Fulminant Myocarditis During Covid–19 Outbreaks: Myths or Reality?

Background Although infections are established triggers, the etiopathogenetic role of SARS–CoV–2 in fulminant myocarditis (FM) remains unproven. Moreover, the concordance between SARS–CoV–2 detection on nasopharyngeal swabs and its identification by molecular analysis of endomyocardial biopsy (EMB) has not been systematically investigated. Aims To compare clinical characteristics, diagnostic findings, and outcomes of FM cases before and after the COVID–19 pandemic in a tertiary referral center. To assess concordance between SARS–CoV–2 detection by serological or molecular testing on nasopharyngeal swabs and viral polymerase chain reaction (PCR) on EMB specimens. Methods We retrospectively analyzed FM cases diagnosed between 2001 and 2025, comparing patients diagnosed before and after March 2020. The primary composite outcome included cardiac death, heart transplantation, or myocarditis relapse. Results Forty–six FM patients (61% male; median age 36 years) were included; 17 (37%) were diagnosed after March 2020. Clinical presentation and diagnostic features were comparable between cohorts. Ventricular fibrillation and ventricular tachycardia occurred in 53% and 33% of patients, respectively. Median left ventricular ejection fraction (LVEF) was 40.0% [27.5–47.0]. Troponin and C–reactive protein were elevated in 89% and 79% of patients, respectively. EMB was performed in 78% of patients, showing predominantly lymphocytic myocarditis (83%), followed by giant–cell (14%) and eosinophilic (3%) forms, without differences between periods. Viral genomes were detected in 26% of EMBs, most commonly parvovirus B19 and enterovirus; SARS–CoV–2 was not identified in any myocardial specimen, including two patients with concurrent SARS–CoV–2 infection. Thirteen patients had received COVID–19 vaccination, with no post–vaccination myocarditis. Immunosuppressive therapy was administered in 28% of patients. Over a median follow–up of 34 months, the composite outcome occurred in 35% of patients, with no differences between pre– and post–pandemic cohorts. On multivariable analysis, baseline LVEF was the only independent predictor of adverse outcome (HR 0.94; 95% CI 0.90–0.98; p = 0.010). Conclusions FM patients showed similar clinical presentation, histopathology, and outcomes before and after the COVID–19 pandemic. The absence of myocardial SARS–CoV–2 detection despite positive nasopharyngeal testing argues against a direct causal role of SARS–CoV–2 in FM within this cohort.