Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2026 Jan;98(1):e70789.
doi: 10.1002/jmv.70789.

SARS-CoV-2 Spike Protein-Mediated Cardiac Dysfunction: Structural Abnormalities, Impaired Calcium Dynamics, and Gene Expression Changes in Human Stem Cell-Derived Cardiomyocytes

Chen-Yu Huang  1   2   3   4   5 , Chia-Chi Cheng  1 , Si-Han Chen  1 , Dayna Cheng  3 , Sheng-Hsuan Wang  1 , Chiao-Hsuan Chao  1   6 , Chi-Yen Lee  1 , Jen-Ren Wang  1   2   3   7   8
Affiliations

SARS-CoV-2 Spike Protein-Mediated Cardiac Dysfunction: Structural Abnormalities, Impaired Calcium Dynamics, and Gene Expression Changes in Human Stem Cell-Derived Cardiomyocytes

Chen-Yu Huang et al. J Med Virol. 2026 Jan.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has resulted in more than 7.1 million deaths worldwide since 2019 and is increasingly recognized for its cardiovascular complications beyond respiratory disease. Growing evidence suggests that the SARS-CoV-2 spike protein itself, present during infection or after vaccination, may directly contribute to cardiac dysfunction, including myocarditis, through interaction with angiotensin-converting enzyme 2 (ACE2) receptors expressed in cardiomyocytes. To investigate these effects, we established a lentiviral-based SARS-CoV-2 pseudovirus system expressing spike proteins from the Wuhan and Delta variants and examined their impact on human embryonic stem cell-derived cardiomyocytes (ESC-CMs). Exposure to pseudovirus resulted in significant increases in sarcomere length and promoted syncytium formation in ESC-CMs. Moreover, infection with either Wuhan or Delta spike pseudoviruses caused marked early disturbances in intracellular calcium transient dynamics as early as 1.5 hours post-infection, with partial recovery observed by 24 hours. Transcriptomic analyses further revealed significant dysregulation of key cardiac-related genes involved in cell junction organization, structural integrity, ion channel function, and calcium handling. Together, these findings demonstrate the utility of a lentiviral pseudovirus platform for modeling SARS-CoV-2-induced cardiac injury and highlight a direct pathogenic role of the spike protein in cardiac structural, functional, and molecular abnormalities.

Keywords: COVID‐19; SARS‐CoV‐2; calcium transient; cardiac dysfunction; pseudovirus; spike protein.

PubMed Disclaimer

References

    1. M. S. Sofi, A. Hamid, and S. U. Bhat, “SARS‐CoV‐2: A Critical Review of Its History, Pathogenesis, Transmission, Diagnosis and Treatment,” Biosafety and Health 2, no. 4 (2020): 217–225.
    1. K. K. Chan, D. Dorosky, P. Sharma, et al., “Engineering Human ACE2 to Optimize Binding to the Spike Protein of SARS Coronavirus 2,” Science 369, no. 6508 (2020): 1261–1265.
    1. W. Tai, L. He, X. Zhang, et al., “Characterization of the Receptor‐Binding Domain (RBD) of 2019 Novel Coronavirus: Implication for Development of RBD Protein as a Viral Attachment Inhibitor and Vaccine,” Cellular & Molecular Immunology 17, no. 6 (2020): 613–620.
    1. R. Amraei, C. Xia, J. Olejnik, et al., “Extracellular Vimentin Is an Attachment Factor That Facilitates SARS‐CoV‐2 Entry Into Human Endothelial Cells,” Proceedings of the National Academy of Sciences 119, no. 6 (2022): e2113874119.
    1. N. Rahimi, “C‐Type Lectin CD209L/L‐SIGN and CD209/DC‐SIGN: Cell Adhesion Molecules Turned to Pathogen Recognition Receptors,” Biology (Basel) 10, no. 1 (2020): 1.

MeSH terms

LinkOut - more resources