Journal
NATURE METABOLISM
Volume 4, Issue 3, Pages 310-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42255-022-00552-6
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Funding
- German Research Foundation [CRC/850, CRC/1160, CRC1479, 441891347-S1, 431984000-S1, CRC841, CRC/1453, CRC/1192, SC 314/1-1, HU 1016/8-2, HU 1016/11-1, HU 1016/12]
- eMed Consortia Fibromap
- MIRACUM Consortia [FKZ 01ZZ1801B]
- Federal Ministry of Education and Research [STOP-FSGS- 01GM1901C, EkoEstMed-FKZ 01ZZ2015]
- GlaxoSmithKline
- Sanofi
- Authorities for Social Welfare (Hamburg, Germany)
- Federal Ministry for Education and Research, Germany
- German Center for Infection Research [TTU 01.921, TTU 01.901]
- DEFEAT PANDEMIcs project - Federal Ministry of Education and Research, Germany [01KX2021]
- Else-Kroner-Fresenius-Stiftung: Else-Kroner-Memorial Stipendium [2021_EKMS.26]
- NHLBI [1R01HL153384-01]
- NIDDK [1R01DK12801201A1, U01-DK119083-03S1]
- Frankel Cardiovascular Center COVID-19: Impact Research Ignitor [U-M G024231]
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The study provides evidence for the hepatic tropism of SARS-CoV-2 and its impact on liver injury in COVID-19 patients. The researchers found viral RNA in autopsy liver specimens and successfully isolated infectious SARS-CoV-2 from liver tissue postmortem. The study also reveals similarities between the liver signatures of COVID-19 and other viral infections.
Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae(1). 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(2,3). 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.
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