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- Title
Viral DNAemia and DNA Virus Seropositivity and Mortality in Pediatric Sepsis.
- Authors
Cabler, Stephanie S.; Storch, Gregory A.; Weinberg, Jason B.; Walton, Andrew H.; Brengel-Pesce, Karen; Aldewereld, Zachary; Banks, Russell K.; Cheynet, Valerie; Reeder, Ron; Holubkov, Richard; Berg, Robert A.; Wessel, David; Pollack, Murray M.; Meert, Kathleen; Hall, Mark; Newth, Christopher; Lin, John C.; Cornell, Tim; Harrison, Rick E.; Dean, J. Michael
- Abstract
Key Points: Question: Are viral DNAemia and DNA virus seropositivity associated with increased mortality in pediatric sepsis? Findings: In this multicenter cohort study of 401 children with severe sepsis, viral DNAemia was common, with at least 1 virus detected in 191 patients (48%). Cytomegalovirus, adenovirus, BK polyomavirus, and human herpesvirus 6 DNAemia and Epstein-Barr virus seropositivity were associated with increased mortality. Meaning: Further study is warranted to determine whether cytomegalovirus, adenovirus, BK polyomavirus, and human herpesvirus 6 DNAemia and Epstein-Barr virus seropositivity only reflect mortality risk or contribute to mortality in children with sepsis. This cohort study assesses the association of mortality with DNA seropositivity and DNAemia among children and adolescents with severe sepsis in the United States. 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.
- Subjects
RESEARCH; CYTOMEGALOVIRUSES; PARVOVIRUS diseases; REVERSE transcriptase polymerase chain reaction; INTENSIVE care units; STATISTICS; DNA; IMMUNOGLOBULINS; CONFIDENCE intervals; VIRAL load; QUANTITATIVE research; PEDIATRICS; SEPSIS; VIREMIA; EPSTEIN-Barr virus; DESCRIPTIVE statistics; HERPESVIRUSES; ODDS ratio; DATA analysis software; LOGISTIC regression analysis; LONGITUDINAL method; CHILDREN
- Publication
JAMA Network Open, 2024, Vol 7, Issue 2, pe240383
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2024.0383