Abstract Background Taiwan, once celebrated for its remarkable control over COVID-19, faced an unexpected surge in pediatric cases during the first wave of the omicron variant in April 2022. Alarming data revealed acute encephalitis emerging in half of the severe or fatal COVID-19 cases in children within the initial two months of the omicron epidemic. This study delves into the intricate microbiota patterns and viral pathogens contributing to encephalitis complications in affected children. Methods The study enrolled 36 pediatric patients, comprising 11 patients with severe encephalitis, 12 patients with mild encephalitis, and 13 normal controls. Nasal swabs were collected for pathogen detection. For respiratory microbiota analysis, 16S rRNA metagenomic sequencing was employed, while the Illumina Respiratory Pathogen ID/AMR Enrichment Panel was used for respiratory pathogen identification. Results Microbiota analysis of nasal swabs from COVID-19 pediatric patients with meningitis complications revealed prevalent Corynebacterium, Staphylococcus, Dolosigranulum, Acinetobacter, Moraxella, and Streptococcus. Conversely. No predominant bacterial species were detected in the normal control group. Nasal swab respiratory pathogen detection identified coinfections, particularly Herpesviridae viruses such as human herpesvirus 6, Epstein-Barr virus, and Cytomegalovirus in pediatric patients with meningitis complications. Notably, two severe encephalitis cases exhibited coinfections involving rhinovirus, SARS-CoV-2, and Herpesviridae viruses (HHV-6, EBV). In one fatal case, distribution of Streptococcus genes among total geneomes reaches 40.69%, 7 drug resistant genes were detected. Conclusions This study suggests a potential link between latent Herpesviridae virus coinfections (HHV-6, CMV, EBV) and meningitis complications in pediatric patients. Furthermore, the presence of a secondary respiratory virus (rhinovirus) coinfection appears to be associated with severe complications. These findings shed light on the complex pathogen dynamics contributing to the emergence of encephalitis in pediatric COVID-19 cases during the omicron variant outbreak in Taiwan.
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