The Landscape of lower respiratory tract herpesviruses in severe pneumonia patients: a multicenter, retrospective study with prospective validation

Abstract

Herpesviruses are widely distributed in the lower respiratory tract, yet no study has comprehensively characterized their clinical features and prognostic impact in severe pneumonia. In this multicenter, retrospective study, we included severe pneumonia patients who underwent bronchoalveolar lavage fluid (BALF) metagenomic testing in intensive care units across 17 medical centers from January 2019 to June 2023. Based on metagenomic results, patients were categorized into herpesvirus-negative, HSV-1, EBV, CMV, HHV-6B, and HHV-7 groups. Propensity score matching and multivariable Cox regression were used to compare mortality between herpesvirus-positive and -negative patients. Interaction analyses were conducted to assess the impact of co-detection of different herpesviruses. Besides, main findings were validated using data from a prospective multicenter cohort. Among 1,737 enrolled patients, the 28-day mortality rate was 41.3% (718/1,737). Herpesviruses were detected in 828 patients. Detection frequencies were: HSV-1 (26.8%), CMV (17.8%), EBV (16.6%), HHV-7 (5.3%), HHV-6B (2.2%), and VZV (0.5%). Clinical characteristics varied across herpesvirus groups. No single herpesvirus was independently associated with increased mortality compared to the negative group. However, co-detection of HSV-1 and CMV was significantly associated with higher 28-day mortality (vs. both negative: adj-HR = 1.439, 95% CI: 1.093–1.894, P = 0.009). This finding was validated in a prospective cohort (adj-HR = 1.656, 95% CI: 1.061–2.585, P = 0.026). Herpesviruses are frequently detected in the lower respiratory tract of patients with severe pneumonia, with distinct clinical features across virus types. Co-detection of HSV-1 and CMV was associated with increased 28-day mortality.