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Singh L, Kumar A, Rai M, Basnet B, Rai N, Khanal P, Lai KS, Cheng WH, Asaad AM, Ansari S. Spectrum of COVID-19 induced liver injury: A review report. World J Hepatol 2024; 16:517-536. [PMID: 38689748 PMCID: PMC11056898 DOI: 10.4254/wjh.v16.i4.517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 01/20/2024] [Accepted: 02/28/2024] [Indexed: 04/24/2024] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has caused changes in the global health system, causing significant setbacks in healthcare systems worldwide. This pandemic has also shown resilience, flexibility, and creativity in reacting to the tragedy. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection targets most of the respiratory tract, resulting in a severe sickness called acute respiratory distress syndrome that may be fatal in some individuals. Although the lung is the primary organ targeted by COVID-19 viruses, the clinical aspect of the disease is varied and ranges from asymptomatic to respiratory failure. However, due to an unorganized immune response and several affected mechanisms, the liver may also experience liver cell injury, ischemic liver dysfunction, and drug-induced liver injury, which can result in respiratory failure because of the immune system's disordered response and other compromised processes that can end in multisystem organ failure. Patients with liver cirrhosis or those who have impaired immune systems may be more likely than other groups to experience worse results from the SARS-CoV-2 infection. We thus intend to examine the pathogenesis, current therapy, and consequences of liver damage concerning COVID-19.
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Affiliation(s)
- Lokjan Singh
- Department of Microbiology, Karnali Academy of Health Science, Teaching Hospital, Jumla 21200, Karnali, Nepal
| | - Anil Kumar
- Department of Microbiology, Karnali Academy of Health Science, Teaching Hospital, Jumla 21200, Karnali, Nepal
| | - Maya Rai
- Department of Microbiology, Karnali Academy of Health Science, Teaching Hospital, Jumla 21200, Karnali, Nepal
| | - Bibek Basnet
- Health Sciences, Asian College of Advance Studies, Purbanchal University, Satdobato 24122, Lalitpur, Nepal
| | - Nishant Rai
- Department of Biotechnology, Graphic Era (Deemed to be University), Dehradun 248002, Uttarakhand, India
| | - Pukar Khanal
- Department of Pharmacology & Toxicology, KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi 590010, Karnataka, India
| | - Kok-Song Lai
- Division of Health Sciences, Abu Dhabi Women's College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates
| | - Wan-Hee Cheng
- Health and Life Sciences, INTI International University, Nilai 71800, Malaysia
| | - Ahmed Morad Asaad
- Department of Microbiology, College of Medicine, Zagazig University, Zagazig 44519, Egypt
| | - Shamshul Ansari
- Division of Health Sciences, Abu Dhabi Women's College, Higher Colleges of Technology, Abu Dhabi 41012, United Arab Emirates.
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Quarleri J, Delpino MV. Molecular mechanisms underlying SARS-CoV-2 hepatotropism and liver damage. World J Hepatol 2024; 16:1-11. [PMID: 38313242 PMCID: PMC10835487 DOI: 10.4254/wjh.v16.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/04/2023] [Accepted: 12/28/2023] [Indexed: 01/23/2024] Open
Abstract
In coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) primarily targets the respiratory system, but evidence suggests extrapulmonary organ involvement, notably in the liver. Viral RNA has been detected in hepatic tissues, and in situ hybridization revealed virions in blood vessels and endothelial cells. Electron microscopy confirmed viral particles in hepatocytes, emphasizing the need for understanding hepatotropism and direct cytopathic effects in COVID-19-related liver injury. Various factors contribute to liver injury, including direct cytotoxicity, vascular changes, inflammatory responses, immune reactions from COVID-19 and vaccinations, and drug-induced liver injury. Although a typical hepatitis presentation is not widely documented, elevated liver biochemical markers are common in hospitalized COVID-19 patients, primarily showing a hepatocellular pattern of elevation. Long-term studies suggest progressive cholestasis may affect 20% of patients with chronic liver disease post-SARS-CoV-2 infection. The molecular mechanisms underlying SARS-CoV-2 infection in the liver and the resulting liver damage are complex. This "Editorial" highlights the expression of the Angiotensin-converting enzyme-2 receptor in liver cells, the role of inflammatory responses, the impact of hypoxia, the involvement of the liver's vascular system, the infection of bile duct epithelial cells, the activation of hepatic stellate cells, and the contribution of monocyte-derived macrophages. It also mentions that pre-existing liver conditions can worsen the outcomes of COVID-19. Understanding the interaction of SARS-CoV-2 with the liver is still evolving, and further research is required.
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Affiliation(s)
- Jorge Quarleri
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1121, Argentina.
| | - M Victoria Delpino
- Instituto de Investigaciones Biomédicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1121, Argentina
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3
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Romero-Velez G, Ponce de Leon-Ballesteros G, Al Zubaidi M, Barajas-Gamboa JS, Dang J, Corcelles R, Strong AT, Navarrete S, Kroh M. Presence of SARS-CoV-2 in abdominal tissues and biologic fluids during abdominal surgery: a systematic review. Surg Endosc 2023:10.1007/s00464-023-10130-w. [PMID: 37219799 DOI: 10.1007/s00464-023-10130-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 05/08/2023] [Indexed: 05/24/2023]
Abstract
BACKGROUND Viral transmission to healthcare providers during surgical procedures was a major concern at the outset of the COVID-19 pandemic. The presence of the severe acute respiratory disease syndrome coronavirus (SARS-CoV-2), the virus responsible for COVID-19, in the abdominal cavity as well as in other abdominal tissues which surgeons are exposed has been investigated in several studies. The aim of the present systematic review was to analyze if the virus can be identify in the abdominal cavity. METHODS We performed a systematic review to identify relevant studies regarding the presence of SARS-CoV-2 in abdominal tissues or fluids. Number of patients included as well as patient's characteristics, type of procedures, samples and number of positive samples were analyzed. RESULTS A total of 36 studies were included (18 case series and 18 case reports). There were 357 samples for detection of SARS-CoV-2, obtained from 295 individuals. A total of 21 samples tested positive for SARS-CoV-2 (5.9%). Positive samples were more frequently encountered in patients with severe COVID-19 (37.5% vs 3.8%, p < 0.001). No health-care provider related infections were reported. CONCLUSION Although a rare occurrence, SARS-CoV-2 can be found in the abdominal tissues and fluids. It seems that the presence of the virus in the abdominal tissues or fluids is more likely in patients with severe disease. Protective measures should be employed in the operating room to protect the staff when operating patients with COVID-19.
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Affiliation(s)
- Gustavo Romero-Velez
- Department of Endocrine Surgery, Cleveland Clinic, 9500 Euclid Avenue, Mail Code F20, Cleveland, OH, 44195, USA.
| | | | - Maryam Al Zubaidi
- Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Juan S Barajas-Gamboa
- Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Jerry Dang
- Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Ricard Corcelles
- Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Andrew T Strong
- Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Salvador Navarrete
- Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Mathew Kroh
- Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
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Liatsos GD. SARS-CoV-2 induced liver injury: Incidence, risk factors, impact on COVID-19 severity and prognosis in different population groups. World J Gastroenterol 2023; 29:2397-2432. [PMID: 37179584 PMCID: PMC10167898 DOI: 10.3748/wjg.v29.i16.2397] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 02/17/2023] [Accepted: 04/07/2023] [Indexed: 04/24/2023] Open
Abstract
Liver is unlikely the key organ driving mortality in coronavirus disease 2019 (COVID-19) however, liver function tests (LFTs) abnormalities are widely observed mostly in moderate and severe cases. According to this review, the overall prevalence of abnormal LFTs in COVID-19 patients ranges from 2.5% to 96.8% worldwide. The geographical variability in the prevalence of underlying diseases is the determinant for the observed discrepancies between East and West. Multifactorial mechanisms are implicated in COVID-19-induced liver injury. Among them, hypercytokinemia with "bystander hepatitis", cytokine storm syndrome with subsequent oxidative stress and endotheliopathy, hypercoagulable state and immuno-thromboinflammation are the most determinant mechanisms leading to tissue injury. Liver hypoxia may also contribute under specific conditions, while direct hepatocyte injury is an emerging mechanism. Except for initially observed severe acute respiratory distress syndrome corona virus-2 (SARS-CoV-2) tropism for cholangiocytes, more recent cumulative data show SARS-CoV-2 virions within hepatocytes and sinusoidal endothelial cells using electron microscopy (EM). The best evidence for hepatocellular invasion by the virus is the identification of replicating SARS-CoV-2 RNA, S protein RNA and viral nucleocapsid protein within hepatocytes using in-situ hybridization and immunostaining with observed intrahepatic presence of SARS-CoV-2 by EM and by in-situ hybridization. New data mostly derived from imaging findings indicate possible long-term sequelae for the liver months after recovery, suggesting a post-COVID-19 persistent live injury.
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Affiliation(s)
- George D Liatsos
- Department of Internal Medicine, Hippokration General Hospital, Athens 11527, Attiki, Greece
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Detection of Porcine Deltacoronavirus RNA in the Upper and Lower Respiratory Tract and Biliary Fluid and the Effect of Infection on Serum Cholesterol Levels and Blood T Cell Population Frequencies in Gnotobiotic Piglets. Vet Sci 2023; 10:vetsci10020117. [PMID: 36851421 PMCID: PMC9962660 DOI: 10.3390/vetsci10020117] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/26/2023] [Accepted: 01/30/2023] [Indexed: 02/09/2023] Open
Abstract
Porcine deltacoronavirus (PDCoV) was first identified approximately a decade ago, but much is still obscure in terms of its pathogenesis. We aimed to further characterize PDCoV infection by investigating the presence of virus in respiratory and biliary tissues or fluids; T cell population frequencies in blood; and altered serum cholesterol levels. Twelve, 6-day-old, gnotobiotic piglets were inoculated oronasally with PDCoV OH-FD22 (2.6 × 107 FFU/pig). Six control piglets were not inoculated. Rectal swab (RS), nasal swab (NS), nasal wash (NW), bronchoalveolar lavage (BAL), and biliary fluid (BF) samples were collected at 2, 4, and 7 days post-inoculation (DPI) and tested for PDCoV RNA by RT-qPCR. Blood T cell populations and serum cholesterol levels were determined by flow cytometry and a colorimetric assay, respectively. Moderate to high, and low to moderate titers of PDCoV RNA were detected in RS and in NS, NW, BAL, and BF samples, respectively, of inoculated piglets. There were trends toward decreased CD4+CD8-, CD4-CD8+, and CD4+CD8+ blood T cell frequencies in inoculated piglets. Furthermore, serum cholesterol levels were increased in inoculated piglets. Overall, we found that PDCoV infection does not exclusively involve the intestine, since the respiratory and biliary systems and cholesterol metabolism also can be affected.
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Schwarz S, Lang C, Harlander M, Štupnik T, Slambrouck JV, Ceulemans LJ, Ius F, Gottlieb J, Kuhnert S, Hecker M, Aigner C, Kneidinger N, Verschuuren EAM, Smits JM, Tschernko E, Schaden E, Faybik P, Markstaller K, Trauner M, Jaksch P, Hoetzenecker K. Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS. J Heart Lung Transplant 2022; 41:1501-1510. [PMID: 35907758 PMCID: PMC9249665 DOI: 10.1016/j.healun.2022.06.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 06/20/2022] [Accepted: 06/24/2022] [Indexed: 01/31/2023] Open
Abstract
BACKGROUND Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. METHODS This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. RESULTS A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). CONCLUSIONS SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing.
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Affiliation(s)
- Stefan Schwarz
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Christian Lang
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Matevz Harlander
- Department of Pulmonary Diseases, University Medical Center, Ljubljana, Slovenia
| | - Tomaz Štupnik
- Department of Thoracic Surgery, University Medical Center, Ljubljana, Slovenia
| | - Jan Van Slambrouck
- Department of Thoracic Surgery, Lab of BREATHE, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Laurens J. Ceulemans
- Department of Thoracic Surgery, Lab of BREATHE, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Fabio Ius
- Department of Cardiothoracic, Transplant and Vascular Surgery, Hannover Medical School, Hannover, Germany
| | - Jens Gottlieb
- Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
| | - Stefan Kuhnert
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine II, University Hospital Giessen, Justus Liebig University of Giessen, Giessen, Germany
| | - Matthias Hecker
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine II, University Hospital Giessen, Justus Liebig University of Giessen, Giessen, Germany
| | - Clemens Aigner
- Department of Thoracic Surgery, West German Cancer Center, University Medicine Essen - Ruhrlandklinik, Essen, Germany
| | - Nikolaus Kneidinger
- Department of Medicine V, University Hospital, LMU Munich, Comprehensive Pneumology Center (CPC), Member of German Center for Lung Research (DZL), Munich, Germany
| | - Erik AM. Verschuuren
- Department of Respiratory Diseases, Tuberculosis and Lung Transplantation, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Edda Tschernko
- Division of Cardiac, Thoracic and Vascular Anesthesia and Intensive Care, Medical University of Vienna, Vienna, Austria
| | - Eva Schaden
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Peter Faybik
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Klaus Markstaller
- Department of Anaesthesia, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Peter Jaksch
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Konrad Hoetzenecker
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria,Reprint requests: Konrad Hoetzenecker, MD PhD, Division of Thoracic Surgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna. Telephone: +43-1-404-005-6440. Fax: +43-1-404-005-1000
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7
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Alnamshan MM. Potential histopathological and immunological effects of SARS-CoV-2 on the liver. BRAZ J BIOL 2022; 82:e262008. [PMID: 36074418 DOI: 10.1590/1519-6984.262008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 07/05/2022] [Indexed: 12/15/2022] Open
Abstract
The coronavirus disease outbreak of 2019 (COVID-19) poses a serious threat to public health worldwide. Lung injury is the most common complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, other organs, including the liver, can also be affected. Currently, there is limited evidence that liver impairment is associated with severe SARS-CoV-2 infection. Clinicians will need to determine whether liver injury is caused by an underlying liver condition, COVID-19 therapy, the virus directly, or immune-mediated inflammation or represents a complicated disease course in the context of COVID-19. To address the scarcity of data on histopathological changes and immunological effects on the liver with COVID-19 positivity, we analyze and summarize recent findings. We searched PubMed, Medline, Google Scholar, Science Direct, Scopus, and Web of Science databases up to December 1, 2021, identifying published studies with the search terms "Histopathology in COVID-19," "COVID-19," "Pathological changes in liver in COVID-19," "Liver pathology in COVID-19," "immunological effects in liver in COVID-19," and "SARS-CoV-2." This concise review will aid clinicians and researchers in better understanding the tissue histopathology and immunological consequences of SARS-CoV-2 on the liver, enabling improved care planning and avoiding future dangers.
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Affiliation(s)
- M M Alnamshan
- Imam Abdulrahman Bin Faisal University, College of Science, Department of Biology, Dammam, Saudi Arabia
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8
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Brogna C, Brogna B, Bisaccia DR, Giuliano M, Montano L, Cristoni S, Petrillo M, Piscopo M. SARS-CoV-2: Reinfection after 18 Months of a Previous Case with Multiple Negative Nasopharyngeal Swab Tests and Positive Fecal Molecular Test. Medicina (B Aires) 2022; 58:medicina58050642. [PMID: 35630059 PMCID: PMC9148128 DOI: 10.3390/medicina58050642] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 04/28/2022] [Accepted: 05/03/2022] [Indexed: 11/16/2022] Open
Abstract
This short communication describes the reinfection after nearly 18 months of the same patient who was previously infected with coronavirus disease 2019 (COVID-19) and who showed multiple negative real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) results by nasal swabs for severe acute respiratory syndrome coronavirus (SARS-CoV-2) but positive results on a fecal sample. We previously noted how, in the presence of symptoms suggestive of pneumonia, visible on a chest computed tomography (CT) scan and confirmed by fecal molecular testing, it was possible to draw the diagnosis of SARS-CoV-2 infection. One year later, the same patient was again affected by SARS-CoV-2. This time, the first antigenic nasal swab showed readily positive results. However, the patient’s clinical course appeared to be more attenuated, showing no signs of pulmonary involvement in the radiographic examinations performed. This case shows a novelty in the pulmonary radiological evaluation of new SARS-CoV-2 infection.
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Affiliation(s)
- Carlo Brogna
- Department of Research, Craniomed Group Facility SRL, 83038 Montemiletto, Italy;
- Correspondence: (C.B.); (B.B.)
| | - Barbara Brogna
- Department of Radiology, Moscati Hospital, Contrada Amoretta, 83100 Avellino, Italy
- Correspondence: (C.B.); (B.B.)
| | | | - Marino Giuliano
- Marsanconsulting Srl Public Health Company, Via dei Fiorentini, 80133 Napoli, Italy;
| | - Luigi Montano
- Andrology Unit and Service of LifeStyle Medicine in Uro-Andrology, Local Health Authority (ASL), 84124 Salerno, Italy;
| | | | | | - Marina Piscopo
- Department of Biology, University of Naples Federico II, 80126 Napoli, Italy;
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Abstract
PURPOSE OF REVIEW The objective of this review is to examine the epidemiology and pathogenesis of liver injury in coronavirus disease 2019 (COVID-19) and the impact of COVID-19 on patients with chronic liver disease (CLD) and liver transplant recipients. RECENT FINDINGS Abnormal liver chemistries occur in up to 60% of COVID-19 patients and are typically mild. COVID-19- associated liver injury may be because of direct viral cytopathic effect, immune-mediated damage, hypoxia, drug-induced liver injury (DILI), or exacerbation of CLD. COVID-19 patients with CLD and who are liver transplant recipients are at risk for severe disease and mortality. COVID-19 precipitated hepatic decompensation in 20-46% of cirrhotic patients. Alcohol consumption and cases of acute alcohol- associated hepatitis increased during the COVID-19 pandemic. Corticosteroids and calcineurin inhibitors are well tolerated to use during COVID-19 but immunomodulators have been associated with mortality. Less than 50% of transplant recipients produce adequate antibody titers after COVID-19 vaccination. SUMMARY COVID-19 patients with CLD should be monitored for liver injury and hepatic decompensation. Patients with CLD and liver transplant recipients should be considered for targeted COVID-19 pharmacotherapeutics and advised vaccination against COVID-19, including a third booster dose. CLD treatments and immunosuppression in liver transplant recipients could generally continue without interruption during COVID-19 infection, with the possible exception of immunomodulators.
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Affiliation(s)
- James Philip Esteban
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Lindsay Sobotka
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University Wexner Medical Center, Colmbus, Ohio
| | - Don C Rockey
- Division of Gastroenterology and Hepatology, Medical University of South Carolina, South Carolina, Charleston, USA
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Wang FS, Chen KL, Chu SW. Human/SARS-CoV-2 genome-scale metabolic modeling to discover potential antiviral targets for COVID-19. J Taiwan Inst Chem Eng 2022; 133:104273. [PMID: 35186172 PMCID: PMC8843340 DOI: 10.1016/j.jtice.2022.104273] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2021] [Revised: 02/06/2022] [Accepted: 02/11/2022] [Indexed: 12/20/2022]
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) has caused a substantial increase in mortality and economic and social disruption. The absence of US Food and Drug Administration-approved drugs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need for new therapeutic drugs to combat COVID-19. METHODS The present study proposed a fuzzy hierarchical optimization framework for identifying potential antiviral targets for COVID-19. The objectives in the decision-making problem were not only to evaluate the elimination of the virus growth, but also to minimize side effects causing treatment. The identified candidate targets could promote processes of drug discovery and development. SIGNIFICANT FINDINGS Our gene-centric method revealed that dihydroorotate dehydrogenase (DHODH) inhibition could reduce viral biomass growth and metabolic deviation by 99.4% and 65.6%, respectively, and increase cell viability by 70.4%. We also identified two-target combinations that could completely block viral biomass growth and more effectively prevent metabolic deviation. We also discovered that the inhibition of two antiviral metabolites, cytidine triphosphate (CTP) and uridine-5'-triphosphate (UTP), exhibits effects similar to those of molnupiravir, which is undergoing phase III clinical trials. Our predictions also indicate that CTP and UTP inhibition blocks viral RNA replication through a similar mechanism to that of molnupiravir.
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Affiliation(s)
- Feng-Sheng Wang
- Department of Chemical Engineering, National Chung Cheng University, Chiayi 621301, Taiwan
| | - Ke-Lin Chen
- Department of Chemical Engineering, National Chung Cheng University, Chiayi 621301, Taiwan
| | - Sz-Wei Chu
- Department of Chemical Engineering, National Chung Cheng University, Chiayi 621301, Taiwan
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11
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Vologzhanin DA, Golota AS, Kamilova TA, Makarenko SV, Scherbak SG. Liver damage in patients with COVID-19. MEDICINE OF EXTREME SITUATIONS 2022. [DOI: 10.47183/mes.2022.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
The clinical spectrum of SARS-CoV-2 infection continues to expand, raising important fundamental issues regarding the SARS-CoV-2 cellular tropism and pathogenic mechanisms. Liver damage is observed in patients with all forms of COVID-19, especially severe and critical forms, which could be due to the direct viral damage, immune dysregulation (systemic inflammatory response and cytokine storm), hypoxia-ischemia, drug-induced hepatotoxicity, and concomitant chronic disorders. Liver damage, defined primarily by elevated transaminase levels, is often observed in patients with COVID-19 and correlates with clinical outcomes, including mortality. Diagnostic criteria, pathogenesis, clinical characteristics, treatment, and prognosis of liver injury in COVID-19 should be clarified in further clinical trials. Currently, there is a critical shortage of proven treatment options for patients with COVID-19, resulting in an urgent need to study the multiple organ failure and liver damage pathogenesis in patients with this disease. The review provides information about the pathophysiological mechanisms of the SARS-CoV-2-induced liver damage and the development of liver failure in COVID-19. Information sources were searched in the PubMed database using the keywords “liver damage in COVID-19” and “immune liver damage in COVID-19”.
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Affiliation(s)
- DA Vologzhanin
- City Clinical Hospital No. 40 of the Kurortny District, Saint Petersburg, Russia
| | - AS Golota
- City Clinical Hospital No. 40 of the Kurortny District, Saint Petersburg, Russia
| | - TA Kamilova
- City Clinical Hospital No. 40 of the Kurortny District, Saint Petersburg, Russia
| | - SV Makarenko
- City Clinical Hospital No. 40 of the Kurortny District, Saint Petersburg, Russia
| | - SG Scherbak
- City Clinical Hospital No. 40 of the Kurortny District, Saint Petersburg, Russia
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12
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Lu LY, Feng PH, Yu MS, Chen MC, Lin AJH, Chen JL, Yu LHL. Current utilization of interferon alpha for the treatment of coronavirus disease 2019: A comprehensive review. Cytokine Growth Factor Rev 2022; 63:34-43. [PMID: 35115233 PMCID: PMC8755267 DOI: 10.1016/j.cytogfr.2022.01.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 01/03/2022] [Accepted: 01/06/2022] [Indexed: 12/14/2022]
Abstract
Recent studies have identified an association between perturbed type I interferon (IFN) responses and the severity of coronavirus disease 2019 (COVID-19). IFNα intervention may normalize the dysregulated innate immunity of COVID-19. However, details regarding its utilization and therapeutic evidence have yet to be systematically evaluated. The aim of this comprehensive review was to summarize the current utilization of IFNα for COVID-19 treatment and to explore the evidence on safety and efficacy. A comprehensive review of clinical studies in the literature prior to December 1st, 2021, was performed to identify the current utilization of IFNα, which included details on the route of administration, the number of patients who received the treatment, the severity at the initiation of treatment, age range, the time from the onset of symptoms to treatment, dose, frequency, and duration as well as safety and efficacy. Encouragingly, no evidence was found against the safety of IFNα treatment for COVID-19. Early intervention, either within five days from the onset of symptoms or at hospital admission, confers better clinical outcomes, whereas late intervention may result in prolonged hospitalization.
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Affiliation(s)
- Ling-Ying Lu
- Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Kaohsiung Veterans General Hospital, No.386, Dazhong 1st Rd., Zuoying District, Kaohsiung City, Taiwan
| | - Po-Hao Feng
- Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, No. 291, Zhongzheng Rd, Zhonghe District, New Taipei City, Taiwan,Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wuxing Street, Xinyi District, Taipei City, Taiwan
| | - Ming-Sun Yu
- Division of Hematology, Conde S. Januário Hospital, Estrada do Visconde de São Januário, Macau, China
| | - Min-Chi Chen
- Graduate Institute of Biomedical Sciences, Chang Gung University, No. 259, Wenhua 1st Road, Guishan District, Taoyuan City, Taiwan
| | - Alex Jia-Hong Lin
- Medical Affairs Department, Panco Healthcare Co., Ltd., a PharmaEssentia Company, 2F-5 No. 3 Park Street, Nangang District, Taipei, Taiwan
| | - Justin L. Chen
- Medical Affairs Department, Panco Healthcare Co., Ltd., a PharmaEssentia Company, 2F-5 No. 3 Park Street, Nangang District, Taipei, Taiwan
| | - Lennex Hsueh-Lin Yu
- Medical Affairs Department, Panco Healthcare Co., Ltd., a PharmaEssentia Company, 2F-5 No. 3 Park Street, Nangang District, Taipei, Taiwan,Corresponding author
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13
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Alam W, Karam K. Gangrenous Cholecystitis as a Potential Complication of COVID-19: A Case Report. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2021; 14:11795476211042459. [PMID: 34471395 PMCID: PMC8404677 DOI: 10.1177/11795476211042459] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 08/10/2021] [Indexed: 01/08/2023]
Abstract
While primarily a respiratory disease, COVID-19 can affect several organ systems and has been recently linked to cases of acalculous cholecystitis. We present a previously healthy elderly patient who presented to the emergency department with sepsis and was found to have COVID-19 after initially testing negative on PCR, along with suspected concomitant acalculous gangrenous cholecystitis. The patient passed away before any surgical intervention could be made. This case aims to discuss the potential relationship between acalculous cholecystitis and COVID-19.
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Affiliation(s)
- Walid Alam
- Global Health Institute, American University of Beirut, Beirut, Lebanon
| | - Karam Karam
- Department of Internal Medicine, Saint George Hospital, Ashrafieh, Beirut, Lebanon
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14
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Nath A. Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Continuum (Minneap Minn) 2021; 27:1051-1065. [PMID: 34623104 PMCID: PMC9527260 DOI: 10.1212/con.0000000000000992] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
PURPOSE OF REVIEW This article describes the spectrum of neurologic complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, their underlying pathology and pathogenic mechanisms, gaps in knowledge, and current therapeutic strategies. RECENT FINDINGS COVID-19 is the clinical syndrome caused by the novel coronavirus SARS-CoV-2. It can affect the entire neuraxis, and presentations in the acute phase are variable, although anosmia is a common manifestation. Encephalopathy is common in patients who are hospitalized and is often associated with multiorgan involvement. Immune-mediated encephalitis is probably underrecognized; however, viral encephalitis is rare. Other manifestations include stroke, seizures, myelitis, and peripheral neuropathies, including Guillain-Barré syndrome, which sometimes has atypical manifestations. Treatment is symptomatic, and immunotherapies have been used successfully in some patients. Long-term complications include dysautonomia, exercise intolerance, malaise, sleep disturbances, cognitive impairment, and mood disorders. SUMMARY Neurologic manifestations of COVID-19 may occur in the acute setting and may be independent of respiratory manifestations. Immune-mediated syndromes and cerebrovascular complications are common. Large populations of patients are expected to have long-term neurologic complications of COVID-19, many of which may emerge only after recovery from the acute illness.
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15
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Intravenous ketamine and progressive cholangiopathy in COVID-19 patients. J Hepatol 2021; 74:1243-1244. [PMID: 33617925 PMCID: PMC7893247 DOI: 10.1016/j.jhep.2021.02.007] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/03/2021] [Accepted: 02/08/2021] [Indexed: 02/07/2023]
Affiliation(s)
- The Keta-Cov research groupMalletVincent1BockKilian23MandenguePaul Doumbe1DufourNicolas4VoigtlaenderTorsten2RicardJean-Damien5IsnardPierre6FrochotVincent78LetavernierEmmanuel78MogaLucile9LandrieuxAmandine9RautouPierre-Emmanuel9Pons-KerjeanNathalie10Vallet-PichardAnaïs1ChouchanaLaurent11GernezCoralie5BurgerCarole12ScemlaAnne12de TymoskiChristian131415DepretFrançois131415DudoignonEmmanuel131415LamhautLionel16FlicoteauRémi17RousseauGéraldine18Duong Van HuyenJean-Paul6CorreasJean-Michel19WedemeyerHeiner23PolStanislas1Université de Paris, AP-HP, Hôpital Cochin, DMU Cancérologie et spécialités médico-chirurgicales, Service d’Hépatologie, Paris, FranceDept. of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Str.1, 30625 Hannover, GermanyGerman Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, FranceCentre Hospitalier René Dubos, 95300 Pontoise, FranceUniversité de Paris, AP-HP, Hôpital Louis Mourier, DMU Esprit, Service de Réanimation Médico-Chirurgicale, Colombes, FranceUniversité de Paris, AP-HP, Hôpital Necker Enfants Malades, DMU Imagina, Service d’Anatomo-Pathologie, Paris, FranceSorbonne Université, AP-HP, Hôpital Tenon, DMU Biogem, Service de Physiologie, F-75020 Paris, FranceINSERM, UMR S 1155, Hôpital Tenon, F-75020 Paris, FranceUniversité de Paris, AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU Digest, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de recherche sur l'inflammation, Inserm, UMR 1149, Paris, FranceAP-HP, Hôpital Beaujon, Service de Pharmacie, DMU Prisme, Paris, FranceUniversité de Paris, AP-HP, Hôpital Cochin, DMU Prime, Service de Pharmacovigilance, Paris, FranceUniversité de Paris, AP-HP, Hôpital Necker Enfants Malades, DMU Carte, Service de Néphrologie et de Transplantation rénale, Paris, FranceUniversité de Paris, AP-HP, Groupe Hospitalier St-Louis-Lariboisière, DMU Parabol, Département d’Anesthésie Réanimation et Centre de Traitement des Brûlés, Paris, FranceFHU Promice, Paris, FranceINI-CRCT, Nancy, FranceUniversité de Paris, AP-HP, Hôpital Necker Enfants Malades, Department of Anesthesiology and Critical Care, Paris, FranceUniversité de Paris, AP-HP, Hôpital Saint Louis, DMU Prisme, Service de Biostatistique et Information Médicale, Paris, FranceService de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Pitié-Salpêtrière, DMU SAPERE - APHP Sorbonne Université, FranceUniversité de Paris, AP-HP, Hôpital Necker Enfants Malades, DMU Imagina, Service de Radiologie, Paris, France
- Corresponding author. Address: Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Hepatology service, 27 rue du Faubourg Saint Jacques, 75014 Paris, France; Tel.: + 33 1 58 41 30 01, fax: + 33 1 58 41 30 14
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16
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Laparoscopic surgery during the COVID-19 pandemic: detection of SARS-COV-2 in abdominal tissues, fluids, and surgical smoke. Langenbecks Arch Surg 2021; 406:1007-1014. [PMID: 33675407 PMCID: PMC7936592 DOI: 10.1007/s00423-021-02142-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 02/28/2021] [Indexed: 11/05/2022]
Abstract
Background There are still concerns over the safety of laparoscopic surgery in coronavirus disease 2019 (COVID-19) patients due to the potential risk of viral transmission through surgical smoke/laparoscopic pneumoperitoneum. Methods We performed a systematic review of currently available literature to determine the presence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in abdominal tissues or fluids and in surgical smoke. Results A total of 19 studies (15 case reports and 4 case series) comprising 29 COVID-19 patients were included. The viral RNA was positively identified in 11 patients (37.9%). The samples that tested positive include the peritoneal fluid, bile, ascitic fluid, peritoneal dialysate, duodenal wall, and appendix. Similar samples, together with the omentum and abdominal subcutaneous fat, tested negative in the other patients. Only one study investigated SARS-COV-2 RNA in surgical smoke generated during laparoscopy, reporting negative findings. Conclusions There are conflicting results regarding the presence of SARS-COV-2 in abdominal tissues and fluids. No currently available evidence supports the hypothesis that SARS-COV-2 can be aerosolized and transmitted through surgical smoke. Larger studies are urgently needed to corroborate these findings. Supplementary Information The online version contains supplementary material available at 10.1007/s00423-021-02142-8.
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17
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Li D, Ding X, Xie M, Tian D, Xia L. COVID-19-associated liver injury: from bedside to bench. J Gastroenterol 2021; 56:218-230. [PMID: 33527211 PMCID: PMC7849620 DOI: 10.1007/s00535-021-01760-9] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 01/04/2021] [Indexed: 02/06/2023]
Abstract
The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a global challenge since December 2019. Although most patients with COVID-19 exhibit mild clinical manifestations, in approximately 5% of these patients, the disease eventually progresses to severe lung injury or even multiorgan dysfunction. This situation represents various challenges to hepatology. In the context of liver injury in patients with COVID-19, several key problems need to be solved. For instance, it is important to determine whether SARS-CoV-2 can directly invade liver, especially when ACE2 appears to be negligibly expressed on hepatocytes. In addition, the mechanisms underlying liver dysfunction in COVID-19 patients are not fully understood, which are likely multifactorial and related to hyperinflammation, dysregulated immune responses, abnormal coagulation and drugs. Here, we systematically describe the potential pathogenesis of COVID-19-associated liver injury and propose several hypotheses about its etiopathogenesis.
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Affiliation(s)
- Dongxiao Li
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Xiangming Ding
- Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou, 450000, Henan Province, China
| | - Meng Xie
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Dean Tian
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
| | - Limin Xia
- Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China.
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18
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Nardo AD, Schneeweiss‐Gleixner M, Bakail M, Dixon ED, Lax SF, Trauner M. Pathophysiological mechanisms of liver injury in COVID-19. Liver Int 2021; 41:20-32. [PMID: 33190346 PMCID: PMC7753756 DOI: 10.1111/liv.14730] [Citation(s) in RCA: 260] [Impact Index Per Article: 65.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/05/2020] [Accepted: 11/06/2020] [Indexed: 02/06/2023]
Abstract
The recent outbreak of coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a world-wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID-19. Although liver failure does not seem to occur in the absence of pre-existing liver disease, hepatic involvement in COVID-19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID-19 may range from direct infection by SARS-CoV-2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS-CoV-2 hepatic tropism as well as acute and possibly long-term liver injury in COVID-19.
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Affiliation(s)
- Alexander D. Nardo
- Hans Popper Laboratory of Molecular HepatologyDivision of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Mathias Schneeweiss‐Gleixner
- Medical Intensive Care Unit 13H1. Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - May Bakail
- Campus ITInstitute of Science and Technology AustriaKlosterneuburgAustria
| | - Emmanuel D. Dixon
- Hans Popper Laboratory of Molecular HepatologyDivision of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Sigurd F. Lax
- Department of PathologyHospital Graz IIAcademic Teaching Hospital of the Medical University of GrazGrazAustria
- School of MedicineJohannes Kepler UniversityLinzAustria
| | - Michael Trauner
- Hans Popper Laboratory of Molecular HepatologyDivision of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Medical Intensive Care Unit 13H1. Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
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19
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Zapor M. Persistent Detection and Infectious Potential of SARS-CoV-2 Virus in Clinical Specimens from COVID-19 Patients. Viruses 2020; 12:E1384. [PMID: 33287245 PMCID: PMC7761721 DOI: 10.3390/v12121384] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 11/26/2020] [Accepted: 12/01/2020] [Indexed: 01/08/2023] Open
Abstract
The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) that emerged in December 2019 as the causative agent of Coronavirus 2019 (COVID-19) and was declared a pandemic by the World Health Organization in March 2020 has several distinctive features, including extensive multiorgan involvement with a robust systemic inflammatory response, significant associated morbidity and mortality, and prolonged persistence of viral RNA in the clinical specimens of infected individuals as detected by Reverse Transcription Polymerase Chain Reaction (RT-PCR) amplification. This review begins with an overview of SARS-CoV-2 morphology and replication and summarizes what is known to date about the detection of the virus in nasal, oropharyngeal, and fecal specimens of patients who have recovered from COVID-19, with a focus on the factors thought to contribute to prolonged detection. This review also provides a discussion on the infective potential of this material from asymptomatic, pre-symptomatic, and convalescing individuals, to include a discussion of the relative persistence and infectious potential of virus in clinical specimens recovered from pediatric COVID-19 patients.
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Affiliation(s)
- Michael Zapor
- Veterans Affairs Medical Center, Martinsburg, WV 25405, USA
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20
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Scutari R, Piermatteo L, Manuelli MC, Iannetta M, Salpini R, Bertoli A, Alteri C, Saccomandi P, Bellocchi MC, Malagnino V, Teti E, Sforza D, Siragusa L, Grande M, Sarmati L, Svicher V, Andreoni M, Ceccherini-Silberstein F. Long-Term SARS-CoV-2 Infection Associated with Viral Dissemination in Different Body Fluids Including Bile in Two Patients with Acute Cholecystitis. Life (Basel) 2020; 10:E302. [PMID: 33238410 PMCID: PMC7700357 DOI: 10.3390/life10110302] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 11/16/2020] [Accepted: 11/21/2020] [Indexed: 12/13/2022] Open
Abstract
Our study aimed to investigate the kinetics of SARS-CoV-2 RNA in bile and in different body fluids of two SARS-CoV-2 positive patients with acute cholecystitis by innovative droplet digital PCR (ddPCR) assays. For each patient, nasopharyngeal- and rectal swabs, bile, urine, and plasma samples were collected at different time points for SARS-CoV-2 RNA quantification by two ddPCR assays. For both patients, ddPCR revealed persistent and prolonged detection of viral RNA in the nasopharyngeal swab despite triple-negative or single-positive results by qRT-PCR. In Patient 1, SARS-CoV-2 RNA dropped more rapidly in bile and rectal-swab and declined slowly in nasopharyngeal swab and plasma, becoming undetectable in all compartments 97 days after symptoms started. Conversely, in patient 2, SARS-CoV-2 RNA was detected, even if at low copies, in all body samples (with the exception of urine) up to 75 days after the onset of symptoms. This study highlights that SARS-CoV-2 RNA can persist for a prolonged time in respiratory samples and in several biological samples despite negativity to qRT-PCR, supporting SARS-CoV-2's ability to provoke persistent and disseminated infection and therefore to contribute to extra-pulmonary clinical manifestations.
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Affiliation(s)
- Rossana Scutari
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.S.); (L.P.); (R.S.); (A.B.); (P.S.); (M.C.B.); (F.C.-S.)
| | - Lorenzo Piermatteo
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.S.); (L.P.); (R.S.); (A.B.); (P.S.); (M.C.B.); (F.C.-S.)
| | - Matteo Ciancio Manuelli
- Surgical Emergency Unit, Emergency Department, Polyclinic Tor Vergata Foundation, 00133 Rome, Italy; (M.C.M.); (D.S.)
| | - Marco Iannetta
- Department of System Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (M.I.); (V.M.); (E.T.); (L.S.); (M.A.)
| | - Romina Salpini
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.S.); (L.P.); (R.S.); (A.B.); (P.S.); (M.C.B.); (F.C.-S.)
| | - Ada Bertoli
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.S.); (L.P.); (R.S.); (A.B.); (P.S.); (M.C.B.); (F.C.-S.)
- Laboratory of Clinical Microbiology and Virology, Polyclinic Tor Vergata Foundation, 00133 Rome, Italy
| | - Claudia Alteri
- Department of Oncology and Hemato-oncology, University of Milan, 20122 Milan, Italy;
| | - Patrizia Saccomandi
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.S.); (L.P.); (R.S.); (A.B.); (P.S.); (M.C.B.); (F.C.-S.)
| | - Maria Concetta Bellocchi
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.S.); (L.P.); (R.S.); (A.B.); (P.S.); (M.C.B.); (F.C.-S.)
| | - Vincenzo Malagnino
- Department of System Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (M.I.); (V.M.); (E.T.); (L.S.); (M.A.)
| | - Elisabetta Teti
- Department of System Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (M.I.); (V.M.); (E.T.); (L.S.); (M.A.)
| | - Daniele Sforza
- Surgical Emergency Unit, Emergency Department, Polyclinic Tor Vergata Foundation, 00133 Rome, Italy; (M.C.M.); (D.S.)
| | - Leandro Siragusa
- Department of Surgical Sciences, University of Rome “Tor Vergata”, 00133 Rome, Italy; (L.S.); (M.G.)
| | - Michele Grande
- Department of Surgical Sciences, University of Rome “Tor Vergata”, 00133 Rome, Italy; (L.S.); (M.G.)
| | - Loredana Sarmati
- Department of System Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (M.I.); (V.M.); (E.T.); (L.S.); (M.A.)
| | - Valentina Svicher
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.S.); (L.P.); (R.S.); (A.B.); (P.S.); (M.C.B.); (F.C.-S.)
| | - Massimo Andreoni
- Department of System Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (M.I.); (V.M.); (E.T.); (L.S.); (M.A.)
| | - Francesca Ceccherini-Silberstein
- Department of Experimental Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy; (R.S.); (L.P.); (R.S.); (A.B.); (P.S.); (M.C.B.); (F.C.-S.)
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21
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Nardo AD, Schneeweiss-Gleixner M, Bakail M, Dixon ED, Lax SF, Trauner M. Pathophysiological mechanisms of liver injury in COVID-19. LIVER INTERNATIONAL : OFFICIAL JOURNAL OF THE INTERNATIONAL ASSOCIATION FOR THE STUDY OF THE LIVER 2020. [PMID: 33190346 DOI: 10.1111/liv.14730.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The recent outbreak of coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a world-wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID-19. Although liver failure does not seem to occur in the absence of pre-existing liver disease, hepatic involvement in COVID-19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID-19 may range from direct infection by SARS-CoV-2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS-CoV-2 hepatic tropism as well as acute and possibly long-term liver injury in COVID-19.
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Affiliation(s)
- Alexander D Nardo
- Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Mathias Schneeweiss-Gleixner
- Medical Intensive Care Unit 13H1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - May Bakail
- Campus IT, Institute of Science and Technology Austria, Klosterneuburg, Austria
| | - Emmanuel D Dixon
- Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Sigurd F Lax
- Department of Pathology, Hospital Graz II, Academic Teaching Hospital of the Medical University of Graz, Graz, Austria.,School of Medicine, Johannes Kepler University, Linz, Austria
| | - Michael Trauner
- Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Medical Intensive Care Unit 13H1. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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