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 journalArticlepeer-review

97 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)310-319
Number of pages10
JournalNature Metabolism
Volume4
Issue number3
DOIs
StatePublished - Mar 2022
Externally publishedYes

ASJC Scopus subject areas

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

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