Hamster and ferret experimental infection with intranasal low dose of a single strain of SARS-CoV-2

Abstract

Understanding the pathogenesis of the SARS-CoV-2 infection is key to developing preventive and therapeutic strategies against COVID-19, in the case of severe illness but also when the disease is mild. The use of appropriate experimental animal models remains central in the in vivo exploration of the physiopathology of infection and antiviral strategies. This study describes SARS-CoV-2 intranasal infection in ferrets and hamsters with low doses of low-passage SARS-CoV-2 clinical French isolate UCN19, describing infection levels, excretion, immune responses and pathological patterns in both animal species. Individual infection with 103 p.f.u. SARS-CoV-2 induced a more severe disease in hamsters than in ferrets. Viral RNA was detected in the lungs of hamsters but not of ferrets and in the brain (olfactory bulb and/or medulla oblongata) of both species. Overall, the clinical disease remained mild, with serological responses detected from 7 days and 10 days post-inoculation in hamsters and ferrets respectively. The virus became undetectable and pathology resolved within 14 days. The kinetics and levels of infection can be used in ferrets and hamsters as experimental models for understanding the pathogenicity of SARS-CoV-2, and testing the protective effect of drugs.

Natural and Experimental SARS-CoV-2 Infection in Domestic and Wild Animals

“…Several different species of hamsters are highly susceptible to SARS-CoV-2 by experimental infection and can transmit the virus to naïve hamsters, although there is currently no evidence of natural human-to-hamster infections [ 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 80 , 81 ]. Syrian golden hamsters ( Mesocricetus auratus ) have been studied most extensively, and exhibit acute disease characterized by mild-to-moderate clinical signs with moderate-to-severe pathological changes in the respiratory tract [ 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ].…”

“…Several different species of hamsters are highly susceptible to SARS-CoV-2 by experimental infection and can transmit the virus to naïve hamsters, although there is currently no evidence of natural human-to-hamster infections [ 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 80 , 81 ]. Syrian golden hamsters ( Mesocricetus auratus ) have been studied most extensively, and exhibit acute disease characterized by mild-to-moderate clinical signs with moderate-to-severe pathological changes in the respiratory tract [ 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. Chinese hamsters ( Cricetulus griseus ), Campbell’s dwarf hamster ( Phodopus campbelli ), and Djungarian hamster ( Phodopus sungorus ) have also been investigated and exhibit a similar susceptibility and disease progression after SARS-CoV-2 infection compared to Syrian hamsters [ 80 , 81 ].…”

“…Syrian golden hamsters have been the most widely used species for experimental SARS-CoV-2 studies. Most studies inoculated 4- to 34-week-old hamsters with 10 3 to 10 5 pfu intranasally [ 71 , 72 , 73 , 74 , 76 , 78 , 79 ]. One study inoculated older Syrian golden hamsters (10 to 20 months old) with 7 × 10 4 pfu SARS-CoV-2 [ 77 ].…”

Modeling Within-Host Dynamics of SARS-CoV-2 Infection: A Case Study in Ferrets

“…Additionally, the infectiousness at the infection site within ferrets may be different from the one estimated in in-vitro experiments, as the virus may adapt to the in-vivo cell environment [62]. Lastly, we note that the infection of SARS-CoV-2 has been successfully established in ferrets with widely varying initial infectious doses and the infection has been reported to depend on the route of transmission [63,64]. Shown here are two representative animals from each of the two groups infected with F13-E SARS-CoV-2 and CTan-H SARS-CoV-2.…”

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

“…SARS-CoV-2 strain UCN1 was amplified as described previously and used at passage 2 [ 35 ]. The viral stock was sequenced by Eurofins Genomics (Ebersberg, Germany) using the Illumina deep sequencing Eurofins Genomics Covid Pipeline v.0.1.…”