hMPV co-infections: Distinct immunopathogenic mechanisms and clinical implications of viral and bacterial pathogenesis.

Human metapneumovirus (hMPV) co-infections with viral and bacterial pathogens are increasingly recognized as major contributors to severe respiratory disease, especially in children, older adults, and immunocompromised individuals. This review summarizes current knowledge of hMPV co-infections with respiratory viruses (e.g., hRSV, influenza, SARS-CoV-2) and bacteria (e.g., Streptococcus pneumoniae, Haemophilus influenzae), highlighting both shared and distinct pathogenic pathways. Viral co-infections often intensify inflammation through prolonged replication and type I interferon (IFN) suppression, whereas bacterial co-infections exploit epithelial injury and mucin overproduction to enhance adhesion, biofilm formation, and antimicrobial resistance. Converging mechanisms include epithelial disruption and IL-6/TNF-α-driven cytokine dysregulation, both of which contribute to worsened outcomes. A structured literature search of PubMed, Scopus, and Web of Science identified studies on hMPV co-infections, immune responses, and clinical outcomes. The novelty of this review lies in its comparative perspective, distinguishing viral from bacterial interactions to clarify overlapping versus pathogen-specific mechanisms. Clinically, this distinction informs diagnostics, highlights gaps in therapeutic strategies, and emphasizes the need for targeted interventions to reduce the burden of severe hMPV-associated respiratory disease.