Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome

Abstract

PurposeCytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients.MethodsWe prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads were determined in plasma weekly. Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable. Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling.ResultsOf 399 ARDS patients, 271 (68 %) were CMV seropositive and reactivation occurred in 74 (27 %) of them. After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95 % CI 1.51–4.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95 % CI 0.86–2.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95 % CI 0.58–1.18). These associations remained in sensitivity analyses. The population-attributable fraction of ICU mortality was 23 % (95 % CI 6–41) by day 30 (risk difference 4.4, 95 % CI 1.1–7.9).ConclusionCMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-015-4071-z) contains supplementary material, which is available to authorized users.

Epidemiology of Multiple Herpes Viremia in Previously Immunocompetent Patients With Septic Shock

“…Although experimental studies are needed to elucidate the pathophysiology of herpesvirus reactivation and its consequences for the host, large observational studies such as ours remain necessary to identify patients who are both at risk for and vulnerable to the effects of virus reactivation. Sepsis and the acute respiratory distress syndrome are well-known risk factors for herpesvirus reactivation [2][3][4]9]. Although we did not develop a formal prediction model, both an abdominal source of infection and high-dose corticosteroid use also appear to be possible risk factors for viremia based on our data ( Table 1).…”

“…However, viral reactivation is not exclusive to "classic" high-risk groups, such as patients infected with the human immunodeficiency virus (HIV), patients receiving chemotherapy, and transplant recipients and may also occur in previously immunocompetent patients when they suffer from severe and prolonged critical illness. Indeed, systemic reactivations of herpesviruses have frequently been reported in intensive care unit (ICU) patients and in those without known prior immune deficiency [2][3][4].…”

Cytomegalovirus infection in immunocompetent critically ill adults: literature review

“…The study found that BAL shell vial culture had a sensitivity/specificity of 53, 92% in comparison with histologic diagnosis. Ong et al [40] studied immunocompetent patients with ARDS and found a CMV reactivation incidence of 27%, which was associated with significant increase in ICU mortality.…”

Sepsis erodes CD8+ memory T cell-protective immunity against an EBV homolog in a 2B4-dependent manner

“…EBV was the most frequently detectable virus, with 53% of septic patients testing positive for EBV viremia, as compared with only 11.8% of nonseptic critically ill patients and 3.6% of healthy controls . These findings are of clinical relevance because studies also showed that viral reactivation is associated with longer hospital stays and increased mortality …”