medwireNews: Detection of viral DNA from cytomegalovirus (CMV), human adenovirus (HAdV), BK polyomavirus (BKPyV), or human herpesvirus (HHV)-6 in the blood of pediatric intensive care unit (PICU) patients with sepsis is associated with increased risk for death, study findings indicate.
“Further investigation of the underlying biology of these viral DNA infections in children with sepsis is warranted to determine whether they only reflect mortality risk or contribute to mortality,” write Joseph Carcillo (University of Pittsburgh, Philadelphia, USA) and co-authors in JAMA Network Open.
The retrospective cohort study included data for 401 patients younger than 18 years (mean age 6 years, 55% male) treated for severe sepsis at nine PICUs. Of these, 38.4% were previously healthy, 26.9% were immunocompromised, and 56.1% had documented infection at enrollment.
The researchers used quantitative real-time polymerase chain reaction (qPCR) to test frozen plasma samples for the presence of CMV, Epstein-Barr virus (EBV), herpes simplex virus (HSV)-1, HHV-6, parvovirus B19 (B19V), BKPyV, HAdV, and torque teno virus (TTV) DNAemia.
Carcillo et al report that 94.1% of patients had TTV DNAemia. Just under half (47.6%) of patients had DNA from at least one other virus in their blood, most frequently HHV-6 (23.8 of 391 patients), EBV (13.8% of 385), CMV (13.3% of 391), HadV (10.5% of 381), BKPyV (8.3% of 385), B19V (7.3% of 385), and HSV-1 (2.9% of 385). The proportion with viral DNAemia excluding TTV was higher among those who were immunocompromised relative to those who were not (58.3 vs 43.7%).
In all, 44 (11.0%) patients died in the PICU. The investigators found that, after adjustment for age, Pediatric Risk of Mortality score, and health status at sepsis onset, the risk for death was significantly higher among patients with CMV DNA (adjusted odds ratio [aOR]=3.01), HAdV DNA (aOR=3.50), BKPyV DNA (aOR=3.02), or HHV-6 DNA (aOR=2.62) in their blood relative to participants with no evidence of these viruses.
The researchers also tested samples from 264 patients for plasma IgG antibodies to HSV-1, CMV, EBV, and HHV-6. They found that seropositivity was common, at rates of 33.3%, 42.1%, 60.6%, and 98.4%.
However, in this case, only EBV IgG seropositivity was associated with an increased risk for death after adjustment for the previous confounders plus receipt of blood products in the PICU (aOR=6.10). Indeed, just 2.0% of patients who were seronegative for EBV died compared with 15.1% of those who were seropositive for EBV.
“Possible explanations may be that EBV seropositivity is a biomarker for more severe illness that may not have been fully accounted for by the multivariate analysis or, alternatively, that being latently infected by EBV renders an individual more vulnerable to mortality from sepsis,” the investigators remark.
When Carcillo and team combined the qPCR and serologic testing results they found that the presence of viral DNAemia was due to viral reactivation rather than primary infection in 90.7% of 43 patients with EBV, 63.3% of 30 patients with CMV, 100% of eight patients with HSV-1, and 61 patients with HHV-6.
The authors conclude that “viral DNAemia was common in pediatric patients admitted to the PICU with severe sepsis, including those who were and were not immunocompromised at the time of sepsis onset.”
They add that although the “study does not address any causal nature of these associations, [it does] identify a group of children at risk for sepsis mortality.”
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