Herpesvirus reactivation during severe COVID-19 and high rate of immune defect

Abstract

Objective : We assessed herpesvirus reactivation in severe SARS-CoV-2 infection. Methods : Retrospective study including consecutive patients admitted to an onco-hematology intensive care unit (ICU) for severe COVID-19. Replication of EBV, CMV, and HSV was evaluated. Competing risk analyses were used to assess the cumulative risk of viral reactivation, and time-dependent Cox and Fine and Gray models to assess risk factors for viral reactivation. Results : Among 100 patients, 38 were immunocompromised. Sixty-three patients presented viral reactivation (12% for HSV, 58% EBV and 19% CMV). Symptomatic patients received treatment. Overall cumulative incidence of viral reactivation was 56.1% [55.9-56.4] at 10 days. After adjustment, a preexisting hematological malignancy (sHR [95%CI]=0.31 [0.11-0.85]) and solid organ transplantation (sHR [95% CI]=2.09 [1.13-3.87]) remained independently associated with viral reactivation. Viral reactivation ( P =0.34) was not associated with mortality. Conclusions : Incidence of herpesvirus reactivation in patients admitted to the ICU for severe COVID-19 was high, but rarely required antiviral treatment.

Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality

“…As in our cohort, the previous small studies reported a CMV reactivation in about a quarter of COVID-19 critical patients, with about 50–60% of these patients showing at least one Herpesviridae reactivation [ 6 , 8 , 29 ]. In COVID-19 patients with a high rate of pre-existing immune defect, Epstein–Barr virus (EBV) was the Herpesviridae with the most frequent reactivation [ 29 ]. Unfortunately, our protocol did not include surveillance of EBV reactivation and then, only a few patients were screened for it.…”

Kaposi’s Sarcoma-Associated Herpesvirus, but Not Epstein-Barr Virus, Co-infection Associates With Coronavirus Disease 2019 Severity and Outcome in South African Patients

“…This has been demonstrated for EBV, suggesting that reactivation of underlying EBV infection may contribute to COVID-19 symptoms, severity and time to recovery (Chen T. et al, 2021;Gold et al, 2021;Paolucci et al, 2021;Saade et al, 2021). In addition, secondary reactivation of herpes simplex virus (HSV) and Cytomegalovirus (CMV) has been reported in patients admitted to ICU with severe COVID-19 (Saade et al, 2021). Furthermore, SARS-CoV-2 encoded proteins have been shown to induce KSHV lytic reactivation in vitro .…”

“…Mounting evidence points to potential interplay between SARS-CoV-2 infection and reactivation of opportunistic herpesvirus infections. This has been demonstrated for EBV, suggesting that reactivation of underlying EBV infection may contribute to COVID-19 symptoms, severity and time to recovery (Chen T. et al, 2021;Gold et al, 2021;Paolucci et al, 2021;Saade et al, 2021). In addition, secondary reactivation of herpes simplex virus (HSV) and Cytomegalovirus (CMV) has been reported in patients admitted to ICU with severe COVID-19 (Saade et al, 2021).…”

Reactivation of Herpes Simplex Virus Type 1 (HSV-1) Detected on Bronchoalveolar Lavage Fluid (BALF) Samples in Critically Ill COVID-19 Patients Undergoing Invasive Mechanical Ventilation: Preliminary Results from Two Italian Centers

“…Critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia requiring invasive mechanical ventilation are at risk of developing bacterial, fungal, and viral superinfections [1][2][3][4]. Reactivation of herpes simplex virus type 1 (HSV-1) has been described in intubated critically ill patients with coronavirus disease 2019 (COVID- 19) pneumonia [2,3,[5][6][7][8].…”

“…Both predictors and prognostic implications of HSV-1 reactivation in this peculiar population remain largely elusive, making its management highly heterogenous in terms of prophylactic and therapeutic approaches [2,3,5]. In the present two-center retrospective experience, we aimed to assess the cumulative risk of HSV-1 reactivation detected on bronchoalveolar fluid (BALF) samples in invasively ventilated COVID-19 patients with worsening respiratory function, as well as to exploratorily assess the predictors of HSV-1 reactivation and its possible prognostic impact.…”