Post-COVID Versus Non-COVID Myocarditis: Comparison of Morphological Activity, Toll-like Receptor Distribution and Responses to Immunosuppressive Therapy

Background: A prior direct clinical and morphological comparison between non-coronavirus disease (COVID) myocarditis diagnosed before the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic and post-COVID myocarditis has not been performed. Purpose: To co...

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Main Authors: Olga V. Blagova, Evgenia A. Kogan, Vladimir M. Novosadov, Valeriy A. Bryukhanov, Nikolay V. Zharkov
Format: Article
Language:English
Published: IMR Press 2025-06-01
Series:Frontiers in Bioscience-Scholar
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Online Access:https://www.imrpress.com/journal/FBS/17/2/10.31083/FBS28262
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author Olga V. Blagova
Evgenia A. Kogan
Vladimir M. Novosadov
Valeriy A. Bryukhanov
Nikolay V. Zharkov
author_facet Olga V. Blagova
Evgenia A. Kogan
Vladimir M. Novosadov
Valeriy A. Bryukhanov
Nikolay V. Zharkov
author_sort Olga V. Blagova
collection DOAJ
description Background: A prior direct clinical and morphological comparison between non-coronavirus disease (COVID) myocarditis diagnosed before the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic and post-COVID myocarditis has not been performed. Purpose: To compare morphological activity, Toll-like receptor distribution, and response to immunosuppressive therapy in patients with non-COVID and post-COVID myocarditis. Methods: In total, 77 patients (52 male and 25 female, 48.7 ± 11.7 years old) with biopsy-proven myocarditis, New York Heart Association (NYHA) class 2 or higher heart failure diagnoses, and an ejection fraction (EF) <45% were included. The exclusion criteria comprised a history of myocardial infarction, verified cardiomyopathies, systemic autoimmune diseases, and viral DNA in the myocardium, except parvovirus B19. A right ventricular endomyocardial biopsy was performed using hematoxylin and eosin and Van Gieson staining assays, alongside the polymerase chain reaction (PCR) for viruses (herpes viruses, parvovirus B19, adeno-, enteroviruses, and SARS-CoV-2). Moreover, immunohistochemical assays were conducted for CD3, CD45, CD68, CD20, nucleocapsid/spike proteins of SARS-CoV-2, and the subcellular distribution of Toll-like receptors (TLRs) type 4 and 9 (in 38 patients). The steroids (methylprednisolone 24–40 mg per day), azathioprine, and mycophenolate mofetil were prescribed. This study was observational and non-interventional. The mean follow-up was 15.0 [6.0; 35.5] months. Results: Myocarditis was diagnosed in 45 patients before the SARS-CoV-2 pandemic (giant cell in one case and lymphocytic in the others). Another 32 patients had post-COVID myocarditis that was positive for RNA or/and proteins of SARS-CoV-2 (giant cell in one case, eosinophilic in three cases, and lymphocytic in the others). There were no differences in age, NYHA classification, C-reactive protein (CRP) and anti-heart antibodies levels, echocardiographic parameters (mean EF: 30.2 ± 7.8 vs. 28.7 ± 6.7%), parvovirus B19 positivity (22 vs. 34%), methylprednisolone dosages (24–40 mg/day), and death/transplantation rate (11.1 vs. 9.4%). Differences between non-COVID and post-COVID myocarditis focused on higher CD3, CD 45*, and toll-like receptors (TLR)-4 (4+ vs. 6+) and TLR-9 (0 vs. 2+) levels, alongside subcellular distribution and a better response to therapy ((10% or more increase in EF in 53 vs. 86%* of patients, mean EF (43.9 ± 12.3 vs. 49.8 ± 7.6%*) by the end of follow-up); *p < 0.05). Conclusion: Post-COVID myocarditis is characterized by different morphological types, higher morphological activity, the tendency to increase TLR expression, and an improved response to immunosuppressive therapy compared to non-COVID myocarditis.
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spelling doaj-art-7e80642d57c54ceea004820a2021e7cf2025-08-20T03:29:39ZengIMR PressFrontiers in Bioscience-Scholar1945-05162025-06-011722826210.31083/FBS28262S1945-0516(25)00128-5Post-COVID Versus Non-COVID Myocarditis: Comparison of Morphological Activity, Toll-like Receptor Distribution and Responses to Immunosuppressive TherapyOlga V. Blagova0Evgenia A. Kogan1Vladimir M. Novosadov2Valeriy A. Bryukhanov3Nikolay V. Zharkov4Department of Faculty Therapy №1, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, RussiaDepartment of Pathology, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, RussiaDepartment of Faculty Therapy №1, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, RussiaDepartment of Pathology, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, RussiaDepartment of Pathology, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119992 Moscow, RussiaBackground: A prior direct clinical and morphological comparison between non-coronavirus disease (COVID) myocarditis diagnosed before the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic and post-COVID myocarditis has not been performed. Purpose: To compare morphological activity, Toll-like receptor distribution, and response to immunosuppressive therapy in patients with non-COVID and post-COVID myocarditis. Methods: In total, 77 patients (52 male and 25 female, 48.7 ± 11.7 years old) with biopsy-proven myocarditis, New York Heart Association (NYHA) class 2 or higher heart failure diagnoses, and an ejection fraction (EF) <45% were included. The exclusion criteria comprised a history of myocardial infarction, verified cardiomyopathies, systemic autoimmune diseases, and viral DNA in the myocardium, except parvovirus B19. A right ventricular endomyocardial biopsy was performed using hematoxylin and eosin and Van Gieson staining assays, alongside the polymerase chain reaction (PCR) for viruses (herpes viruses, parvovirus B19, adeno-, enteroviruses, and SARS-CoV-2). Moreover, immunohistochemical assays were conducted for CD3, CD45, CD68, CD20, nucleocapsid/spike proteins of SARS-CoV-2, and the subcellular distribution of Toll-like receptors (TLRs) type 4 and 9 (in 38 patients). The steroids (methylprednisolone 24–40 mg per day), azathioprine, and mycophenolate mofetil were prescribed. This study was observational and non-interventional. The mean follow-up was 15.0 [6.0; 35.5] months. Results: Myocarditis was diagnosed in 45 patients before the SARS-CoV-2 pandemic (giant cell in one case and lymphocytic in the others). Another 32 patients had post-COVID myocarditis that was positive for RNA or/and proteins of SARS-CoV-2 (giant cell in one case, eosinophilic in three cases, and lymphocytic in the others). There were no differences in age, NYHA classification, C-reactive protein (CRP) and anti-heart antibodies levels, echocardiographic parameters (mean EF: 30.2 ± 7.8 vs. 28.7 ± 6.7%), parvovirus B19 positivity (22 vs. 34%), methylprednisolone dosages (24–40 mg/day), and death/transplantation rate (11.1 vs. 9.4%). Differences between non-COVID and post-COVID myocarditis focused on higher CD3, CD 45*, and toll-like receptors (TLR)-4 (4+ vs. 6+) and TLR-9 (0 vs. 2+) levels, alongside subcellular distribution and a better response to therapy ((10% or more increase in EF in 53 vs. 86%* of patients, mean EF (43.9 ± 12.3 vs. 49.8 ± 7.6%*) by the end of follow-up); *p < 0.05). Conclusion: Post-COVID myocarditis is characterized by different morphological types, higher morphological activity, the tendency to increase TLR expression, and an improved response to immunosuppressive therapy compared to non-COVID myocarditis.https://www.imrpress.com/journal/FBS/17/2/10.31083/FBS28262post-covid myocarditisendomyocardial biopsytoll-like receptorsimmunosuppressive therapycorticosteroids
spellingShingle Olga V. Blagova
Evgenia A. Kogan
Vladimir M. Novosadov
Valeriy A. Bryukhanov
Nikolay V. Zharkov
Post-COVID Versus Non-COVID Myocarditis: Comparison of Morphological Activity, Toll-like Receptor Distribution and Responses to Immunosuppressive Therapy
Frontiers in Bioscience-Scholar
post-covid myocarditis
endomyocardial biopsy
toll-like receptors
immunosuppressive therapy
corticosteroids
title Post-COVID Versus Non-COVID Myocarditis: Comparison of Morphological Activity, Toll-like Receptor Distribution and Responses to Immunosuppressive Therapy
title_full Post-COVID Versus Non-COVID Myocarditis: Comparison of Morphological Activity, Toll-like Receptor Distribution and Responses to Immunosuppressive Therapy
title_fullStr Post-COVID Versus Non-COVID Myocarditis: Comparison of Morphological Activity, Toll-like Receptor Distribution and Responses to Immunosuppressive Therapy
title_full_unstemmed Post-COVID Versus Non-COVID Myocarditis: Comparison of Morphological Activity, Toll-like Receptor Distribution and Responses to Immunosuppressive Therapy
title_short Post-COVID Versus Non-COVID Myocarditis: Comparison of Morphological Activity, Toll-like Receptor Distribution and Responses to Immunosuppressive Therapy
title_sort post covid versus non covid myocarditis comparison of morphological activity toll like receptor distribution and responses to immunosuppressive therapy
topic post-covid myocarditis
endomyocardial biopsy
toll-like receptors
immunosuppressive therapy
corticosteroids
url https://www.imrpress.com/journal/FBS/17/2/10.31083/FBS28262
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