Introduction As SARS-CoV-2 has evolved, so has its effects on the pediatric population.1 While early variants typically resulted in lower respiratory infections, the recently identified Omicron variant may exhibit a predilection for the upper airways.2 The relatively smaller upper respiratory tract in children compared to adults has been thought to predispose them to more severe clinical presentations resembling laryngotracheobronchitis, or croup. Caused by viral-induced subglottic airway inflammation, croup is classically characterized by sudden onset “barking cough”, inspiratory stridor, and respiratory distress. Endemic coronaviruses have been linked to croup, however only sparse case reports have described croup specifically associated with SARS-CoV-2 and it remains unclear if croup cases constitute a causative relationship or result of co-infection with another virus.3–6 To address this knowledge gap, we performed a retrospective analysis of the incidence and clinical characteristics of croup associated with SARS-CoV-2 infection at a large freestanding children’s hospital.

Background Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide (CO2), possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that CO2-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. Methods We conducted a case-control analysis (N=414 PD cases, 846 healthy controls) of ACCN2single nucleotide polymorphisms (SNPs) and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n=1,048) and/or task-evoked reactivity to emotional stimuli (n=103) in healthy individuals. Results Two SNPs at the ACCN2 locus showed evidence of association with PD: rs685012 (OR=1.32, gene-wise corrected p=0.011) and rs10875995 (OR=1.26, gene-wise corrected p=0.046). The association appeared to be stronger when early-onset (age ≤ 20) PD cases and when cases with prominent respiratory symptoms were compared to controls. The PD risk allele at rs10875995 was associated with increased amygdala volume (p=0.035), as well as task-evoked amygdala reactivity to fearful and angry faces (p=0.0048). Conclusions Genetic variation at ACCN2 appears to be associated with PD and with amygdala phenotypes that have been linked to anxiety proneness. These results support the possibility that modulation of acid-sensing ion channels may have therapeutic potential for PD.

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