Persistent dyspnea in post-COVID patients in the absence of pulmonary embolism: added value of lung perfusion scintigraphy

ABSTRACT

Aim/Introduction: While there's a wide literature on Computed Tomography (CT) abnormalities in COVID-19 sequelae, the role of lung perfusion scintigraphy has been scarcely investigated. Recent findings reported lung microvascular and endothelial alterations in patients recovered from COVID-19 without pulmonary embolism (PE), presenting persistent dyspnea (post-COVID). We compared perfusion scintigraphy and CT findings of post-COVID patients with dyspneic subjects in whom lung scintigraphy excluded pulmonary embolism (non-COVID). The correlation between lung perfusion scintigraphy findings and 1) CT abnormalities and 2) clinical/biochemical parameters were also assessed. Material(s) and Method(s) 18 post-COVID and 20 non-COVID patients who underwent lung perfusion scintigraphy and chest high-resolution CT for dyspnea from March 2020 to April 2022 were retrospectively enrolled. From lung perfusion scintigraphy images, counting rates for upper, middle, and lower fields were normalized for the total lung counts to calculate the corresponding ratios (UTR, MTR, and LTR, respectively). CT images were analyzed using a semiautomated segmentation algorithm of 3DSlicer (www.slicer. org), obtaining total, emphysematous, infiltrated and collapsed volumes, normalized for the total lung volumes. Similarly, blood vessel's volumes were collected to compute the vascular density. White blood cells (WBC) count, PT, INR, PTT and D-dimer of both groups, and the infection duration of post-COVID patients were collected from clinical records and blood tests performed before the lung perfusion scintigraphy. Result(s) At the per lung analysis, post-COVID patients with persistent dyspnea showed reduced LTR (24.67>5.08) and higher MTR (52.51>5.22) compared to non-COVID patients (29.85>5.05 and 46.66>3.94, respectively;p<0.0001 for both), while UTR resulted bilaterally superimposable between the two groups. At CT imaging, the rates of emphysematous, infiltrated and collapsed volumes and the vascular density were bilaterally similar in both groups. In post-COVID patients, LTR correlated with the percentage of emphysematous (r=0.498;p<0.01), infiltrated (r=-0.464;p=<0.01) and collapsed (r=-0.463;p<0.01) lungs, while no significant correlations were observed between LTR and CTderived volumes in non-COVID subjects. There was no correlation between lung perfusion scintigraphy parameters with infection duration in post-COVID, WBC, and coagulation biomarkers in both groups. Conclusion(s) Lung perfusion scintigraphy can reveal reduced perfusion rates of lower pulmonary fields in post-COVID patients with persistent dyspnea without pulmonary embolism. This phenomenon is correlated with structural lung modifications, including lung parenchymal emphysema, infiltration and collapse, and is independent of infection duration and coagulation biomarkers. Although mechanisms underlying these findings need to be supported by pathological lung tissue examination, pulmonary non-thrombotic microvascular and endothelial dysfunction may be involved.