@article{aa620eb464fe4cc58f8b86d28fee9580,
title = "Viral DNAemia and Immune Suppression in Pediatric Sepsis",
abstract = "Objectives: Demonstrate that DNA viremia is common in pediatric sepsis and quantitate its associations with host immune function and secondary infection risk. Design: Retrospective analysis of a prospective cohort study. Patients: Seventy-three children admitted with sepsis-induced organ failure. Interventions: None. Measurements and Main results: This study was performed as an ancillary investigation to a single-center prospective study of children with severe sepsis. Longitudinally collected, batched, frozen plasma was examined using real time-polymerase chain reaction for the presence of cytomegalovirus, Epstein-Barr virus, herpes simplex virus, human herpes virus-6, torque teno virus, and adenovirus DNA. Innate immune function was also measured longitudinally via quantification of ex vivo lipopolysaccharide -induced tumor necrosis factor-α production capacity. Viral DNAemia with a virus other than torque teno virus was detected in 28 of 73 subjects (38%) and included cytomegalovirus 5%, Epstein-Barr virus 11%, herpes simplex virus 4%, human herpes virus-6 8%, and adenovirus 26%. In addition, torque teno virus was detected in 89%. Epstein-Barr virus DNAemia was associated with preexisting immune suppression (p = 0.007) Viral DNAemia was associated with preexisting immune suppression and high risk for the subsequent development of secondary infection (p < 0.05 for both). Subjects with viral DNAemia had lower innate immune function over time compared with those who were virus negative (p < 0.05). Conclusions: DNAemia from multiple viruses can be detected in septic children and is strongly associated with preexisting immune suppression and secondary infection risk. The role of DNA viruses in the perpetuation of impaired host defense in this setting should be the subject of prospective study.",
keywords = "immunology, immunosuppression, inflammation, pediatrics, sepsis, viruses",
author = "Sam Davila and Halstead, {E. Scott} and Hall, {Mark W.} and Allan Doctor and Russell Telford and Richard Holubkov and Carcillo, {Joseph A.} and Storch, {Gregory A.}",
note = "Funding Information: 1Washington University in St. Louis, St. Louis, MO. 2University of Pittsburgh, Pittsburgh, PA. 3Nationwide Children{\textquoteright}s Hospital, Columbus, OH. 4University of Utah, Salt Lake City, UT. Supported, in part, by the Washington University Institute of Clinical and Translational Science grant UL1TR000448 from the National Center for Advancing Translational Sciences; by R01GM108618 (to Dr. Carcillo) from the National Institute of General Medical Sciences; and by the fol- lowing cooperative agreements from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services: U10HD049983, U10HD050096, U10HD049981, U10HD063108, U10HD063106, U10HD063114, U10HD050012, and U01HD049934. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Davila received support for article research from the National Institutes of Health (NIH). Dr. Doctor received support for article research from the NIH, and his institution received funding from the NIH, Department of Defense, and Children{\textquoteright}s Discovery Institute. Dr. Telford received support for article research from the NIH, and his institution received funding from the NIH. Dr. Holubkov received support for article research from the NIH, and disclosed that he is a Data Safety and Monitoring Board (DSMB) member for Fibrocell and Armaron Bio; his institution received funding from the NIH/National Institute of Child Health and Human Development Funding Information: Medical (past; biostatistical consultant), and Medimmune (DSMB). Dr. (NICHD) and he received funding from Pfizer (DSMB Member), St. Jude Sepsis is associated with mortality rates as high as 25% Carcillo received support for article research from the NIH, and his institu-in pediatric patients (1). For decades, evidence-based tion received funding from NICHD and National Institute of General Medi- treatment of sepsis has been limited to antimicrobi-any potential conflicts of interest.cal Services. The remaining authors have disclosed that they do not have als, supportive care, and source control. Failure of novel For information regarding this article, E-mail: samuel.davila@utsouthwest- therapeutics may reflect a limited understanding of the ern.edu host response to sepsis. Improved understanding of this Publisher Copyright: {\textcopyright} 2017 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.",
year = "2018",
month = jan,
day = "1",
doi = "10.1097/PCC.0000000000001376",
language = "English (US)",
volume = "19",
pages = "e14--e22",
journal = "Pediatric Critical Care Medicine",
issn = "1529-7535",
publisher = "Lippincott Williams and Wilkins",
number = "1",
}