Morphological Changes in the Myocardium of Patients with Post-Acute Coronavirus Syndrome: A Study of Endomyocardial Biopsies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Histological Examination, Immunohistochemistry, and SARS-CoV-2 RT-ddPCR Test
2.3. Immunofluorescence Test
2.4. Statistical Analysis
3. Results
3.1. Subgroup of Subjects with Chronic Lymphocytic Myocarditis
3.2. Subgroup of Subjects without Chronic Lymphocytic Myocarditis
4. Discussion
5. Conclusions
6. Study Limitation
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACE 2 | angiotensin-converting enzyme 2 |
AF | atrial fibrillation |
EMB | endomyocardial biopsy |
HF | heart failure |
IFM | immunofluorescence microscopy |
IHC | immunohistochemistry |
LVEF | left ventricular ejection fraction |
PASC | post-acute sequelae of SARS-CoV-2 infection |
VWF | von Willebrand factor |
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Patient’s Parameters | Patients with Myocarditis with the PASC (n = 29) | Patients with Myocarditis in the Comparison Group (n = 33) | Patients without Myocarditis with the PASC (n = 9) | Patients without Myocarditis in the Comparison Group (n = 8) |
---|---|---|---|---|
Age, year (50%, 25%, and 75% percentiles) | 35 (32; 44) | 38 (30; 45) | 42 (38; 46) | 41 (36; 48) |
Clinical suspicion of myocarditis (n, %) | 29 (100%) | 33 (100%) | 9 (100%) | 41 (100%) |
Hs-cTnT > 100 ng/L (n, %) | 5 (17%) | 7 (21%) | 0 | 1 (13%) |
Clinic of chronic heart failure (n, %) | 23 (79%) | 27 (82%) | 8 (89%) | 8 (100%) |
Ventricular rhythm disorders (n, %) | 6 (21%) | 9 (27%) | 3 (33%) | 2 (25%) |
Association with viral infection (n, %) | 29 (100%) | 30 (91%) | 9 (100%) | 6 (75%) |
Association with vaccination (n) | 0 | 0 | 0 | 0 |
Left ventricular ejection fraction at initial examination (n, 25% and 75% percentiles) | 28 (23; 33) % | 26 (20; 34) % | 27 (23; 30) % | 26 (22; 38) % |
Presence of a clinical phenotype of dilated cardiomyopathy (n, %) | 12 (41%) | 17 (52%) | 7 (78%) | 4 (50%) |
Immunohistochemical Markers | Patients without Myocarditis (n = 9) | Patients with Myocarditis Total (n = 29) | Patients with Borderline Myocarditis (n = 10) | Patients with Active Myocarditis (n = 19) |
---|---|---|---|---|
CD3 + cells/mm2 | 4.0 (3.0; 5.0) | 19.0 (13.0; 27.0) | 11.5 (8.0; 12.25) | 20.0 (16.5; 31.0) |
CD68 + cells/mm2 | 8.0 (5.0; 14.0) | 11,5 (8.75; 14.5) | 11.0 (8.25; 15.5) | 12.0 (10.0; 17.5) |
HLA-DR (score) | 1.0 (0.0; 3.0) | 3.0 (2.75; 4.0) | 3.0 (2.25; 4.0) | 3.0 (3.0; 4.0) |
MHCI (score) | 4.0 (4.0; 4.0) | 4.0 (4.0; 4.0) | 4.0 (4.0; 4.0) | 4.0 (4.0; 4.0) |
C1q (score) | 1.0 (1.0; 2.0) | 3.0 (2.0; 4.0) | 2.0 (2.0; 3.0) | 3.0 (2.0; 4.0) |
VP1-EntV in vessels, score | 0.0 (0.0; 0.0) | 1.0 (1.0; 2.0) | 1.0 (1.0; 2.0) | 1.0 (0.0; 1.5) |
VP1-EntV in cardiomyocytes, score | 0.0 (0.0; 0.0) | 2.0 (1.0; 2.0) | 1.5 (1.0; 2.0) | 2.0 (1.0; 2.0) |
VWF in vessels, score | 1.0 (1.0; 1.75) | 1.0 (1.0; 2.0) | 1.0 (1.0; 2.0) | 1.0 (1.0; 1.5) |
VWF in cardiomyocytes, score | 0.0 (0.0; 0.0) | 0.0 (0.0; 0.0) | 0.0 (0.0; 0.0) | 0.0 (0.0; 0.0) |
Ang1 in vessels, score | 4.0 (4.0; 4.0) | 3.0 (2.0; 4.0) | 4.0 (3.0; 4.0) | 2.0 (1.0; 2.5) |
Ang1 in cardiomyocytes, score | 0.0 (0.0; 0.75) | 3.0 (2.0; 4.0) | 2.0 (2.0; 3.0) | 3.0 (2.0; 4.0) |
VEGF in vessels, score | 2.5 (1.25; 3.75) | 3.0 (3.0; 4.0) | 3.0 (3.0; 3.0) | 4.0 (3.0; 4.0) |
VEGF in cardiomyocytes, score | 0.0 (0.0; 0.0) | 0.0 (0.0; 0.0) | 0.0 (0.0; 0.0) | 0.0 (0.0; 0.0) |
SARS-CoV-2 spike protein in infiltrate cells, score | 2.0 (1.0; 2.0) | 1.0 (0.0; 1.25) | 0.0 (0.0; 1.0) | 1.0 (0.0; 1.25) |
SARS-CoV-2 spike protein in endothelium, score | 1.0 (0.0; 1.0) | 0.0 (0.0; 1.0) | 0.0 (0.0; 1.0) | 0.0 (0.0; 1.0) |
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Makarov, I.; Mayrina, S.; Makarova, T.; Karonova, T.; Starshinova, A.; Kudlay, D.; Mitrofanova, L. Morphological Changes in the Myocardium of Patients with Post-Acute Coronavirus Syndrome: A Study of Endomyocardial Biopsies. Diagnostics 2023, 13, 2212. https://doi.org/10.3390/diagnostics13132212
Makarov I, Mayrina S, Makarova T, Karonova T, Starshinova A, Kudlay D, Mitrofanova L. Morphological Changes in the Myocardium of Patients with Post-Acute Coronavirus Syndrome: A Study of Endomyocardial Biopsies. Diagnostics. 2023; 13(13):2212. https://doi.org/10.3390/diagnostics13132212
Chicago/Turabian StyleMakarov, Igor, Sofya Mayrina, Taiana Makarova, Tatiana Karonova, Anna Starshinova, Dmitry Kudlay, and Lubov Mitrofanova. 2023. "Morphological Changes in the Myocardium of Patients with Post-Acute Coronavirus Syndrome: A Study of Endomyocardial Biopsies" Diagnostics 13, no. 13: 2212. https://doi.org/10.3390/diagnostics13132212