Increased luminal area of large conducting airways in patients with COVID-19 and post-acute sequelae of COVID-19: a retrospective case-control study.

Coronavirus disease 2019 (COVID-19) is associated with enlarged luminal areas of large conducting airways. In 10-30% of patients with acute COVID-19 infection, symptoms persist for more than 4 wk (referred to as post-acute sequelae of COVID 19, or PASC), and it is unknown if airway changes are associated with this persistence. Thus, we aim to investigate whether luminal area of large conducting airways is different between patients with PASC and COVID-19 and healthy controls. In this retrospective case-control study, 75 patients with PASC (48 females) were age-, height-, and sex-matched to 75 patients with COVID-19 and 75 healthy controls. Using three-dimensional digital reconstruction from computed tomography imaging, we measured luminal areas of seven conducting airways, including trachea, right and left main bronchi, bronchus intermediate, right and left upper lobe, and left lower lobe bronchi. Kruskal-Wallis H test was used to compare measurements between the three groups, as appropriate. Airway luminal areas between COVID-19 and PASC groups were not different (all, > 0.66). There were no group differences in airway luminal area (PASC vs. control) for trachea and right main bronchus. However, in the remaining five airways, airway luminal areas were 12-39% larger among patients with PASC than in controls (all, < 0.05). Patients diagnosed with COVID-19 and PASC have greater airway luminal area in most large conducting airways compared with healthy controls. No differences in luminal area between patients with COVID-19 and PASC suggest persistence of changes or insufficient time for reversal of changes. Three-dimensional reconstruction of airways has shown increased luminal area in patients with COVID-19 and post-acute sequelae of COVID-19 when compared with healthy controls. These findings suggest the role of large conducting airways in the pathogenesis of post-acute sequelae of COVID 19.