Interaction of SARS-CoV-2 with cardiomyocytes: Insight into the underlying molecular mechanisms of cardiac injury and pharmacotherapy
Open accessAbstract
SARS-CoV-2 causes respiratory illness with a spectrum of systemic complications. However, the mechanism for cardiac infection and cardiomyocyte injury in COVID-19 patients remains unclear. The current literature supports the notion that SARS-CoV-2 particles access the heart either by the circulating blood cells or by extracellular vesicles, originating from the inflamed lungs, and encapsulating the virus along with its receptor (ACE2). Both cardiomyocytes and pericytes (coronary arteries) express the necessary accessory proteins for access of SARS-CoV-2 particles (i.e. ACE2, NRP-1, TMPRSS2, CD147, integrin α5β1, and CTSB/L). These proteins facilitate the SARS-CoV-2 interaction and entry into the pericytes and cardiomyocytes thus leading to cardiac manifestations. Subsequently, various signaling pathways are altered in the infected cardiomyocytes (i.e. increased ROS production, reduced contraction, impaired calcium homeostasis), causing cardiac dysfunction. The currently adopted pharmacotherapy in severe COVID-19 subjects exhibited side effects on the heart, often manifested by electrical abnormalities. Nonetheless, cardiovascular adverse repercussions have been associated with the advent of some of the SARS-CoV-2 vaccines with no clear mechanisms underlining these complications. We provide herein an overview of the pathways involved with cardiomyocyte in COVID-19 subjects to help promoting pharmacotherapies that can protect against SARS-CoV-2-induced cardiac injuries.
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Cardiomyocytes and pericytes express ACE2 and TMPRSS2, as well as other accessory proteins needed for viral infection by SARS-CoV-2.
“Thus, cardiomyocytes and pericytes express ACE2 and TMPRSS2, as well as other accessory proteins (ie, NRP1 [neuropilin-1 receptor], CD147 , integrin α 5 β 1, and cathepsin B/L) needed for viral infection by SARS-CoV-2”
From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [22]
Section 2.1 (page unavailable) says cardiomyocytes express ACE2, TMPRSS2, NRP1, CD147 and α5β1 integrin, and discusses cathepsins B/L in cardiomyocyte entry. It also says pericytes express CD147 and α5β1 integrin and may be infected, but it does not establish that pericytes express ACE2, TMPRSS2 and every other protein listed in the citing sentence. (LLM, conf=0.86)
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COVID-19, Myocarditis and Pericarditis
Fairweather, D., Beetler, D. J., Di Florio, D. N., Musigk, N., Heidecker, B., & Cooper, L. T. (2023) · Circulation Research · doi:10.1161/circresaha.123.321878 · Cited by 181 · see citing works
“…NRP1 [neuropilin-1 receptor], CD147, integrin α5β1, and cathepsin B/L) needed for viral infection by SARS-CoV-2 (Figure 1; reviewed in the study by Abdi et al22).23–27 In a study examining the prevalence of ACE2 on immune cells, it was found to be expressed primarily on activated tissue…”
- Authors
- Abdi, A., AlOtaiby, S., Badarin, F. A., Khraibi, A., Hamdan, H., & Nader, M.
- Affiliations
- Khalifa University of Science and Technology (AE)
- King Fahd Medical City (SA)
- Corresponding author
- Nader, Moni
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 146
- Pages
- 112518
- ISSN
- 0753-3322 (ISSN-L)
- PMC
- PMC8654598
- OpenAlex
- W4200428562
- Cited by
- 47
- References
- 10
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 16 · 2023: 10 · 2022: 15
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Keywords
- SARS-CoV-2, COVID-19 pandemic, cardiomyocyte injury, cardiac injury, ACE2, pericytes, extracellular vesicles, viral entry, TMPRSS2, neuropilin-1, CD147, alpha5beta1 integrin, reactive oxygen species, calcium homeostasis, cardiac dysfunction, pharmacotherapy side effects, cardiac arrhythmias, COVID-19 vaccines, vaccine adverse events, cardioprotection
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, COVID-19 Drug Treatment, Animals, Antiviral Agents, Heart Diseases, Humans, Myocardium, Myocytes, Cardiac
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