TY - JOUR
T1 - Syrian hamsters as a model of lung injury with SARS-CoV-2 infection
T2 - Pathologic, physiologic, and detailed molecular profiling
AU - BEDNASH, JOSEPH S.
AU - KAGAN, VALERIAN E.
AU - ENGLERT, JOSHUA A.
AU - FARKAS, DANIELA
AU - TYURINA, YULIA Y.
AU - TYURIN, VLADIMIR A.
AU - SAMOVICH, SVETLANA N.
AU - FARKAS, LASZLO
AU - ELHANCE, A. J.I.T.
AU - JOHNS, FINNY
AU - LEE, HYUNWOOK
AU - CHENG, LIJUN
AU - MAJUMDAR, ABHISHEK
AU - JONES, DANIEL
AU - MEJIA, OSCAR ROSAS
AU - RUANE-FOSTER, MARISA
AU - LONDINO, JAMES D.
AU - MALLAMPALLI, RAMA K.
AU - ROBINSON, RICHARD T.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/2
Y1 - 2022/2
N2 - The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. Knowledge of molecular mechanisms driving host responses to SARS-CoV-2 is limited by the lack of reliable preclinical models of COVID-19 that recapitulate human illness. Further, existing COVID-19 animal models are not characterized as models of experimental acute lung injury (ALI) or ARDS. Acknowledging differences in experimental lung injury in animal models and human ARDS, here we systematically evaluate a model of experimental acute lung injury as a result of SARS-CoV-2 infection in Syrian golden hamsters. Following intranasal inoculation, hamsters demonstrate acute SARS-CoV-2 infection, viral pneumonia, and systemic illness but survive infection with clearance of virus. Hamsters exposed to SARS-CoV-2 exhibited key features of experimental ALI, including histologic evidence of lung injury, increased pulmonary permeability, acute inflammation, and hypoxemia. RNA sequencing of lungs indicated upregulation of inflammatory mediators that persisted after infection clearance. Lipidomic analysis demonstrated significant differences in hamster phospholipidome with SARS-CoV-2 infection. Lungs infected with SARS-CoV-2 showed increased apoptosis and ferroptosis. Thus, SARS-CoV-2 infected hamsters exhibit key features of experimental lung injury supporting their use as a preclinical model of COVID-19 ARDS.
AB - The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. Knowledge of molecular mechanisms driving host responses to SARS-CoV-2 is limited by the lack of reliable preclinical models of COVID-19 that recapitulate human illness. Further, existing COVID-19 animal models are not characterized as models of experimental acute lung injury (ALI) or ARDS. Acknowledging differences in experimental lung injury in animal models and human ARDS, here we systematically evaluate a model of experimental acute lung injury as a result of SARS-CoV-2 infection in Syrian golden hamsters. Following intranasal inoculation, hamsters demonstrate acute SARS-CoV-2 infection, viral pneumonia, and systemic illness but survive infection with clearance of virus. Hamsters exposed to SARS-CoV-2 exhibited key features of experimental ALI, including histologic evidence of lung injury, increased pulmonary permeability, acute inflammation, and hypoxemia. RNA sequencing of lungs indicated upregulation of inflammatory mediators that persisted after infection clearance. Lipidomic analysis demonstrated significant differences in hamster phospholipidome with SARS-CoV-2 infection. Lungs infected with SARS-CoV-2 showed increased apoptosis and ferroptosis. Thus, SARS-CoV-2 infected hamsters exhibit key features of experimental lung injury supporting their use as a preclinical model of COVID-19 ARDS.
UR - http://www.scopus.com/inward/record.url?scp=85120422843&partnerID=8YFLogxK
U2 - 10.1016/j.trsl.2021.10.007
DO - 10.1016/j.trsl.2021.10.007
M3 - Article
C2 - 34740873
AN - SCOPUS:85120422843
SN - 1931-5244
VL - 240
SP - 1
EP - 16
JO - Translational Research
JF - Translational Research
ER -