Publication

Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza

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  • 06/25/2025
Type of Material
Authors
    Tanya Novak, Boston Children's HospitalJeremy Chase Crawford, Boston Children's HospitalGeorg Hahn, Brigham and Women's HospitalMark W Hall, Nationwide Children’s Hospital, ColumbusSimone A Thair, Boston Children's HospitalMargaret M Newhams, Boston Children's HospitalJanet Chou, Harvard Medical SchoolPeter M Mourani, University of ArkansasKeiko M Tarquinio, Emory UniversityBarry Markovitz, Children's Hospital Los AngelesLaura L Loftis, Baylor College of MedicineScott L Weiss, Nemours Children’s Hospital DelawareRenee Higgerson, St. David’s Children’s Hospital, AustinAdam J Schwarz, Children’s Hospital of Orange CountyNeethi P Pinto, The Children's Hospital of PhiladelphiaNeal J Thomas, Penn State UniversityRainer G Gedeit, Children's Hospital of WisconsinRonald C Sanders, Jr, University of ArkansasSidharth Mahapatra, University of NebraskaBria M Coates, Northwestern University FeinbergNatalie Z Cvijanovich, UCSF Benioff Children’s Hospital, OaklandKate G Ackerman, University of RochesterDavid W Tellez, Phoenix Children’s HospitalPatrick McQuillen, University of California, San FranciscoStephen C Kurachek, Children’s Minnesota, MinneapolisSteven L Shein, University Hospitals Rainbow Babies and Children’s HospitalChristoph Lange, Harvard UniversityPaul G Thomas, St Jude Children’s Research Hospital, MemphisAdrienne G Randolph, Boston Children's Hospital
Language
  • English
Date
  • 2023-01-01
Publisher
  • Frontiers Media
Publication Version
Copyright Statement
  • © 2023 Novak, Crawford, Hahn, Hall, Thair, Newhams, Chou, Mourani, Tarquinio, Markovitz, Loftis, Weiss, Higgerson, Schwarz, Pinto, Thomas, Gedeit, Sanders, Mahapatra, Coates, Cvijanovich, Ackerman, Tellez, McQuillen, Kurachek, Shein, Lange, Thomas and Randolph
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 14
Start Page
  • 1220028
End Page
  • 1220028
Grant/Funding Information
  • NIH AI084011 and R21HD095228 (AGR), AI154470 (AGR, PGT), The Anesthesia Trailblazer Award from The Department of Anesthesiology, Critical Care, and Pain Medicine, Boston Children’s Hospital (TN), and The American Lebanese Syrian Associated Charities (JCC, PGT). This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contracts No. 75N93021C00018 (University of Georgia) and 75N93021C00016 (St. Jude) for the NIAID Centers of Excellence for Influenza Research and Response (CEIRR).
Supplemental Material (URL)
Abstract
  • Background: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection. Methods: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05). Results: Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week. Conclusion: Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.
Author Notes
Keywords
Research Categories
  • Biology, Biostatistics
  • Engineering, Biomedical
  • Health Sciences, Immunology
  • Health Sciences, Public Health

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