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Enterovirus D68 in Critically Ill Children: A Comparison With Pandemic H1N1 Influenza*

Rao, Suchitra MBBS; Messacar, Kevin MD; Torok, Michelle R. PhD; Rick, Anne-Marie MD, MPH; Holzberg, Jeffrey MD, MSc; Montano, Aaron MD; Bagdure, Dayanand MD, MPH; Curtis, Donna J. MD, MPH; Oberste, M. Steven PhD; Nix, W. Allan BS; de Masellis, Gina MD; Robinson, Christine C. PhD; Dominguez, Samuel R. MD, PhD

doi: 10.1097/PCC.0000000000000922
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Objective: In 2014, the Unites States experienced an outbreak of enterovirus D68 associated with severe respiratory illness. The clinical characteristics associated with severe illness from enterovirus D68 during this outbreak compared with those associated with the 2009 H1N1 influenza virus outbreak are unknown.

Design and Setting: In this retrospective cohort study, we characterized the clinical features of children with enterovirus D68 admitted to the PICU between August 1, 2014, and November 1, 2014, and compared them with critically ill children infected with H1N1 influenza during the pandemic admitted between May 1, 2009, and January 31, 2010.

Patients: PICU patients.

Interventions: None.

Measurements and Main Results: Ninety-seven severely ill children with enterovirus D68 infections were compared with 68 children infected with H1N1 influenza during the 2009 pandemic. Children with enterovirus D68 were more likely to have asthma (62% vs 23%; p < 0.001) and present with reactive airway disease exacerbations, with greater receipt of albuterol (94% vs 49%) and steroids (89% vs 40%; p < 0.0001 for both). Although more children with enterovirus D68 were admitted to the ICU compared with those with H1N1 influenza, they had a shorter hospital length of stay (4 vs 7 d; p < 0.0001), with lower intubation rates (7% vs 44%), vasopressor use (3% vs 32%), acute respiratory distress syndrome (3% vs 24%), shock (0% vs 16%), and death (0% vs 12%; p < 0.05 for all). Compared with children with other enteroviruses and rhinoviruses, children with enterovirus D68 were more likely to have a history of asthma (64% vs 45%) or multiple prior wheezing episodes (54% vs 34%; p < 0.01 for both).

Conclusions: Critically ill children with enterovirus D68 were more likely to present with reactive airway disease exacerbations, whereas children with H1N1 influenza were more likely to present with pneumonia. Compared with the pandemic H1N1 influenza outbreak, the enterovirus D68 outbreak resulted in more children requiring admission to the ICU, but was associated with less severe outcomes.

1Department of Pediatrics (Hospital Medicine and Infectious Diseases), University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, CO.

2Department of Pediatrics (Hospital Medicine), University of Colorado School of Medicine; Adult and Child Center for Health Outcomes Research and Delivery Science, Aurora, CO.

3Department of Pediatrics, University of Colorado School of Medicine, and Children’s Hospital Colorado, Aurora, CO.

4University of Colorado School of Medicine, Aurora, CO.

5Department of Pediatrics (Critical Care), University of Maryland School of Medicine, Baltimore, MD.

6Department of Pediatrics (Infectious Diseases), University of Colorado School of Medicine, and Children’s Hospital Colorado, Aurora, CO.

7Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA.

8Department of Pediatrics (Critical Care), University of Colorado School of Medicine, and Children’s Hospital Colorado, Aurora, CO.

9Department of Microbiology (Virology), Children’s Hospital Colorado, Aurora, CO.

*See also p. 1088.

Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.

Our study demonstrated a high volume of morbidity and reactive airway disease exacerbations among children infected with enterovirus D68, but the spectrum of illness was less severe compared to illness in influenza A H1N1–infected children during the pandemic period.

Supported, in part, by a grant from the National Institutes of Health/National Center for Research Resources (Colorado Clinical and Translational Sciences Institute grant number UL1 TR001082).

Dr. Rao received support for article research from the National Institutes of Health (NIH). Her institution received funding (This work was supported by a grant from the NIH/National Center for Research Resources [Colorado Clinical and Translational Sciences Institute grant number UL1 TR001082]). Dr. Holzberg’s institution received grant. Dr. Curtis disclosed other support (salary support as part of an investigator-initiated study of QLAIV vaccine in HIV-infected children and youth. Sponsor was MedImmune and support ended November 2014. She also receives support in the form of free vaccine from Sanofi-Pasteur for a study of Fluzone High Dose in immunocompromised children. She never received any support for work related to the study in this manuscript). Dr. Oberste disclosed government work. His institution received grant support from the Bill and Melinda Gates Foundation and Zeptometrix. Dr. Nix disclosed government work. Dr. Robinson disclosed off-label product use (Some cases included in this study were confirmed by testing lower respiratory tract specimens by the Film Array Respiratory Pathogen PCR [Biofire]. This test is FDA-cleared only for testing of nasopharygeal swabs; however the accuracy of results using lower respiratory tract specimens was verified by their laboratory, using the criteria of the College of American Pathologists). Dr. Dominguez received support for article research from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: suchitra.rao@childrenscolorado.org

©2016The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies