Metatranscriptomic insights into host-microbiome interactions underlying asymptomatic COVID-19 cases

Coronavirus disease 2019 (COVID-19) remains a major global health concern, with emerging evidence highlighting the role of the human microbiome in influencing disease severity. While extensive research has been conducted on COVID-19, studies examining host-pathogen interactions at the transcriptomic level remain limited. In this study, we investigated the metatranscriptomic profiles of forty nasopharyngeal samples collected from COVID-19 patients across different Bangladeshi cohorts. Sequencing data were processed to analyze taxonomic composition, microbial diversity, and antimicrobial resistance gene (ARG) patterns using multiple bioinformatic pipelines. COVID-19 positive and asymptomatic patients exhibited a higher abundance of pathogenic and multidrug-resistant bacteria, whereas COVID-19 negative individuals showed increased fungal diversity. Differential gene expression analysis revealed significant upregulation of immune response related genes, including pro-inflammatory cytokines, in COVID-19 positive cases. Notably, asymptomatic patients demonstrated reduced TLR4 expression, suggesting a potential reducing of innate immune activation, which may contribute to asymptomatic clinical outcomes. Additionally, functional enrichment highlighted active ARG expression in positive cases, indicating potential links between the respiratory microbiome and host immune modulation. These findings provide insights into the host-microbiome interplay underlying COVID-19 severity and highlight the need for further validation in larger, ethnically diverse cohorts with comprehensive clinical metadata.