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440 Role of angiotensin II in SARS-CoV-2 pathophysiology in a hamster model of COVID-19

Published online by Cambridge University Press:  24 April 2023

Branka Milicic Stanic
Affiliation:
Departments of Medicine and 3 Pharmacology & Physiology, Georgetown University, Washington, DC
Nisha Dugal
Affiliation:
Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA
Nataliia Shults
Affiliation:
Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA
Hong Ji
Affiliation:
Departments of Medicine and 3 Pharmacology & Physiology, Georgetown University, Washington, DC
Aline M.A. de Souza
Affiliation:
Departments of Medicine and 3 Pharmacology & Physiology, Georgetown University, Washington, DC
Seth Hawkins
Affiliation:
Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA
Xie Wu
Affiliation:
Departments of Medicine and 3 Pharmacology & Physiology, Georgetown University, Washington, DC
Juan M. Saavedra
Affiliation:
Department of Biomedical Sciences and Pathobiology, Virginia Tech, Blacksburg, VA
Kathryn Sandberg
Affiliation:
Departments of Medicine and 3 Pharmacology & Physiology, Georgetown University, Washington, DC
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Abstract

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OBJECTIVES/GOALS: Hamsters develop COVID-19 similarly to people because the SARS-CoV-2 spike protein binds with high affinity to hamster ACE2 resulting in host cell entry and replication. Our goal was to establish a hamster model that mirrors the lung and brain pathophysiology observed in COVID-19. METHODS/STUDY POPULATION: Hamsters infected with SARS CoV-2 are sacrificed on day 1 and day 6 postinfection. Lung histopathology scoring model was implemented for assessment all pathological relevant changes in the lungs of infected animals on tissue sections stained with hematoxylin and eosin. To quantify the extent and severity of lung pathology, two scoring systems were used: the first evaluated all relevant changes in the lungs of the infected animals and the second evaluated only the pathology associated with the pulmonary vasculature. Percentage of airway affected, airway severity, bronchiolar epithelial hyperplasia, alveoli affected, alveolar severity, type II pneumocyte hyperplasia and vessels affected were analyzed. Total airway score plus total lung alveolar score give lung histopathology score. RESULTS/ANTICIPATED RESULTS: Compared to the control hamster, the hamsters day 1 postinfection, exhibited a higher total airway score [9.00 ± 1.35 vs. 0.25 ± 0.1; p DISCUSSION/SIGNIFICANCE: Establishing this outstanding small animal model of COVID-19 will facilitate studies investigating diagnostics, prognosis and response to treatment in COVID-19 disease. These studies will provide insights that will complement on-going clinical trials on angiotensin type 1 receptor (AT1R) blockers (ARBs) in COVID-19.

Type
Team Science
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NCCreative Common License - ND
This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.
Copyright
© The Author(s), 2023. The Association for Clinical and Translational Science