tetano
Editor, Senior Moderator
Transl Res
. 2021 Nov 2;S1931-5244(21)00263-2.
doi: 10.1016/j.trsl.2021.10.007. Online ahead of print.
Syrian hamsters as a model of lung injury with SARS-CoV-2 infection: pathologic, physiologic and detailed molecular profiling
Joseph S Bednash[SUP] 1 [/SUP], Valerian E Kagan[SUP] 2 [/SUP], Joshua A Englert[SUP] 3 [/SUP], Daniela Farkas[SUP] 3 [/SUP], Yulia Y Tyurina[SUP] 2 [/SUP], Vladimir A Tyurin[SUP] 2 [/SUP], Svetlana N Samovich[SUP] 2 [/SUP], Laszlo Farkas[SUP] 3 [/SUP], Ajit Elhance[SUP] 3 [/SUP], Finny Johns[SUP] 3 [/SUP], Hyunwook Lee[SUP] 3 [/SUP], Lijun Cheng[SUP] 4 [/SUP], Abhishek Majumdar[SUP] 4 [/SUP], Daniel Jones[SUP] 5 [/SUP], Oscar Rosas Mejia[SUP] 6 [/SUP], Marisa Ruane-Foster[SUP] 6 [/SUP], James D Londino[SUP] 3 [/SUP], Rama K Mallampalli[SUP] 3 [/SUP], Richard T Robinson[SUP] 7 [/SUP]
Affiliations
Abstract
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.
Keywords: ARDS; Covid-19; Pneumonia; SARS-CoV-2; acute lung injury.
. 2021 Nov 2;S1931-5244(21)00263-2.
doi: 10.1016/j.trsl.2021.10.007. Online ahead of print.
Syrian hamsters as a model of lung injury with SARS-CoV-2 infection: pathologic, physiologic and detailed molecular profiling
Joseph S Bednash[SUP] 1 [/SUP], Valerian E Kagan[SUP] 2 [/SUP], Joshua A Englert[SUP] 3 [/SUP], Daniela Farkas[SUP] 3 [/SUP], Yulia Y Tyurina[SUP] 2 [/SUP], Vladimir A Tyurin[SUP] 2 [/SUP], Svetlana N Samovich[SUP] 2 [/SUP], Laszlo Farkas[SUP] 3 [/SUP], Ajit Elhance[SUP] 3 [/SUP], Finny Johns[SUP] 3 [/SUP], Hyunwook Lee[SUP] 3 [/SUP], Lijun Cheng[SUP] 4 [/SUP], Abhishek Majumdar[SUP] 4 [/SUP], Daniel Jones[SUP] 5 [/SUP], Oscar Rosas Mejia[SUP] 6 [/SUP], Marisa Ruane-Foster[SUP] 6 [/SUP], James D Londino[SUP] 3 [/SUP], Rama K Mallampalli[SUP] 3 [/SUP], Richard T Robinson[SUP] 7 [/SUP]
Affiliations
- PMID: 34740873
- DOI: 10.1016/j.trsl.2021.10.007
Abstract
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.
Keywords: ARDS; Covid-19; Pneumonia; SARS-CoV-2; acute lung injury.