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Publications

Journal Article Research Support, N.I.H., Extramural Epublish 1 citation

PubMed: 37889528 DOI: 10.1097/HC9.0000000000000290

SARS-CoV-2 viral liver aggregates and scarce parenchymal infection implicate systemic disease as a driver of abnormal liver function.

Hepatol Commun 7(11)

Authors: Brian J Pepe-Mooney, Colton J Smith, Marc S Sherman, Trista E North, Robert F Padera, Wolfram Goessling

Affiliations

  • Genetics Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, USA.
  • Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts, USA.
  • Developmental and Regenerative Biology Program, Harvard Medical School, Boston, Massachusetts, USA.
  • Harvard Stem Cell Institute, Cambridge, Massachusetts, USA.
  • Department of Pathology, Brigham and Women's Hospital, Boston Massachusetts, USA.
  • Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

Abstract

BACKGROUND

Liver function tests (LFTs) are elevated in >50% of hospitalized individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with increased enzyme levels correlating with a more severe COVID-19 course. Despite these observations, evaluations of viral presence within liver parenchyma and viral impact on liver function remain controversial.

METHODS AND RESULTS

Our work is a comprehensive immunopathological evaluation of liver tissue from 33 patients with severe, and ultimately fatal, cases of SARS-CoV-2 infection. Coupled with clinical data, we reveal the absence of SARS-CoV-2 infection in cholangiocytes and hepatocytes despite dramatic systemic viral presence. Critically, we identify significant focal viral sinusoidal aggregates in 2/33 patients and single viral RNA molecules circulating in the hepatic sinusoids of 15/33 patients. Utilizing co-immunofluorescence, focal viral liver aggregates in patients with COVID-19 were colocalized to platelet and fibrin clots, indicating the presence of virus-containing sinusoidal microthrombi. Furthermore, this patient cohort, from the initial months of the COVID-19 pandemic, demonstrates a general downtrend of LFTs over the course of the study timeline and serves as a remarkable historical time point of unattenuated viral replication within patients.

CONCLUSIONS

Together, our findings indicate that elevated LFTs found in our patient cohort are not due to direct viral parenchymal infection with SARS-CoV-2 but rather likely a consequence of systemic complications of COVID-19. This work aids in the clinical treatment considerations of patients with SARS-CoV-2 as therapies for these patients may be considered in terms of their direct drug hepatotoxity rather than worsening hepatic function due to direct infection.

MeSH

Infections, Work, Liver Diseases, Therapeutics, Rna, Viral, Sars Virus, Covid-19, Sars-Cov-2