Infective Myocarditis in Children
1. Dr. Osmonova Gulnaz Zhenishbaevna
2. Ganesh Soni
3. Manish Yadav
(1. Teacher, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.
2. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.
3. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic.)
Abstract
Viral myocarditis is a major cause of pediatric cardiac inflammation and contributes to dilated cardiomyopathy and sudden cardiac death. Despite its impact, most mechanistic insights derive from adult models, limiting understanding of pediatric disease. This review highlights age-specific differences in immune responses, viral tropism, and clinical outcomes. We summarize the major viral pathogens associated with pediatric myocarditis and their distinct roles in acute and chronic cardiac injury. We discuss experimental infection models with attention to viral species, host strain, and route of administration, each influencing disease severity and translational relevance. Pediatric-focused models demonstrate vulnerabilities of the immune system, including limited memory responses and altered viral persistence. At the cellular and molecular level, we describe mechanisms of myocardial damage such as viral cytotoxicity, dysregulated cytokine production, maladaptive immune recruitment, and mitochondrial dysfunction. We further examine cardiomyocyte and endothelial signaling, viral evasion strategies, and the progression from acute inflammation to fibrosis and dilated cardiomyopathy. Finally, we consider anatomical and physiological differences between murine and human hearts that restrict translation and emphasize the need for pediatric-specific models to define mechanisms and guide targeted therapies. Advancing such models will be essential for reducing morbidity and mortality in affected children.
Introduction
Viral myocarditis, defined as inflammation of the heart muscle with immune cell infiltration and cardiomyocyte injury,1,2 typically resolves in children without long-term consequences. In some cases, however, persistent inflammation disrupts myocardial structure and function, leading to dilated cardiomyopathy (DCM), a condition in which the heart enlarges, weakens, becomes increasingly prone to heart failure and can lead to death.3 Myocarditis occurs in approximately 1 to 2 per 100,000 children annually4 and accounts for an estimated 3 to 12 percent of sudden cardiac deaths5,6 and 12 to 16 percent of pediatric DCM cases.7,8,9 Among children hospitalized with myocarditis, African American and Hispanic patients have higher odds of death than White children, as well as increased rates of cardiac arrest. These differences reflect a combination of biological factors and social determinants of health, including disparities in access to care and treatment.10 At the same time, the burden of pediatric viral myocarditis is likely underestimated, as some children experience mild or asymptomatic disease and do not undergo clinical evaluation. Among those who do present for care, clinical presentation of myocarditis in children varies by age. In newborns and infants, symptoms are often nonspecific and include fever, irritability, poor feeding, tachypnea, and/or cyanosis. Older children may report chest pain, fatigue, abdominal discomfort, cough, and/or edema.11,12 Diagnosis is challenging and often relies on a combination of clinical findings, laboratory markers, and cardiac imaging. Troponin and B-type natriuretic peptide (BNP) levels may indicate myocardial injury and stress.13,14 Conduction abnormalities may be found via electrocardiography, and echocardiography may reveal reduced signs of diminished cardiac output with reduced ejection fraction, chamber enlargement, wall motion abnormalities, or valvular regurgitation.13,15 However, these measures largely reflect downstream functional impairment rather than the initiating disease mechanisms.
Pediatric Myocarditis: Causes, Diagnosis, and Management in the COVID-19 Era
Myocarditis—inflammation of the heart muscle (cardiac myocytes) leading to edema, injury, or necrosis—remains a serious but often under-recognized condition in children. It is a leading cause of sudden cardiac death in pediatric patients and young athletes, yet many mild cases go unreported. A 2023 review in Cardiology and Therapy by Williams, Jacobs, and Lee provides a timely update, emphasizing viral causes, the impact of SARS-CoV-2 infection and mRNA vaccines, and the growing role of cardiac magnetic resonance (CMR) imaging.
Incidence and Risk Factors Exact rates are unknown but estimated at 0.80–2.13 cases per 100,000 children, with a clear male predominance (especially after age 6). Cases show a bimodal age distribution: infants and adolescents.
Causes
• Classic myocarditis: Primarily viral (parvovirus B19, human herpesvirus 6, adenovirus, enterovirus). Less common triggers include bacterial, fungal, autoimmune, hypersensitivity, or toxins.
• SARS-CoV-2-related: Children face higher risk from COVID-19 infection (including multisystem inflammatory syndrome in children, MIS-C) than from mRNA vaccination. MIS-C myocarditis often shows more global involvement and septal late gadolinium enhancement (LGE) on CMR.
• Vaccine-associated: Rare, mostly after the second dose of Pfizer-BioNTech or Moderna mRNA vaccines in adolescents and young adults (predominantly males). Risk ratio is significantly lower than with natural infection (3.24 vs. 18.28).
Clinical Presentation
Symptoms range from asymptomatic to fulminant cardiogenic shock. Common features include:
• Fever and viral prodrome (>50%)
• Chest pain, dyspnea, palpitations, gastrointestinal symptoms
• Exercise intolerance or syncope (10–12%)
Vaccine-related cases often present with severe chest pain and rapid recovery. MIS-C myocarditis tends to cause more critical illness but quicker ventricular function recovery.
Diagnosis
• Labs: Elevated troponin, BNP/pro-BNP, CK-MB; inflammatory markers.
• ECG: Abnormalities common (wide QRS-T angle, low voltage, prolonged QTc linked to worse outcomes).
• Echocardiography: First-line; assesses function, dilation, effusions, thrombi. Myocardial strain imaging detects subclinical dysfunction.
• Endomyocardial biopsy: Historical gold standard (Dallas criteria) but now used sparingly due to sampling error, complications (higher in young children), and CMR availability.
• CMR (key advance): Non-invasive reference tool using the revised Lake Louise Criteria (2018):
◦ At least one T1-based criterion (prolonged native T1, elevated extracellular volume, or LGE) AND
◦ At least one T2-based criterion (edema on T2 mapping or increased T2 signal).
Parametric mapping improves sensitivity to ~87.5%. LGE location and persistence help predict outcomes; myocardial strain adds prognostic value. CMR distinguishes myocarditis from simple myocardial involvement after COVID-19.
Management
• Supportive care: Heart-failure regimen (ACE inhibitors/ARBs, beta-blockers, diuretics, aldosterone antagonists).
• Severe cases: Inotropes (milrinone preferred), mechanical circulatory support (ECMO or VADs).
• Immunomodulation: IVIG and/or high-dose steroids commonly used, especially in MIS-C (99% and 93% of protocols, respectively). Mixed evidence overall, but beneficial in some cohorts.
• Athletes: Strict restriction from competitive sports for 3–6 months; return-to-play requires normalized imaging, labs, and Holter monitoring.
Outcomes and Prognosis Most children recover ventricular function, especially those with vaccine-associated or MIS-C myocarditis (76–100% recovery vs. ~47% in classic viral cases). However, persistent LGE, scar, arrhythmias, or later dilated cardiomyopathy can occur. Poor prognostic factors: ventricular dysfunction at presentation, elevated troponin/BNP, tachyarrhythmias, and mid-wall or anteroseptal LGE. Long-term CMR follow-up is recommended.
Key Takeaways
• COVID-19 infection poses a greater myocarditis risk than mRNA vaccination.
• CMR with revised Lake Louise Criteria and parametric mapping has largely replaced biopsy as the cornerstone of diagnosis.
• Early recognition, supportive care, and targeted immunomodulation improve outcomes in this potentially life-threatening condition.
This concise update underscores the importance of prompt diagnosis and individualized management in pediatric myocarditis, particularly amid evolving infectious and vaccine-related etiologies. Clinicians should maintain a high index of suspicion in children with chest pain or unexplained heart failure symptoms.
Reference:
[1] Immunology Group of Dermatology and Venereology Branch of Chinese Medical Association, Collaborative Research Center for Atopic Dermatitis. Chinese Guidelines for the Diagnosis and Treatment of Atopic Dermatitis (2020 Edition) [J]. Chinese Journal of Dermatology, 2020, 053(002):81-88.
[2] Salava A, Perälä M, Pelkonen A, Mäkelä M, Remitz A. Safety of tacrolimus 0.03% and 0.1% ointments in young children with atopic dermatitis: a 36-month follow-up study. Clin Exp Dermatol. 2022 May;47(5):889-902.
[3] Tadicherla S, Ross K, Shenefelt D. Topical corticosteroids in dermatology. Journal of Drugs in Dermatology 2009; 12:1093.
[4] Immunology Group of Dermatology and Venereology Branch of Chinese Medical Association, Collaborative Research Center for Atopic Dermatitis. Chinese Guidelines for the Diagnosis and Treatment of Atopic Dermatitis (2020 Edition) [J]. Chinese Journal of Dermatology, 2020, 053(002):81-88.
[5] Expert consensus on the diagnosis and treatment of allergic diseases in children by the Pediatrics Branch of the Chinese Medical Association [J]. Chinese Journal of Pediatrics, 2019, 57(3):8.
[6] Pereira U,Boulais N,Lebonvallet N et al. Mechanisms of the sensory effects of tacrolimus on the skin.[J] .Br J Dermatol, 2010, 163: 70-7.
[7] Drucker AM, Eyerich K, de Bruin-Weller MS, etal. Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement. Br J Dermatol. 2018 Mar;178(3):768-775.