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

Background 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 weeks (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 if luminal area of large conducting airways is different between PASC and COVID–19 patients, and healthy controls. Methods In this retrospective case–control study seventy–five patients with PASC (48 females) were age–, height–, and sex–matched to 75 individuals 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. Findings Airway luminal areas between COVID–19 and PASC groups were not different (p>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% to 39% larger among PASC patients compared to controls (p<0.05). Interpretation Patients diagnosed with COVID–19 and PASC have greater airway luminal area in most large conducting airways compared to healthy controls. No differences in luminal area between patients with COVID–19 and PASC suggest persistence of changes or insufficient time for complete reversal of changes. Funding National Heart, Lung, and Blood Institute (F32HL154320 to JWS; 5R35HL139854 to MJJ); Postdoctoral Fellowship from the Natural Sciences and Engineering Research Council of Canada (AHR).