Liver Pathology and SARS-CoV-2 Detection in Formalin-Fixed Tissue of Patients With COVID-19

Overview

Journal Am J Clin Pathol

Publisher Oxford University Press

Specialty Pathology

Date 2021 Apr 29

PMID 33914058

Citations 19

Authors

Yevgen Chornenkyy

Melissa Mejia-Bautista

Melanie Brucal

Timothy Blanke

David Dittmann

Anjana Yeldandi

Justin R Boike

Jon W Lomasney

Ritu Nayar

Lawrence J Jennings

Maryam Kherad Pezhouh

Affiliations

Soon will be listed here.

Abstract

Objectives: The novel coronavirus, severe acute respiratory syndrome coronavirus 2, causing coronavirus disease 2019 (COVID-19) remains a global health threat and a significant source of human morbidity and mortality. While the virus primarily induces lung injury, it also has been reported to cause hepatic sequelae.

Methods: We aimed to detect the virus in formalin-fixed tissue blocks and document the liver injury patterns in patients with COVID-19 compared with a control group.

Results: We were able to detect viral RNA in the bronchioalveolar cell blocks (12/12, 100%) and formalin-fixed, paraffin-embedded tissue of the lung (8/8, 100%) and liver (4/9, 44%) of patients with COVID-19. Although the peak values of the main liver enzymes and bilirubin were higher in the patients with COVID-19 compared with the control group, the differences were not significant. The main histologic findings were minimal to focal mild portal tract chronic inflammation (7/8, 88%, P < .05) and mild focal lobular activity (6/8, 75%, P = .06).

Conclusions: We found that most patients who died of COVID-19 had evidence of mild focal hepatitis clinically and histologically; however, the virus was detected in less than half of the cases.

Citing Articles

Exploring the Role of Ki67 in the Liver of Diabetic Rats.

Ababneh S, Siyam A, Alqaraleh M, Al-Rawashde F, Abbas M, Ababneh S Mater Sociomed. 2025; 36(4):250-256.

PMID: 39963446 PMC: 11830229. DOI: 10.5455/msm.2024.36.250-256.

Hepatic endotheliitis in Golden Syrian hamsters (Mesocricetus auratus) experimentally infected with SARS-CoV-2.

de Souza A, Souza Filho A, Zimpel C, Ayupe M, Araujo M, Machado R Rev Inst Med Trop Sao Paulo. 2024; 66:e44.

PMID: 39082483 PMC: 11295288. DOI: 10.1590/S1678-9946202466044.

Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention.

Lim J, Njei B Hepat Med. 2023; 15:151-164.

PMID: 37814605 PMC: 10560482. DOI: 10.2147/HMER.S385133.

Unraveling the Molecular and Cellular Pathogenesis of COVID-19-Associated Liver Injury.

Akkiz H Viruses. 2023; 15(6).

PMID: 37376587 PMC: 10304875. DOI: 10.3390/v15061287.

An Updated Systematic Review and Meta-Analysis of the Association between the De Ritis Ratio and Disease Severity and Mortality in Patients with COVID-19.

Mangoni A, Zinellu A Life (Basel). 2023; 13(6).

PMID: 37374107 PMC: 10303964. DOI: 10.3390/life13061324.

References

Lagana S, Kudose S, Iuga A, Lee M, Fazlollahi L, Remotti H . Hepatic pathology in patients dying of COVID-19: a series of 40 cases including clinical, histologic, and virologic data. Mod Pathol. 2020; 33(11):2147-2155. PMC: 7424245. DOI: 10.1038/s41379-020-00649-x. View

Foschini M, Sarti F, Dina R, Dal Monte P, Eusebi V . Standardized reporting of histological diagnoses for non-neoplastic liver conditions in needle biopsies. Virchows Arch. 1995; 426(6):593-6. DOI: 10.1007/BF00192114. View

Lagana S, De Michele S, Lee M, Emond J, Griesemer A, Tulin-Silver S . COVID-19 Associated Hepatitis Complicating Recent Living Donor Liver Transplantation. Arch Pathol Lab Med. 2020; . DOI: 10.5858/arpa.2020-0186-SA. View

Hamming I, Timens W, Bulthuis M, Lely A, Navis G, van Goor H . Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004; 203(2):631-7. PMC: 7167720. DOI: 10.1002/path.1570. View

Vasquez-Bonilla W, Orozco R, Argueta V, Sierra M, Zambrano L, Munoz-Lara F . A review of the main histopathological findings in coronavirus disease 2019. Hum Pathol. 2020; 105:74-83. PMC: 7395947. DOI: 10.1016/j.humpath.2020.07.023. View

Zhao C, Rapkiewicz A, Maghsoodi-Deerwester M, Gupta M, Cao W, Palaia T . Pathological findings in the postmortem liver of patients with coronavirus disease 2019 (COVID-19). Hum Pathol. 2020; 109:59-68. PMC: 7722493. DOI: 10.1016/j.humpath.2020.11.015. View

Qi F, Qian S, Zhang S, Zhang Z . Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020; 526(1):135-140. PMC: 7156119. DOI: 10.1016/j.bbrc.2020.03.044. View

Li F, Li W, Farzan M, Harrison S . Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science. 2005; 309(5742):1864-8. DOI: 10.1126/science.1116480. View

Paizis G, Tikellis C, Cooper M, Schembri J, Lew R, Smith A . Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut. 2005; 54(12):1790-6. PMC: 1774784. DOI: 10.1136/gut.2004.062398. View

10.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S . SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. PMC: 7102627. DOI: 10.1016/j.cell.2020.02.052. View

11.

Yao X, Li T, He Z, Ping Y, Liu H, Yu S . [A pathological report of three COVID-19 cases by minimal invasive autopsies]. Zhonghua Bing Li Xue Za Zhi. 2020; 49(5):411-417. DOI: 10.3760/cma.j.cn112151-20200312-00193. View

12.

Baiocchini A, Del Nonno F, Taibi C, Visco-Comandini U, DOffizi G, Piacentini M . Liver sinusoidal endothelial cells (LSECs) modifications in patients with chronic hepatitis C. Sci Rep. 2019; 9(1):8760. PMC: 6584733. DOI: 10.1038/s41598-019-45114-1. View

13.

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J . A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382(8):727-733. PMC: 7092803. DOI: 10.1056/NEJMoa2001017. View

14.

Varga Z, Flammer A, Steiger P, Haberecker M, Andermatt R, Zinkernagel A . Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020; 395(10234):1417-1418. PMC: 7172722. DOI: 10.1016/S0140-6736(20)30937-5. View

15.

Martines R, Ritter J, Matkovic E, Gary J, Bollweg B, Bullock H . Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States. Emerg Infect Dis. 2020; 26(9):2005-2015. PMC: 7454055. DOI: 10.3201/eid2609.202095. View

16.

Zhang H, Penninger J, Li Y, Zhong N, Slutsky A . Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020; 46(4):586-590. PMC: 7079879. DOI: 10.1007/s00134-020-05985-9. View

17.

Pawlotsky J . COVID-19 and the liver-related deaths to come. Nat Rev Gastroenterol Hepatol. 2020; 17(9):523-525. PMC: 7288259. DOI: 10.1038/s41575-020-0328-2. View

18.

KRAFFT , Duncan , Bijwaard , Taubenberger , Lichy . Optimization of the Isolation and Amplification of RNA From Formalin-fixed, Paraffin-embedded Tissue: The Armed Forces Institute of Pathology Experience and Literature Review. Mol Diagn. 1999; 2(3):217-230. DOI: 10.1054/MODI00200217. View

19.

Sonzogni A, Previtali G, Seghezzi M, Alessio M, Gianatti A, Licini L . Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations. Liver Int. 2020; 40(9):2110-2116. PMC: 7404964. DOI: 10.1111/liv.14601. View

20.

Schaller T, Hirschbuhl K, Burkhardt K, Braun G, Trepel M, Markl B . Postmortem Examination of Patients With COVID-19. JAMA. 2020; 323(24):2518-2520. PMC: 7243161. DOI: 10.1001/jama.2020.8907. View