Herpes simplex virus type 2 encephalitis in critically ill adults: A retrospective analysis of EURECA and Herpetics cohort studies

Background: Herpes simplex virus type 1 (HSV-1) is the leading cause of sporadic infectious encephalitis. Although typically associated with benign meningitis, HSV-2 can also cause encephalitis in adults, a condition that remains poorly characterized in intensive care unit (ICU). We aimed to compare the characteristics, management, and outcomes of critically ill adult with HSV-2 and HSV-1 encephalitis. Methods: We performed a retrospective analysis of adults with herpes simplex encephalitis (HSE) admitted to the ICU in two large multicenter cohorts. Patients were classified according to cerebrospinal fluid (CSF) HSV genotype. The primary endpoint was unfavourable outcome at 3 months, defined as a modified Rankin Scale score 3–6. Results: Among 285 HSE patients, 17 (6%) had HSV-2 encephalitis (age 60 [53–67] years, female sex 58.8%). Although the proportion of immunocompromised status did not differ significantly between groups (29.4% vs 15.4%, p = 0.13), HSV-2 cases had a significantly higher prevalence of HIV infection (17.6 vs 1.5%, p < 0.01), less frequent brain MRI abnormalities (85.7% vs 97.7%, p = 0.01) and similar CSF findings compared to HSV-1 cases. The duration of intravenous acyclovir treatment was shorter for HSV-2 cases (18 [4–21] days) versus 21[20–21] days, p = 0.04). Unfavourable outcome occurred in 9/16 (56.3%) patients with HSV-2 encephalitis and in 175/236 (74.2%) patients with HSV-1 encephalitis (p = 0.25). Conclusion: Encephalitis caused by HSV-2 represent a consistent proportion of severe HSE. Clinical presentation and outcomes and broadly comparable to those of HSV-1 cases, underscoring the importance of early recognition and standardized management of encephalitis caused by HSV, regardless of genotype.