A new study finds a link between long COVID-a wide range of health problems patients continue to experience more than 4 weeks after being infected with COVID-19-and disease of the small airways in the lungs. Writing in the journal Radiology, a team led by University of Iowa researchers noted that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, primarily infects the respiratory tract and causes a wide range of disease severity, including respiratory failure due to acute respiratory distress syndrome (2022; https://doi.org/10.1148/radiol.212170).
The investigators pointed out that the long-term effects of SARS-CoV-2 infection on pulmonary structure and function "remain incompletely characterized," and they sought to test whether SARS-CoV-2 infection leads to small airways disease in patients with persistent symptoms.
Led by Alejandro Comellas, MD, Clinical Professor of Internal Medicine-Pulmonary, Critical Care, and Occupational Medicine at the University of Iowa, the team conducted a single-center study including adults with confirmed COVID-19 who remained symptomatic more than 30 days following diagnosis.
Study Details
The researchers enrolled 100 patients between June and December 2020, comparing them to 106 healthy participants prospectively enrolled between March and August 2018. Patients with post-acute sequelae of COVID-19 (PASC) were characterized as ambulatory, hospitalized, or requiring the intensive care unit (ICU) based on the highest level of care received during acute infection. Confirmed COVID-19 was defined as a positive rapid antigen or reverse transcriptase PCR test from a nasopharyngeal or oropharyngeal swab or a positive SARS-CoV-2 antibody test, and the period of acute infection with SARS-CoV-2 was defined as 21 days following diagnosis.
The researchers collected symptoms, pulmonary function tests, and computed tomography (CT) images, performing quantitative CT analysis using supervised machine learning to measure regional ground glass opacities (GCO) and inspiratory and expiratory image-matching to measure regional air trapping. Overall, 67 of the patients in the PASC group were classified as ambulatory, 17 were hospitalized, and 16 required ICU care.
Among the hospitalized and ICU groups, the mean percent of total lung classified as GCO was 12 percent and 29 percent, respectively, and was higher than that seen in the ambulatory group. The mean percentage of total lung affected by air trapping was 25 percent, 35 percent, and 27 percent in the ambulatory, hospitalized, and ICU groups, and 7 percent in healthy controls. Air trapping correlated with the residual volume to total lung capacity ratio, according to the authors, noting that small airways disease "occurred independently of initial infection severity" in survivors of COVID-19, with the long-term consequences still unknown.
In survivors of COVID-19, quantitative analysis of expiratory chest CT images demonstrated that small airways disease with the presence of air trapping "is a long-listing sequelae of SARS-CoV-2 infection," the researchers wrote.
Initially, the authors set up the clinic "to see patients who had been hospitalized with COVID," Comellas noted. "However, we began getting referrals for patients who had only mild acute illness with no hospitalization. All were complaining of shortness of breath. Their lung functions were normal. Conversely, we began seeing evidence of air trapping in many patients independent of initial disease severity. We decided to systematically examine whether patients had air trapping as a surrogate of small airway disease."
The results the study produced are the product of implementing an expiratory CT. "In the absence of this breathing maneuver, we would have missed this finding," Comellas noted. "At this time, we are unclear if the small airway disease is due to inflammation versus fibrosis of the airway. The former could be reversible, while the latter is not."
A critical message to emerge from the study is that health care providers "should obtain expiratory CTs in patients who are still symptomatic months later, after initial SARS CoV-2 infection. A normal inspiratory CT, normal lung function, or initial severity of illness are not predictive of whether patients could be suffering from small airways diseases manifested as air trapping," he said. "In addition, this finding can help in deciding some therapies and referral to pulmonary rehabilitation."
Mark McGraw is a contributing writer.