Acute Upper Airway Disease in Children With the Omicron (B.1.1.529) Variant of SARS-CoV-2—A Report From the US National COVID Cohort Collaborative

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.