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Observational Study
. 2025 May 1;8(5):e259131.
doi: 10.1001/jamanetworkopen.2025.9131.

Enterovirus D68-Associated Respiratory Illness in Children

Benjamin R Clopper  1 , Adriana S Lopez  1 , Leah A Goldstein  1 , Terry Fei Fan Ng  1 , Ariana P Toepfer  1 , Mary A Staat  2 , Elizabeth P Schlaudecker  2 , Leila C Sahni  3   4 , Julie A Boom  3 , Jennifer E Schuster  5 , Rangaraj Selvarangan  5 , Natasha B Halasa  6 , Laura S Stewart  6 , John V Williams  7   8 , Marian G Michaels  7 , Geoffrey A Weinberg  9 , Peter G Szilagyi  9   10 , Eileen J Klein  11   12 , Janet A Englund  11   12 , Meredith L McMorrow  1   13 , Heidi L Moline  1   13 , Claire M Midgley  1
Affiliations
Observational Study

Enterovirus D68-Associated Respiratory Illness in Children

Benjamin R Clopper et al. JAMA Netw Open. .

Abstract

Importance: Enterovirus D68 (EV-D68) typically causes mild to severe acute respiratory illness (ARI). Testing and surveillance for EV-D68 in the US are limited, and important epidemiologic gaps remain.

Objective: To characterize the epidemiology and clinical severity of EV-D68 among US children seeking care for ARI from 2017 to 2022, using a multisite, active, systematic surveillance network.

Design, setting, and participants: This cross-sectional study collected data from the New Vaccine Surveillance Network, an active, prospective, population-based surveillance system of emergency departments (EDs) and hospitals at 7 US academic medical centers. Children with ARI and EV-D68-positive results were enrolled during platform-wide EV-D68 testing periods (July to October 2017, July to November 2018, July to November 2020, and July 2021 to December 2022). Included children were aged younger than 18 years, reported 1 or more qualifying ARI symptoms, with a symptom duration less than 14 days at enrollment. Data were analyzed from in October 2024.

Exposures: Laboratory-confirmed EV-D68 infection, including overall infections or those without viral codetection.

Main outcomes and measures: Trends and characteristics of EV-D68, including demographics, underlying conditions, and clinical severity by health care setting, were explored. Among hospitalized children with EV-D68-positive results without viral codetection, multivariable logistic regression was used to examine factors associated with receipt of (1) supplemental oxygen or (2) intensive care.

Results: From 2017 to 2022, 976 children with EV-D68-positive results were identified (median [IQR] age, 47 [18-63] months; 391 [40.1%] female); most were enrolled in 2018 (382 children) and 2022 (533 children). Among these, 856 had no viral codetection, of which 320 were discharged home from the ED (median [IQR] age, 33 [16-59] months; 180 male [56.3%]; 237 [74.1%] with no reported underlying conditions) and 536 were hospitalized (median [IQR] age, 40 [19-69] months; 330 male [61.6%]; 268 [50.0%] with no reported underlying conditions). Among those hospitalized, 199 (37.1%) reported a history of asthma or reactive airway disease (RAD) and 77 (14.4%) reported a condition other than asthma or RAD. Having an underlying condition other than asthma or RAD was associated with increased odds of receiving supplemental oxygen (adjusted odds ratio, 2.72; 95% CI, 1.43-5.18) or intensive care admission (adjusted odds ratio, 3.09; 95% CI, 1.72-5.56); neither age group nor history of asthma or RAD were associated with oxygen receipt or intensive care admission.

Conclusions and relevance: In this cross-sectional study of children with medically attended EV-D68 infections, EV-D68 was associated with severe disease in otherwise healthy children of all ages, and children with nonasthma or RAD comorbidities were at higher risk for severe outcomes when hospitalized.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Staat reported receiving grants from the National Institutes of Health outside the submitted work. Dr Schlaudecker reported receiving grants from Pfizer and serving on an advisory committee for Sanofi Pasteur outside the submitted work. Dr Sahni reported receiving travel support from the Bill and Melinda Gates Foundation outside the submitted work. Dr Selvarangan reported receiving grants from Biomerieux, Hologic, and Cepheid outside the submitted work. Dr Halasa reported receiving grants from Merck and personal fees from CSL Seqirus outside the submitted work. Dr Michaels reported receiving grants from the National Institutes of Health outside the submitted work. Dr Weinberg reported receiving grants from the New York State Department of Health AIDS Institute and consulting fees from the New York State Department of Health AIDS Institute, Inhalon Biopharma, Merck & Co, and Emory University (as a member of the data and safety monitoring board) outside the submitted work. Dr Englund reported receiving grants from AstraZeneca, Pfizer, and GlaxoSmithKline; and personal fees from AstraZeneca, GlaxoSmithKline, Pfizer, Meissa Vaccines, Moderna, Shionogi, Cidarra (as a member of the data and safety monitoring board), and Merck outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Enterovirus-D68 Detections by Year and Site, New Vaccine Surveillance Network, 2017-2022
Figure 2.
Figure 2.. Enterovirus D68 (EV-D68) Detections Among Rhinovirus (RV) and EV Positive Cases and All Acute Respiratory Infection (ARI) Cases by Care Setting, New Vaccine Surveillance Network (2017-2022)
See this image and copyright information in PMC

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