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

Mem Inst Oswaldo Cruz. 2024 Oct 21:119:e240100. doi: 10.1590/0074-02760240100. eCollection 2024.

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.

MeSH terms

  • Animals
  • Brazil
  • COVID-19* / pathology
  • Cricetinae
  • Disease Models, Animal*
  • Epithelial Cells* / virology
  • Lung / pathology
  • Lung / virology
  • Lung Injury / pathology
  • Lung Injury / virology
  • Male
  • Mesocricetus*
  • RNA, Viral / analysis
  • SARS-CoV-2*
  • Viral Load

Substances

  • RNA, Viral

Supplementary concepts

  • SARS-CoV-2 variants

Grants and funding

FAPERJ (1-Ação Emergencial COVID-19, chamada C, Apoio a projetos em Redes de Pesquisa em SARS-CoV-2/COVID-19, Grant numbers: E-26/210.189/2020, 2-Segunda Chamada Emergencial de Projetos para combater os efeitos da COVID 19, Grant number: E-26/210.242/2020, 3- Projetos Temáticos: grant number: E-26/210.045/2023), CNPq [grant numbers: 402639/2023-5, 304797/2022-7 (suportes MAP’s research fellowship)]