The therapeutic potential of regulatory T cells in reducing cardiovascular complications in patients with severe COVID-19

doi:10.1016/j.lfs.2022.120392

Review

. 2022 Apr 1:294:120392.

doi: 10.1016/j.lfs.2022.120392. Epub 2022 Feb 8.

The therapeutic potential of regulatory T cells in reducing cardiovascular complications in patients with severe COVID-19

Nafiseh Saghafi¹, Seyed Abdolrahim Rezaee², Amir Abbas Momtazi-Borojeni³, Fataneh Tavasolian⁴, Thozhukat Sathyapalan⁵, Elham Abdollahi⁶, Amirhossein Sahebkar⁷

Affiliations

¹ Department of Gynecology, Woman Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
² Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Research Center for HIV/AIDS, HTLV and Viral Hepatitis, Iranian Academic Center for Education, Culture and Research (ACECR), Mashhad Branch, Mashhad, Iran; Inflammation and Inflammatory Diseases Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
³ Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴ Toronto Western Hospital, Toronto, Canada.
⁵ Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, UK.
⁶ Department of Gynecology, Woman Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Abdollahie@mums.ac.ir.
⁷ Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Medicine, The University of Western Australia, Perth, Australia; Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: sahebkara@mums.ac.ir.

PMID: 35149115
PMCID: PMC8824166
DOI: 10.1016/j.lfs.2022.120392

Review

The therapeutic potential of regulatory T cells in reducing cardiovascular complications in patients with severe COVID-19

Nafiseh Saghafi et al. Life Sci. 2022.

. 2022 Apr 1:294:120392.

doi: 10.1016/j.lfs.2022.120392. Epub 2022 Feb 8.

Authors

Nafiseh Saghafi¹, Seyed Abdolrahim Rezaee², Amir Abbas Momtazi-Borojeni³, Fataneh Tavasolian⁴, Thozhukat Sathyapalan⁵, Elham Abdollahi⁶, Amirhossein Sahebkar⁷

Affiliations

¹ Department of Gynecology, Woman Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
² Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Research Center for HIV/AIDS, HTLV and Viral Hepatitis, Iranian Academic Center for Education, Culture and Research (ACECR), Mashhad Branch, Mashhad, Iran; Inflammation and Inflammatory Diseases Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
³ Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴ Toronto Western Hospital, Toronto, Canada.
⁵ Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, UK.
⁶ Department of Gynecology, Woman Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Abdollahie@mums.ac.ir.
⁷ Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Medicine, The University of Western Australia, Perth, Australia; Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: sahebkara@mums.ac.ir.

PMID: 35149115
PMCID: PMC8824166
DOI: 10.1016/j.lfs.2022.120392

Abstract

The SARS coronavirus 2 (SARS CoV-2) causes Coronavirus Disease (COVID-19), is an emerging viral infection. SARS CoV-2 infects target cells by attaching to Angiotensin-Converting Enzyme (ACE2). SARS CoV-2 could cause cardiac damage in patients with severe COVID-19, as ACE2 is expressed in cardiac cells, including cardiomyocytes, pericytes, and fibroblasts, and coronavirus could directly infect these cells. Cardiovascular disorders are the most frequent comorbidity found in COVID-19 patients. Immune cells such as monocytes, macrophages, and T cells may produce inflammatory cytokines and chemokines that contribute to COVID-19 pathogenesis if their functions are uncontrolled. This causes a cytokine storm in COVID-19 patients, which has been associated with cardiac damage. Tregs are a subset of immune cells that regulate immune and inflammatory responses. Tregs suppress inflammation and improve cardiovascular function through a variety of mechanisms. This is an exciting research area to explore the cellular, molecular, and immunological mechanisms related to reducing risks of cardiovascular complications in severe COVID-19. This review evaluated whether Tregs can affect COVID-19-related cardiovascular complications, as well as the mechanisms through which Tregs act.

Keywords: COVID-19; Cardiovascular complications; SARS CoV-2; Treatment; Tregs.

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Conflict of interest statement

A conflicting interest exists when professional judgment concerning a primary interest (such as patient's welfare or the validity of research) may be influenced by a secondary interest (such as financial gain or personal rivalry). It may arise for the authors when they have financial interest that may influence their interpretation of their results or those of others. Examples of potential conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding.

Figures

Unlabelled Image — **Graphical abstract**

**Fig. 1**
Proposed mechanisms of cardiac injury. Cardiac tissue may be influenced by SARSCov2 infection (or Covid19) directly or indirectly. ACE2 expression by cardiac cells could directly infect these cells by a coronavirus. Indirectly, inflammatory cytokines that are the leading cause of cytokine storms are implicated in cardiac damage.

**Fig. 2**
A- Tregs impairment in severe COVID-19. B- Proposed mechanisms of actions of Tregs in alleviating cardiovascular complications in COVID-19. Tregs regulate Th17 and Th1 cell inflammatory activation by molecular interactions (like CD25 and CTLA-4 with ligands on target cells), TGF-β, and IL-10 secretion (as the tolerogenic cytokines). Tregs may enhance cardiac wound healing *via* activating M2 macrophages, reducing p38 MAP kinase, and increasing Akt activation. Notably, IL-10 and TGF-β could accelerate extracellular matrix deposition and cardiac healing by enhancing collagen deposition and triggering osteopontin release from monocytes and macrophages.

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References

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[1] Fried J., Ramasubbu K., Bhatt R., Topkara V., Clerkin K., Horn E., et al. The variety of cardiovascular presentations of COVID-19. Circulation. 2020;141(23):1930–1936. - PMC - PubMed

[2] Fried J., Ramasubbu K., Bhatt R., Topkara V., Clerkin K., Horn E., et al. The variety of cardiovascular presentations of COVID-19. Circulation. 2020;141(23):1930–1936. - PMC - PubMed

[3] Choi H.M., Moon S.Y., Yang H.I., Kim K.S. Understanding viral infection mechanisms and patient symptoms for the development of COVID-19 therapeutics. Int. J. Mol. Sci. 2021;22(4):1737. - PMC - PubMed

[4] Choi H.M., Moon S.Y., Yang H.I., Kim K.S. Understanding viral infection mechanisms and patient symptoms for the development of COVID-19 therapeutics. Int. J. Mol. Sci. 2021;22(4):1737. - PMC - PubMed

[5] Duong D. What’s important to know about the new COVID-19 variants? Can. Med. Assoc. J. 2021;193(4):E141–E142. - PMC - PubMed

[6] Duong D. What’s important to know about the new COVID-19 variants? Can. Med. Assoc. J. 2021;193(4):E141–E142. - PMC - PubMed

[7] Abdool Karim S.S., de Oliveira T., Loots G. Appropriate names for COVID-19 variants. Science. 2021;371(6535):1215. - PubMed

[8] Abdool Karim S.S., de Oliveira T., Loots G. Appropriate names for COVID-19 variants. Science. 2021;371(6535):1215. - PubMed

[9] Maslo C., Friedland R., Toubkin M., Laubscher A., Akaloo T., Kama B. Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 omicron wave compared with previous waves. JAMA. 2021 doi: 10.1001/jama.2021.24868. - DOI - PMC - PubMed

[10] Maslo C., Friedland R., Toubkin M., Laubscher A., Akaloo T., Kama B. Characteristics and outcomes of hospitalized patients in South Africa during the COVID-19 omicron wave compared with previous waves. JAMA. 2021 doi: 10.1001/jama.2021.24868. - DOI - PMC - PubMed

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The therapeutic potential of regulatory T cells in reducing cardiovascular complications in patients with severe COVID-19

Affiliations

The therapeutic potential of regulatory T cells in reducing cardiovascular complications in patients with severe COVID-19

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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Cited by

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

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