tetano
Editor, Senior Moderator
Nat Metab
. 2022 Mar 28.
doi: 10.1038/s42255-022-00552-6. Online ahead of print.
Molecular consequences of SARS-CoV-2 liver tropism
Nicola Wanner[SUP] #[/SUP][SUP] 1 [/SUP], Geoffroy Andrieux[SUP] #[/SUP][SUP] 2 [/SUP], Pau Badia-I-Mompel[SUP] 3 [/SUP], Carolin Edler[SUP] 4 [/SUP], Susanne Pfefferle[SUP] 5 [/SUP], Maja T Lindenmeyer[SUP] 1 [/SUP], Christian Schmidt-Lauber[SUP] 1 [/SUP], Jan Czogalla[SUP] 1 [/SUP], Milagros N Wong[SUP] 1 [/SUP], Yusuke Okabayashi[SUP] 1 [/SUP], Fabian Braun[SUP] 1 [/SUP], Marc Lütgehetmann[SUP] 5 [/SUP], Elisabeth Meister[SUP] 1 [/SUP], Shun Lu[SUP] 1 [/SUP], Maria L M Noriega[SUP] 6 [/SUP], Thomas Günther[SUP] 7 [/SUP], Adam Grundhoff[SUP] 7 [/SUP], Nicole Fischer[SUP] 5 [/SUP], Hanna Bräuninger[SUP] 8 9 [/SUP], Diana Lindner[SUP] 8 9 [/SUP], Dirk Westermann[SUP] 8 9 [/SUP], Fabian Haas[SUP] 1 [/SUP], Kevin Roedl[SUP] 10 [/SUP], Stefan Kluge[SUP] 10 [/SUP], Marylyn M Addo[SUP] 11 12 [/SUP], Samuel Huber[SUP] 11 [/SUP], Ansgar W Lohse[SUP] 11 [/SUP], Jochen Reiser[SUP] 13 [/SUP], Benjamin Ondruschka[SUP] 4 [/SUP], Jan P Sperhake[SUP] 4 [/SUP], Julio Saez-Rodriguez[SUP] 3 [/SUP], Melanie Boerries[SUP] 2 14 [/SUP], Salim S Hayek[SUP] 15 [/SUP], Martin Aepfelbacher[SUP] 5 [/SUP], Pietro Scaturro[SUP] 7 [/SUP], Victor G Puelles[SUP] 16 [/SUP], Tobias B Huber[SUP] 17 [/SUP]
Affiliations
Abstract
Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae[SUP]1[/SUP]. 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[SUP]2,3[/SUP]. 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.
. 2022 Mar 28.
doi: 10.1038/s42255-022-00552-6. Online ahead of print.
Molecular consequences of SARS-CoV-2 liver tropism
Nicola Wanner[SUP] #[/SUP][SUP] 1 [/SUP], Geoffroy Andrieux[SUP] #[/SUP][SUP] 2 [/SUP], Pau Badia-I-Mompel[SUP] 3 [/SUP], Carolin Edler[SUP] 4 [/SUP], Susanne Pfefferle[SUP] 5 [/SUP], Maja T Lindenmeyer[SUP] 1 [/SUP], Christian Schmidt-Lauber[SUP] 1 [/SUP], Jan Czogalla[SUP] 1 [/SUP], Milagros N Wong[SUP] 1 [/SUP], Yusuke Okabayashi[SUP] 1 [/SUP], Fabian Braun[SUP] 1 [/SUP], Marc Lütgehetmann[SUP] 5 [/SUP], Elisabeth Meister[SUP] 1 [/SUP], Shun Lu[SUP] 1 [/SUP], Maria L M Noriega[SUP] 6 [/SUP], Thomas Günther[SUP] 7 [/SUP], Adam Grundhoff[SUP] 7 [/SUP], Nicole Fischer[SUP] 5 [/SUP], Hanna Bräuninger[SUP] 8 9 [/SUP], Diana Lindner[SUP] 8 9 [/SUP], Dirk Westermann[SUP] 8 9 [/SUP], Fabian Haas[SUP] 1 [/SUP], Kevin Roedl[SUP] 10 [/SUP], Stefan Kluge[SUP] 10 [/SUP], Marylyn M Addo[SUP] 11 12 [/SUP], Samuel Huber[SUP] 11 [/SUP], Ansgar W Lohse[SUP] 11 [/SUP], Jochen Reiser[SUP] 13 [/SUP], Benjamin Ondruschka[SUP] 4 [/SUP], Jan P Sperhake[SUP] 4 [/SUP], Julio Saez-Rodriguez[SUP] 3 [/SUP], Melanie Boerries[SUP] 2 14 [/SUP], Salim S Hayek[SUP] 15 [/SUP], Martin Aepfelbacher[SUP] 5 [/SUP], Pietro Scaturro[SUP] 7 [/SUP], Victor G Puelles[SUP] 16 [/SUP], Tobias B Huber[SUP] 17 [/SUP]
Affiliations
- PMID: 35347318
- DOI: 10.1038/s42255-022-00552-6
Abstract
Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae[SUP]1[/SUP]. 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[SUP]2,3[/SUP]. 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.