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

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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.

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