==== Front JAMA Health Forum JAMA Health Forum JAMA Health Forum 2689-0186 American Medical Association 37389862 10.1001/jamahealthforum.2023.1582 ald230017 Research Research Research Letter Online Only Comments Seasonality in Respiratory Syncytial Virus Hospitalizations and Immunoprophylaxis Seasonality in RSV Hospitalizations and Immunoprophylaxis Seasonality in RSV Hospitalizations and Immunoprophylaxis Kusma Jennifer D. MD MS 1 Macy Michelle L. MD MS 2 Kociolek Larry K. MD MSCI 3 Davis Matthew M. MD MAPP 4 Ramgopal Sriram MD 5 1 Division of Advanced General Pediatrics and Primary Care, Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois 2 Mary Ann & J. Milburn Smith Child Health Outcomes, Research, and Evaluation Center, Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois 3 Division of Infectious Disease, Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois 4 Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois 5 Division of Emergency Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois Article Information Accepted for Publication: April 20, 2023. Published: June 30, 2023. doi:10.1001/jamahealthforum.2023.1582 Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2023 Kusma JD et al. JAMA Health Forum. Corresponding Author: Jennifer D. Kusma, MD, MS, Division of Advanced General Pediatrics and Primary Care, Ann & Robert H. Lurie Children’s Hospital, 225 E Chicago Ave, Box 162, Chicago, IL 60611 (jkusma@luriechildrens.org). Author Contributions: Drs Kusma and Ramgopal had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Kusma, Macy, Davis. Acquisition, analysis, or interpretation of data: Kusma, Macy, Kociolek, Ramgopal. Drafting of the manuscript: Kusma, Kociolek. Critical revision of the manuscript for important intellectual content: Macy, Kociolek, Davis, Ramgopal. Statistical analysis: Kusma, Ramgopal. Administrative, technical, or material support: Kociolek. Supervision: Macy, Kociolek, Davis, Ramgopal. Conflict of Interest Disclosures: Dr Kociolek reported receiving grants from Merck outside the submitted work. No other disclosures were reported. Data Sharing Statement: See Supplement 2. 30 6 2023 6 2023 30 6 2023 4 6 e2315822 2 2023 20 4 2023 Copyright 2023 Kusma JD et al. JAMA Health Forum. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the CC-BY License. jamahealthforum-e231582.pdf This cross-sectional study assesses whether current guidance on respiratory syncytial virus supports the current epidemiologic characteristics, treatment, and hospitalization patterns in respiratory syncytial virus. ==== Body pmcIntroduction Respiratory syncytial virus (RSV) frequently causes hospitalization,1 particularly among children with hemodynamically significant congenital heart disease, chronic lung disease, or prematurity (<29 weeks’ gestation).2 Immunoprophylaxis administration to high-risk children during active RSV circulation periods is cost-effective.3 American Academy of Pediatrics (AAP) guidelines recommended that high-risk children receive RSV immunoprophylaxis with monoclonal antibodies.2 Insurers typically cover RSV immunoprophylaxis annually (November-March) in accordance with RSV seasonality.2,4 Since the COVID-19 pandemic, RSV has been characterized by unexpected interseasonal spikes. During the 2021 summer RSV surge, the AAP recommended RSV immunoprophylaxis for high-risk children,5 but adoption has varied among states and insurers. Interseasonal spikes and policy lag create periods in which RSV immunoprophylaxis provides no protection, which potentially undermines its cost-benefit ratio. We investigated patterns in RSV-related hospitalizations and RSV-immunoprophylaxis administration timing to account for changing RSV epidemiological characteristics to inform policy discussions between clinicians and public and commercial insurance. Methods This retrospective cross-sectional study identified children younger than 2 years who were hospitalized for RSV between July 2017 and November 2022 using the Pediatric Health Information System (PHIS). The Ann & Robert H. Lurie Children’s Hospital of Chicago Institutional Review Board deemed this study exempt from review and waived the informed consent requirement because it used deidentified data. We followed the STROBE reporting guideline. International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes (eMethods in Supplement 1) were used to identify RSV-related hospitalizations and children with RSV-immunoprophylaxis eligibility. We defined RSV seasons as months during which RSV-related hospitalizations exceeded by 3 SDs mean monthly hospitalization counts (June-September; >350 per month).6 Using χ2 test, we compared hospitalizations between 2017 to 2020 and 2021 to 2022 RSV seasons and in interseasons. Two-sided P < .05 indicated statistical significance. Analysis was performed with R 4.1.2 (R Core Team). Results We identified 4 RSV seasons with 109 185 RSV-related hospitalizations (Figure) among 104 898 children (median [IQR] age, 4.7 [2.0-10.6] months; 45 931 girls [43.8%], 58 947 boys [56.2%]). Seasonal spikes between 2017 and 2019 began in October. High-risk children represented a larger proportion of hospitalizations during interseasons (Table). Children with public insurance constituted the largest proportion of hospitalizations, and even larger during interseasons. Figure. Respiratory Syncytial Virus (RSV) Hospitalization Patterns With RSV Seasons and RSV Immunoprophylaxis From 2017 to 2022 High risk was defined as having hemodynamically significant congenital heart disease, chronic lung disease of prematurity, or less than 29 weeks’ gestation. In the 2021 to 2022 season, states had variable start and stop dates for RSV immunoprophylaxis. Table. Comparison of RSV Hospitalizations by Season From 2017 to 2022 Variable Participants, No. (%) P value Combined 2017- 2019 seasons (n = 56 579) 2021-2022 season (n = 49 475) Interseason (n = 3131) Age categories, mo <2 15 775 (27.9) 11 621 (23.5) 740 (23.6) <.001 2 to <4 11 332 (20.0) 9531 (19.3) 599 (19.1) 4 to <6 7200 (12.7) 6124 (12.4) 373 (11.9) 6 to <9 6660 (11.8) 6271 (12.7) 420 (13.4) 9 to <12 4619 (8.2) 4466 (9.0) 315 (10.1) 12 to <24 10 993 (19.4) 11 462 (23.2) 684 (21.8) Sexa Female 24 807 (43.8) 21 507 (43.5) 1336 (42.7) .69 Male 31 763 (56.1) 27 958 (56.5) 1794 (57.3) Race and ethnicityb Hispanic 12 966 (22.9) 10 768 (21.8) 908 (29.0) <.001 Non-Hispanic Black 8954 (15.8) 8454 (17.1) 740 (23.6) Non-Hispanic White 27 332 (48.3) 24 054 (48.6) 1116 (35.6) >1 or otherc 5082 (9.0) 4189 (8.5) 255 (8.1) None documented 2245 (4.0) 2010 (4.1) 112 (3.6) Census region Midwest 16 297 (28.8) 14 302 (28.9) 640 (20.4) <.001 Northeast 4800 (8.5) 5629 (11.4) 178 (5.7) South 24 235 (42.8) 23 318 (47.1) 1992 (63.6) West 11 247 (19.9) 6226 (12.6) 321 (10.3) RSV immunoprophylaxis– eligibled 1668 (2.9) 1355 (2.7) 185 (5.9) <.001 CHD 322 (0.6) 222 (0.4) 38 (1.2) <.001 Chronic lung disease of prematurity 1128 (2.0) 900 (1.8) 135 (4.3) <.001 Prematurity: <29 weeks’ gestation 565 (1.0) 576 (1.2) 56 (1.8) <.001 Insurance type Public 34 940 (61.8) 28 440 (57.5) 2143 (68.4) <.001 Private 19 783 (35.0) 18 801 (38.0) 883 (28.2) Othere 1542 (2.7) 1821 (3.7) 86 (2.7) Unknown 314 (0.6) 413 (0.8) 19 (0.6) ICU admission 17 800 (31.5) 13 115 (26.5) 1217 (38.9) <.001 Mechanical ventilation 6794 (12.0) 4179 (8.4) 495 (15.8) <.001 Abbreviations: CHD, congenital heart disease; ICU, intensive care unit; RSV, respiratory syncytial virus. a Sex data were unavailable for 20 patients. b Race and ethnicity data were obtained from local hospital records, which may include self-reported or electronic health record–based data. c Other race and ethnicity included Alaska Native, American Indian, Asian, Pacific Islander, and other. d Defined as having hemodynamically significant congenital heart disease, chronic lung disease of prematurity, or less than 29 weeks’ gestation. e Other insurance type included charity, no bill, self-pay, and other payer. Seasonal hospitalization pattern from 2017 to 2019 (starting in November, ending in March) aligned with RSV immunoprophylaxis availability. However, the 2021 RSV season started in May (579 hospitalizations per month). Public and commercial insurance in most states did not approve RSV immunoprophylaxis until September or later.5 Although RSV immunoprophylaxis ended between January and March 2022 and restarted in October or November 2022, RSV season was continuous, with monthly hospitalizations larger than the interseasonal threshold. The 2021 to 2022 RSV season consisted of 45% of all hospitalizations over the study period. Discussion We found that RSV-related hospitalizations deviated from expected seasonality pattern during the pandemic. The AAP guidelines encouraged out-of-season RSV immunoprophylaxis authorization.5 The RSV surge was missed by the time insurance covered RSV immunoprophylaxis. Many high-risk children could not receive RSV immunoprophylaxis during peak months. Study limitations included reliance on hospital administrative data to identify RSV cases. Generally, few hospitals submit ambulatory data to PHIS, and children are inconsistently tested for RSV in the outpatient setting. This analysis suggests that current RSV-immunoprophylaxis guidance based on historical seasonality does not align with current RSV-related hospitalization patterns. To maximize benefits of RSV immunoprophylaxis, preventing hospitalization and death among high-risk children,2 policies must be responsive to atypical epidemiological patterns. Surveillance is not a universal public health activity. Even among jurisdictions that perform RSV surveillance, data may not be pediatric-specific and/or available in real time to inform policy decisions. Existing public health–hospital relationships and data infrastructure could be leveraged for real-time pediatric surveillance to guide RSV immunoprophylaxis initiation and cessation. Additionally, policymakers may establish flexible models that are responsive to timely regional RSV epidemiological data, maximizing coverage during periods of high RSV activity and minimizing unnecessary doses when RSV activity is low. Supplement 1. eMethods. Click here for additional data file. Supplement 2. Data Sharing Statement Click here for additional data file. ==== Refs References 1 Hall CB, Weinberg GA, Iwane MK, . The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009;360 (6 ):588-598. doi:10.1056/NEJMoa0804877 19196675 2 American Academy of Pediatrics Committee on Infectious Diseases; American Academy of Pediatrics Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134 (2 ):415-420. doi:10.1542/peds.2014-1665 25070315 3 Mac S, Sumner A, Duchesne-Belanger S, Stirling R, Tunis M, Sander B. Cost-effectiveness of palivizumab for respiratory syncytial virus: a systematic review. Pediatrics. 2019;143 (5 ):e20184064. doi:10.1542/peds.2018-4064 31040196 4 Midgley CM, Haynes AK, Baumgardner JL, . Determining the seasonality of respiratory syncytial virus in the United States: the impact of increased molecular testing. J Infect Dis. 2017;216 (3 ):345-355. doi:10.1093/infdis/jix275 28859428 5 American Academy of Pediatrics. Interim guidance for use of palivizumab prophylaxis to prevent hospitalization from severe respiratory syncytial virus infection during the current atypical interseasonal RSV spread. September 23, 2021. Accessed October 6, 2021. https://www.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/interim-guidance-for-use-of-palivizumab-prophylaxis-to-prevent-hospitalization/ 6 Glick AF, Kjelleren S, Hofstetter AM, Subramony A. RSV hospitalizations in comparison with regional RSV activity and inpatient palivizumab administration, 2010-2013. Hosp Pediatr. 2017;7 (5 ):271-278. doi:10.1542/hpeds.2016-0124 28381595