Can chronic sinonasal inflammation cause systemic herpesvirus reactivation?

Chronic rhinosinusitis, particularly eosinophilic disease with nasal polyps, is a biologically active mucosal inflammatory condition. It can sustain local immune-cell recruitment and cytokine signaling, but this should not be interpreted as evidence that it causes systemic herpesvirus reactivation.

Local immune activation

• Human sinonasal tissue studies support ongoing local immune activation in chronic rhinosinusitis with nasal polyps (CRSwNP). The clearest evidence is for type-2–predominant disease, with increased local IL-4, IL-5, and IL-13, especially in IL-5-positive, eosinophil-dominant, and plasma-cell–dominant polyp subgroups.
• Single-cell analyses identify ALOX15-positive macrophages in eosinophilic CRSwNP. These cells express chemokines associated with recruitment of eosinophils, monocytes, and Th2 cells. In human macrophages, ALOX15 inhibition reduced pro-inflammatory chemokine release, supporting a potentially self-reinforcing local inflammatory circuit.
• These findings are not uniform across all chronic rhinosinusitis: disease without polyps may show type-1, type-3, mixed, or no dominant canonical inflammatory signature.

Herpesvirus reactivation

• Direct human evidence does not show that chronic sinonasal inflammation triggers systemic HSV, VZV, EBV, or CMV reactivation. Available studies generally examine viral DNA or related findings in sinonasal tissue rather than serial quantitative blood PCR demonstrating active systemic replication or viremia.
• Local viral detection is not equivalent to active systemic infection. In one cross-sectional study, EBV DNA was detected in 26.4% of polyp samples versus 10.5% of controls, without a statistically significant difference; HSV-1 and CMV were each found in 1.1%, while HSV-2 and VZV were absent. Low-level EBV tissue detection may reflect latency.

Bottom line

• Chronic sinonasal inflammation can maintain substantial local immune activation, especially in eosinophilic CRSwNP, but current evidence does not establish it as a trigger of systemic herpesvirus reactivation or support antiviral treatment for chronic rhinosinusitis on that basis.