key: cord-0765497-2sst2426
authors: Martin, B.; DeWitt, P. E.; Russell, S.; Sanchez-Pinto, L. N.; Haendel, M. A.; Moffitt, R.; Bennett, T. D.
title: Acute upper airway disease in children with the omicron (B.1.1.529) variant of SARS-CoV-2: a report from the National COVID Cohort Collaborative (N3C)
date: 2022-01-30
journal: nan
DOI: 10.1101/2022.01.27.22269865
sha: d1bfb9fa5a21bad7312d27a86ad61cddf1e1282e
doc_id: 765497
cord_uid: 2sst2426

Background: Reports of SARS-CoV-2 causing laryngotracheobronchitis (commonly known as croup) have been limited to small case series. Early reports suggest the Omicron (B.1.1.529) strain of SARS-CoV-2 (the dominant circulating US strain since the week of 12/25/2021) replicates more efficiently in the conducting airways. This may increase the risk of a croup phenotype in children as they have smaller airway calibers. Methods: Description of the incidence, change over time, and characteristics of children with SARS-CoV-2 and upper airway infection (UAI) diagnoses within the National COVID Cohort Collaborative (N3C) before and during the rise of the Omicron variant. We compare the demographics, comorbidities, and clinical outcomes of hospitalized SARS-CoV-2 positive children with and without UAI. Results: SARS-CoV-2 positive UAI cases increased to the highest number per month (N = 170) in December 2021 as the Omicron variant became dominant. Of 15,806 hospitalized children with SARS-CoV-2, 1.5% (234/15,806) had an UAI diagnosis. Those with UAI were more likely to be male, younger, white, have asthma and develop severe disease as compared to those without UAI. Conclusions: Pediatric acute UAI cases have increased during the Omicron variant surge with many developing severe disease. Improved understanding of this emerging clinical phenotype could aid in therapeutic decision-making and healthcare resource planning.

SARS-CoV-2 can cause severe pediatric disease including acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) 1 . Published reports of SARS-CoV-2 causing laryngotracheobronchitis (commonly known as "croup"), however, have been limited to small case series 2 . Other coronaviruses (e.g. type NL63) are known to cause croup.

The Omicron (B.1.1.529) strain of SARS-CoV-2 became dominant in the U.S. during the week of 12/25/2021 3 . Early reports suggest Omicron may cause lower severity disease than the Delta variant 4 . This may be because Omicron replicates less efficiently in lung parenchyma and more efficiently in the conducting airways 5 . However, these mechanistic hypotheses have not been confirmed.

Young children are especially vulnerable to acute upper airway infection (UAI) because their airways are small and relatively collapsible. Inflammation from UAI can rapidly decrease air flow. Accordingly, croup is classically an early childhood disease. We conducted this retrospective cohort study to determine if acute UAI is more common as Omicron has become the dominant U.S. SARS-CoV-2 variant.

We leveraged the National COVID Cohort Collaborative (N3C) 6 and a pipeline we built for a NIHfunded pediatric COVID-19 dashboard (https://covid.cd2h.org/pediatrics-dashboard/) to conduct this study. Among all children in N3C <19-years-old with a positive SARS-CoV-2 test (polymerase chain reaction, antigen, or antibody), we identified those with a croup or tracheitis diagnosis. We included bacterial tracheitis because it can be difficult to distinguish from -and can be a complication ofviral croup. We compared groups using chi-square and Fisher exact tests for categorical variables and Mood's Median test and t-tests for continuous variables. The N3C Data Enclave, data transfer from sites to N3C, and this analysis were approved under separate institutional review board protocols as documented elsewhere 1 . 

Overall, pediatric acute UAI has increased during the Omicron variant surge. Nearly a third of affected children develop severe disease. This observed clinical phenotype of pediatric infection by the Omicron variant appears to confirm recent mechanistic reports.

A limitation of this analysis is that diagnosis codes will only be present for completed hospitalizations in N3C; children who are still hospitalized are not represented.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted January 30, 2022. ; https://doi.org/10.1101/2022.01.27.22269865 doi: medRxiv preprint Although many children with acute UAI are managed as outpatients, those with severe croup and/or tracheitis are at risk of cardiac arrest from rapid-onset upper airway obstruction. They may require therapies typically provided in intensive care units including frequent administration of nebulized racemic epinephrine, helium/oxygen mixtures, and intubation. While SARS-CoV-2 pediatric UAI rates are not overwhelmingly high, understanding this new clinical phenotype is important to health systems under severe strain. Anticipation of the potential for acute upper airway obstruction may guide therapeutic decision-making and hospital planning for available equipment and personnel. -. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted January 30, 2022. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted January 30, 2022. ; https://doi.org/10.1101/2022.01.27.22269865 doi: medRxiv preprint with a BMI ≥ 95th percentile for age and sex. Percentages reported in the "Obese ( ≥ 95th percentile)" row represent the percent of patients with a known BMI value who had a BMI greater than 95th percentile for age and sex.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted January 30, 2022. ; https://doi.org/10.1101/2022.01.27.22269865 doi: medRxiv preprint

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The N3C was funded by NCATS grant number U24 TR002306 and other support as documented at https://covid.cd2h.org/acknowledgements. This analysis was supported by NICHD grant number R01HD105939-01S1.