Our study aimed to reassess the rate of pulmonary HSV reactivation in patients with SARS-CoV-2 pneumonia. We explored the impact of HSV replication on SARS-CoV-2 replication, and conversely, along with the sensitivity of HSV strains to antiviral therapies
Patients in intensive care units (ICUs) requiring mechanical ventilation, particularly those with SARS-CoV-2 infection, are highly susceptible to Herpes simplex virus (HSV) reactivation. Given the lack of data on the SARS-CoV-2 Omicron variant, our study aimed to reassess the rate of pulmonary HSV reactivation in patients with SARS-CoV-2 pneumonia. We explored the impact of HSV replication on SARS-CoV-2 replication, and conversely, along with the sensitivity of HSV strains to antiviral therapies. This retrospective study involved 409 ICU patients from three units within the Hospices Civils de Lyon.  Overall, 105 patients (25.7%) experienced HSV reactivation, with a higher rate in COVID-19-positive patients (32.3%) compared to COVID-19-negative patients (22.5%; p.value=0.023). Notably, HSV reactivation was more frequent with the Delta variant (46.3%) than with Omicron (26.4%; p.value=0.026). HSV replication was not significantly influenced by SARS-CoV-2, nor was SARS-CoV-2 by HSV. Furthermore, acyclovir resistance mutations were observed in UL23 gene from 13.6% of HSV-1 strains from the second BAL, collected at least 7 days apart from the first, in patients with a HSV load above 105copies/mL. Antivirogram identified 3 novel polymorphisms in UL30 gene. Treatment in ICU patients on mechanical ventilation with HSV lung reactivation remains to be further explored.