Details

Autor(en) / Beteiligte

• Bailey, Adam L.
• Dmytrenko, Oleksandr
• Greenberg, Lina
• Bredemeyer, Andrea L.
• Ma, Pan
• Liu, Jing
• Penna, Vinay
• Winkler, Emma S.
• Sviben, Sanja
• Brooks, Erin
• Nair, Ajith P.
• Heck, Kent A.
• Rali, Aniket S.
• Simpson, Leo
• Saririan, Mehrdad
• Hobohm, Dan
• Stump, W. Tom
• Fitzpatrick, James A.
• Xie, Xuping
• Zhang, Xianwen
• Shi, Pei-Yong
• Hinson, J. Travis
• Gi, Weng-Tein
• Schmidt, Constanze
• Leuschner, Florian
• Lin, Chieh-Yu
• Diamond, Michael S.
• Greenberg, Michael J.
• Lavine, Kory J.

Titel

SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis

Ist Teil von

• JACC. Basic to translational science, 2021-04, Vol.6 (4), p.331-345

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• [Display omitted] •SARS-CoV-2 directly infects cardiomyocytes in patients with COVID-19 myocarditis and does not infect cardiac macrophages, fibroblasts, or endothelial cells.•COVID-19 myocarditis is characterized by a myeloid-rich inflammatory infiltrate.•SARS-CoV-2 infects cardiomyocytes through an ACE2 and endosomal cysteine protease dependent pathway.•Infection of hPSC-derived cardiomyocytes and engineered heart tissues show that cytokine production, sarcomere disassembly, and cell death were a direct consequence of cardiomyocyte infection.•SARS-CoV-2 reduces cardiomyocyte contractility through sarcomere breakdown and cardiomyocyte cell death. 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.