Study shows small airways disease with the presence of air trapping is a long-lasting sequelae of SARS-CoV-2 infection

By Shanet Susan AlexReviewed by Danielle Ellis, B.Sc.Mar 18 2022

In a recent study published in Radiology, researchers investigated whether small airway diseases are present following acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 

Background

Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 predominantly infects the respiratory tract and induces a broad spectrum of illnesses such as acute respiratory distress syndrome (ARDS) and respiratory failure. COVID-19 convalescents demonstrate lung function abnormalities that last weeks to months following resolution of acute infection. Lung parenchymal abnormalities are typically seen on pulmonary imaging following severe SARS-CoV-2 infection.

Previous studies suggest that half of the adult SARS-CoV-2 survivors experience "long COVID" or post-acute sequelae of COVID-19 (PASC). About 30% of PASC patients experience respiratory symptoms, such as dyspnea and cough. PASC was even reported by those who had mild SARS-CoV-2 and were not hospitalized. Considering the millions of SARS-CoV-2 infections globally, most of whom had a mild illness, the potential burden of PASC on the healthcare systems is significant. Nonetheless, the long-term consequences of PASC on lung anatomy and function are still unknown.

About the study

In the current single-center study, the researchers tested if SARS-CoV-2 infection causes functional small airway disease (fSAD) in people who have had COVID-19 symptoms for a long time. The study was conducted at a university teaching hospital (University of Iowa, United States).

A total of 100 adults with confirmed SARS-CoV-2 infection who had symptoms for more than 30 days after diagnosis were prospectively recruited for the study from June to December 2020. Written informed consent was obtained from all subjects before inclusion. In addition, 106 healthy subjects prospectively enrolled during March to August 2018 as part of a different protocol served as controls. 

A confirmed SARS-CoV-2 infection was defined as a positive reverse transcription-polymerase chain reaction (RT-PCR), rapid antigen detection, or SARS-CoV-2 antibody test result. The 21 days following COVID-19 diagnosis was considered as period acute illness. Based on the level of treatment obtained during acute SARS-CoV-2 infection, subjects with PASC were categorized as requiring the intensive care unit (ICU), ambulatory, or hospitalized. 

Data on lung function tests, chest computed tomography (CT) images, and symptoms were procured. A quantitative CT test was carried out employing supervised machine learning to quantify regional ground-glass opacities (GGO). Further, inspiratory and expiratory image matching was conducted to identify regional air trapping. The participants were compared using multivariable linear regression and univariable evaluations.

Results

The results indicated that of the 100 PASC patients, 66 were females, and the mean age of the subjects was 48 years. There were 67, 17, and 16 PASC patients in the ambulatory, hospitalized and requiring ICU categories, respectively. The mean proportion of total lung classified as GGO was 0.06%, 3.7%, 13.2%, and 28.7% in controls, ambulatory, hospitalized, and ICU groups, respectively.

Although lung volumes and spirometry in ambulatory subjects were similar to the healthy controls, the proportion of lungs affected by GGO was elevated in the ambulatory group. This observation implies persistent lung edema, fibrosis, or inflammation in the ambulatory patients following SARS-CoV-2.

Further, the mean percent of total lung impacted by air trapping was 27.3%, 34.6%, 25.4%, and 7.2% in the ICU, hospitalized, ambulatory, and control groups, respectively. This indicates that the proportion of lungs impacted by air trapping was comparable among all PASC groups. Persistence in air trapping was observed in eight out of nine subjects imaged over 200 days following COVID-19 diagnosis. While air trapping was complementary to the residual volume to total lung capacity ratio, it did not correlate with spirometry. Thus, these findings indicate that COVID-19 could lead to air trapping and fSAD in the lungs.

Conclusions

The present prospective cross-sectional study demonstrates that among COVID-19 survivors with PASC, fSAD with air trapping was revealed in the quantitative examination of expiratory chest CT images irrespective of the severity of the initial infection. Thus, the fSAD represents the long-term sequelae of COVID-19. However, their long-standing ramifications remain uncertain.

Although spirometry often misses air trapping, plethysmography and inspiratory and expiratory CT imaging could identify it. Studies targeting the natural history of fSAD in PASC patients, and the molecular processes that underpin these findings, are urgently required to develop therapeutic and preventive measures. Furthermore, longitudinal studies will be needed to see if fSAD improves over time in people with PASC or if it leads to a permanent or worsening lung illness.