In October 2021, the US Food and Drug Administration granted emergency use authorization for the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine to be used in children aged 5 to 11 years to reduce costly hospitalizations. By that time, for children in this age group, there had been 1.8 million people diagnosed with SARS-CoV-2 infection and 143 deaths, with more than 8000 hospitalizations.1 However, very little is known about the severity of these hospitalizations relative to the 2 most common childhood viruses, the influenza virus and respiratory syncytial virus (RSV), which resemble the SARS-CoV-2 virus. In this study, we compared the January through March 2021 hospitalizations of children aged 5 to 11 years who were diagnosed with SARS-CoV-2 infection and multisystem inflammatory syndrome in children (MIS-C; a sequela of COVID-19 disease)2 with those hospitalizations of children aged 5 to 11 years infected with influenza and RSV.
This cross-sectional study was conducted from September 17 to December 13, 2021, using 2021 quarterly inpatient data from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality. These data were from the first 11 states with complete first-quarter data as of October 2021: Colorado, Georgia, Iowa, Kentucky, Michigan, Missouri, Mississippi, Ohio, New Jersey, Washington, and Wisconsin. Data from these states represented 24% of the US population of children aged 5 to 11 years.3 We examined all 1333 community hospitals in these states during the first quarter of 2021 (January to March) because the number of COVID-19–related diagnoses peaked in January. We used the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes to identify COVID-19, MIS-C, influenza, and RSV. Because diagnoses of influenza and RSV were rare during the COVID-19 pandemic, we also used data from the first quarter of 2017 of the State Inpatient Databases, when influenza was at its mean 10-year level (2019 and 2020 had below average influenza rates, whereas 2018 rates were above average).4 We examined 46 complications in the following body systems: cardiovascular, respiratory, neurologic, hematologic, kidney failure, gastrointestinal, and musculoskeletal. Total costs and charges were adjusted for the US Centers for Medicare & Medicaid Services wage index and inflation adjusted to 2021. Race and ethnicity data were collected from the database; children were identified as Asian or Pacific Islander, Black, Hispanic, non-Hispanic White, or other (included Native American or other as reported by the Healthcare Cost and Utilization Project). Race and ethnicity data collection was a requirement of the funding body. This study was approved by the institutional review board of the Agency for Healthcare Research and Quality, and followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. The need for patient informed consent was waived owing to the use of deidentified patient data. The eMethods in the Supplement contains information on diagnostic codes and missing race imputations. All 2-sided P values were generated from linear regression analyses using Stata/MP, version 17 (StataCorp), and a P value < .05 was considered significant.
This cross-sectional study included the patient data from a total of 2269 children (mean [SD] age, 7.6 [2.0] years; 999 girls [44.0%]; 1270 boys [56.0%]; 50 Asian or Pacific Islander [2.2%], 265 Black [11.7%], 539 Hispanic [23.8%], 1305 non-Hispanic White [57.5%], 110 other [4.8%]). In the Table, for every COVID-19 hospitalization, there was a corresponding MIS-C hospitalization. Combined, COVID-19 and MIS-C hospitalizations occurred at a rate of 10.8 per 100 000 children. Influenza and RSV were rare during the first quarter of 2021 (23 discharges combined), but in 2017, influenza and RSV had 17.0 and 6.2 hospitalizations per 100 000, respectively. A total of 56.8% (95% CI, 51.0%-62.7%) children who were Asian or Pacific Islander, Black, Hispanic, or other race and ethnicity had diagnoses of MIS-C compared with 28.4% (95% CI, 23.7%-33.1%) for RSV. Inpatient death for all viruses was rare. MIS-C had the highest rates of cardiovascular (29.8%; 95% CI, 25.2%-34.4%; P = .001), hematologic (55.4%; 95% CI, 50.4%-60.4%; P = .001), kidney (21.9%; 95% CI, 17.7%-26.1%; P = .001), and gastrointestinal (47.2%; 42.2%-52.3%; P = .001) complications. Children with RSV had the highest rate of respiratory complications (75.8%; 95% CI, 71.6%-79.9%; P = .001), whereas children with COVID-19 (without MIS-C) had the highest rate of neurologic complications (9.6%; 95% CI, 6.5%-12.8%; P = .03). Children with influenza had the highest rate of musculoskeletal complications (9.5%; 95% CI, 7.8%-11.2%; P = .001).5 Children with MIS-C had the longest median (IQR) length of stay (5 [3-7] days), at a median (IQR) cost of $23 585 ($15 040-$39 122) per stay, compared with children with a diagnosis of influenza (median [IQR]: length of stay, 2 [1-4] days; cost, $5200 [$2959-$9449]).
MIS-C was more severe for children who were Asian or Pacific Islander, Black, Hispanic, and other race and ethnicity. In the Figure, aggregate inpatient days for children who were Asian or Pacific Islander, Black, Hispanic, and other race and ethnicity with MIS-C was almost twice that of non-Hispanic White children (1647 days vs 867 days; P = .047), despite children who were Asian or Pacific Islander, Black, Hispanic, and other race and ethnicity accounting for only 56.8% of the cases. Non-Hispanic White children accounted for more total days for SARS-CoV-2, influenza, and RSV infection than children who were Asian or Pacific Islander, Black, Hispanic, and other race and ethnicity (combined, 5174 days vs 3197 days; P = .01). Children were hospitalized for approximately the same number of days for COVID-19 infection and MIS-C combined as for influenza (4384 days vs 4202 days; P = .65), despite having a lower hospitalization rate (10.8 per 100 000 children vs 17.0 per 100 000 children).
This cross-sectional study revealed that during the winter of 2020-2021, for children aged 5 to 11 years, there was 1 MIS-C hospitalization for every COVID-19 hospitalization. This finding suggests that MIS-C may not be as rare of a COVID-19 sequela as previously thought. Other long-term COVID-19 complications may also be of concern for children aged 5 to 11 years. Although rarer than influenza infection, the extreme severity of MIS-C made the total economic and health burden of COVID-19 infection combined with MIS-C just as high as that of past influenza outbreaks. One study limitation was that the percentage of children aged 5 to 11 years who were Asian or Pacific Islander, Black, Hispanic, and other race and ethnicity for the studied 11 states was 39.4% compared with 50.2% for all US states. Thus, our data possibly underestimated the national rate and severity of MIS-C. It is our hope that our study results may provide important data points for public health planning efforts, including racial and ethnic minority group outreach, to help reduce the disease burden of both COVID-19/MIS-C and influenza.
Accepted for Publication: December 15, 2021.
Published Online: February 21, 2022. doi:10.1001/jamapediatrics.2021.6566
Corresponding Author: William Encinosa, PhD, Agency for Healthcare Research and Quality, 5600 Fishers Ln, Rockville, MD 20857 (william.encinosa@ahrq.hhs.gov).
Author Contributions: Dr Encinosa had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Encinosa, Elias.
Acquisition, analysis, or interpretation of data: Encinosa, Figueroa.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: Encinosa, Figueroa.
Statistical analysis: Encinosa.
Obtained funding: Encinosa.
Administrative, technical, or material support: All authors.
Supervision: Encinosa.
Conflict of Interest Disclosures: Ms Figueroa reported receiving personal fees from Navitas Clinical Research Inc, Technical Resources International Inc, The Johns Hopkins University, and Georgetown University Medical Center outside the submitted work. No other disclosures were reported.
Funding/Support: This work was supported by the Agency for Healthcare Research and Quality.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Disclaimer: The views expressed in this article are those of the authors, and no official endorsement by the US Department of Health and Human Services and Agency for Healthcare Research and Quality is intended or should be inferred.
Additional Contributions: We thank Kyung Moon, PhD, of the Division of Blood Diseases and Resources, National Heart, Lung and Blood Institute, National Institutes of Health, for her invaluable advice and insight into the COVID-19 pandemic. She did not receive financial compensation for her contribution. We thank the Healthcare Cost and Utilization Project Partner organizations for contributing data to the Healthcare Cost and Utilization Project State Inpatient Databases used in this study. A full list of Healthcare Cost and Utilization Project Data Partners can be found at https://www.hcup-us.ahrq.gov/db/hcupdatapartners.jsp. The data partners received no financial compensation for their contribution.