Evidence map›Paper›PMID 39760326›Full record

ArticleJournal of medical virology2025

SARS-CoV-2 Productively Infects Human Hepatocytes and Induces Cell Death.

Chunkyu Ko, Cho-Chin Cheng, Daniele Mistretta, Shubhankar Ambike, Julia Sacherl, Stoyan Velkov, Bo-Hung Liao, Romina Bester, Merve Gültan, Olga Polezhaeva and 14 more

Abstract read
In one paragraph

Article in Journal of medical virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Article
  3. COVID-19, the disease that changed the world.Medicine and pharmacy reports · 2026
    Review
  4. Article
  5. Hepatic involvement in major respiratory viral infections.Clinical and experimental hepatology · 2025
    Review
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors.

Chunkyu KoInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.ORCID 0000-0001-6512-1602
Cho-Chin ChengInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Daniele MistrettaInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Shubhankar AmbikeInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Julia SacherlInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Stoyan VelkovInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Bo-Hung LiaoInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Romina BesterInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Merve GültanInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Olga PolezhaevaInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Alexander HerrmannInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Constanze A JakwerthCenter of Allergy & Environment (ZAUM), Technical University of Munich/Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany.
Carsten B Schmidt-WeberCenter of Allergy & Environment (ZAUM), Technical University of Munich/Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany.
Joachim J BugertDepartment of Viruses and Intracellular Pathogens, Bundeswehr Institute of Microbiology, Munich, Germany.
Roman WölfelDepartment of Viruses and Intracellular Pathogens, Bundeswehr Institute of Microbiology, Munich, Germany.
Vincent GrassInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Sandra EssbauerDepartment of Viruses and Intracellular Pathogens, Bundeswehr Institute of Microbiology, Munich, Germany.
Daniel SchnepfInstitute of Virology, Medical Center University of Freiburg, Freiburg, Germany.
Oliver T KepplerGerman Centre for Infection Research (DZIF), Partner Sites Munich and Hannover-Braunschweig, Munich, Germany.
Florian W R VondranGerman Centre for Infection Research (DZIF), Partner Sites Munich and Hannover-Braunschweig, Munich, Germany.
Andreas PichlmairInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Carolin MoglerInstitute of Pathology, Technical University of Munich, Munich, Germany.
Gregor EbertInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.
Ulrike ProtzerInstitute of Virology, Technical University of Munich/Helmholtz Munich, Munich, Germany.

Funding

This study was supported by the German Research Foundation (DFG) via SFB-TRR179 (project 272983813 to U.P.), TRR22 (project 398577603 to C.S.W.) and TRR353 (project 471011418 to G.E.), by the State of Bavaria via research network FOR-COVID and Bay-VOC, by the project "Virological and immunological determinants of COVID-19 pathogenesis-lessons to get prepared for future pandemics" (KA1-Co-02 "COVIPA" to U.P.) and "Airborne Transmission of SARS Coronavirus - From Fundamental Science to Efficient Air Cleaning Systems" (KA1-Co-06 "CORAERO" to G.E.), grants from the Helmholtz Association's Initiative and Networking Fund, by the European Commission FET Open Grant VIROFIGHT (grant no. 899619), by the State of Bavaria and the European Union via a grant for regional infrastructure development (EFRE - REACT, to U.P. and G.E.), by the State of Bavaria via research networks FOR-COVID and Bay-VOC (to U.P. and O.T.K.) by the Federal Ministry of Education and Research (project ESCAPE; 01KI20169A to C.S.W.), and by the Medical Biological Defense Research Program of the Bundeswehr Medical Service (to J.J.B.). In addition, this research was supported by intramural funds from KRICT (project KK2432-10 and BSF24-111 to C.K.).
6 · The paper itself

Abstract

SARS-CoV-2 infection is accompanied by elevated liver enzymes, and patients with pre-existing liver conditions experience more severe disease. While it was known that SARS-CoV-2 infects human hepatocytes, our study determines the mechanism of infection, demonstrates viral replication and spread, and highlights direct hepatocyte damage. Viral replication was readily detectable upon infection of primary human hepatocytes and hepatoma cells with the ancestral SARS-CoV-2, Delta, and Omicron variants. Hepatocytes express the SARS-CoV-2 receptor ACE2 and the host cell protease TMPRSS2, and knocking down ACE2 and TMPRSS2 impaired SARS-CoV-2 infection. Progeny viruses released from infected hepatocytes showed the typical coronavirus morphology by electron microscopy and proved infectious when transferred to fresh cells, indicating that hepatocytes can contribute to virus spread. Importantly, SARS-CoV-2 infection rapidly induced hepatocyte death in a replication-dependent fashion, with the Omicron variant showing faster onset but less extensive cell death. C57BL/6 wild-type mice infected with a mouse-adapted SARS-CoV-2 strain showed high levels of viral RNA in liver and lung tissues. ALT peaked when viral RNA was cleared from the liver. Liver histology revealed profound tissue damage and immune cell infiltration, indicating that direct cytopathic effects of SARS-CoV-2 and immune-mediated killing of infected hepatocytes contribute to liver pathology.

Indexed as

Angiotensin-Converting Enzyme 2Cell DeathCOVID-19HepatocytesMice, Inbred C57BLSARS-CoV-2Serine EndopeptidasesVirus ReplicationAnimalsHumansMiceACE2 protein, humanAngiotensin-Converting Enzyme 2Serine EndopeptidasesTMPRSS2 protein, humanACE2COVID‐19hepatocytesliverSARS‐CoV‐2TMPRSS2tropism

Identifiers

PMID39760326
PMCPMC11702151

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.