Cytokine storm divergence in viral infections of the upper respiratory tract.

Cytokine storm (CS) is a pathological state of dysregulated, hyperactive host immunity that arises in the context of infection, malignancy, or immunotherapy. CS is characterized by the sustained, markedly elevated release of multiple pro-inflammatory mediators, ultimately leading to tissue damage and multi-organ dysfunction. Upper respiratory viral infections, including SARS, MERS, SARS-CoV-2, influenza, adenovirus, and respiratory syncytial virus (RSV), are among the most prominent CS triggers. Inflammatory storms triggered by different pathogens exhibit distinct variations in their cytokine profiles and downstream immune signaling pathways. Underlying comorbidities-such as diabetes, obesity, and cardiovascular disease-together with complications such as coagulopathies and secondary infections, can profoundly alter both the threshold and the magnitude of the cytokine storm. This review systematically compares cytokine profiles elicited by distinct upper respiratory pathogens, with population stratification by age and underlying comorbidities, to clarify how these patterns relate to disease severity and complication risk. Collectively, the available evidence supports a shared inflammatory backbone across respiratory virus-induced cytokine storms, overlaid by pathogen-specific cytokine fingerprints and host-dependent plasticity that shapes clinical trajectories and outcomes.