Clinical and metagenomic characterization of HHV-6 versus HHV-7 encephalitis in immunocompetent children.

Background: Human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7) are betaherpesviruses that can cause encephalitis/encephalopathy in immunocompetent children. However, early clinical manifestations, routine laboratory tests, and neuroimaging findings often lack specificity, making etiological characterization challenging. This study aimed to characterize the clinical features and metagenomic findings of HHV-6 and HHV-7 encephalitis in immunocompetent children. Methods: This single-center retrospective cohort study included children (<18 years) with suspected central nervous system infection who underwent lumbar puncture and cerebrospinal fluid (CSF) next-generation sequencing (mNGS) testing at The First Affiliated Hospital of Zhengzhou University between January 2020 and December 2024. Patients with HHV-6 or HHV-7 sequences detected in CSF by mNGS, together with compatible clinical features and exclusion of other more likely etiologies, were included. Demographic characteristics, clinical manifestations, laboratory and CSF findings, neuroimaging features, mNGS results, treatments, and short-term outcomes were analyzed. Results: A total of 20 children with CSF HHV-6 or HHV-7 sequence detection were included (HHV-6, n=5; HHV-7, n=15). HHV-6 cases mainly occurred in infants and young children, whereas HHV-7 cases were predominantly observed in older children. Fever and seizure-related symptoms were the most common clinical manifestations. Peripheral inflammatory markers, CSF parameters, and neuroimaging findings showed heterogeneous patterns among patients. CSF mNGS detected HHV-6 or HHV-7 sequences in all included cases, with variable sequencing read counts (HHV-6: median 257 reads, range 55-52, 686; HHV-7: median 2, 635 reads, range 457-26, 355). The median turnaround time of mNGS reporting was 1 day (range, 1-2 days). All patients received antiviral therapy, with some receiving adjunctive corticosteroids and/or intravenous immunoglobulin. Short-term outcomes at discharge were generally favorable, and only one patient developed secondary autoimmune encephalitis. Conclusions: HHV-6 and HHV-7 encephalitis in immunocompetent children share overlapping clinical characteristics and lack specific early laboratory or imaging features. CSF mNGS enabled rapid and unbiased detection of HHV-6 and HHV-7 sequences and provided complementary etiological information when interpreted together with clinical and ancillary findings.