Quantitative Chest CT Assessment of Small Airways Disease in Post-Acute SARS-CoV-2 Infection

Abstract

Background The long-term effects of SARS-CoV-2 infection on pulmonary structure and function remain incompletely characterized. Purpose To test whether SARS-CoV-2 infection leads to small airways disease in patients with persistent symptoms. Materials and Methods In this single-center study at a university teaching hospital, adults with confirmed COVID-19 who remained symptomatic more than 30 days following diagnosis were prospectively enrolled from June to December 2020 and compared with healthy participants (controls) prospectively enrolled from March to August 2018. Participants with post-acute sequelae of COVID-19 (PASC) were classified as ambulatory, hospitalized, or having required the intensive care unit (ICU) based on the highest level of care received during acute infection. Symptoms, pulmonary function tests, and chest CT images were collected. Quantitative CT analysis was performed using supervised machine learning to measure regional ground-glass opacity (GGO) and using inspiratory and expiratory image-matching to measure regional air trapping. Univariable analyses and multivariable linear regression were used to compare groups. Results Overall, 100 participants with PASC (median age, 48 years; 66 women) were evaluated and compared with 106 matched healthy controls; 67% (67 of 100) of the participants with PASC were classified as ambulatory, 17% (17 of 100) were hospitalized, and 16% (16 of 100) required the ICU. In the hospitalized and ICU groups, the mean percentage of total lung classified as GGO was 13.2% and 28.7%, respectively, and was higher than that in the ambulatory group (3.7%, P < .001 for both comparisons). The mean percentage of total lung affected by air trapping was 25.4%, 34.6%, and 27.3% in the ambulatory, hospitalized, and ICU groups, respectively, and 7.2% in healthy controls (P < .001). Air trapping correlated with the residual volume-to-total lung capacity ratio (ρ = 0.6, P < .001). Conclusion In survivors of COVID-19, small airways disease occurred independently of initial infection severity. The long-term consequences are unknown. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Elicker in this issue.

Graphical abstract

Figure 1:

Flowchart of study participants. ICU = intensive care unit, PASC = post-acute sequelae of COVID-19.

Figure 2:

Bar graphs show results of pulmonary function testing in post-acute COVID-19 according to participant group. (A) Percent predicted forced vital capacity (FVC). (B) Percent predicted forced expiratory volume in 1 second (FEV1). (C) Percent of FVC exhaled in the first second (FEV1/FVC). (D) Percent predicted total lung capacity (TLC). (E) Percent predicted residual volume (RV). (F) Percent predicted diffusing capacity of the lung for carbon monoxide (DLCO). Data are displayed as means with standard error measurements. Horizontal dashed lines indicate the lower limit of normal. P values were calculated using the Dunn test for post hoc comparisons between groups. AMB = ambulatory, HC = healthy controls, HOSP = hospitalized, ICU = intensive care unit.

Figure 3:

Quantitative chest CT and correlation with pulmonary function. (A) Chest CT images in a 60-year-old man with post-acute sequelae of COVID-19 (hospitalized group). Representative coronal image from inspiratory noncontrast chest CT (left) obtained at total lung capacity (TLC). The corresponding texture analysis map (right) highlights ground-glass opacity (GGO) in blue. (B) Bar graphs show quantification of GGO measured with texture analysis. (C) Bar graphs show correlation of GGO with percent predicted TLC (left) and diffusing capacity of the lung for carbon monoxide (DLCO; right). (D) Chest CT images in a 61-year-old woman with PASC (ambulatory group). Representative coronal image from expiratory noncontrast chest CT obtained at residual volume (RV) (left). The corresponding disease probability measure map (right) highlights air trapping in pink. (E) Bar graph shows quantification of air trapping measured per the disease probability measure. (F) Bar graphs show RV/TLC ratio measured with plethysmography (left) and correlation of air trapping with the RV/TLC ratio (right). Images in A and D were prepared using topographic multiplanar reformat rendering, which serves to display the airways and associated parenchyma on the same plane (17,27). Data in B, E, and F are displayed as means with standard error measurements. Yellow circles on graphs indicate ambulatory group (AMB); red circles, hospitalized group (HOSP); and blue circles, intensive care unit (ICU) group. P values in B, E, and F were calculated using the Dunn test for post hoc comparisons between groups. The Spearman correlation was used to calculate ρ values in C and F. HC = healthy controls.