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Molecular consequences of SARS-CoV-2 liver tropism
Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae(1). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also dir...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964418/ https://www.ncbi.nlm.nih.gov/pubmed/35347318 http://dx.doi.org/10.1038/s42255-022-00552-6 |
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author | Wanner, Nicola Andrieux, Geoffroy Badia-i-Mompel, Pau Edler, Carolin Pfefferle, Susanne Lindenmeyer, Maja T. Schmidt-Lauber, Christian Czogalla, Jan Wong, Milagros N. Okabayashi, Yusuke Braun, Fabian Lütgehetmann, Marc Meister, Elisabeth Lu, Shun Noriega, Maria L. M. Günther, Thomas Grundhoff, Adam Fischer, Nicole Bräuninger, Hanna Lindner, Diana Westermann, Dirk Haas, Fabian Roedl, Kevin Kluge, Stefan Addo, Marylyn M. Huber, Samuel Lohse, Ansgar W. Reiser, Jochen Ondruschka, Benjamin Sperhake, Jan P. Saez-Rodriguez, Julio Boerries, Melanie Hayek, Salim S. Aepfelbacher, Martin Scaturro, Pietro Puelles, Victor G. Huber, Tobias B. |
author_facet | Wanner, Nicola Andrieux, Geoffroy Badia-i-Mompel, Pau Edler, Carolin Pfefferle, Susanne Lindenmeyer, Maja T. Schmidt-Lauber, Christian Czogalla, Jan Wong, Milagros N. Okabayashi, Yusuke Braun, Fabian Lütgehetmann, Marc Meister, Elisabeth Lu, Shun Noriega, Maria L. M. Günther, Thomas Grundhoff, Adam Fischer, Nicole Bräuninger, Hanna Lindner, Diana Westermann, Dirk Haas, Fabian Roedl, Kevin Kluge, Stefan Addo, Marylyn M. Huber, Samuel Lohse, Ansgar W. Reiser, Jochen Ondruschka, Benjamin Sperhake, Jan P. Saez-Rodriguez, Julio Boerries, Melanie Hayek, Salim S. Aepfelbacher, Martin Scaturro, Pietro Puelles, Victor G. Huber, Tobias B. |
author_sort | Wanner, Nicola |
collection | PubMed |
description | Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae(1). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated(2,3). Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets. |
format | Online Article Text |
id | pubmed-8964418 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89644182022-04-07 Molecular consequences of SARS-CoV-2 liver tropism Wanner, Nicola Andrieux, Geoffroy Badia-i-Mompel, Pau Edler, Carolin Pfefferle, Susanne Lindenmeyer, Maja T. Schmidt-Lauber, Christian Czogalla, Jan Wong, Milagros N. Okabayashi, Yusuke Braun, Fabian Lütgehetmann, Marc Meister, Elisabeth Lu, Shun Noriega, Maria L. M. Günther, Thomas Grundhoff, Adam Fischer, Nicole Bräuninger, Hanna Lindner, Diana Westermann, Dirk Haas, Fabian Roedl, Kevin Kluge, Stefan Addo, Marylyn M. Huber, Samuel Lohse, Ansgar W. Reiser, Jochen Ondruschka, Benjamin Sperhake, Jan P. Saez-Rodriguez, Julio Boerries, Melanie Hayek, Salim S. Aepfelbacher, Martin Scaturro, Pietro Puelles, Victor G. Huber, Tobias B. Nat Metab Letter Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae(1). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated(2,3). Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets. Nature Publishing Group UK 2022-03-28 2022 /pmc/articles/PMC8964418/ /pubmed/35347318 http://dx.doi.org/10.1038/s42255-022-00552-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Letter Wanner, Nicola Andrieux, Geoffroy Badia-i-Mompel, Pau Edler, Carolin Pfefferle, Susanne Lindenmeyer, Maja T. Schmidt-Lauber, Christian Czogalla, Jan Wong, Milagros N. Okabayashi, Yusuke Braun, Fabian Lütgehetmann, Marc Meister, Elisabeth Lu, Shun Noriega, Maria L. M. Günther, Thomas Grundhoff, Adam Fischer, Nicole Bräuninger, Hanna Lindner, Diana Westermann, Dirk Haas, Fabian Roedl, Kevin Kluge, Stefan Addo, Marylyn M. Huber, Samuel Lohse, Ansgar W. Reiser, Jochen Ondruschka, Benjamin Sperhake, Jan P. Saez-Rodriguez, Julio Boerries, Melanie Hayek, Salim S. Aepfelbacher, Martin Scaturro, Pietro Puelles, Victor G. Huber, Tobias B. Molecular consequences of SARS-CoV-2 liver tropism |
title | Molecular consequences of SARS-CoV-2 liver tropism |
title_full | Molecular consequences of SARS-CoV-2 liver tropism |
title_fullStr | Molecular consequences of SARS-CoV-2 liver tropism |
title_full_unstemmed | Molecular consequences of SARS-CoV-2 liver tropism |
title_short | Molecular consequences of SARS-CoV-2 liver tropism |
title_sort | molecular consequences of sars-cov-2 liver tropism |
topic | Letter |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964418/ https://www.ncbi.nlm.nih.gov/pubmed/35347318 http://dx.doi.org/10.1038/s42255-022-00552-6 |
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