• Christina M Osborne, Charles Langelier, Jack Kamm, Kayla Williamson, Lilliam Ambroggio, Ron W Reeder, Christopher Locandro, Kirk HarrisJJDepartment of Pediatrics, Section of Pulmonary Medicine, University of Colorado School of Medicine, Aurora, CO., Brandie D Wagner, Aline B Maddux, Saharai Caldera, Amy Lyden, Victoria Soesanto, SimõesEric A FEAFDepartment of Pediatrics, Section of Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO., Matthew K Leroue, Todd C Carpenter, Mark W Hall, Athena F Zuppa, Joseph A Carcillo, Kathleen L Meert, Murray M Pollack, Patrick S McQuillen, Daniel A Notterman, Joseph DeRisi, Peter M Mourani, and National Institute for Child Health and Human Development Collaborative Pediatric Critical Care Research Network.
• Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO.
• Pediatr Crit Care Me. 2024 Jan 1; 25 (1): e1e11e1-e11.

ObjectivesViral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs).DesignThis is an analysis of of a seven-center prospective cohort study.SettingSeven PICUs within academic children's hospitals in the United States.PatientsCritically ill children (from 1 mo to 18 yr) who required mechanical ventilation via endotracheal tube for greater than or equal to 72 hours.InterventionsWe evaluated agreement in viral detection between paired upper and LRT samples. Results of clinical nasopharyngeal RT-PCR were compared with TA RNA-Seq. Positive and negative predictive agreement and Cohen's Kappa were used to assess agreement.Measurements And Main ResultsOf 295 subjects with paired testing available, 200 (68%) and 210 (71%) had positive viral testing by RT-PCR from nasopharyngeal and RNA-Seq from TA samples, respectively; 184 (62%) were positive by both nasopharyngeal RT-PCR and TA RNA-Seq for a virus, and 69 (23%) were negative by both methods. Nasopharyngeal RT-PCR detected the most abundant virus identified by RNA-Seq in 92.4% of subjects. Among the most frequent viruses detected, respiratory syncytial virus demonstrated the highest degree of concordance (κ = 0.89; 95% CI, 0.83-0.94), whereas rhinovirus/enterovirus demonstrated lower concordance (κ = 0.55; 95% CI, 0.44-0.66). Nasopharyngeal PCR was more likely to detect multiple viruses than TA RNA-Seq (54 [18.3%] vs 24 [8.1%], p ≤ 0.001).ConclusionsViral nucleic acid detection in the upper versus LRT reveals good overall agreement, but concordance depends on the virus. Further studies are indicated to determine the utility of LRT sampling or the use of RNA-Seq to determine LRTI etiology.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

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