tetano
Editor, Senior Moderator
JACC Basic Transl Sci
. 2021 Feb 26.
doi: 10.1016/j.jacbts.2021.01.002. Online ahead of print.
SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis
Adam L Bailey[SUP] 1 [/SUP], Oleksandr Dmytrenko[SUP] 2 [/SUP], Lina Greenberg[SUP] 3 [/SUP], Andrea L Bredemeyer[SUP] 2 [/SUP], Pan Ma[SUP] 2 [/SUP], Jing Liu[SUP] 2 [/SUP], Vinay Penna[SUP] 2 [/SUP], Emma S Winkler[SUP] 1 [/SUP], Sanja Sviben[SUP] 4 [/SUP], Erin Brooks[SUP] 5 [/SUP], Ajith P Nair[SUP] 6 [/SUP], Kent A Heck[SUP] 7 [/SUP], Aniket S Rali[SUP] 8 [/SUP], Leo Simpson[SUP] 6 [/SUP], Mehrdad Saririan[SUP] 9 [/SUP], Dan Hobohm[SUP] 9 [/SUP], W Tom Stump[SUP] 3 [/SUP], James A Fitzpatrick[SUP] 4 10 [/SUP], Xuping Xie[SUP] 11 [/SUP], Xianwen Zhang[SUP] 11 [/SUP], Pei-Yong Shi[SUP] 11 [/SUP], J Travis Hinson[SUP] 12 13 [/SUP], Weng-Tein Gi[SUP] 14 [/SUP], Constanze Schmidt[SUP] 14 [/SUP], Florian Leuschner[SUP] 14 [/SUP], Chieh-Yu Lin[SUP] 1 [/SUP], Michael S Diamond[SUP] 1 2 15 [/SUP], Michael J Greenberg[SUP] 3 [/SUP], Kory J Lavine[SUP] 1 2 16 [/SUP]
Affiliations
Abstract
There is ongoing debate as to whether cardiac complications of coronavirus disease 2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease.
Keywords: ACE2, angiotensin converting enzyme 2; COVID-19, coronavirus disease-2019; EHT, engineered heart tissues; LV, left ventricle; SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; cardiomyocyte; coronavirus disease 2019; engineered heart tissue; hPSC, human pluripotent stem cell(s); myocarditis; severe acute respiratory syndrome coronavirus 2.
. 2021 Feb 26.
doi: 10.1016/j.jacbts.2021.01.002. Online ahead of print.
SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis
Adam L Bailey[SUP] 1 [/SUP], Oleksandr Dmytrenko[SUP] 2 [/SUP], Lina Greenberg[SUP] 3 [/SUP], Andrea L Bredemeyer[SUP] 2 [/SUP], Pan Ma[SUP] 2 [/SUP], Jing Liu[SUP] 2 [/SUP], Vinay Penna[SUP] 2 [/SUP], Emma S Winkler[SUP] 1 [/SUP], Sanja Sviben[SUP] 4 [/SUP], Erin Brooks[SUP] 5 [/SUP], Ajith P Nair[SUP] 6 [/SUP], Kent A Heck[SUP] 7 [/SUP], Aniket S Rali[SUP] 8 [/SUP], Leo Simpson[SUP] 6 [/SUP], Mehrdad Saririan[SUP] 9 [/SUP], Dan Hobohm[SUP] 9 [/SUP], W Tom Stump[SUP] 3 [/SUP], James A Fitzpatrick[SUP] 4 10 [/SUP], Xuping Xie[SUP] 11 [/SUP], Xianwen Zhang[SUP] 11 [/SUP], Pei-Yong Shi[SUP] 11 [/SUP], J Travis Hinson[SUP] 12 13 [/SUP], Weng-Tein Gi[SUP] 14 [/SUP], Constanze Schmidt[SUP] 14 [/SUP], Florian Leuschner[SUP] 14 [/SUP], Chieh-Yu Lin[SUP] 1 [/SUP], Michael S Diamond[SUP] 1 2 15 [/SUP], Michael J Greenberg[SUP] 3 [/SUP], Kory J Lavine[SUP] 1 2 16 [/SUP]
Affiliations
- PMID: 33681537
- PMCID: PMC7909907
- DOI: 10.1016/j.jacbts.2021.01.002
Abstract
There is ongoing debate as to whether cardiac complications of coronavirus disease 2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease.
Keywords: ACE2, angiotensin converting enzyme 2; COVID-19, coronavirus disease-2019; EHT, engineered heart tissues; LV, left ventricle; SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; cardiomyocyte; coronavirus disease 2019; engineered heart tissue; hPSC, human pluripotent stem cell(s); myocarditis; severe acute respiratory syndrome coronavirus 2.