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

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de Souza, Alex Junior Souza ; de Souza, Antonio Francisco ; Zimpel, Cristina Kraemer ; Ayupe, Marina Cacador ; de Araujo, Marcelo Valdemir ; Machado, Rafael Rahal Guaragna ; Salles, Erika ; Salgado, Caio Loureiro ; Tavares, Mariana Silva ; Silva-Pereira, Taiana Taina ; de Souza, Paula Carolina ; Durigon, Edison Luiz ; Heinemann, Marcos Bryan ; Brandao, Paulo Eduardo ; da Fonseca, Denise Morais ; Guimaraes, Ana Marcia de Sa ; de Sa, Lilian Rose Marques

• Document type: Journal article
• Source: Revista do Instituto de Medicina Tropical de São Paulo; v. 66, p. 6-pg., 2024-01-01.

Abstract

Hepatic injuries in COVID-19 are not yet fully understood and indirect pathways (without viral replication in the liver) have been associated with the activation of vascular mechanisms of liver injury in humans infected with SARS-CoV-2. Golden Syrian hamsters are an effective model for experimental reproduction of moderate and self-limiting lung disease during SARS-CoV-2 infection. As observed in humans, this experimental model reproduces lesions of bronchointerstitial pneumonia and pulmonary vascular lesions, including endotheliitis (attachment of lymphoid cells to the luminal surface of endothelium). Extrapulmonary vascular lesions are well documented in COVID-19, but such extrapulmonary vascular lesions have not yet been described in the Golden Syrian hamster model of SARS-CoV-2 infection. The study aimed to evaluate microscopic liver lesions in Golden Syrian hamsters experimentally infected with SARS-CoV-2. In total, 38 conventional Golden Syrian hamsters, divided into infected group (n=24) and mock-infected group (n=14), were euthanized at 2-, 3-, 4-, 5-, 7-, 14-, and 15-days post infection with SARS-CoV-2. Liver fragments were evaluated by histopathology and immunohistochemical detection of SARS-CoV-2 Spike S2 antigens. The frequencies of portal vein endotheliitis, lobular activity, hepatocellular degeneration, and lobular vascular changes were higher among SARS-CoV-2-infected animals. Spike S2 antigen was not detected in liver. The main results indicate that SARS-CoV-2 infection exacerbated vascular and inflammatory lesions in the liver of hamsters with pre-existing hepatitis of unknown origin. A potential application of this animal model in studies of the pathogenesis and evolution of liver lesions associated with SARS-CoV-2 infection still needs further evaluation. (AU)

• FAPESP's process: 21/02736-0 - Good practices and operation of biosafety level 3+ laboratories
• Grantee: Mariana Silva Tavares
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 21/06881-5 - Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease
• Grantee: Denise Morais da Fonseca
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 20/06409-1 - Evaluation of humoral immune response and inflammatory response in patients with confirmed diagnosis of COVID-19 at Hospital Sírio Libanês and correlation with disease severity
• Grantee: Edison Luiz Durigon
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/00532-4 - Immunological scar development and impairment of the tissue-specific immune response after COVID-19
• Grantee: Marcelo Valdemir de Araujo
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/24769-2 - Zika virus in postpartum women and newborns: seroepidemiology and molecular characterization
• Grantee: Rafael Rahal Guaragna Machado
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/07251-2 - Evaluation of Syrian hamsters (Mesocricetus auratus) as model of infection and disease by SARS-CoV-2
• Grantee: Ana Marcia de Sá Guimarães
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/10896-8 - Transcriptomic and metabolic features of Mycobacterium tuberculosis and Mycobacterium bovis during human macrophage infection
• Grantee: Cristina Kraemer Zimpel
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 20/09149-0 - Evaluation of Syrian hamsters (Mesocricetus auratus) as an experimental model of SARS-CoV-2 infection and disease
• Grantee: Antonio Francisco de Souza Filho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 16/20045-7 - Antigen discovery and development of serological diagnostic methods and vaccine approaches against the Zika Virus (ZIKV)
• Grantee: Luis Carlos de Souza Ferreira
• Support Opportunities: Research Projects - Thematic Grants