Discussion
This is the first international database to examine complications of SARS-CoV-2 infection in children with EA-TEF. Our dataset was representative of a normal EA-TEF cohort with 81% of patients having Type C, EA-TEF, comparative to 78-90% rates in the literature11, 15, 16, cardiovascular anomalies in 33% , comparative to 29% reported in the literature17.
19% of our cohort were on inhaled bronchodilators, inhaled corticosteroids or montelukast, consistent with reported rates of asthma of 10-30%18, 19 and 25% of our cohort had tracheomalacia, comparative to rates of 17%-78%20.
Recurrent strictures were noted in 33% of our cohort and third of patients were on proton pump inhibitor (PPI), again, comparative to rates of 18-50%21 and gastroesophageal reflux disease (GERD) rates of 15-66%22-24 respectively.
Our population had a high rate of admission to hospital comparative to a pediatric population, where rates of hospitalization have been documented at 1.2-2.9%25. This high rate is likely reflective of the fact that patients with EA-TEF are more susceptible to respiratory deterioration given high rates of comorbidities such as chronic lung disease (a known risk factor for severe SARS-CoV-2 infection26) secondary to airway anomalies, reactive airway disease or chronic aspiration; and be reflective of decreased respiratory reserve.
It is paramount for the clinician and carers to be mindful of this increased acute morbidity with respiratory tract infections in those with EA-TEF, and longer-term morbidity with recurrent lower respiratory tract infections leading to bronchiectasis, poor lung function and lower quality of life in adulthood14. Concomitant infections may also impact on oral intake and nutrition. For these reasons, it is important that EA-TEF patients continue to receive multidisciplinary care, for early detection and management of risk factors for chronic lung disease as well as advocacy for access to primary prevention mechanisms, such as vaccination.
It is interesting to note that medication use for any reason was associated with an increased risk of hospitalization, however that individual medication use was not. This may be due to that fact that those on medications are likely to have more severe comorbidities and therefore risk factors for chronic lung disease than those not on medications.
We did not see an association with PPI use and hospitalization. PPI use has been postulated to be associated with more severe infection8, 27, possibly secondary to increased virus survival in those with higher gastric pH, although this has not been demonstrated in children.
Our study had several limitations. As EA-TEF is a rare disease, only 42 patients were able to be included in this cohort. There is the possibility that patients may have under-reported infections if asymptomatic or well, thereby skewing this dataset towards patients with more severe SARS-CoV-2. Demographic data such as birthweight, gestational age at birth – traditionally associated with more severe morbidity were not included to focus on other modifiable risk factors. Finally, there was an increased rate of hospitalization in the first 12 months of the database, which may represent worse outcomes before widespread pediatric vaccination or increased caution early in the pandemic from clinicians.
Future avenues for research include long term pulmonary and extra-pulmonary outcomes for those infected with SARS-CoV-2 as well as risk factors for ‘long covid’ or PIMS-TS in the EA/TEF population.