Epstein–Barr virus, Cytomegalovirus, and Herpes Simplex-1/2 reactivations in critically ill patients with COVID-19

Objectives To assess the incidences of Herpes Simplex-1 and 2 (HSV-1, HSV-2), Cytomegalovirus (CMV), Epstein-Barr Virus (EBV) reactivations in critically ill COVID-19 patients. To determine the association between viral reactivation and in-hospital mortality, Intensive Care Unit Bloodstream infection (ICU-BSI), ventilator-associated pneumonia (VAP).Design Observational retrospective cohort study.Setting COVID-19 Intensive Care Unit.Patients From November 2020 to May 2021, one hundred and twenty patients with COVID-19 severe pneumonia were enrolled and tested for HSV-1, HSV-2, CMV and EBV at the admission in ICU and weekly until discharge or death. The presence of VAP and ICU-BSI was evaluated according to clinical judgement and specific diagnostic criteria.Measurements and main results One hundred and twenty patients were enrolled. Multiple reactivations occurred in 75/120 (63%) patients, single reactivation in 27/120 patients (23%). The most reactivated Herpesvirus was EBV, found in 78/120 (65%) patients. The multivariate analysis demonstrated that viral reactivation is a strong independent risk factor for in-hospital mortality (OR = 2.46, 95% CI 1.02-5.89), ICU-BSI (OR = 2.37, 95% CI 1.06-5.29) and VAP (OR = 2.64, 95% CI 1.20-5.82).Conclusions Human Herpesviruses reactivations in critically ill patients with COVID-19 severe Pneumonia are associated with mortality and with a higher risk to develop both VAP and ICU-BSI.Question: The impact of Human Herpesviruses reactivations on the morbidity and mortality of COVID-19 critically ill patients is controversial.Findings: Critically ill patients with COVID-19 are at high risk for both EBV, HSV and CMV reactivations.Meanings: Further large prospective studies will be necessary to clarify if the presence of active viral replication must be considered causal agent affecting mortality or the indirect manifestation of immune paralysis in the worst patients.