430: VIRAL DNAEMIA IS ASSOCIATED WITH MORTALITY IN PEDIATRIC PATIENTS WITH SEVERE SEPSIS

Introduction: Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the contribution of latent and reactivated viral infection to critical illness in children with sepsis. We report a large multicenter study of viral DNAemia and herpesvirus seropositivity in pediatric patients with severe sepsis. Methods: We enrolled 401 pediatric patients from 9 Pediatric Intensive Care Units (PICUs). Patient samples were tested via qPCR for EBV, CMV, HSV, adenovirus, HHV6, BK and parvovirus B19 DNA. CMV, EBV, HSV and HHV6 IgG were also measured to classify patients as having no infection (IgG-negative without DNAemia), acute infection (IgG-negative with DNAemia), reactivated infection (IgG-positive with DNAemia), or latent infection without reactivation (IgG-positive without DNAemia). Results: 55% of enrolled patients were male, 39% previously healthy, and 27% immunocompromised. 56% had documented infection(s) on enrollment (63% bacterial, 50% viral, and 2% fungal). 10% died in the PICU. Viral DNAemia was detected in 61% of immunocompromised patients and 46% of non-immunocompromised patients. DNAemia with 2 or more viruses on study, detected in 21% of patients, was independently associated with increased mortality in both immunocompromised (OR 5.51 [1.6, 22.6] p=0.023) and non-immunocompromised patients (OR 3.93 [1.4, 11.5] p=0.015). Viral detection was due to reactivated infection in 91% of patients with EBV DNAemia, 63% with CMV, and 100% with HSV and HHV-6, making acute infection rare. Viral seropositivity (HSV 33%, CMV 42%, EBV 61%, HHV6 98%) and latent infection (HSV 30%, CMV 35%, EBV 45%, HHV6 75%) were both common. Adjusted mortality was higher in patients seropositive for EBV (OR 9.1 [2.78, 172.8], p=0.002) compared to those seronegative for EBV. For HHV-6, mortality was higher in patients with viral reactivation compared to latent infection (18% vs. 7%, p=0.024). Mortality in patients with no detected viral infection (IgG-negative without DNAemia) was low (≤ 5% for each virus). Conclusions: Viral DNAemia was common and associated with mortality in pediatric patients with severe sepsis. DNAemia with 2 or more viruses increased mortality, even in previously healthy patients. EBV seropositivity was strongly associated with PICU mortality, independent of concurrent viral DNAemia.