Identification of potential pathogenic viruses in patients with acute myocarditis using next‐generation sequencing

Abstract

Myocarditis is an inflammatory disease of the myocardium and leads to cardiac dysfunction and heart failure. Although viral infections are considered to be the most common etiology of myocarditis, the identification of the causative virus is still challenging. Recently, next-generation sequencing (NGS) has been applied in the diagnosis of infectious diseases. The aim of the current study was to comprehensively analyze potential pathogenic microorganisms using NGS in the sera of patients with myocarditis. Twelve pediatric and five adult patients hospitalized for acute myocarditis were included. Serum samples in the acute phase were obtained and analyzed using NGS to detect pathogen-derived DNA and RNA. Viral sequence reads were detected in 7 (41%) of the 17 myocarditis patients by NGS. Among these patients, detection of Epstein-Barr virus, human parvovirus B19, torque teno virus, and respiratory syncytial virus reads by NGS was consistent with polymerase chain reaction or antigen test results in one patient each. A large number of human pegivirus reads were detected from one patient by RNA sequencing; however, its pathogenicity to human is unknown. Conversely, the number of detected virus-derived reads was small in most cases, and the pathophysiological role of these viruses remains to be clarified. No significant bacterial or fungal reads other than normal bacterial flora was detected. These data indicate that comprehensive detection of virus-derived DNA and RNA using NGS can be useful for the identification of potential pathogenic viruses in myocarditis.

Comprehensive pathogen detection in sera of Kawasaki disease patients by high-throughput sequencing: a retrospective exploratory study

“…Additionally, we comprehensively examined RNA viruses in the present study. Although our HTS method previously revealed the profile of an RNA virus in serum samples from patients with acute liver failure/fulminant hepatitis and myocarditis [9,10], no pathogenic RNA virus could be detected from sera in the present study. Recent studies support the hypothesis that KD pathogenesis is closely associated with dysregulation of immune responses to various viruses or microbes [30,31].…”

Semi‐quantitative duplex RT ‐ PCR reveals the low occurrence of Porcine Pegivirus and Atypical Porcine Pestivirus in diagnostic samples from the United States

“…Human pegivirus is prevalent in 5% of the world's population and was reported as co‐infections with other viruses, such as hepatitis C virus and HIV infected individuals (Berg et al., ; Jordier et al., ; N'Guessan et al., ; Schwarze‐Zander, Blackard, & Rockstroh, ; Wang et al., ). In addition, human pegivirus strains can be associated with febrile illness, haemophilia, acute mycocarditis and lymphoma (Bijvand et al., ; Fama et al., ; Takeuchi et al., ; Williams et al., ). In horses, a pathogenic pegivirus ‘Theiler disease‐associated virus’ (TDAV) and non‐pathogenic equine pegivirus (EPgV) have been identified indicating not all strains of pegivirus are pathogenic (Kapoor et al., ; Smith, Chalmers, & Wedel, ; Sturgeon, ).…”

“…The 2012;Wang et al, 2018). In addition, human pegivirus strains can be associated with febrile illness, haemophilia, acute mycocarditis and lymphoma (Bijvand et al, 2018;Fama et al, 2018;Takeuchi et al, 2018;Williams et al, 2018). In horses, a pathogenic pegivirus 'Theiler disease-associated virus' (TDAV) and non-pathogenic equine pegivirus (EPgV) have been identified indicating not all strains of pegivirus are pathogenic (Kapoor et al, 2013;Smith, Chalmers, & Wedel, 1991;Sturgeon, 2017).…”

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

“…Successful integration of these omics techniques into existing diagnostic algorithms will contribute to a more sensitive, specific and cost-effective approach for the personalized treatment of patients with inflammatory cardiomyopathy 211 . Use of NGS will also facilitate the detection of so-far-unknown pathogenic, cardiotropic agents, such as DNA and RNA viruses, in myocarditis 212 .…”