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Pita-Juarez Y, Karagkouni D, Kalavros N, Melms JC, Niezen S, Delorey TM, Essene AL, Brook OR, Pant D, Skelton-Badlani D, Naderi P, Huang P, Pan L, Hether T, Andrews TS, Ziegler CGK, Reeves J, Myloserdnyy A, Chen R, Nam A, Phelan S, Liang Y, Gregory M, He S, Patrick M, Rane T, Wardhani A, Amin AD, Biermann J, Hibshoosh H, Veregge M, Kramer Z, Jacobs C, Yalcin Y, Phillips D, Slyper M, Subramanian A, Ashenberg O, Bloom-Ackermann Z, Tran VM, Gomez J, Sturm A, Zhang S, Fleming SJ, Warren S, Beechem J, Hung D, Babadi M, Padera RF, MacParland SA, Bader GD, Imad N, Solomon IH, Miller E, Riedel S, Porter CBM, Villani AC, Tsai LTY, Hide W, Szabo G, Hecht J, Rozenblatt-Rosen O, Shalek AK, Izar B, Regev A, Popov YV, Jiang ZG, Vlachos IS. A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients. Genome Biol 2025; 26:56. [PMID: 40087773 PMCID: PMC11907808 DOI: 10.1186/s13059-025-03499-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 02/07/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. RESULTS We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, and a central role in a pro-fibrotic TGFβ signaling cell-cell communications network. Integrated analysis and comparisons with healthy controls reveal extensive changes in the cellular composition and expression states in COVID-19 liver, providing the underpinning of hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis characteristic of COVID-19 cholangiopathy. We also observe Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition is dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. CONCLUSIONS Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
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Affiliation(s)
- Yered Pita-Juarez
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Dimitra Karagkouni
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Nikolaos Kalavros
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Spatial Technologies Unit, HMS Initiative for RNA Medicine / Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Johannes C Melms
- Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA
- Columbia Center for Translational Immunology, New York, NY, USA
| | - Sebastian Niezen
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Toni M Delorey
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Adam L Essene
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Olga R Brook
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Deepti Pant
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Disha Skelton-Badlani
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Pourya Naderi
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Pinzhu Huang
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Liuliu Pan
- NanoString Technologies, Inc., Seattle, WA, USA
| | | | - Tallulah S Andrews
- Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada
| | - Carly G K Ziegler
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA, USA
- Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
- Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA
- Harvard Stem Cell Institute, Cambridge, MA, USA
- Program in Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
- Program in Immunology, Harvard Medical School, Boston, MA, USA
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
| | | | - Andriy Myloserdnyy
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Rachel Chen
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Andy Nam
- NanoString Technologies, Inc., Seattle, WA, USA
| | | | - Yan Liang
- NanoString Technologies, Inc., Seattle, WA, USA
| | | | - Shanshan He
- NanoString Technologies, Inc., Seattle, WA, USA
| | | | - Tushar Rane
- NanoString Technologies, Inc., Seattle, WA, USA
| | | | - Amit Dipak Amin
- Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA
- Columbia Center for Translational Immunology, New York, NY, USA
| | - Jana Biermann
- Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA
- Columbia Center for Translational Immunology, New York, NY, USA
| | - Hanina Hibshoosh
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Molly Veregge
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Zachary Kramer
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Christopher Jacobs
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Yusuf Yalcin
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Devan Phillips
- Present Address: Genentech, 1 DNA Way, South San Francisco, CA, USA
| | - Michal Slyper
- Present Address: Genentech, 1 DNA Way, South San Francisco, CA, USA
| | | | - Orr Ashenberg
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Zohar Bloom-Ackermann
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Victoria M Tran
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - James Gomez
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Alexander Sturm
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Shuting Zhang
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Stephen J Fleming
- Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Precision Cardiology Laboratory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | | | | | - Deborah Hung
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Genetics, Harvard Medical School, Boston, MA, USA
- Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA
| | - Mehrtash Babadi
- Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Precision Cardiology Laboratory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Robert F Padera
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
| | - Sonya A MacParland
- Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA, USA
- Department of Immunology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Gary D Bader
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- The Donnelly Centre, Toronto, ON, Canada
| | - Nasser Imad
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Isaac H Solomon
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
| | - Eric Miller
- NanoString Technologies, Inc., Seattle, WA, USA
| | - Stefan Riedel
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Caroline B M Porter
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Alexandra-Chloé Villani
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Linus T-Y Tsai
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Winston Hide
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Gyongyi Szabo
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Jonathan Hecht
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Orit Rozenblatt-Rosen
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Present Address: Genentech, 1 DNA Way, South San Francisco, CA, USA
| | - Alex K Shalek
- Harvard Medical School, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA, USA.
- Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
- Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA.
- Harvard Stem Cell Institute, Cambridge, MA, USA.
- Program in Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
- Program in Immunology, Harvard Medical School, Boston, MA, USA.
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
| | - Benjamin Izar
- Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
- Columbia Center for Translational Immunology, New York, NY, USA.
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA.
- Program for Mathematical Genomics, Columbia University Irving Medical Center, New York, NY, USA.
- Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA.
| | - Aviv Regev
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Present Address: Genentech, 1 DNA Way, South San Francisco, CA, USA.
| | - Yury V Popov
- Harvard Medical School, Boston, MA, USA.
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA.
| | - Z Gordon Jiang
- Harvard Medical School, Boston, MA, USA.
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA.
| | - Ioannis S Vlachos
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
- Harvard Medical School, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Spatial Technologies Unit, HMS Initiative for RNA Medicine / Beth Israel Deaconess Medical Center, Boston, MA, USA.
- Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
- Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA.
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Mahmoud S, Sarkar A, AlMahmoud L, Alladaboina S, Syed LF, Yaghmour M, Elmoh S, AlShebani M, Aly K, Al-Ansari H, Al-Mohamedi M, Yagan L, Zakaria D. Solid Organ Transplants Caused by COVID-19 Infection and the Outcome of Transplantation Post-COVID-19: A Systematic Review. Biomedicines 2025; 13:428. [PMID: 40002841 PMCID: PMC11852956 DOI: 10.3390/biomedicines13020428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 01/22/2025] [Accepted: 01/27/2025] [Indexed: 02/27/2025] Open
Abstract
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has imposed several medical and economic challenges since its onset in 2019. This is due to its ability to target the respiratory system as well as other organs, resulting in significant impacts and necessitating organ transplants. Our goal is to compile information from the existing literature to investigate how COVID-19 affects outcomes following organ transplantation. A comprehensive literature search was conducted to target studies reporting post-COVID-19 complications. We included 45 studies reporting data related to solid organ transplants, where either the recipient, organ, or donor was affected by SARS-CoV-2. The majority of the included studies concluded that organ transplantation following COVID-19 infection could be performed safely and with similar outcomes to non-COVID-19 patients, regardless of whether the organ, donor, or recipient was affected by COVID-19. No deviation from standard immunosuppression regimens or surgical protocols was necessary either, further re-assuring the feasibility of these transplants as viable treatment options. This applies to organ transplants involving the lungs, kidneys, liver, or heart. However, there was a limited number of studies in some areas, which warrants the need for additional research in order to reach more concrete conclusions pertaining to COVID-19's effect on organ transplants.
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Affiliation(s)
- Shadi Mahmoud
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Aparajita Sarkar
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Latifa AlMahmoud
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Sushanth Alladaboina
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Leena F. Syed
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Mohammad Yaghmour
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Safaa Elmoh
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Meera AlShebani
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Kareem Aly
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Haya Al-Ansari
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Mohammed Al-Mohamedi
- Department of Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
| | - Lina Yagan
- Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Dalia Zakaria
- Department of Pre-Medical Education, Weill Cornell Medicine-Qatar, Doha 24144, Qatar
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3
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Kiyak M, Ayhan R, Yavuz M, Demirtas C, Çakmak S, Altunöz E, İpek S. Is post COVID-19 cholangiopathy an appropriate indication for liver transplantation? REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2024; 116:336-337. [PMID: 37314132 DOI: 10.17235/reed.2023.9740/2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The effect of severe acute respiratory syndrome coronavirus-2, which has infected more than 765 million people in the world to date, has decreased gradually, but the effect of late complications after the disease has begun to increase. Post-coronavirus disease 2019 cholangiopathy can be considered as one of the late complications identified in patients recovering from SARS-CoV-2 infection. A 38-year-old man was admitted to our emergency department with fever up to 39,5ºC, dry cough, anosmia, and dyspnea for 4 days. In the chest computed tomography, extensive opacity areas were compatible with multifocal pneumonia. A throat swab confirmed SARS-CoV-2 infection. The patient was treated in the intensive care unit with mechanical ventilator support during 4 weeks. A significant increase in cholestasis enzymes was observed in the patient's control blood. The results of Magnetic Resonance Cholangiopancreatography, Endoscopic Retrograde Cholangio Pancreatography and liver biopsy performed for the etiology of the patient were compatible with post-COVID-19 cholangiopathy. Liver transplantation from a living donor was performed in the patient whose cholangiopathy continued in the first year of follow-up. The patient's clinical course was positive after liver transplantation. It emphasizes that despite the improvement in the lung involvement of COVID-19, the virus can cause long-term liver damage. Liver transplantation may sometimes be required in the treatment of post-COVID-19 cholangiopathy, as in our patient. The persistence of the patient's liver disease for approximately 1 year after Covid-19 and its positive course after liver transplantation show that post-COVID-19 cholangiopathy is a suitable indication for transplantation. The persistence of elevated cholestasis enzymes and bilirubin values after recovery from COVID-19 may help identify patients with post-COVID-19 cholangiopathy in the early period. Early recognition of the occurrence of post-COVID-19 cholangiopathy is important to decide the appropriate course of action.
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Affiliation(s)
- Mevlut Kiyak
- Gastroenterology, Health Science University. Faculty of Medicine, Türkiye
| | - Recep Ayhan
- Gastroenterology, Health Science University. Faculty of Medicine
| | - Mehtap Yavuz
- Gastroenterology, Health Science University. Faculty of Medicine
| | - Cemile Demirtas
- Gastroenterology, Health Science University. Faculty of Medicine
| | - Serdal Çakmak
- Gastroenterology, Health Science University. Faculty of Medicine
| | - Erhan Altunöz
- Gastroenterology, Health Science University. Faculty of Medicine
| | - Serkan İpek
- Gastroenterology, Health Science University. Faculty of Medicine
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4
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Sambommatsu Y, Mouch C, Kulkarni AV, Bruno DA, Eslami M, Imai D, Lee SD, Khan AA, Sharma A, Saeed M, Cotterell AH, Levy MF, Morales MK, Montenovo MI, Rao PN, Reddy R, Menon B, Kumaran V. Liver transplantation for post-COVID-19 cholangiopathy: A case series. Clin Transplant 2023; 37:e15141. [PMID: 37755152 DOI: 10.1111/ctr.15141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Accepted: 09/17/2023] [Indexed: 09/28/2023]
Abstract
BACKGROUND Post-COVID-19 cholangiopathy is an emerging cholestatic liver disease observed in patients recovering from severe COVID-19 infection. Its prognosis is poor, necessitating liver transplantation in some cases. This study aimed to investigate the outcomes of liver transplantation for post-COVID-19 cholangiopathy. METHODS Seven patients who underwent liver transplantation for post-COVID-19 cholangiopathy at three institutions between 2020 and 2022 were included in this retrospective multi-center case series. RESULTS At the time of initial COVID-19 infection, all patients developed acute respiratory distress syndrome, and six patients (86%) required ICU admission. Median time intervals from the initial COVID-19 diagnosis to the diagnosis of post-COVID-19 cholangiopathy and liver transplantation were 4 and 12 months, respectively. Four patients underwent living donor liver transplantation, and three patients underwent deceased donor liver transplantation. The median MELD score was 22 (range, 10-38). No significant intraoperative complications were observed. The median ICU and hospital stays were 2.5 and 12.5 days, respectively. One patient died due to respiratory failure 5 months after liver transplantation. Currently, the patient and graft survival rate is 86% at a median follow-up of 11 months. CONCLUSIONS Liver transplantation is a viable option for patients with post-COVID-19 cholangiopathy with acceptable outcome. Timely identification of this disease and appropriate management, including evaluation for liver transplantation, are essential.
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Affiliation(s)
- Yuzuru Sambommatsu
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Charles Mouch
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - David A Bruno
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Mehdi Eslami
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Daisuke Imai
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Seung Duk Lee
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Aamir A Khan
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Amit Sharma
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Muhammad Saeed
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Adrian H Cotterell
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Marlon F Levy
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Megan K Morales
- Department of Internal Medicine, Division of Infectious Disease, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - Martin I Montenovo
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Padaki N Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad, India
| | - Raghuram Reddy
- Department of Liver Transplantation and Hepatobiliary Surgery, Asian Institute of Gastroenterology, Hyderabad, India
| | - Balachandran Menon
- Department of Liver Transplantation and Hepatobiliary Surgery, Asian Institute of Gastroenterology, Hyderabad, India
| | - Vinay Kumaran
- Department of Surgery, Division of Transplant Surgery, Hume-Lee Transplant Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
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5
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Bhangui P. Impact of the COVID-19 Pandemic on Patients with End-Stage Liver Disease: One Virus-A Plethora of Consequences. J Clin Exp Hepatol 2023; 13:725-727. [PMID: 37693270 PMCID: PMC10482993 DOI: 10.1016/j.jceh.2023.07.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/12/2023] Open
Affiliation(s)
- Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta – the Medicity, Gurgaon, Delhi NCR, India
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6
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Bartoli A, Cursaro C, Seferi H, Andreone P. Secondary Sclerosing Cholangitis After SARS-CoV2: ICU Ketamine Use or Virus-Specific Biliary Tropism and Injury in the Context of Biliary Ischemia in Critically Ill Patients? Hepat Med 2023; 15:93-112. [PMID: 37547355 PMCID: PMC10404108 DOI: 10.2147/hmer.s384220] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 07/12/2023] [Indexed: 08/08/2023] Open
Abstract
Purpose From the beginning of the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV2) pandemic, different cases of a cholangiopathy with features of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) have been reported. Patients developing it are generally recovering from severe Coronavirus disease 19 (COVID-19) and required intensive care unit (ICU) admission and mechanical ventilation. Many of them have been administered with ketamine during their ICU stay. The pathogenesis of this novel disease is still debated, and, since prognosis is poor, efforts are needed in order to better understand it. Patients and Methods In this review, we focused our attention on COVID-19 SSC clinical, imaging, and histology findings in order to clarify the different pathogenetic options, particularly in regard of the ischemic-direct viral damage and ketamine-related theories, beginning with a recapitulation of SSC-CIP and ketamine-induced cholangiopathy in abusers. The research has been conducted using PubMed and Google Scholar databases. Key-words were "Secondary Sclerosing Cholangiopathy", "SSC-CIP", "Secondary Sclerosing Cholangiopathy in critically ill patients", "Ketamine and cholangiopathy", "Ketamine abusers and liver disease", "Ketamine-related cholangiopathy", "SARS-CoV2 infection and liver disease", "post Covid-19 secondary sclerosing cholangitis", "Covid-19 cholangiopathy". Results Many authors, based on the clinical, histological, imaging, and prognostic features of the disease, have pointed out the similarities between post COVID-19 SSC and SSC-CIP; however, peculiar features in the former were not previously observed. Therefore, a direct viral cytopathic action and SARS-CoV2-related coagulopathy are considered the most likely causes. On the other hand, ketamine, with the available data, cannot be surely linked as the main determinant cause of cholangiopathy. Moreover, ketamine-induced cholangitis (KIC) presentation is different from post COVID-19 SSC. Its role as a cofactor precipitating the disease cannot be ruled out. Conclusion Post COVID-19 SSC is a rare clinical entity following severe COVID-19 disease. The most accepted theory is that a sum of different insults determines the disease: biliary ischemia, direct viral damage, toxic bile, possibly worsened by ketamine and hyperinflammation due to the cytokine storm. Given the severe prognosis of the disease, with persistent cholangiopathy, organ failure, and orthotopic liver transplantation (OLT), further study on this novel clinical entity is needed.
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Affiliation(s)
- Alessandra Bartoli
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy
- Post Graduate School of Allergy and Clinical Immunology, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy
| | - Carmela Cursaro
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy
| | - Hajrie Seferi
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Ospedale Civile di Baggiovara, University of Modena and Reggio Emilia, Modena, Italy
| | - Pietro Andreone
- Chief of Division of Internal Medicine and metabolism, Department of Internal Medicine, University Hospital of Modena, Modena, Italy
- Chief of Post Graduate School of Allergy and Clinical Immunology, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy
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7
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Zippi M, Fiorino S, Hong W, de Biase D, Gallo CG, Grottesi A, Centorame A, Crispino P. Post-COVID-19 cholangiopathy: A systematic review. World J Meta-Anal 2023; 11:229-237. [DOI: 10.13105/wjma.v11.i5.229] [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] [Indexed: 04/28/2023] Open
Abstract
BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entailed various long-term complications, including post-infectious cholangiopathy.
AIM To identify the available studies concerning post-coronavirus disease 2019 (COVID-19) cholangiopathy.
METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles (retrospective and prospective studies, cohort studies, case series and case reports) published between January 1, 2020 and August 22, 2022, using both MeSH terms and free-language keywords: cholangiopathy; COVID-19; post-COVID-19 cholangiopathy; SARS-CoV-2.
RESULTS Thirteen studies fulfilled the inclusion criteria, which included 64 patients suffering from this condition. The patients were male in 82.8% of cases. Liver transplant was executed in 6 patients and scheduled in 7 patients, while 2 patients refused the surgical approach. Therefore in 23.4% of the cases, performing this procedure appeared to be necessary.
CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient, inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.
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Affiliation(s)
- Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | | | - Alfonso Grottesi
- Unit of General Surgery, Sandro Pertini Hospital, Rome 00157, Italy
| | | | - Pietro Crispino
- Unit of Emergency Medicine, Santa Maria Goretti Hospital, Latina 04100, Italy
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8
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Veerankutty FH, Sengupta K, Vij M, Rammohan A, Jothimani D, Murali A, Rela M. Post-COVID-19 cholangiopathy: Current understanding and management options. World J Gastrointest Surg 2023; 15:788-798. [PMID: 37342848 PMCID: PMC10277943 DOI: 10.4240/wjgs.v15.i5.788] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/10/2023] [Accepted: 04/07/2023] [Indexed: 05/26/2023] Open
Abstract
Post-coronavirus disease 2019 (COVID-19) cholangiopathy (PCC) is a rare but life-threatening complication of COVID-19 infection. PCC typically presents when patients recovering from the contagion and manifests as cholestasis in patients with no history of pre-existing liver disease. The pathogenesis of PCC is little understood. Hepatic injury in PCC could be mediated by the predilection of severe acute respiratory syndrome coronavirus 2 for cholangiocytes. Though PCC shows some resemblance to secondary sclerosing cholangitis in critically ill patients, it is considered as a separate and unique entity in the literature. Various treatment options like ursodeoxycholic acid, steroids, plasmapheresis, and endoscopic retrograde cholangiopancreatography guided interventions have been tried but with limited success. We have noticed significant improvement in liver function with antiplatelet therapy in a couple of patients. PCC can progress to end-stage liver disease necessitating liver transplantation. In this article, we discuss the current knowledge of PCC focusing on its pathophysiology, clinical manifestations, and management strategies.
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Affiliation(s)
- Fadl H Veerankutty
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Research Centre, Chennai 600044, India
| | - Kushan Sengupta
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai 600044, India
| | - Mukul Vij
- Department of Pathology, Institute of Liver Disease and Transplantation, Chennai 600044, India
| | - Ashwin Rammohan
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai 600044, India
| | - Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai 600044, India
| | | | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr. Rela Institute and Medical Centre, Chennai 600044, India
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9
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Yadlapati S, Jarrett SA, Baik D, Chaaya A. COVID-19 related biliary injury: A review of recent literature. World J Gastroenterol 2023; 29:2127-2133. [PMID: 37122603 PMCID: PMC10130971 DOI: 10.3748/wjg.v29.i14.2127] [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: 11/19/2022] [Revised: 03/11/2023] [Accepted: 03/21/2023] [Indexed: 04/13/2023] Open
Abstract
Since its emergence in 2019, it has become apparent that coronavirus 2019 (COVID-19) infection can result in multi systemic involvement. In addition to pulmonary symptoms, hepatobiliary involvement has been widely reported. Extent of hepatic involvement ranges from minor elevation in liver function tests (LFTs) to significant hepatocellular or cholestatic injury. In majority of cases, resolution of hepatic injury or improvement in LFTs is noted as patients recover from COVID-19 infection. However, severe biliary tract injury progressing to liver failure has been reported in patients requiring prolonged intensive care unit stay or mechanical ventilation. Due to the timing of its presentation, this form of progressive cholestatic injury has been referred to as COVID-19 cholangiopathy or post-COVID-19 cholangiopathy, and can result in devastating consequences for patients. COVID-19 cholangiopathy is recognized by dramatic elevation in serum alkaline phosphatase and bilirubin and radiologic evidence of bile duct injury. Cholangiopathy in COVID-19 occurs weeks to months after the initial infection and during the recovery phase. Imaging findings and pathology often resemble bile duct injury associated with primary or secondary sclerosing cholangitis. Etiology of COVID-19 cholangiopathy is unclear. Several mechanisms have been proposed, including direct cholangiocyte injury, vascular compromise, and cytokine release syndromes. This review summarizes existing data on COVID-19 cholangiopathy, including reported cases in the literature, proposed pathophysiology, diagnostic testing, and long-term implications.
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Affiliation(s)
- Sujani Yadlapati
- Department of Gastroenterology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - Simone A. Jarrett
- Department of Internal Medicine, Einstein Medical Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19140, United States
| | - Daniel Baik
- Department of Gastroenterology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
| | - Adib Chaaya
- Department of Gastroenterology, Cooper University Hospital, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
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10
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Mansour S, Marjieh R, Kluger Y, Gilshtein H, Khuri S. Post-COVID-19 Cholangiopathy: A Recent Indication for Liver Transplantation. J Clin Med Res 2023; 15:250-254. [PMID: 37187714 PMCID: PMC10181353 DOI: 10.14740/jocmr4914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 04/04/2023] [Indexed: 05/15/2023] Open
Affiliation(s)
- Subhi Mansour
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
| | - Rozan Marjieh
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
| | - Yoram Kluger
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
- HPB and Surgical Oncology Unit, Rambam Medical Center, Haifa, Israel
| | - Hayim Gilshtein
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
- Colorectal Surgery Unit, Rambam Medical Center, Haifa, Israel
| | - Safi Khuri
- Department of General Surgery, Rambam Medical Center, Haifa, Israel
- HPB and Surgical Oncology Unit, Rambam Medical Center, Haifa, Israel
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11
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Gildea DT, Woo SM, O’Connor CE, Rangnekar AS. COVID-19-Associated Liver Injury. Hepat Med 2023; 15:1-9. [PMID: 36852138 PMCID: PMC9960793 DOI: 10.2147/hmer.s384108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 02/11/2023] [Indexed: 03/01/2023] Open
Abstract
This review analyzes data regarding liver injury associated with COVID-19 infection. We discuss reported effects on the liver from both COVID-19 and COVID-19 treatment as well as pathophysiology, review the potential role of drug-induced liver injury as an etiology of COVID-19-associated liver injury, and touch on other reports of significant outcomes including COVID-19 cholangiopathy and autoimmune hepatitis. Finally, we review the implications of COVID-19 infection in liver transplant recipients.
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Affiliation(s)
- Daniel T Gildea
- Department of Internal Medicine, MedStar Georgetown University Hospital, Washington, DC, USA,Correspondence: Daniel T Gildea, Tel +1 302-985-7777, Email
| | - Stephanie M Woo
- Department of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC, USA
| | | | - Amol S Rangnekar
- MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Washington, DC, USA
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12
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Ali FEM, Abd El-Aziz MK, Ali MM, Ghogar OM, Bakr AG. COVID-19 and hepatic injury: cellular and molecular mechanisms in diverse liver cells. World J Gastroenterol 2023; 29:425-449. [PMID: 36688024 PMCID: PMC9850933 DOI: 10.3748/wjg.v29.i3.425] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/15/2022] [Accepted: 12/23/2022] [Indexed: 01/12/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) represents a global health and economic challenge. Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases. Besides, other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2, including cytokine storm, hypoxia, endothelial cells, and even some treatments for COVID-19. On the other hand, several groups of people could be at risk of hepatic COVID-19 complications, such as pregnant women and neonates. The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury, hepatic illness comorbidity, and risk factors. Besides, it is focused on the vaccination process and the role of developed vaccines in preventing hepatic injuries due to SARS-CoV-2 infection.
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Affiliation(s)
- Fares E M Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
| | | | - Mahmoud M Ali
- Department of Pharmacology, Al-Azhar University, Assiut 71524, Egypt
| | - Osama M Ghogar
- Department of Biochemistry Faculty of Pharmacy, Badr University in Assiut, Egypt
| | - Adel G Bakr
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
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13
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Zippi M, Fiorino S, Hong W, de Biase D, Gallo CG, Grottesi A, Centorame A, Crispino P. Post-COVID-19 cholangiopathy: A systematic review. World J Meta-Anal 2023; 11:29-37. [DOI: 10.13105/wjma.v11.i1.29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/13/2022] [Accepted: 11/23/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entailed various long-term complications, including post-infectious cholangiopathy.
AIM To identify the available studies concerning post-coronavirus disease 2019 (COVID-19) cholangiopathy.
METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles (retrospective and prospective studies, cohort studies, case series and case reports) published between January 1, 2020 and August 22, 2022, using both MeSH terms and free-language keywords: cholangiopathy; COVID-19; post-COVID-19 cholangiopathy; SARS-CoV-2.
RESULTS Thirteen studies fulfilled the inclusion criteria, which included 64 patients suffering from this condition. The patients were male in 82.8% of cases. Liver transplant was executed in 6 patients and scheduled in 7 patients, while 2 patients refused the surgical approach. Therefore in 23.4% of the cases, performing this procedure appeared to be necessary.
CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient, inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.
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Affiliation(s)
- Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40126, Italy
| | | | - Alfonso Grottesi
- Unit of General Surgery, Sandro Pertini Hospital, Rome 00157, Italy
| | | | - Pietro Crispino
- Unit of Emergency Medicine, Santa Maria Goretti Hospital, Latina 04100, Italy
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14
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Sarkis Y, Saleem N, Vuppalanchi R, Gromski M. COVID-Associated Cast-Forming Cholangiopathy: A Commentary on Disease Mechanism, Treatment, and Prognosis. Hepat Med 2023; 15:27-32. [PMID: 37013139 PMCID: PMC10066716 DOI: 10.2147/hmer.s384176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Accepted: 03/23/2023] [Indexed: 04/05/2023] Open
Abstract
The complete impact of COVID-19 infection continues to develop since the onset of the COVID-19 pandemic. COVID-19 cholangiopathy has been recently described in a subset of patients who recovered from severe COVID-19 infection. The most common phenotype of patients suffering from COVID-19 cholangiopathy had severe infection requiring a stay in the intensive care unit, mechanical ventilation and vasopressor medications. Patients with COVID-cholangiopathy present with severe and prolonged cholestatic liver injury. In cases where biliary cast formation is identified, we defined the entity as "COVID-19 cast-forming cholangiopathy". This subset of COVID-19 cholangiopathy is not well understood and there are no standardized diagnosis or management to this date. The reported clinical outcomes are variable, from resolution of symptoms and liver test abnormalities to liver transplant and death. In this commentary, we discuss the proposed pathophysiology, diagnosis, management, and prognosis of this disease.
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Affiliation(s)
- Yara Sarkis
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Nasir Saleem
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Mark Gromski
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
- Correspondence: Mark Gromski, Gastroenterology and Hepatology Department, Indiana University Hospital, 550 N. University Blvd, Suite 1634, Indianapolis, IN, 46202, USA, Tel +317-944-0925, Fax +317-968-1265, Email
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15
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Theocharidou E, Adebayo D. Challenges in liver transplantation in the context of a major pandemic. World J Transplant 2022; 12:347-358. [PMID: 36437846 PMCID: PMC9693897 DOI: 10.5500/wjt.v12.i11.347] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/27/2022] [Accepted: 09/22/2022] [Indexed: 11/17/2022] Open
Abstract
Coronavirus disease-2019 (COVID-19) has led to a temporary suspension of liver transplant activity across the world and the remodeling of care for patients on the waiting list and transplant recipients with the increasing use of remote consultations. Emerging evidence shows that patients with more advanced liver disease are at increased risk of severe COVID-19 and death, whereas transplant recipients have similar risk with the general population which is mainly driven by age and metabolic comorbidities. Tacrolimus immunosuppression might have a protective role in the post-transplant population. Vaccines that have become rapidly available seem to be safe in liver patients, but the antibody response in transplant patients is likely suboptimal. Most transplant centers were gradually able to resume activity soon after the onset of the pandemic and after modifying their pathways to optimize safety for patients and workforce. Preliminary evidence regarding utilizing grafts from positive donors and/or transplanting recently recovered or infected recipients under certain circumstances is encouraging and may allow offering life-saving transplant to patients at the greatest need. This review summarizes the currently available data on liver transplantation in the context of a major pandemic and discusses areas of uncertainty and future challenges. Lessons learnt from the COVID-19 pandemic might provide invaluable guidance for future pandemics.
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Affiliation(s)
- Eleni Theocharidou
- 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Konstantinoupoleos 49, 54642, Thessaloniki, Greece
| | - Danielle Adebayo
- Department of Gastroenterology and Hepatology, Royal Berkshire NHS Foundation Trust, London Road, Reading, RG1 5AN, United Kingdom
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16
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Post-Covid- 19 Cholangiopathy:A Systematic Review. J Clin Exp Hepatol 2022; 13:489-499. [PMID: 36337085 PMCID: PMC9618303 DOI: 10.1016/j.jceh.2022.10.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 10/07/2022] [Accepted: 10/23/2022] [Indexed: 11/07/2022] Open
Abstract
OBJECTIVES Post COVID-19 cholangiopathy is a rare but poorly understood and serious complication of COVID-19 infection. We sought to better understand the epidemiology, mechanism of action, histology, imaging findings and outcomes of post-COVID-19 cholangiopathy. METHODS We searched PubMed, Cochrane Library, Embase, and Web of Science from December 2019 to December 2021. Mesh words used "post-Covid-19 cholangiopathy", "COVID-19 liver injury"," Covid-19 and cholangiopathy", and COVID-19 liver disease". The data on epidemiology, mechanism of action, histology, imaging findings and outcomes were collected. RESULTS Post COVID-19 cholangiopathy was reported in 30 cases during the study period. The mean (standard deviation [SD]) age was 53.7 (5). Men accounted for cases (83.3%). All patients had required intensive level of care and mechanical ventilation. Mean (SD) number of days from COVID infection to severe disease or liver disease was 63.5(38). Peak mean (SD) alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin were 2014 (831.8) U/L, 1555 (2432.8) U/L, 899.72 (1238.6) U/L, and 10.32 (9.32) mg/dl, respectively. Four patients successfully underwent liver transplantation. CONCLUSION Post COVID-19 cholangiopathy is a severe and progressive complication of COVID-19 infection. More research is needed to better understand the pathophysiology and best treatment approach. Clinicians should suspect post COVID-19 cholangiopathy in patients with cholestatic liver injury following COVID-19 infection.
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17
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Pita-Juarez Y, Karagkouni D, Kalavros N, Melms JC, Niezen S, Delorey TM, Essene AL, Brook OR, Pant D, Skelton-Badlani D, Naderi P, Huang P, Pan L, Hether T, Andrews TS, Ziegler CGK, Reeves J, Myloserdnyy A, Chen R, Nam A, Phelan S, Liang Y, Amin AD, Biermann J, Hibshoosh H, Veregge M, Kramer Z, Jacobs C, Yalcin Y, Phillips D, Slyper M, Subramanian A, Ashenberg O, Bloom-Ackermann Z, Tran VM, Gomez J, Sturm A, Zhang S, Fleming SJ, Warren S, Beechem J, Hung D, Babadi M, Padera RF, MacParland SA, Bader GD, Imad N, Solomon IH, Miller E, Riedel S, Porter CBM, Villani AC, Tsai LTY, Hide W, Szabo G, Hecht J, Rozenblatt-Rosen O, Shalek AK, Izar B, Regev A, Popov Y, Jiang ZG, Vlachos IS. A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2022:2022.10.27.514070. [PMID: 36324805 PMCID: PMC9628199 DOI: 10.1101/2022.10.27.514070] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
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Affiliation(s)
- Yered Pita-Juarez
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Dimitra Karagkouni
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Nikolaos Kalavros
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Spatial Technologies Unit, HMS Initiative for RNA Medicine / Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Johannes C Melms
- Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA
- Columbia Center for Translational Immunology, New York, NY, USA
| | - Sebastian Niezen
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
| | - Toni M Delorey
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Adam L Essene
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Olga R Brook
- Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Deepti Pant
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Disha Skelton-Badlani
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
| | - Pourya Naderi
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Pinzhu Huang
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
| | - Liuliu Pan
- NanoString Technologies, Inc., Seattle, WA, USA
| | | | - Tallulah S Andrews
- Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada
| | - Carly G K Ziegler
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA, USA
- Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
- Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA
- Harvard Stem Cell Institute, Cambridge, MA, USA
- Program in Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
- Program in Immunology, Harvard Medical School, Boston, MA, USA
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
| | | | - Andriy Myloserdnyy
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
| | - Rachel Chen
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
| | - Andy Nam
- NanoString Technologies, Inc., Seattle, WA, USA
| | | | - Yan Liang
- NanoString Technologies, Inc., Seattle, WA, USA
| | - Amit Dipak Amin
- Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA
- Columbia Center for Translational Immunology, New York, NY, USA
| | - Jana Biermann
- Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA
- Columbia Center for Translational Immunology, New York, NY, USA
| | - Hanina Hibshoosh
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Molly Veregge
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Zachary Kramer
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Christopher Jacobs
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Yusuf Yalcin
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
| | - Devan Phillips
- Current address: Genentech, 1 DNA Way, South San Francisco, CA, USA
| | - Michal Slyper
- Current address: Genentech, 1 DNA Way, South San Francisco, CA, USA
| | | | - Orr Ashenberg
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Zohar Bloom-Ackermann
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Victoria M Tran
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - James Gomez
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Alexander Sturm
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Shuting Zhang
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Stephen J Fleming
- Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Precision Cardiology Laboratory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | | | | | - Deborah Hung
- Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Genetics, Harvard Medical School, Boston, MA, USA
- Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA
| | - Mehrtash Babadi
- Data Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Precision Cardiology Laboratory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Robert F Padera
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
| | - Sonya A MacParland
- Ajmera Transplant Centre, Toronto General Research Institute, University Health Network, Toronto, ON, Canada
- Department of Immunology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Gary D Bader
- Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
- The Donnelly Centre, Toronto, ON, Canada
| | - Nasser Imad
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Isaac H Solomon
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
| | - Eric Miller
- NanoString Technologies, Inc., Seattle, WA, USA
| | - Stefan Riedel
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Caroline B M Porter
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Alexandra-Chloé Villani
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Linus T-Y Tsai
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Boston Nutrition and Obesity Research Center Functional Genomics and Bioinformatics Core, Boston, MA, USA
| | - Winston Hide
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Gyongyi Szabo
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
| | - Jonathan Hecht
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Orit Rozenblatt-Rosen
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Current address: Genentech, 1 DNA Way, South San Francisco, CA, USA
| | - Alex K Shalek
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Program in Health Sciences & Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA, USA
- Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA, USA
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
- Harvard Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA
- Harvard Stem Cell Institute, Cambridge, MA, USA
- Program in Computational & Systems Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
- Program in Immunology, Harvard Medical School, Boston, MA, USA
- Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA
| | - Benjamin Izar
- Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA
- Columbia Center for Translational Immunology, New York, NY, USA
- Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY, USA
- Program for Mathematical Genomics, Columbia University Irving Medical Center, New York, NY, USA
- Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA
| | - Aviv Regev
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Current address: Genentech, 1 DNA Way, South San Francisco, CA, USA
| | - Yury Popov
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Z Gordon Jiang
- Harvard Medical School, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Medicine, Beth Israel Deaconess Medical Center, MA, USA
| | - Ioannis S Vlachos
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Spatial Technologies Unit, HMS Initiative for RNA Medicine / Beth Israel Deaconess Medical Center, Boston, MA, USA
- Cancer Research Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Harvard Medical School Initiative for RNA Medicine, Boston, MA, USA
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18
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Pita-Juarez Y, Karagkouni D, Kalavros N, Melms JC, Niezen S, Delorey TM, Essene AL, Brook OR, Pant D, Skelton-Badlani D, Naderi P, Huang P, Pan L, Hether T, Andrews TS, Ziegler CGK, Reeves J, Myloserdnyy A, Chen R, Nam A, Phelan S, Liang Y, Amin AD, Biermann J, Hibshoosh H, Veregge M, Kramer Z, Jacobs C, Yalcin Y, Phillips D, Slyper M, Subramanian A, Ashenberg O, Bloom-Ackermann Z, Tran VM, Gomez J, Sturm A, Zhang S, Fleming SJ, Warren S, Beechem J, Hung D, Babadi M, Padera RF, MacParland SA, Bader GD, Imad N, Solomon IH, Miller E, Riedel S, Porter CBM, Villani AC, Tsai LTY, Hide W, Szabo G, Hecht J, Rozenblatt-Rosen O, Shalek AK, Izar B, Regev A, Popov Y, Jiang ZG, Vlachos IS. A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2022. [PMID: 36324805 DOI: 10.1101/2022.08.06.503037] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we performed single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis and comparisons with healthy controls revealed extensive changes in the cellular composition and expression states in COVID-19 liver, reflecting hepatocellular injury, ductular reaction, pathologic vascular expansion, and fibrogenesis. We also observed Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas, resembling similar responses in liver injury in mice and in sepsis, respectively. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition was dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells. Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
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