Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters

Abstract

In late 2019, an outbreak of a severe respiratory disease caused by an emerging coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans. Complete understanding of COVID-19, the multi-faceted disease caused by SARS-CoV-2, requires suitable small animal models, as does the development and evaluation of vaccines and antivirals. Since age-dependent differences of COVID-19 were identified in humans, we compared the course of SARS-CoV-2 infection in young and aged Syrian hamsters. We show that virus replication in the upper and lower respiratory tract was independent of the age of the animals. However, older hamsters exhibited more pronounced and consistent weight loss. In situ hybridization in the lungs identified viral RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. Histopathology revealed clear age-dependent differences, with young hamsters launching earlier and stronger immune cell influx than aged hamsters. The latter developed conspicuous alveolar and perivascular edema, indicating vascular leakage. In contrast, we observed rapid lung recovery at day 14 after infection only in young hamsters. We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information, as this small-animal model appears to mirror age-dependent differences in human patients.

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

“…principally similar to what has been described in Syrian hamsters ( Figure 2) (Chan et al, 2020;Gruber et al, 2020;Imai et al, 2020;Kreye et al, 2020;Osterrieder et al, 2020;Sia et al, 2020). However, the course of bronchitis and pneumonia was in general milder than in Syrian hamsters, and pneumonia was more prolonged.…”

Multi-species ELISA for the detection of antibodies against SARS-CoV-2 in animals

“…Eight ferret, 20 hamster, 16 raccoon dog and two cattle SARS-CoV-2 antibody-positive sera originated from experimental infection studies and were collected between 8 and 28 days post infection (dpi) (Freuling et al, 2020; Osterrieder et al, 2020; Schlottau et al, 2020; Ulrich, Wernike, Hoffmann, Mettenleiter, & Beer, 2020; Balkema-Buschmann, Rissmann et al, unpublished). With the exception of the bovine samples, all sera tested positive in a VNT, in an iIFA, or in both, with the iIFA being more sensitive for antibody detection early after infection (Schlottau et al, 2020).…”

“…The majority of SARS-CoV-2-infections in animals were directly linked to SARS-CoV-2-infected owners or animal caretakers. Under experimental conditions, the susceptibility of additional species including ferrets, hamsters, and fruit bats has been demonstrated (Osterrieder et al, 2020; Richard et al, 2020; Schlottau et al, 2020; Shi et al, 2020). However, the level of natural infections is largely unknown.…”

3D reconstruction of SARS-CoV-2 infection in ferrets emphasizes focal infection pattern in the upper respiratory tract

“…For the EtOH-ECi-based TOC approach used here, a 50% volume reduction, equaling to a change of about 20% in tissue diameters, has been determined [59]. The limited degree of infection is particularly interesting in view of the amounts of infectious virus and genome copies that can be isolated from the URT of ferrets [29–31] and other animal species, like Syrian hamsters [32–34] and rhesus macaques [42–44]. Clustering of SARS-CoV-2 infection foci in narrow areas of the URT might also have implications for the likelihood of isolation of infectious virus and the detection of viral RNA from nasal swabs in comparison to nasal washes from ferrets and possibly other animal models.…”

“…receptor usage [25], and necessary research tools, including reverse genetics systems [26,27], became rapidly available. Furthermore, a variety of animal studies to investigate susceptibility and suitability as animal models have been conducted in a number of animal species (reviewed in [28]): ferrets [29–31], hamsters [32–34], cats [31,35], dogs [31], raccoon dogs [36], rabbits [37], transgenic mice [38–40], pigs [30,31], cattle [41], monkeys [42–44], poultry [30,31,45], and fruit bats [30].…”