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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
Nature metabolism, 03/2022, Volume: 4, Issue: 3Journal Article
Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae . 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 . 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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