Decoding emerging viral sepsis: Molecular crosstalk, dysregulation, and precision strategies

Emerging and re-emerging viral pathogens pose a major challenge to global public health systems. One of the most significant complications associated with these viruses is viral sepsis, a severe condition characterized by organ dysfunction resulting from an unregulated host response to a viral infection. The present review comprehensively describes the molecular mechanisms underlying viral sepsis induced by emerging and re-emerging viral pathogens, such as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), influenza virus, dengue virus (DENV), Ebola virus (EBOV), and human immunodeficiency virus (HIV). It discusses the complex molecular interactions between particular viral factors and host cellular pathways, highlighting significant dysregulations in various immune responses, metabolic reprogramming, and endothelial integrity that induce sepsis development. Furthermore, this review thoroughly addresses nascent precision strategies, including advanced diagnostics, targeted therapeutics, and immunomodulatory interventions, carefully tailored to distinct viral etiologies and host endotypes. By shedding light on the intricate molecular landscape of viral sepsis, this review aims to provide a robust framework for future mechanistic research and accelerate the development of effective, personalized interventions to combat this challenging complication.