About: Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge

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About: Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge
Creator	Hallis, Bassam Rayner, Emma Druce, Julian Bewley, Kevin Charlton, Sue Funnell, Simon Taylor, Irene Carroll, Miles Hunter, Laura Watson, Robert Buttigieg, Karen Salguero, Francisco Gooch, Karen Ho, Marriott, Anthony Pullan, Steven Thomas, Stephen Tree, Julia Carter, Daniel Allen, Lauren Coombes, Naomi Godwin, Kerry Tipton, Tom Aram, Marilyn Brown, Phillip Brunt, Cavell, Breeze Cobb, Rebecca Dennis, Mike Fotheringham, Susan Gouriet, Jade Harris, Debbie Hiscox, A Humphries, Holly Julian, Kennard, Chelsea Leung, Stephanie Ngabo, Didier Osman, Karen Paterson, Jemma Penn, Elizabeth Ryan, Kathryn Steeds, Kimberley Whittaker, Catherine Wiblin, Nathan
source	BioRxiv
abstract	In December 2019 an outbreak of coronavirus disease (COVID-19) emerged in Wuhan, China. The causative agent was subsequently identified and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which rapidly spread worldwide causing a pandemic. Currently there are no licensed vaccines or therapeutics available against SARS-CoV-2 but numerous candidate vaccines are in development and repurposed drugs are being tested in the clinic. There is a vital need for authentic COVID-19 animal models to further our understanding of pathogenesis and viral spread in addition to pre-clinical evaluation of candidate interventions. Here we report a dose titration study of SARS-CoV-2 to determine the most suitable infectious dose to use in the ferret model. We show that a high (5×106 pfu) and medium (5×104 pfu) dose of SARS-CoV-2 induces consistent upper respiratory tract (URT) viral RNA shedding in both groups of six challenged animals, whilst a low dose (5×102 pfu) resulted in only one of six displaying signs of URT viral RNA replication. The URT shedding lasted up to 21 days in the high dose animals with intermittent positive signal from day 14. Sequential culls revealed distinct pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung, observed on day 3 in high and medium dosed animals, with presence of mild broncho-interstitial pneumonia on day 7 onwards. No obvious elevated temperature or signs of coughing or dyspnoea were observed although animals did present with a consistent post-viral fatigue lasting from day 9-14 in the medium and high dose groups. After virus shedding ceased, re-challenged ferrets were shown to be fully protected from acute lung pathology. The endpoints of URT viral RNA replication in addition to distinct lung pathology and post viral fatigue were observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease (as displayed by 80% of patients infected with SARS-CoV-2). In addition, intermittent viral shedding on days 14-21 parallel observations reported in a minority of clinical cases.
has issue date	2020-05-29(xsd:dateTime)
bibo:doi	10.1101/2020.05.29.123810
has license	biorxiv
sha1sum (hex)	50c3cb38513abfe5a5ba5aa3208c2ab44a673579
schema:url	https://doi.org/10.1101/2020.05.29.123810
resource representing a document's title	Dose-dependent response to infection with SARS-CoV-2 in the ferret model: evidence of protection to re-challenge
schema:publication	bioRxiv
resource representing a document's body	covid:50c3cb38513abfe5a5ba5aa3208c2ab44a673579#body_text
is schema:about of	named entity 'evidence' named entity 'Professor' named entity 'response' named entity 'emerged' named entity 'numerous' named entity 'COVID-19' named entity 'SARS-CoV-2' named entity 'SARS-CoV-2' named entity 'infection' named entity 'viral RNA' named entity 'ferret' named entity 'SARS-CoV-2' named entity 'control group' named entity '4/6' named entity 'pathology' named entity 'viral RNA' named entity 'Viral Shedding' named entity 'viral RNA' named entity 'quality control' named entity '3/3' named entity 'RNA' named entity 'viral RNA' named entity 'RNA' named entity 'weight loss' named entity 'limit of quantification' named entity 'VTM' named entity 'virus' named entity 'RNA' named entity 'viral RNA' named entity 'furin' named entity 'AVL' named entity 'viral RNA' named entity 'challenge groups' named entity 'viral RNA' named entity 'viral RNA' named entity 'cleavage site' named entity 'RNA' named entity 'bronchoalveolar lavage' named entity 'throat swab' named entity 'infection'

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