Exploring impacts of long-COVID-19 on the lungs: A triad of PET scans for perfusion, inflammation and tissue remodeling

BackgroundCOVID-19 patients may experience long-lasting complications, particularly impairment of lung function. The persistence of inflammation may lead to tissue remodeling, but the impact on the lungs in these patients remains unclear. Research QuestionIs there evidence of neutrophil-mediated inflammation, tissue remodeling, and altered lung perfusion in individuals with long COVID-19 experiencing dyspnea and reduced diffusion capacity? Additionally, can the PET imaging findings be correlated with proteomic data reflecting inflammatory status and clinical information? Study Design and MethodsPatient experiencing persistent dyspnea and reduced diffusion capacity for carbon monoxide 20 to 30 months after severe COVID-19 illness were recruited and underwent sequential PET scans using [15O]water, [68Ga]Ga-FAPI-46, and [11C]NES. Clinical lung function and 6-minute walking tests were performed before the scans. Blood samples were collected for plasma analysis using proximity extension analysis, which enabled the measurement of 96 inflammation-related biomarkers. ResultsSix male patients were recruited (age 64 {+/-} 7 [median {+/-} range] years). Patients with known impaired lung function prior to COVID-19 illness were excluded. [15O]water did not show a clear reduction in areas with signs of inflammation or tissue remodeling. However, all patients showed uptake of [68Ga]Ga-FAPI-46 and [11C]NES in the lungs, especially in areas associated with inflammation and remodeling. Patients were categorized into two groups based on tracer uptake: a low-uptake group and a high-uptake group. While the plasma inflammatory profiles differed between long-COVID-19 patients and healthy individuals, there was no clear correlation between the lung uptake of [68Ga]Ga-FAPI-46 and [11C]NES in long-COVID-19 patients. Similar observations were made regarding clinical parameters. InterpretationSequential PET scans using [15O]water, [68Ga]Ga-FAPI-46, and [11C]NES, allowed observation of signs of neutrophil-mediated inflammation and tissue remodeling in patients with long-COVID-19. However, no association with lung perfusion was demonstrated. Additionally, the results from the PET scans could not be clearly associated with clinical parameters or inflammatory proteomics.