Small Airways Disease is a Post-Acute Sequelae of SARS-CoV-2 Infection

 Josalyn L. Cho,  

View ORCID ProfileRaul Villacreses, Prashant Nagpal, Junfeng Guo,  View ORCID ProfileAlejandro A. Pezzulo, Andrew L. Thurman,  View ORCID ProfileNabeel Y. Hamzeh, Robert J. Blount,  View ORCID ProfileSpyridon Fortis,  View ORCID ProfileEric A. Hoffman,  View ORCID ProfileJoseph Zabner,  View ORCID ProfileAlejandro P. Comellas

doi: https://doi.org/10.1101/2021.05.27.21257944

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.05.27.21257944v1.full.pdf

Abstract

Background The sequelae of SARS-CoV-2 infection on pulmonary structure and function remain incompletely characterized.

Methods Adults with confirmed COVID-19 who remained symptomatic more than thirty days following diagnosis were enrolled and classified as ambulatory, hospitalized or requiring the intensive care unit (ICU) based on the highest level of care received during acute infection. Symptoms, pulmonary function tests and chest computed tomography (CT) findings were compared across groups and to healthy controls. CT images were quantitatively analyzed using supervised machine-learning to measure regional ground glass opacities (GGO) and image-matching to measure regional air trapping. Comparisons were performed using univariate analyses and multivariate linear regression.

Results Of the 100 patients enrolled, 67 were in the ambulatory group. All groups commonly reported cough and dyspnea. Pulmonary function testing revealed restrictive physiology in the hospitalized and ICU groups but was normal in the ambulatory group. Among hospitalized and ICU patients, the mean percent of total lung classified as GGO was 13.2% and 28.7%, respectively, and was higher than in ambulatory patients (3.7%, P<0.001). The mean percentage of total lung affected by air trapping was 25.4%, 34.5% and 27.2% in the ambulatory, hospitalized and ICU groups and 7.3% in healthy controls (P<0.001). Air trapping measured by quantitative CT correlated with the residual volume to total lung capacity ratio (RV/TLC; ρ=0.6, P<0.001).

Conclusions Air trapping is present in patients with post-acute sequelae of COVID-19 and is independent of initial infection severity, suggesting obstruction at the level of the small airways. The long-term consequences are not known.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

This was not a clinical trial and just an observational cohort

Funding Statement

This work was supported by grants from the National Institutes of Health (R01HL112986 and S10OD018526 to EAH; R01HL136813, P01HL152960, P01HL091842, P30DK054759 and T32HL007638 to JZ).

https://www.medrxiv.org/content/10.1101/2021.05.27.21257944v1