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Further developments in the fight against the pandemic: new evidences of SARS-CoV-2/ACE-2 interactions on cardiomyocytes

A comment by the ESC WG on Cellular Biology of the Heart

Biomaterials, Tissue Engineering

Covid-19, the disease caused by the SARS-CoV-2 coronavirus, can damage heart muscle and affect heart function. In addition, several studies reveal COVID-19 mRNA vaccines to trigger myocarditis, especially in young man [1-4].

To study the underlying mechanism, research groups utilized the human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to model SARS-CoV-2 spread in cardiac tissue [5, 6]. The drawback of these model systems was the peak expression of the SARS-CoV-2 receptor named angiotensin-converting enzyme 2 (ACE2), as such limiting infection with SARS-CoV-2.

In the study of Navaratnarajah et al. these limitations have been overcome by engineering an expression vector coding for the spike protein with a monomeric emerald-green fluorescent protein fused to its cytoplasmic tail (S-mEm). The findings showed spreading of S-mEm signal from cell to cell through membrane fusion, resulting in syncytia generation which was independent of TMPRSS2 or TMPRSS13 proteases, as observed in airway epithelial cells [7]. These observations suggest a role for a different protease in cardiomyocyte fusion.

In summary, hiPSC-CMs are useful model systems to study the molecular mechanism of SARS-Cov-2 as well as spike protein-induced cardiomyocyte damage, as observed in clinical COVID-19 and myo/pericarditis after COVID-19 vaccination.


  1. Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y, et al. Myocarditis after Covid-19 Vaccination in a Large Health Care Organization. N Engl J Med. 2021. Epub 2021/10/07. doi: 10.1056/NEJMoa2110737. PubMed PMID: 34614329; PubMed Central PMCID: PMCPMC8531986.
  2. Truong DT, Dionne A, Muniz JC, McHugh KE, Portman MA, Lambert LM, et al. Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults. Circulation. 2021. Epub 2021/12/07. doi: 10.1161/CIRCULATIONAHA.121.056583. PubMed PMID: 34865500.
  3. Bozkurt B, Kamat I, Hotez PJ. Myocarditis With COVID-19 mRNA Vaccines. Circulation. 2021;144(6):471-84. Epub 2021/07/21. doi: 10.1161/CIRCULATIONAHA.121.056135. PubMed PMID: 34281357; PubMed Central PMCID: PMCPMC8340726.
  4. Rosner CM, Genovese L, Tehrani BN, Atkins M, Bakhshi H, Chaudhri S, et al. Myocarditis Temporally Associated With COVID-19 Vaccination. Circulation. 2021;144(6):502-5. Epub 2021/06/17. doi: 10.1161/CIRCULATIONAHA.121.055891. PubMed PMID: 34133885; PubMed Central PMCID: PMCPMC8340723.
  5. Bailey AL, Dmytrenko O, Greenberg L, Bredemeyer AL, Ma P, Liu J, et al. SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. JACC Basic Transl Sci. 2021;6(4):331-45. Epub 2021/03/09. doi: 10.1016/j.jacbts.2021.01.002. PubMed PMID: 33681537; PubMed Central PMCID: PMCPMC7909907.
  6. Perez-Bermejo JA, Kang S, Rockwood SJ, Simoneau CR, Joy DA, Silva AC, et al. SARS-CoV-2 infection of human iPSC-derived cardiac cells reflects cytopathic features in hearts of patients with COVID-19. Sci Transl Med. 2021;13(590). Epub 2021/03/17. doi: 10.1126/scitranslmed.abf7872. PubMed PMID: 33723017; PubMed Central PMCID: PMCPMC8128284.
  7. Lin L, Li Q, Wang Y, Shi Y. Syncytia formation during SARS-CoV-2 lung infection: a disastrous unity to eliminate lymphocytes. Cell Death Differ. 2021;28(6):2019-21. Epub 2021/05/14. doi: 10.1038/s41418-021-00795-y. PubMed PMID: 33981020; PubMed Central PMCID: PMCPMC8114657.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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