Molekulare Charakterisierung von SARS-COV-2-vermittelten Leberschäden
Zusammenfassung der Projektergebnisse
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. In this project we obtained for the first time clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We found 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 provided 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 identified 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 provided a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, increasing our understanding of the molecular consequences of severe COVID-19. Altogether, these information could be useful for the identification of organ-specific pharmacological targets.
Projektbezogene Publikationen (Auswahl)
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Molecular consequences of SARS-CoV-2 liver tropism. Nature Metabolism, 4(3), 310-319.
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 ... & Huber, Tobias B.
