Herpes simplex virus reactivation in patients with COVID-19 and acute respiratory distress syndrome: a prospective cohort study

Background There is a paucity of data about the occurrence and risk factors of herpes simplex virus (HSV) reactivation among patients with severe COVID-19 presenting with acute respiratory distress syndrome (ARDS). Methods We performed a nested case-control study among a cohort of SARS-CoV-2 infected patients with ARDS. Between March and April 2020, all consecutive mechanically ventilated patients ≥18 years old with a positive PCR for SARS-CoV-2 on mucocutaneous samples were included in the study. We collected data on demographics, medical history, laboratory variables, administration of antivirals and other agents, respiratory and organ support procedures, microbiological results, and management of ARDS with prone positioning and the use of steroids. Univariate and multivariable Cox regression models were performed in order to identify predictors of HSV reactivation. Results Eighty-three patients with laboratory-confirmed SARS-CoV-2 infection were admitted to the ICU for mechanical ventilation. 18/83 (21.7%) patients developed mucocutaneous herpes simplex virus reactivation after a median of 17 days (IQR, 14–20). Prone positioning was the only independent risk factor for HSV reactivation (adj. hazard ratios, 1.60; 95% CI, 1.11–2.30; P = 0.009). All patients with mucocutaneous HSV reactivation were treated with antivirals. The outcome in terms of ventilator-associated pneumonia, catheter-related bloodstream infections, and in-hospital mortality was similar for patients with and without HSV reactivation. Conclusions HSV reactivation is frequent in COVID-19 patients with ARDS, especially if prolonged invasive mechanical ventilation with prone positioning is needed. Prompt testing for HSV and initiation of antiviral therapy should be performed in case of mucocutaneous lesions in this population.