Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

SARS-CoV-2 Disease Severity in the Golden Syrian Hamster Model of Infection is Related to the Volume of Intranasal Inoculum.

Alastair Handley
* ,
Kathryn A. Ryan
ORCID logo ,
Elizabeth R. Davies
,
Kevin R. Bewley
ORCID logo ,
Oliver T. Carnell
,
Amy Challis
,
Naomi S. Coombes
ORCID logo ,
Susan A. Fotheringham
,
Karen E. Gooch
,
Michael Charlton
,
Debbie J. Harris
,
Chelsea Kennard
,
Didier Ngabo
,
Thomas M. Weldon
,
Francisco J. Salguero
,
Simon G. P. Funnell
ORCID logo ,
Yper Hall
Version 1 : Received: 27 January 2023 / Approved: 10 February 2023 / Online: 10 February 2023 (01:22:19 CET)

A peer-reviewed article of this Preprint also exists.

Handley, A.; Ryan, K.A.; Davies, E.R.; Bewley, K.R.; Carnell, O.T.; Challis, A.; Coombes, N.S.; Fotheringham, S.A.; Gooch, K.E.; Charlton, M.; Harris, D.J.; Kennard, C.; Ngabo, D.; Weldon, T.M.; Salguero, F.J.; Funnell, S.G.P.; Hall, Y. SARS-CoV-2 Disease Severity in the Golden Syrian Hamster Model of Infection Is Related to the Volume of Intranasal Inoculum. Viruses 2023, 15, 748. Handley, A.; Ryan, K.A.; Davies, E.R.; Bewley, K.R.; Carnell, O.T.; Challis, A.; Coombes, N.S.; Fotheringham, S.A.; Gooch, K.E.; Charlton, M.; Harris, D.J.; Kennard, C.; Ngabo, D.; Weldon, T.M.; Salguero, F.J.; Funnell, S.G.P.; Hall, Y. SARS-CoV-2 Disease Severity in the Golden Syrian Hamster Model of Infection Is Related to the Volume of Intranasal Inoculum. Viruses 2023, 15, 748.

Abstract

The Golden Syrian hamster (Mesocricetus auratus) is now commonly used in preclinical research for the study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the assessment of vaccines, drugs and therapeutics. Here we show that hamsters inoculated via the intranasal route with the same infectious virus dose of prototypical SARS-CoV-2 administered in a different volume present with different clinical signs, weight loss and viral shedding, with a reduced volume resulting in reduced severity of disease similar to that obtained by a 500-fold reduction in challenge dose. The tissue burden of virus and the severity of pulmonary pathology were also significantly affected by different challenge inoculum volumes. These findings suggest that direct comparison between the severity of SARS-CoV-2 variants or studies assessing the efficacy of treatments determined by hamster studies cannot be made unless both the challenge dose and inoculation volume are matched when using the intranasal route. Additionally, analysis of sub-genomic and total genomic RNA PCR data demonstrated no link between sub-genomic and live viral titres and that sub-genomic analyses do not provide any information beyond that provided by more sensitive total genomic PCR.

Keywords

SARS-CoV-2; Syrian hamster; animal model; coronavirus

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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