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Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 119 | 2024

Research Articles

Detached epithelial cell plugs from the upper respiratory tract favour distal lung injury in Golden Syrian hamsters (Mesocricetus auratus) when experimentally infected with the A.2 Brazilian SARS-CoV-2 strain

Marcelo Pelajo-Machado¹, Alexandre dos Santos da Silva², Daniela del Rosario Flores Rodrigues², Milla Bezerra Paiva¹, Rodrigo Muller³, Luciana Jesus da Costa⁴, Pedro Paulo Abreu Manso¹, João Paulo Rodrigues dos Santos¹, Emanuelle de Souza Ramalho Ferreira da Silva⁵, Arthur Daniel Rocha Alves², Jaqueline Mendes Oliveira², Marcelo Alves Pinto^2,+

¹Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Medicina Experimental e Saúde, Rio de Janeiro, RJ, Brasil
²Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Desenvolvimento Tecnológico em Virologia, Rio de Janeiro, RJ, Brasil
³Fundação Oswaldo Cruz-Fiocruz, Bio-Manguinhos, Vice-Diretoria de Inovação, Departamento Experimental e Pré-Clínico, Laboratório de Ensaios Pré-Clínicos, Rio de Janeiro, RJ, Brasil
⁴Universidade Federal do Rio de Janeiro, Instituto de Microbiologia Paulo de Góes, Departamento de Virologia, Laboratório de Genética e Imunologia das Infecções Virais, Rio de Janeiro, RJ, Brasil
⁵Fundação Oswaldo Cruz-Fiocruz, Central Analítica COVID-19, Rio de Janeiro, RJ, Brasil

DOI: 10.1590/0074-02760240100

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ABSTRACT

BACKGROUND The Golden Syrian hamster (Mesocricetus auratus), Ferrets (Mustela putorius furo), and macaques have been described as useful laboratory animals naturally susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
OBJECTIVES To study the mechanism of lung injury, we describe the histopathological features of SARS-CoV-2 infection in Golden Syrian hamsters inoculated intranasally with the A.2 Brazilian strain.
METHODS Hamsters were intranasally inoculated with the A.2 variant and euthanised at 3-, 5-, 10- and 15-days post-inoculation. The physical examination and body weight were recorded daily. Neutralising antibodies and viral RNA load of the respiratory tract were assessed during necropsies.
FINDINGS The coronavirus disease 2019 (COVID-19) model presented body weight loss, high levels of respiratory viral RNA load, severe segmentary pneumonitis, and bronchial fistula besides lymphatic trapping and infiltration, like the human SARS-COV-2 pathogenesis. The presence of subepithelial lymphoeosinophilic infiltrate was highlighted in our results; it contributed to the detachment of SARS-CoV-2 nucleocapsid-positive epithelial cells resulting in the infectious cell plugs.
MAIN CONCLUSIONS The SARS-CoV-2 caused segmentary pneumonia and vascular damage. In our comprehension, the infectious cell plugs, as being aspirated from the upper respiratory tract into the terminal bronchial lumen, work as a “Trojan horse”, thus contributing to the dissemination of the SARS-CoV-2 infection into specific regions of the deep lung parenchyma.

key words: A2 SARS-CoV-2 Brazilian strain rodent model Mesocricetus auratus pathogeny infectious epithelial plugs segmentary pneumonia acute lung injury

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