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A recent study by French researchers has shown that experimental exposure to severe acute respiratory coronavirus 2 (SARS-CoV-2) is capable of inducing a mild infection in hamsters and ferrets within 7 to 10 days after exposure. However, the infection resolves completely in 14 days. The study is currently available at bioRxiv* prepress server.
SARS-CoV-2, the pathogen that causes the coronavirus disease 2019 (COVID-19) pandemic, emerged in December 2019 in China, most likely due to zoonotic transmission from an animal to a human. Later, the virus has gained the ability to spread from person to person.
Understanding the pathogenesis and nature of SARS-CoV-2 infection is the key to identifying effective therapeutic and preventive interventions to mitigate the trajectory of COVID-19. In this context, non-human primates, such as monkeys, cats, hamsters, and ferrets, serve as suitable experimental models to study the pathogenesis of SARS-CoV-2 infection.
Histopathological findings in hamsters inoculated with the SARS-CoV-2 UCN19 strain. Mild inflammatory cell infiltration observed in the trachea in D2 (A, 400x) with high presence of viral RNA by ISH within respiratory epithelial cells (B, 400x). In D2 (C, 100x) and D4 (E, 200x) inflammatory infiltrates are observed with the lung parenchyma, mainly within the bronchial and bronchiolar mucosa, but also the surrounding airways and blood vessels. The presence of inflammatory infiltrates correlates with viral RNA staining in sequential sections in D2 (D, 100x) and D4 (F, 200x).
Current study design
In this study, the scientists aimed to evaluate pathogenicity, immune responses, and clinical outcomes in hamsters and ferrets infected with low doses of a low-passage SARS-CoV-2 clinical isolate.
According to the scientists, the study will help identify appropriate animal models to develop therapeutic interventions against SARS-CoV-2 infection.
Histopathological findings in the lungs of ferrets inoculated with the UNC19 SARS-CoV-2 strain. Perivascular cuff (A, 400x, arrows) and mild bronchiolitis (B, 200x, arrow) were observed in D2, with minimal presence of viral RNA (B, insert, 400x) within the alveolar walls not related to histopathological lesions. A perivascular cuff was also seen in D4 (C, 200x, arrows) and D7 (E, 200x, arrows). Mild bronchiolitis with the presence of intraluminal inflammatory infiltrates was observed in D4 (D, 200x, arrow). Scattered foci of parenchymal inflammation were also observed in D7 (F, 400x, arrow)
Important remarks
Regarding clinical symptoms, some ferrets developed foam after 7 days of infection and none of the infected animals presented hyperthermia. No changes in body weight were observed in ferrets; however, a mean increase in body weight was observed in all hamsters. Most importantly, none of the infected animals died from the SARS-CoV-2 infection.
Viral RNA was detected in many tissues (respiratory tissues, liver, spleen, kidney, intestine, olfactory bulb, and spinal bulb) within 2 days of infection, and mostly resolved after 14 days of infection.
The viral load was highest in the nasal turbinate, trachea and lungs. However, the tissue variability of viral load was higher in ferrets than in hamsters.
The infectious virus was present in the nasal turbinate, trachea and lungs of all the experimental hamsters on day 2 and day 4 of infection. However, in ferrets, no infectious virus was detected in the lungs.
In infected hamsters, infiltration of macrophages, lymphocytes, and neutrophils into the lungs was observed within 2 to 7 days after infection. In the trachea, mild inflammatory infiltration and mild epithelial cell necrosis were observed between day 2 and day 7 of infection.
In ferrets, inflammatory infiltration of neutrophils, macrophages, lymphocytes, and eosinophils was observed along with mild bronchiolitis within the bronchiolar laminae on day 2 of infection.
Regarding the serological characteristics, the presence of immunoglobulin G (IgG) was observed at 7 and 10 days of infection in hamsters and ferrets, respectively.
In hamsters, the IgG level remained high until day 14 of infection; however, in ferrets, a more gradual increase in IgG level was observed from day 10 of infection.
Neutralizing antibodies were detected in hamsters and ferrets after 7 and 10 days of infection, respectively. However, there was no correlation between IgG levels and neutralizing antibody titers.
In hamsters, the IgG level remained stable until day 14 of infection, while neutralizing antibody titers were reduced by 50% between day 7 and day 14. However, in a ferret, neutralizing titers they were reduced by 50% on day 14 of infection. while in another ferret, the titles doubled from day 10 to day 14.
Importance of the current study
Unlike other animal studies, the current study used relatively lower doses of SARS-CoV-2, which is more comparable to natural infection in humans.
The study shows that a low dose of exposure to SARS-CoV-2 intranasally is capable of inducing mild symptoms of COVID-19 in hamsters. Compared to hamsters, ferrets require higher doses of viral inoculation to induce similar levels of lung infection.
Serological observations suggest that both hamsters and ferrets successfully develop robust adaptive immune responses against SARS-CoV-2 shortly after viral exposure, which is accompanied by the disappearance of the infectious virus.
*Important news
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice / health-related behavior, or be treated as established information.
