Myocarditis encompasses a broad spectrum of clinical manifestations, ranging from mild, localized conditions that can spontaneously disappear to arrhythmia, thrombotic complications, and fatal cardiogenic shock (Cooper, 2009; Cheung et al., 2017). Such diverse and non-specific symptoms make establishing a definitive diagnosis of myocarditis challenging. Meanwhile, the prognosis and treatment of myocarditis are contingent on the underlying etiology (Ammirati et al., 2018), even when other factors (Felker et al., 2000; Liu et al., 2001; Magnani et al., 2006; Schultz et al., 2009; Hidron et al., 2010; Kindermann et al., 2012; Pollack et al., 2015; Chimenti et al., 2022; Yang et al., 2022), such as opportunistic infections by pathogens and toxins or noninfectious causes including inflammation secondary to cytokine storm, systemic autoimmune disorders, and physical agents can trigger fulminant myocarditis. However, the condition is typically caused by the viral infections and/or post-viral immune-mediated responses (Cooper, 2009; Pollack et al., 2015; Akhmerov et al., 2020).

SARS-CoV-2 has caused significant morbidity and mortality worldwide. Notwithstanding the typical clinical manifestation caused by SARS-CoV-2 infection, including respiratory failure, chest discomfort, chest tightness, shortness of breath, and palpitations, the pathological mechanisms of pyroptosis in infected monocytes and macrophages can result in systemic inflammation (cytokine storm), coagulation dysfunction, hypoxemia, endothelial injury, fever, and electrolyte imbalance. This affects the cardiovascular system and leads to myocardial injury, myocardial infarction, and arrhythmias (Junqueira et al., 2022). As the number of confirmed cases of COVID-19 increased, along with accumulated clinical evidence, including endomyocardial biopsy (EMB) and elevation of hypersensitive cardiac troponin I and T (cTnI, cTnT) (Ammirati et al., 2018; Huang et al., 2020), many cases were diagnosed with acute myocardial damage (Abate et al., 2021; Halushka et al., 2021; Castiello et al., 2022; Junqueira et al., 2022). The recent systematic study underscores that myocarditis has been a persistent complication across different waves of the COVID-19 pandemic, with no significant differences in incidence between the initial and subsequent waves (Caldonazo et al., 2023). This indicates a consistent risk for myocardial injury across different pandemic phase.

Amid the dramatic surge in COVID-19 infections subsequent to the prevention and control policy revised in China (Pan et al., 2023), two patients exhibiting acute conditions were hospitalized. Upon admission, oropharyngeal and anal swabs were obtained for SARS-CoV-2 screening via quantitative real-time polymerase chain reaction (qRT-PCR). Later, during the hospitalization course when the two patients were diagnosed with fulminant myocarditis, additional specimens, including pericardial effusion from one patient and myocardial tissue from the other, were promptly collected to elucidate whether the fulminant myocarditis could be etiologically attributed to COVID-19 triggered by SARS-CoV-2 infection via exhaustive analysis through meta-transcriptomics, immunohistochemistry (IHC) and immunofluorescence (IF) assays of these bio-specimens.