Herpes simplex virus and Cytomegalovirus reactivation among severe ARDS patients under veno-venous ECMO

Abstract

Background: Herpesviridae reactivation among non-immunocompromised critically ill patients is associated with impaired prognosis, especially during acute respiratory distress syndrome (ARDS). However, little is known about herpes simplex virus (HSV) and Cytomegalovirus (CMV) reactivation occurring in patients with severe ARDS under veno-venous extracorporeal membrane oxygenation (ECMO). We tried to determine the frequency of Herpesviridae reactivation and its impact on patients' prognosis during ECMO for severe ARDS.Results: During a 5-year period, 123 non-immunocompromised patients with a severe ARDS requiring a venovenous ECMO were included. Sixty-seven patients (54%) experienced HSV and/or CMV reactivation during ECMO course (20 viral co-infection, 40 HSV alone, and 7 CMV alone). HSV reactivation occurred earlier than CMV after the beginning of MV [(6-15) vs. 19 (13-29) days; p < 0.01] and after ECMO implementation [(2-8) vs. 14 (10-20) days; p < 0.01]. In univariate analysis, HSV/CMV reactivation was associated with a longer duration of mechanical ventilation [(22-52.5) vs. 17.5 (9-28) days; p < 0.01], a longer duration of .5) vs. 9 (5-14) days; p < 0.01], and a prolonged .5) vs. 16 (9-30) days; p < 0.01] and hospital stay [44 (29-63.5) vs. 24 (11-43) days; p < 0.01] as compared to non-reactivated patients. However, in multivariate analysis, viral reactivation remained associated with prolonged MV only. When considered separately, both HSV and CMV reactivation were associated with a longer duration of MV as compared to non-reactivation patients [29 (19.5-41) and 28 (20.5-37), respectively, vs. 17.5 (9-28) days; p < 0.05]. Co-reactivation patients had a longer duration of .3); p < 0.05] and ICU stay [51.5 (32.5-69) vs. 27.5 (17.75-35.5) and 29 (20-30.5), respectively] as compared to patients with HSV or CMV reactivation alone. In multivariate analysis, HSV reactivation remained independently associated with a longer duration of MV and hospital length of stay. Conclusions:Herpesviridae reactivation is frequent among patients with severe ARDS under veno-venous ECMO and is associated with a longer duration of mechanical ventilation. The direct causative link between HSV and CMV reactivation and respiratory function worsening under ECMO remains to be confirmed.

Herpesviridae reactivation for poor outcome in ARDS patients with ECMO: criminal or witness?

“…We read with interest of the report by Hraiech and colleagues [1] about the Herpesviridae reactivation among non-immunocompromised critically ill patients with acute respiratory distress syndrome (ARDS) supported with extracorporeal membrane oxygenation (ECMO). They found that Herpesviridae reactivation is frequent among patients with severe ARDS under ECMO and is associated with a longer duration of mechanical ventilation.…”

“…On the one hand, Herpesviridae reactivation may indicate an active infection and related damage to the organ function, which lead to a poor prognosis. However, in Hraiech's study [1], the definition of reactivation by a positive airway sample could not interpreted as true infection. And they reported that alveolar procollagen III level, an indicator of pulmonary fibrosis, was not different between both groups.…”

“…Thus, when looking for the association of reactivation and the outcome, we suggested that only patients with a seropositivity for Herpesviridae should be included. Furthermore, Hraiech and colleagues [1] found that HSV reactivation occurred earlier than CMV reactivation. In our study, airway sample may show an earlier and higher positivity than serum samples for EBV [3].…”

“…From our point of view, a few other concerns related to who, how and why for the Herpesviridae reactivation affects outcome in ARDS could be raised.First, who has a Herpesviridae reactivation should be focused? In Hraiech's study [1], they determined the frequency of Herpesviridae reactivation and its impact on prognosis only in patients during ECMO for severe ARDS. However, Herpesviridae reactivation occurring in all ARDS patients should be investigated.…”

“…Within all ARDS patients, by comparing the reactivation related to ARDS with no-ECMO support, and the reactivation after ECMO insertion, whether a Herpesviridae reactivation was worsening under ECMO could be confirmed.The second question is how a Herpesviridae reactivation or active infection should be defined in ARDS patients? In Hraiech's report [1], Herpes Simplex Virus (HSV) reactivation was diagnosed mainly by throat or BAL samples, and only 3 patients (5%) exhibited a positive HSV viremia, and cytomegalovirus (CMV) reactivation was diagnosed mainly from blood PCR. However, whether a positive PCR from the airway sample should be treated as a reactivation or as an evidence of infection is still debatable [2].…”