-19–induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19–related death, as well as possible therapeutic interventions to reduce it. Primary Funding Source: University Medical Center Hamburg-Eppendorf.
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            Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

            Furong Qi, Shen Qian, Shuye Zhang … (2020)
            The new coronavirus (SARS-CoV-2) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by SARS-CoV-2 to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. SARS-CoV-2 may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted “CellPhoneDB” analysis to understand the cell crosstalk between CoV-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis.
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              Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

              Xiaoqiang Chai, Longfei Hu, Yan Yan Zhang … (2020)
              A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.
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                Author and article information

                Contributors
                Jean-Michel Pawlotsky:
                ORCID: http://orcid.org/0000-0003-0745-7559
                jean-michel.pawlotsky@aphp.fr
                Journal
                Journal ID (nlm-ta): Nat Rev Gastroenterol Hepatol
                Journal ID (iso-abbrev): Nat Rev Gastroenterol Hepatol
                Title: Nature Reviews. Gastroenterology & Hepatology
                Publisher: Nature Publishing Group UK (London )
                ISSN (Print): 1759-5045
                ISSN (Electronic): 1759-5053
                Publication date (Electronic): 11 June 2020
                Pages: 1-3
                Affiliations
                [1 ]ISNI 0000 0001 2149 7878, GRID grid.410511.0, Department of Virology, Hôpital Henri Mondor, , Université Paris-Est, ; Créteil, France
                [2 ]ISNI 0000 0004 0386 3258, GRID grid.462410.5, Viruses, Hepatology, Cancer research team, INSERM U955, ; Créteil, France
                Author information
                http://orcid.org/0000-0003-0745-7559
                Article
                Publisher ID: 328
                DOI: 10.1038/s41575-020-0328-2
                PMC ID: 7288259
                PubMed ID: 32528138
                SO-VID: 25fdfa69-3c26-4dc5-a9ed-8c71f7bf7f8d
                Copyright © © Springer Nature Limited 2020
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Categories
                Subject: Comment

                Keywords: microbiology,sars-cov-2
                Data availability:
                Keywords: microbiology, sars-cov-2

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