Features of Myocarditis: Morphological Differential Diagnosis in Post-COVID-19 Children

Abstract

Myocarditis is characterized by dysfunction and destruction of cardiomyocytes, infiltrative inflammation, and development of fibrosis. Late diagnosis of myocarditis has been a serious global health problem, especially due to the spread of a new coronavirus infection. The aim of this review is to identify differences between myocarditis of viral etiology, including SARS-CoV-2 lesions, based on instrumental and pathomorphological findings.

Material and methods: We analyzed publications covering the period from December 2019 to May 2023, published in publicly accessible international databases ("Medline", "PubMed", "Scopus"), with queries for the keywords "myocarditis", "children", "cardiovascular inflammation", "COVID-19", "SARS-CoV-2", "severe acute respiratory syndrome coronavirus 2", "differential diagnosis".

Results: It was found that no unambiguous morphological criteria for the diagnosis of myocarditis coupled to SARS-CoV-2 lesions were identified. However, the detected histopathological changes such as virus-associated degeneration, apoptosis, cardiomyocyte necrosis, moderate interstitial hyperemia, myocardial tissue oedema, and capillary endothelial cell dysfunction were the major markers of SARS-CoV-2 infection.

Conclusion: It is necessary further reconsider morphological criteria to diagnose SARS-CoV-2-caused myocarditis, rather than solely relying on detecting viral RNA by PCR as the sole evidence-based criterion. Similar issues accompany diagnostics of myocardial lesions associated with other viral infections. Evidence for an etiological diagnosis of myocarditis can be provided by a comprehensive analysis of the diagnostic criteria obtained, confirming virus exposure, followed by development of distinct clinical symptoms, MRI and CT changes, and morphological criteria.

Keywords: SARS-CoV-2 infection; heart transplantation; immunohistochemical and ultrastructural myocardial studies; virus transmission.

Figure 1

Focal acute polymorphic cell myocarditis (A,B), pathological alterations in intramural blood vessels (C), and expression of SARS-CoV-2 spike antigen (D) by endothelial and smooth muscle cells of myocardial blood vessels. A—H&E, B—IHH, mouse monoclonal anti-CD45-specific staining (Thermo, Waltham, MA, USA); C—IHH, mouse monoclonal anti-CD31-specific staining (Thermo, Waltham, MA, USA); D—IHH, rabbit polyclonal anti-SARS-CoV-2 Spike-specific staining (GeneTex, Irvine, CA, USA), DAB. Scale range: segment (A)—2000 μm, (B,C)—100 μm; (D)—500 µm.

Figure 2

Expression of antigens of herpes simplex virus type 2 (brown staining) in non-parenchymal myocardial cells in generalized intrauterine herpes virus infection. IHH, rabbit polyclonal anti-HSV-2 (BioGenex, Fremont, CA, USA), DAB. SW. ×200.

Figure 3

Expression of cytomegalovirus antigens (brown staining) in transformed endothelial cells during generalized intrauterine cytomegalovirus infection. IHH, mouse monoclonal anti-CMV-specific staining (DAKO, Santa Clara, CA, USA), DAB. SW. ×400.

Figure 4

Expression of Epstein–Barr virus antigens (brown staining) in cardiomyocytes, lymphocytes, and endotheliocytes in generalized Epstein–Barr virus infection. IHH, mouse monoclonal anti-EBV (Thermo, Waltham, MA, USA), DAB. SW. ×200.

Figure 5

Expression of enterovirus antigens (brown staining) in cardiomyocytes, smooth muscle cells of blood vessels, and lymphocytes in enterovirus myocarditis. IHH, mouse monoclonal anti-Enterovirus VP-1-specific staining (Leica, New York, NY, USA), DAB. SW. ×200.

Figure 6

Expression of Parvovirus B19 antigens (brown staining) in cardiomyocytes. IHH, mouse monoclonal anti-Parvovirus B-19-specific staining (Leica, New York, NY, USA). SW. ×1000.