RT Journal Article
SR Electronic
T1 Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.19.161612
DO 10.1101/2020.06.19.161612
A1 Rebecca L. Brocato
A1 Lucia M. Principe
A1 Robert K. Kim
A1 Xiankun Zeng
A1 Janice A. Williams
A1 Yanan Liu
A1 Rong Li
A1 Jeffrey M. Smith
A1 Joseph W. Golden
A1 Dave Gangemi
A1 Sawsan Youssef
A1 Zhongde Wang
A1 Jacob Glanville
A1 Jay W. Hooper
YR 2020
UL http://biorxiv.org/content/early/2020/06/19/2020.06.19.161612.abstract
AB Animal models recapitulating human COVID-19 disease, especially with severe disease, are urgently needed to understand pathogenesis and evaluate candidate vaccines and therapeutics. Here, we develop novel severe disease animal models for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to SARS-CoV-2 by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease that were more severe than in immunocompetent hamsters, notably weight loss, viral loads, and fatality (RAG2 KO only). Disease was prolonged in transiently immunosuppressed hamsters and uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody and found that pretreatment, even in immunosuppressed animals, limited infection. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2, but also play an early role in protection from acute disease.One Sentence Summary An antibody targeting the spike protein of SARS-CoV-2 limits infection in immunosuppressed Syrian hamster models.Competing Interest StatementThe authors have declared no competing interest.