Molecular consequences of SARS-CoV-2 liver tropism

Nicola Wanner; Geoffroy Andrieux; Pau Badia-i-Mompel; Carolin Edler; Susanne Pfefferle; Maja T. Lindenmeyer; Christian Schmidt-Lauber; Jan Czogalla; Milagros N. Wong; Yusuke Okabayashi; Fabian Braun; Marc Lütgehetmann; Elisabeth Meister; Shun Lu; Maria L.M. Noriega; Thomas Günther; Adam Grundhoff; Nicole Fischer; Hanna Bräuninger; Diana Lindner; Dirk Westermann; Fabian Haas; Kevin Roedl; Stefan Kluge; Marylyn M. Addo; Samuel Huber; Ansgar W. Lohse; Jochen Reiser; Benjamin Ondruschka; Jan P. Sperhake; Julio Saez-Rodriguez; Melanie Boerries; Salim S. Hayek; Martin Aepfelbacher; Pietro Scaturro; Victor G. Puelles; Tobias B. Huber

doi:10.1038/s42255-022-00552-6

Molecular consequences of SARS-CoV-2 liver tropism

Nicola Wanner, Geoffroy Andrieux, Pau Badia-i-Mompel, Carolin Edler, Susanne Pfefferle, Maja T. Lindenmeyer, Christian Schmidt-Lauber, Jan Czogalla, Milagros N. Wong, Yusuke Okabayashi, Fabian Braun, Marc Lütgehetmann, Elisabeth Meister, Shun Lu, Maria L.M. Noriega, Thomas Günther, Adam Grundhoff, Nicole Fischer, Hanna Bräuninger, Diana LindnerDirk Westermann, Fabian Haas, Kevin Roedl, Stefan Kluge, Marylyn M. Addo, Samuel Huber, Ansgar W. Lohse, Jochen Reiser, Benjamin Ondruschka, Jan P. Sperhake, Julio Saez-Rodriguez, Melanie Boerries, Salim S. Hayek, Martin Aepfelbacher, Pietro Scaturro, Victor G. Puelles, Tobias B. Huber

Research output: Contribution to journal › Article › peer-review

Abstract

Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae¹. 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.

Original language	English (US)
Pages (from-to)	310-319
Number of pages	10
Journal	Nature Metabolism
Volume	4
Issue number	3
DOIs	https://doi.org/10.1038/s42255-022-00552-6
State	Published - Mar 2022
Externally published	Yes

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Physiology (medical)
Cell Biology

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10.1038/s42255-022-00552-6

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Wanner, N., Andrieux, G., Badia-i-Mompel, P., Edler, C., Pfefferle, S., Lindenmeyer, M. T., Schmidt-Lauber, C., Czogalla, J., Wong, M. N., Okabayashi, Y., Braun, F., Lütgehetmann, M., Meister, E., Lu, S., Noriega, M. L. M., Günther, T., Grundhoff, A., Fischer, N., Bräuninger, H., ... Huber, T. B. (2022). Molecular consequences of SARS-CoV-2 liver tropism. Nature Metabolism, 4(3), 310-319. https://doi.org/10.1038/s42255-022-00552-6

Wanner, N, Andrieux, G, Badia-i-Mompel, P, Edler, C, Pfefferle, S, Lindenmeyer, MT, Schmidt-Lauber, C, Czogalla, J, Wong, MN, Okabayashi, Y, Braun, F, Lütgehetmann, M, Meister, E, Lu, S, Noriega, MLM, Günther, T, Grundhoff, A, Fischer, N, Bräuninger, H, Lindner, D, Westermann, D, Haas, F, Roedl, K, Kluge, S, Addo, MM, Huber, S, Lohse, AW, Reiser, J, Ondruschka, B, Sperhake, JP, Saez-Rodriguez, J, Boerries, M, Hayek, SS, Aepfelbacher, M, Scaturro, P, Puelles, VG & Huber, TB 2022, 'Molecular consequences of SARS-CoV-2 liver tropism', Nature Metabolism, vol. 4, no. 3, pp. 310-319. https://doi.org/10.1038/s42255-022-00552-6

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title = "Molecular consequences of SARS-CoV-2 liver tropism",

abstract = "Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. 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 debated2,3. 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.",

author = "Nicola Wanner and Geoffroy Andrieux and Pau Badia-i-Mompel and Carolin Edler and Susanne Pfefferle and Lindenmeyer, {Maja T.} and Christian Schmidt-Lauber and Jan Czogalla and Wong, {Milagros N.} and Yusuke Okabayashi and Fabian Braun and Marc L{\"u}tgehetmann and Elisabeth Meister and Shun Lu and Noriega, {Maria L.M.} and Thomas G{\"u}nther and Adam Grundhoff and Nicole Fischer and Hanna Br{\"a}uninger and Diana Lindner and Dirk Westermann and Fabian Haas and Kevin Roedl and Stefan Kluge and Addo, {Marylyn M.} and Samuel Huber and Lohse, {Ansgar W.} and Jochen Reiser and Benjamin Ondruschka and Sperhake, {Jan P.} and Julio Saez-Rodriguez and Melanie Boerries and Hayek, {Salim S.} and Martin Aepfelbacher and Pietro Scaturro and Puelles, {Victor G.} and Huber, {Tobias B.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = mar,

doi = "10.1038/s42255-022-00552-6",

language = "English (US)",

volume = "4",

pages = "310--319",

journal = "Nature Metabolism",

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T1 - Molecular consequences of SARS-CoV-2 liver tropism

AU - Wanner, Nicola

AU - Andrieux, Geoffroy

AU - Badia-i-Mompel, Pau

AU - Edler, Carolin

AU - Pfefferle, Susanne

AU - Lindenmeyer, Maja T.

AU - Schmidt-Lauber, Christian

AU - Czogalla, Jan

AU - Wong, Milagros N.

AU - Okabayashi, Yusuke

AU - Braun, Fabian

AU - Lütgehetmann, Marc

AU - Meister, Elisabeth

AU - Lu, Shun

AU - Noriega, Maria L.M.

AU - Günther, Thomas

AU - Grundhoff, Adam

AU - Fischer, Nicole

AU - Bräuninger, Hanna

AU - Lindner, Diana

AU - Westermann, Dirk

AU - Haas, Fabian

AU - Roedl, Kevin

AU - Kluge, Stefan

AU - Addo, Marylyn M.

AU - Huber, Samuel

AU - Lohse, Ansgar W.

AU - Reiser, Jochen

AU - Ondruschka, Benjamin

AU - Sperhake, Jan P.

AU - Saez-Rodriguez, Julio

AU - Boerries, Melanie

AU - Hayek, Salim S.

AU - Aepfelbacher, Martin

AU - Scaturro, Pietro

AU - Puelles, Victor G.

AU - Huber, Tobias B.

PY - 2022/3

Y1 - 2022/3

N2 - Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. 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 debated2,3. 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.

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Molecular consequences of SARS-CoV-2 liver tropism

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