Molecular consequences of SARS-CoV-2 liver tropism.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.