Vol 81, No 3 (2023)
Letter to the Editor
Published online: 2023-02-06

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Coronary microvascular dysfunction in the context of long COVID-19: What is the effect of anti-inflammatory treatment? Author’s reply

Adrian Doroszko1, Piotr Rola23, Szymon Włodarczak4, Maciej Lesiak5, Adrian Włodarczak13
Pubmed: 36745532
Kardiol Pol 2023;81(3):320-321.

Abstract

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Letter to the Editor

Coronary microvascular dysfunction in the context of long COVID-19: What is the effect of anti-inflammatory treatment? Author’s reply

Adrian Doroszko1Piotr Rola23Szymon Włodarczak4Maciej Lesiak5Adrian Włodarczak24
1Clinical Department of Internal Medicine and Occupational Diseases, Hypertension and Clinical Oncology, Faculty of Medicine, Wroclaw Medical University, Wrocław, Poland
2Witelon Collegium State University, Legnica, Poland
3Department of Cardiology, Provincial Specialized Hospital in Legnica, Legnica, Poland
4Department of Cardiology, The Copper Health Center (MCZ), Lubin, Poland
51st Department of Cardiology, Poznan University of Medical Sciences, Poznań, Poland

Correspondence to:

Piotr Rola, MD, PhD,

Witelon Collegium State University,

Sejmowa 5A, 59–220 Legnica, Poland,

phone: +48 76 721 14 43,

e-mail: piotr.rola@gmail.com

Copyright by the Author(s), 2023

DOI: 10.33963/KP.a2023.0040

Received: January 26, 2023

Accepted: February 6, 2023

Early publication date: February 6, 2023

We have read with great interest the “Letter to the Editor” by Patoulias et al. [1] with comments on our study [2].

The anticipated more severe course of COVID-19 is partially mediated by endothelial damage. Cytokines, including IL-1, IL-2, IL-6, IL-7, and TNF alpha, which regulate the immune response, are among the causes of the deterioration of the condition of patients who suffer from proinflammatory cytokine storm that occurs during SARS-CoV-2 infection [3]. IL-6 promotes vascular remodeling via increased transforming growth factor-β1(TGF-β1)-mediated matrix metalloproteinases (MMPs)2 and 3 signaling. During COVID-19, a wide spectrum of complications affecting organs appears to be caused by a “cytokine storm”, with an increased inflammatory and immune response [4]. Subsequent activation of matrix MMPs leads to endothelial vasodilatory dysfunction resulting in increased coronary resistance, impaired flow-mediated dilation (FMD), and finally impaired coronary flow reserve. Under physiological conditions, the endothelial glycocalyx promotes flow-mediated dilation by transducing the shear stress [5]. Pathophysiological conditions, such as inflammation and oxidative stress, are associated with glycocalyx structural alterations, and its damage by pro-inflammatory cytokines such as IL-1 and IL-6 leads to alterations in vascular permeability with associated interstitial fluid shift and generalized edema [6]. Currently, there is no specific treatment: anti-inflammatory, antioxidant, or limiting the viral replication and aiming at the sequels of thrombo-inflammation, which results in acute oxidative stress in the course of infection. Nevertheless, some drugs aiming precisely at inhibiting the inflammatory cascade could become a promising therapeutic strategy for limiting the burden of coronary endothelial damage. Since IL-6 is a drug target for several diseases of inflammatory origin, pharmacological blockers of the IL-6 signaling pathway, including tocilizumab, were postulated to blunt the abnormal SARS-CoV-2-induced cytokine release and could thus limit endothelial damage. It has already been demonstrated that treatment with tocilizumab limits endothelial inflammatory dysfunction and improves endothelial glycocalyx thickness with subsequent significant improvement in vasodilatory function, as assessed by FMD [7].

The subjects enrolled in our pilot study included both those previously hospitalized in the COVID-19 center and COVID-19 convalescents treated without hospitalization, who received specialistic post-COVID outpatient care. The “ambulatory COVID-19” subpopulation had 17 subjects, whereas the remaining 7 had been previously hospitalized. As result, the number of subjects where specific treatment (including tocilizumab, remdesivir, or convalescent plasma) had been applied was too low to provide statistically relevant data. Therefore those subjects could be described only as a very small case series without any analyses. Furthermore, numerous comorbidities affecting endothelial function make this group relatively heterogenous, which could blur the clarity of “tocilizumab-effect” assessment. Hence, we have decided to present only the raw data on the whole population without subsequent sub-analyses. Nevertheless, we believe that the authors of the letter have a great idea for performing such analyses, which should be conducted on a greater number of cases preferably from numerous centers and we are ready to provide our data for such analysis.

Article information

Conflict of interest: None declared.

Funding: None.

Open access: This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, which allows downloading and sharing articles with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. For commercial use, please contact the journal office at kardiologiapolska@ptkardio.pl.

REFERENCES

  1. Dimitrios P, Dimosiari A, Michailidis T. Coronary microvascular dysfunction in the context of long COVID-19: What is the effect of anti-inflammatory treatment? Kardiol Pol. 2023, 81(3): 318319, doi: 10.33963/KP.a2022.0272, indexed in Pubmed: 36446075.
  2. Rola P, Włodarczak A, Włodarczak S, et al. Invasive assessment of coronary microvascular dysfunction in patients with long COVID: Outcomes of a pilot study. Kardiol Pol. 2022; 80(12): 12521255, doi: 10.33963/KP.a2022.0239, indexed in Pubmed: 36288615.
  3. Carnevale D, Wenzel P. Mechanical stretch on endothelial cells interconnects innate and adaptive immune response in hypertension. Cardiovasc Res. 2018; 114(11): 14321434, doi: 10.1093/cvr/cvy148, indexed in Pubmed: 29912294.
  4. Zheng YY, Ma YT, Zhang JY, et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020; 17(5): 259260, doi: 10.1038/s41569-020-0360-5.
  5. Yilmaz O, Afsar B, Ortiz A, et al. The role of endothelial glycocalyx in health and disease. Clin Kidney J. 2019; 12(5): 611619, doi: 10.1093/ckj/sfz042, indexed in Pubmed: 31583086.
  6. Chelazzi C, Villa G, Mancinelli P, et al. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit Care. 2015; 19(1): 26, doi: 10.1186/s13054-015-0741-z, indexed in Pubmed: 25887223.
  7. Bacchiega BC, Bacchiega AB, Usnayo MJ, et al. Interleukin 6 Inhibition and Coronary Artery Disease in a High-Risk Population: A Prospective Community-Based Clinical Study. J Am Heart Assoc. 2017; 6(3), doi: 10.1161/JAHA.116.005038, indexed in Pubmed: 28288972.



Polish Heart Journal (Kardiologia Polska)