Risk factors for Herpes simplex virus and Cytomegalovirus infections in critically-ill COVID-19 patients

Abstract

Background: To assess the prevalence of Herpes simplex and Cytomegalovirus infection in respiratory samples of critically-ill COVID-19 patients, its role in outcome and mortality and the influence of dexamethasone treatment in the early stage of SARS-CoV-2 infection. Methods: All mechanically ventilated COVID-19 patients treated on ICU between March 2020 and January 2021 were included. Respiratory specimens were tested for Herpes simplex virus (HSV) type 1, 2 and Cytomegalovirus (CMV) by quantitative real-time PCR. Clinical parameters were compared in the cohort cohorts with and without HSV-1-infection.Results: 134 patients with a median age of 72.5 years (73.0% male, n=98) were included. HSV-1 reactivation occurred in 61 patients (45.5%), after median 9 (7-13) days of mechanical ventilation. The main factor for reactivation was length of stay on ICU (24 days vs 13 days, p<0.001) and duration of mechanical ventilation (417 vs 214 hours, p<0.001). Treatment with dexamethasone and a history of immunosuppression did not associate with HSV-infection in the univariate analysis (39 vs 41, p=0.462 and 27.9% vs 23.3%, p=0.561, respectively). Both ICU and hospital mortality were not significantly different in the cohorts with and without HSV-infection (57.4% vs 45.2%, p=0.219).Conclusions: Our study shows a high prevalence of HSV-infection in critically-ill COVID-19 patients which was unexpectedly higher than the prevalence of CMV-infections and unrelated to dexamethasone treatment. The main risk factors for HSV and CMV in the studied cohorts were the length of ICU stay and duration of mechanical ventilation. Therefore, we recommend routine monitoring of critically ill COVID-19 patients for these viral co-infections and consider treatment in those patients.

CMV seropositivity is a potential novel risk factor for severe COVID-19 in non-geriatric patients

“…HSV reactivation has been more often described in critically-ill COVID-19 patients, despite its impact on hospital mortality is still controversial [ 22 , 23 , 42 ]. Moreover, HSV reactivation was associated to the length of stay on ICU and mechanical ventilation [ 42 ].…”

“…HSV reactivation has been more often described in critically-ill COVID-19 patients, despite its impact on hospital mortality is still controversial [ 22 , 23 , 42 ]. Moreover, HSV reactivation was associated to the length of stay on ICU and mechanical ventilation [ 42 ]. However, HSV reactivation seems to broadly occur in immunocompetent patients with acute respiratory distress syndrome in relation to ICU admission [ 43 ].…”

Herpes Simplex Virus 1 (HSV-1) Reactivation in Critically Ill COVID-19 Patients: A Brief Narrative Review

“…Among 134 mechanically ventilated patients with COVID-19, respiratory samples for HSV-1 PCR testing (endotracheal aspirate and BALF samples) were routinely collected twice weekly [ 58 ]. HSV-1 reactivation on respiratory samples (defined as at least 10 3 copies/ml) was detected in 46% of patients (61/134) patients.…”

“…In an adjusted logistic regression model, no association was observed between treatment with steroids and HSV-1 reactivation (OR 1.55, with 95% CI from 0.62 to 3.94, p = 0.348). Crude ICU mortality was 57% and 45% in patients with and without HSV-1 reactivation, respectively ( p = 0.219) [ 58 ].…”

“…Regarding antiviral treatment, the proportion of critically ill patients with HSV-1 reactivation detected by PCR who received antiviral treatment with acyclovir ranged from 70 to 92% across the different studies [ 15 , 16 , 58 ]. In the study by Franceschini et al, patients with COVID-19 pneumonia admitted to the ICU or receiving non-invasive ventilation received acyclovir prophylaxis [ 14 ].…”