PMID- 38407904 OWN - NLM STAT- MEDLINE DCOM- 20240227 LR - 20240327 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 7 IP - 2 DP - 2024 Feb 5 TI - Viral DNAemia and DNA Virus Seropositivity and Mortality in Pediatric Sepsis. PG - e240383 LID - 10.1001/jamanetworkopen.2024.0383 [doi] LID - e240383 AB - IMPORTANCE: Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis. OBJECTIVE: To assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study. DESIGN, SETTING, AND PARTICIPANTS: This cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG antibodies to CMV, EBV, HSV-1, or HHV-6. A total of 401 patients younger than 18 years with severe sepsis were enrolled from 9 pediatric intensive care units (PICUs) in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Data were collected from 2015 to 2018. Samples were assayed from 2019 to 2022. Data were analyzed from 2022 to 2023. MAIN OUTCOMES AND MEASURES: Death while in the PICU. RESULTS: Among the 401 patients included in the analysis, the median age was 6 (IQR, 1-12) years, and 222 (55.4%) were male. One hundred fifty-four patients (38.4%) were previously healthy, 108 (26.9%) were immunocompromised, and 225 (56.1%) had documented infection(s) at enrollment. Forty-four patients (11.0%) died in the PICU. Viral DNAemia with at least 1 virus (excluding TTV) was detected in 191 patients (47.6%) overall, 63 of 108 patients (58.3%) who were immunocompromised, and 128 of 293 (43.7%) who were not immunocompromised at sepsis onset. After adjustment for age, Pediatric Risk of Mortality score, previously healthy status, and immunocompromised status at sepsis onset, CMV (adjusted odds ratio [AOR], 3.01 [95% CI, 1.36-6.45]; P = .007), HAdV (AOR, 3.50 [95% CI, 1.46-8.09]; P = .006), BKPyV (AOR. 3.02 [95% CI, 1.17-7.34]; P = .02), and HHV-6 (AOR, 2.62 [95% CI, 1.31-5.20]; P = .007) DNAemia were each associated with increased mortality. Two or more viruses were detected in 78 patients (19.5%), with mortality among 12 of 32 (37.5%) who were immunocompromised and 9 of 46 (19.6%) who were not immunocompromised at sepsis onset. Herpesvirus seropositivity was common (HSV-1, 82 of 246 [33.3%]; CMV, 107 of 254 [42.1%]; EBV, 152 of 251 [60.6%]; HHV-6, 253 if 257 [98.4%]). After additional adjustment for receipt of blood products in the PICU, EBV seropositivity was associated with increased mortality (AOR, 6.10 [95% CI, 1.00-118.61]; P = .049). CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that DNAemia for CMV, HAdV, BKPyV, and HHV-6 and EBV seropositivity were independently associated with increased sepsis mortality. 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. FAU - Cabler, Stephanie S AU - Cabler SS AD - Department of Pediatrics, Washington University in St Louis, St Louis, Missouri. FAU - Storch, Gregory A AU - Storch GA AD - Department of Pediatrics, Washington University in St Louis, St Louis, Missouri. FAU - Weinberg, Jason B AU - Weinberg JB AD - Department of Pediatrics, University of Michigan, Ann Arbor. FAU - Walton, Andrew H AU - Walton AH AD - Department of Pediatrics, Washington University in St Louis, St Louis, Missouri. FAU - Brengel-Pesce, Karen AU - Brengel-Pesce K AD - bioMerieux, France. FAU - Aldewereld, Zachary AU - Aldewereld Z AD - Department of Pediatrics and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. FAU - Banks, Russell K AU - Banks RK AD - Department of Pediatrics, University of Utah, Salt Lake City. FAU - Cheynet, Valerie AU - Cheynet V AD - bioMerieux, France. FAU - Reeder, Ron AU - Reeder R AD - Department of Pediatrics, University of Utah, Salt Lake City. FAU - Holubkov, Richard AU - Holubkov R AD - Department of Pediatrics, University of Utah, Salt Lake City. FAU - Berg, Robert A AU - Berg RA AD - Department of Anesthesiology, Pediatrics, University of Pennsylvania, Philadelphia. FAU - Wessel, David AU - Wessel D AD - Department of Pediatrics, George Washington University, Washington, DC. FAU - Pollack, Murray M AU - Pollack MM AD - Department of Pediatrics, George Washington University, Washington, DC. FAU - Meert, Kathleen AU - Meert K AD - Department of Pediatrics, Central Michigan University, Detroit. FAU - Hall, Mark AU - Hall M AD - Department of Pediatrics, The Ohio State University, Columbus. FAU - Newth, Christopher AU - Newth C AD - Department of Anesthesiology, University of Southern California, Los Angeles. FAU - Lin, John C AU - Lin JC AD - Department of Pediatrics, Washington University in St Louis, St Louis, Missouri. FAU - Cornell, Tim AU - Cornell T AD - Department of Pediatrics, University of Michigan, Ann Arbor. FAU - Harrison, Rick E AU - Harrison RE AD - Department of Pediatrics, University of California, Los Angeles. FAU - Dean, J Michael AU - Dean JM AD - Department of Pediatrics, University of Utah, Salt Lake City. FAU - Carcillo, Joseph A AU - Carcillo JA AD - Department of Pediatrics and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20240205 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (DNA, Viral) SB - IM EIN - JAMA Netw Open. 2024 Mar 4;7(3):e249203. PMID: 38536178 MH - Adolescent MH - Humans MH - Male MH - Child MH - Infant MH - Child, Preschool MH - Female MH - DNA, Viral MH - Cohort Studies MH - *Epstein-Barr Virus Infections MH - Herpesvirus 4, Human MH - DNA Viruses MH - *Sepsis MH - *Herpesvirus 1, Human MH - *Cytomegalovirus Infections PMC - PMC10897747 COIS- Conflict of Interest Disclosures: Dr Storch reported receiving salary support from the National Institutes of Health and grant and nonfinancial support from bioMerieux outside the submitted work. Mr Banks reported receiving grant funding from the NIH and the University of Utah during the conduct of the study. Dr Reeder reported receiving grant funding from the NIH during the conduct of the study. Dr Holubkov reported grant funding from the NIH during the conduct of the study and serving on the data safely monitoring board of Pfizer Inc, MedImmune LLC, Armaron Bio, and St Jude Medical and consulting for Physicians Committee for Responsible Medicine and DURECT Corporation outside the submitted work. Dr Berg reported receiving grant funding from the NIH during the conduct of the study and grant funding from the NIH outside the submitted work. Dr Wessel reported receiving grant funding from the NIH during the conduct of the study. Dr Pollack reported receiving grant funding from the NIH during the conduct of the study and research support from Mallinckrodt Pharmaceuticals outside the submitted work. Dr Meert reported receiving grant funding from the NIH during the conduct of the study. Dr Hall reported receiving grant funding from the NIH during the conduct of the study and consulting for La Jolla Pharmaceutical Company, serving on the data safety monitoring board for AbbVie, receiving nonfinancial support from Partner Therapeutics Inc and Sobi for clinical trials, and serving as a subboard member of the American Board of Pediatrics outside the submitted work. Dr Newth reported receiving grant funding from the NIH during the conduct of the study and funding from Philips Research North America outside the submitted work. Dr Cornell reported being cofounder of Pre-Dixon Bio. Dr Harrison reported grant funding from the NIH during the conduct of the study. Dr Dean reported grant funding from the NIH during the conduct of the study. Dr Carcillo reported receiving grant funding from the NIH and the National Institute of General Medical Sciences during the conduct of the study. No other disclosures were reported. EDAT- 2024/02/26 12:42 MHDA- 2024/02/27 06:45 PMCR- 2024/02/26 CRDT- 2024/02/26 11:58 PHST- 2024/02/27 06:45 [medline] PHST- 2024/02/26 12:42 [pubmed] PHST- 2024/02/26 11:58 [entrez] PHST- 2024/02/26 00:00 [pmc-release] AID - 2815462 [pii] AID - zoi240035 [pii] AID - 10.1001/jamanetworkopen.2024.0383 [doi] PST - epublish SO - JAMA Netw Open. 2024 Feb 5;7(2):e240383. doi: 10.1001/jamanetworkopen.2024.0383.