Analysis of COVID-19–Related Croup and SARS-CoV-2 Variant Predominance in the US (2024)

Research Letter

Emergency Medicine

BrianLefchak,MD, MPH1; AmandaNickel,MPH2; SheaLammers,MS1; et al DaveWatson,PhD2; Gabrielle Z.Hester,MD, MS3; Kelly R.Bergmann,DO, MS1

Author Affiliations Article Information

Recent reports have found an association between SARS-CoV-2 and croup.^1-3 We aimed to investigate whether SARS-CoV-2 variants were associated with the proportion of children with croup, as well as hospital and intensive care unit (ICU) admissions and racemic epinephrine (RE) treatment.

This cross-sectional study was approved by the Children’s Minnesota Institutional Review Board with exemption of informed consent and adhered to the STROBE reporting guideline. The study included children aged 3 months to 8 years with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnoses of COVID-19 and croup between January 1, 2021, and March 26, 2022, using data from 43 US children’s hospitals in the Pediatric Health Information System. We excluded children with croup-mimicking (eg, tracheitis) or complex chronic conditions.⁴ SARS-CoV-2 variant predominance (ie, Alpha or other variant, Delta, and Omicron) was determined from the Centers for Disease Control and Prevention (CDC) COVID Data Tracker and defined as more than 50% of SARS-CoV-2 diagnoses attributable to a particular variant. CDC data report estimated variant proportions based on genomic surveillance and account for longitudinal sampling between and within states. The primary outcome was encounters for COVID-19–related croup, summarized by week and variant predominance. Secondary outcomes included hospital and ICU admissions and RE treatment. We used mixed-effects logistic regression to evaluate the association of variant predominance with hospitalization and RE use after adjusting for age, sex, race and ethnicity, insurance, and census region. Analyses were conducted using Stata statistical software version 16 (StataCorp), and 2-sided P values < .05 were considered statistically significant.

We identified 5152 children with COVID-19–related croup (3329 [64.6%] boys; median [IQR] age, 17 [9-31] months) (Table). The proportion of children with COVID-19–related croup was significantly increased during Omicron (10.9%) compared with Alpha or other variant (4.1%) and Delta (3.6%) periods (P < .001) (Figure). Odds of hospitalization during Alpha or other variant (adjusted odds ratio [aOR], 1.28; 95% CI, 0.97-1.70) or Delta (aOR, 0.92; 95% CI, 0.74-1.15) periods were not significantly different compared with the period of Omicron predominance. Treatment with RE was less likely during the Delta period (aOR, 0.73; 95% CI, 0.61-0.87) and did not differ in the Alpha or other variant periods (aOR, 1.03; 95% CI, 0.81-1.31) compared with the period of Omicron predominance. The frequency of ICU admission was not statistically different across time periods (Table).

The results of this cross-sectional study expand on recent single-center studies^1,2 showing that hospitalizations for COVID-19–related croup increased after the onset of the Omicron variant. A more recent national investigation³ found that the percentage of children diagnosed with SARS-CoV-2 hospitalized with upper-airway infections increased significantly from pre-Omicron (1.4%) compared with Omicron (4.1%) periods. The hospitalization rate was higher in our study, which may be associated with use of ICD-10 codes rather than positive SARS-CoV-2 test results for COVID-19 data.

Findings for association with COVID-19–related croup severity were mixed in our study. We noted a significant increase in the proportion of children requiring RE during Alpha or other variant and Omicron periods compared with the period of Delta predominance. However, we also observed no difference in the median number of RE doses, which was comparable to an estimate prior to COVID-19.⁵ The overall ICU admission rate in our sample was lower than a rate described prior to COVID-19,⁵ which may be associated with constraints on ICU capacity or, alternatively, less severe illness.

Our study has several limitations. Hospital practice changes, including limitation of aerosol-generating procedures early in the pandemic, may have influenced RE administration. It is also possible that conditions other than croup influenced hospitalization rates.

Given that COVID-19 is likely to become endemic, our findings suggest that pediatric health systems should consider variation in SARS-CoV-2 phenotypes and their association with patient care. This may be especially true when other viral infections lead to surges in patient volume.

Accepted for Publication: May 16, 2022.

Published: July 1, 2022. doi:10.1001/jamanetworkopen.2022.20060

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Lefchak B et al. JAMA Network Open.

Corresponding Author: Kelly R. Bergmann, DO, MS, Department of Emergency Medicine, Children’s Minnesota, 2525 Chicago Ave S, Mail Stop 32-1488, Minneapolis, MN, 55404, (kelly.bergmann@childrensmn.org).

Author Contributions: Dr Bergmann had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Lefchak, Nickel, Lammers, Hester, Bergmann.

Acquisition, analysis, or interpretation of data: Lefchak, Nickel, Watson, Hester, Bergmann.

Drafting of the manuscript: Lefchak, Lammers, Bergmann.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Lefchak, Nickel, Watson.

Administrative, technical, or material support: Lammers.

Supervision: Bergmann.

Conflict of Interest Disclosures: None reported.