Intrinsic host susceptibility among multiple species to intranasal SARS-CoV-2 identifies diverse virological, biodistribution and pathological outcomes

Berry, N; Ferguson, D; Kempster, S; Hall, J; Ham, C; Jenkins, A; Rannow, V; Giles, E; Leahy, R; Goulding, S; Fernandez, A; Adedeji, Y; Vessillier, S; Rajagopal, D; Prior, S; Le Duff, Y; Hurley, M; Gilbert, S; Fritzsche, M; Mate, R; Rose, N; Francis, RJ; MacLellan-Gibson, K; Suarez-Bonnet, A; Priestnall, S; Almond, N

Abstract

SARS-CoV-2 exhibits a diverse host species range with variable outcomes, enabling differential host susceptibility studies to assess suitability for pre-clinical countermeasure and pathogenesis studies. Baseline virological, molecular and pathological outcomes were determined among multiple species-one Old World non-human primate (NHP) species (cynomolgus macaques), two New World NHP species (red-bellied tamarins; common marmosets) and Syrian hamsters-following single-dose, atraumatic intranasal administration of SARS-CoV-2/Victoria-01. After serial sacrifice 2, 10 and 28-days post-infection (dpi), hamsters and cynomolgus macaques displayed differential virus biodistribution across respiratory, gastrointestinal and cardiovascular systems. Uniquely, New World tamarins, unlike marmosets, exhibited high levels of acute upper airway infection, infectious virus recovery associated with mild lung pathology representing a host previously unrecognized as susceptible to SARS-CoV-2. Across all species, lung pathology was identified post-clearance of virus shedding (antigen/RNA), with an association of virus particles within replication organelles in lung sections analysed by electron microscopy. Disrupted cell ultrastructure and lung architecture, including abnormal morphology of mitochondria 10-28 dpi, represented on-going pathophysiological consequences of SARS-CoV-2 in predominantly asymptomatic hosts. Infection kinetics and host pathology comparators using standardized methodologies enables model selection to bridge differential outcomes within upper and lower respiratory tracts and elucidate longer-term consequences of asymptomatic SARS-CoV-2 infection.

Citation

Berry, N., Ferguson, D., Kempster, S., Hall, J., Ham, C., Jenkins, A., Rannow, V., Giles, E., Leahy, R., Goulding, S., Fernandez, A., Adedeji, Y., Vessillier, S., Rajagopal, D., Prior, S., Le Duff, Y., Hurley, M., Gilbert, S., Fritzsche, M., Mate, R., …Almond, N. (2022). Intrinsic host susceptibility among multiple species to intranasal SARS-CoV-2 identifies diverse virological, biodistribution and pathological outcomes. Scientific Reports, 12(1), https://doi.org/10.1038/s41598-022-23339-x

• Journal Article Type: Article
• Acceptance Date: Oct 29, 2022
• Online Publication Date: Nov 4, 2022
• Publication Date: 2022
• Deposit Date: Jun 24, 2024
• Publicly Available Date: Jun 24, 2024
• Electronic ISSN: 2045-2322
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 1
• DOI: https://doi.org/10.1038/s41598-022-23339-x
• Keywords: MODEL