Background Several SARS-CoV-2 patients experience severe lung disease that can progress to multiple organ failure and death due to dysregulated cytokine release, known as a “cytokine storm.” Although cytokine storms were first described in 1993, their underlying mechanisms remain incompletely understood. Methods Lung and blood transcriptomic gene co-expression networks were constructed to identify gene clusters associated with cytokine storm, along with enriched biological functions. A protein–protein interaction network was then built from cytokine storm–related genes to examine potential interplay between lung and blood. KEGG pathway information was integrated to provide deeper insight into coordinated molecular activity across tissues. Results Our analysis suggests a potential interplay between lung and blood through the chemokine signaling pathway, which activates NF-κB signaling and promotes inflammatory responses. This cross-tissue connection highlights the complex molecular landscape of cytokine storms in COVID-19 patients. Conclusion These findings indicate that cytokine storms may involve coordinated inflammatory signaling between lung and blood tissues, particularly mediated through chemokine and NF-κB pathways. Understanding this interplay offers a systems-level perspective that may inform the development of targeted approaches for managing severe SARS-CoV-2 infections.
Buana et al. (2026) studied this question.