Pulmonary HSV load linked to alveolar inflammation, but clinical outcome associations remain inconsistent

A prospective observational study in Critical Care examined pulmonary herpesvirus reactivation in mechanically ventilated adults with acute respiratory failure and a clinical indication for bronchoalveolar lavage (BAL). Conducted from March 2020 to July 2024, it compared BAL and plasma inflammatory biomarkers and BAL immune-cell profiles by viral load, and assessed successful extubation and mortality using complementary statistical models.

Among 299 HSV-seropositive patients, 102 (34%) developed high pulmonary HSV load, defined as ≥10⁴ copies/mL, generally late during ventilation. High load was associated with increased selected alveolar inflammatory mediators, while major BAL immune-cell lineages were largely preserved. In the principal time-dependent analysis, associations with successful extubation (HR 0.80, 95% CI 0.56–1.14) and mortality (HR 1.39, 95% CI 0.96–2.01) were not statistically significant.

However, a day-14 landmark analysis associated high HSV load with reduced successful extubation (HR 0.58, 95% CI 0.34–0.98). A joint model associated each 1-log₁₀ increase in HSV load with higher mortality (HR 1.39, 95% credible interval 1.08–2.30), but not successful extubation. Only 15 of 258 CMV-seropositive patients (6%) developed high CMV load, limiting inference.

These findings support an association between high pulmonary HSV load and localized inflammation, not an established causal effect on clinical outcomes. The single-centre observational design, BAL-selected population and model-dependent outcome associations limit interpretation. Whether HSV-directed treatment improves outcomes requires randomized evaluation.