SARS-CoV-2 infection of Chinese hamsters (Cricetulus griseus) reproduces COVID-19 pneumonia in a well-established small animal model

Abstract

The SARS-CoV-2 pandemic has caused a yet unresolved global crisis. Effective medical intervention by vaccination or therapy seems to be the only possibility to control the pandemic. In this context, animal models are an indispensable tool for basic and applied research to combat SARS-CoV-2 infection. Here, we established a SARS-CoV-2 infection model in Chinese hamsters suitable for studying pathogenesis of the disease as well as pre-clinical testing of vaccines and therapies. This species of hamster is susceptible to SARS-CoV-2 infection as demonstrated by robust virus replication in the upper and lower respiratory tract accompanied by bronchitis and pneumonia as well as significant body weight loss following infection. The Chinese hamster features advantages compared to the Syrian hamster model, including more pronounced clinical symptoms, its small size, well-characterized genome, transcriptome and translatome data and availability of molecular tools.

Keywords: coronavirus; experimental animal models; histopathology.

Figure 1

Body weight changes, body temperatures and virus loads of mock‐infected and SARS‐CoV‐2‐infected Chinese hamsters. (a) Individual relative body weights of mock‐infected (green) and SARS‐CoV‐2‐infected (red) hamsters over the course of 14 days after infection. p‐values indicate significant differences (Mann–Whitney U test). (b) Temperature changes (as means with SD). Virus loads were determined from total RNA in (c) 2.5 mg homogenized right cranial lung lobes, in (d) bucco‐laryngeal swabs and (e) 2.5 µl of whole blood samples by RT‐qPCR [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 2

Histopathological assessment of mock‐infected and SARS‐CoV‐2‐infected Chinese hamsters. Histopathology of haematoxylin–eosin‐stained lung sections from SARS‐CoV‐2‐infected Chinese hamsters revealed suppurative bronchitis (a, b; arrow: neutrophils) and necrosuppurative pneumonia (c, d) at 2 and 3 dpi. At 5 dpi (e, f), additional hyperplasia of alveolar epithelial cells (AEC)‐type II was salient (f, arrow). Tissue damage, cell influx and hyperplasia of AEC‐II (h, arrow) were milder but still present at 14 dpi (g, h). Of note, acute alveolar damage (I, arrows) was multifocally distributed throughout the lungs across all time points investigated. None of these lesions was detected in mock‐infected animals (j, k). Bars: 1 mm (a, c, e, g, j) or 50 µm (b, d, f, h, i, k) [Colour figure can be viewed at wileyonlinelibrary.com]