Development of a Hamster Natural Transmission Model of SARS-CoV-2 Infection

Abstract

The global pandemic of coronavirus disease (COVID-19) caused by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to an international thrust to study pathogenesis and evaluate interventions. Experimental infection of hamsters and the resulting respiratory disease is one of the preferred animal models since clinical signs of disease and virus shedding are similar to more severe cases of human COVID-19. The main route of challenge has been direct inoculation of the virus via the intranasal route. To resemble the natural infection, we designed a bespoke natural transmission cage system to assess whether recipient animals housed in physically separate adjacent cages could become infected from a challenged donor animal in a central cage, with equal airflow across the two side cages. To optimise viral shedding in the donor animals, a low and moderate challenge dose were compared after direct intranasal challenge, but similar viral shedding responses were observed and no discernible difference in kinetics. The results from our natural transmission set-up demonstrate that most recipient hamsters are infected within the system developed, with variation in the kinetics and levels of disease between individual animals. Common clinical outputs used for the assessment in directly-challenged hamsters, such as weight loss, are less obvious in hamsters who become infected from naturally acquiring the infection. The results demonstrate the utility of a natural transmission model for further work on assessing the differences between virus strains and evaluating interventions using a challenge system which more closely resembles human infection.

Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model

“…In agreement with previous studies (Dowall et al, 2021; Gruber et al, 2020; Nouailles et al, 2021), SARS-CoV-2 infected lung tissue showed pulmonary lesions consisting of broncho-interstitial pneumonia extending into the alveoli and multifocal areas of consolidation, consistent with inflammatory cell infiltration and oedema (Fig.4A, Supplementary Fig.5) . Digital image analysis showed that FG-4592 treatment did not alter the severity of lung histopathology (Fig.4C) .…”

Characterisation of Particle Size and Viability of SARS-CoV-2 Aerosols from a Range of Nebuliser Types Using a Novel Sampling Technique

“…Similarly, most animal studies exploring SARS-CoV-2 have challenged animals intra-nasally, intra-ocularly, or intra-orally, with few delivered by the aerosol route [ 14 , 15 , 16 , 17 , 18 ]. Only one recent study examined natural transmission between intra-nasally infected hamsters to naïve animals [ 47 ]. Our study sought to characterise the MMAD and viability of SARS-CoV-2 aerosols generated with different relative humidities from six nebulisers.…”

“…Future work employing different aerosol capture methods, such as the Goldberg drum or spider microthreads, could explore decay rates over longer time periods, of virus in different temperature and relative humidities, and also incorporate electron microscopy images of the virus to determine physical effects of nebulisation compared to those observed in sputum. Future work may also involve comparison of natural transmission in animal models [ 47 ] to those animals infected via nebuliser-generated aerosols; such work may aid elucidation of the particle sizes and concentrations generated by intra-nasally infected animals, in aerosol infection models.…”

Characterisation of Particle size and Viability of SARS-CoV-2 Aerosols from a Range of Nebuliser Types Using a Novel Sampling Technique

“…[14][15][16][17][18] Only one recent study examined natural transmission between intra-nasally infected hamsters to naïve animals. [47] Our study sought to characterise the MMAD and viability of SARS-CoV-2 aerosols generated with different relative humidities from six nebulisers. To date, no other work has compared nebulisation effects on SARS-CoV-2 across such devices; nor attempted to characterise by size-fractionation, viable SARS-CoV-2 virus particles, using these methods.…”

“…Future work employing different aerosol capture methods, such as the Goldberg drum or spider microthreads, could explore decay rates of virus in different temperature and relative humidities, and also incorporate electron microscopy images of the virus to determine physical effects of nebulisation compared to those observed in sputum. Future work may also involve comparison of natural transmission in animal models [47] to those animals infected via nebuliser-generated aerosols; such work may aid elucidation of the particle sizes and concentrations generated by intra-nasally infected animals, in aerosol infection models.…”