Quantitative analysis of HSV‑1 shedding as a predictor of cerebral vasospasm severity in patients with subarachnoid hemorrhage

Cerebral vasospasm (CV) is a critical determinant of outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Despite advances in neurocritical care, modifiable risk factors for CV remain poorly understood, and identifying them could significantly enhance patient management and treatment strategies. The present study explored the potential link between the reactivation of herpes simplex virus type 1 (HSV-1), a common resident virus in cranial nerves, and CV severity. It was hypothesized that higher HSV-1 viral load in saliva may be associated with increased CV severity. Saliva samples were collected on days 4, 7, 10 and 14 post-aSAH, and HSV-1 DNA levels were measured using quantitative PCR. CV severity was assessed using the Lindegaard ratio (LR), with an LR >3 considered the diagnostic threshold for CV. A total of 36 patients were enrolled, and 139 saliva samples were collected. HSV-1 DNA was detected in 19.4% of samples (27/139), and 44% of patients (16/36) developed CV. HSV-1 seropositive patients made up 88.9% (32/36) of the cohort, with 50% exhibiting viral shedding during the study period. None of the HSV-1 seronegative patients (11.1%, 4/36) exhibited viral shedding or developed CV. Regression analysis showed a positive association between HSV-1 viral load and CV severity, with viral load explaining 27.8% of the variability (P=0.005). Age was also significant, with older patients experiencing less severe CV (P<0.001). Supervised machine learning identified viral load thresholds that aligned with standard LR values for moderate and severe CV. While the small sample size and observational design limit the generalizability of the results, these findings suggested that earlier detection and intervention for CV could be informed by assessing HSV-1 serostatus and monitoring viral activity through saliva samples or other non-invasive methods, highlighting the need for larger, controlled studies to validate these results.