Hidden viral infections in myocarditis: metagenomic sequencing links undetected viruses to impaired left ventricular function
C Baumeier, B Altmann, G Wiegleb, D Harms, G Aleshcheva, T Bock, S Niendorf, F Escher, H P SchultheissAbstract
Background
Viral infections are a leading cause of myocarditis; however, conventional polymerase chain reaction (PCR) often fails to detect causative pathogens, limiting diagnostic precision and therapeutic decision-making.
Purpose
We evaluated whether targeted metagenomic next-generation sequencing (NGS) improves viral detection in endomyocardial biopsies (EMB) compared with standard PCR and assessed its clinical relevance.
Methods
EMB samples from 144 patients with clinically suspected myocarditis underwent histologic and immunohistochemical assessment of myocardial inflammation. All samples were analyzed using conventional PCR for common cardiotropic viruses and compared with a targeted NGS panel covering 84 cardiotropic viruses. Viral detection and transcriptional activity were assessed and correlated with myocardial inflammation and left ventricular ejection fraction (LVEF).
Results
EMB confirmed myocarditis in 127 (88%) cases. NGS detected all 45 viral genomes identified by PCR and revealed an additional 31 viral genomes in PCR-positive patients, increasing diagnostic yield by 69%. Among PCR-negative patients, NGS identified viral genomes in 56%, uncovering high number of previously undiagnosed infections. Frequently detected viruses included parvovirus B19, Epstein-Barr virus, human herpesvirus 6, cytomegalovirus, and adenovirus, as well as less commonly recognized agents such as herpesvirus 7/8, adeno-associated virus, tetraparvovirus, and pegivirus C. Transcriptionally active parvovirus B19 was more frequently detected by NGS than PCR (31% vs. 14%). Patients with NGS-confirmed viral infections had significantly lower LVEF compared with virus-negative patients.
Conclusions
Targeted metagenomic sequencing substantially improves viral detection in EMB and identifies clinically relevant infections missed by PCR. These findings support the potential role of NGS as a complementary diagnostic tool in virus-associated myocarditis and heart failure.