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.
ABSTRACT
Background-Aim: While there's a wide literature on CT abnormalities in COVID-19 sequelae, the role of lung perfusion scintigraphy have been scarcely investigated. Recent findings reported lung microvascular and endothelial alterations in patients recovered from COVID-19 without pulmonary embolism, presenting persistent dyspnea (POST-COVID). We compared perfusion scintigraphy and CT findings of these patients with dyspneic subjects in whom lung scintigraphy excluded pulmonary embolism (NON-COVID). In POST-COVID patients, the correlation between lung perfusion scintigraphic findings and (1) CT abnormalities, and (2) clinical/ biochemical parameters were also assessed. Methods: 24 POST-COVID and 33 NON-COVID patients who underwent lung perfusion scintigraphy for dyspnea from March 2020 to December 2021 were retrospectively enrolled. High-resolution chest CT performed 15 days before/after lung perfusion scintigraphy were available in 15/24 POST-COVID and 15/33 NON-COVID patients. From scintigraphic images counting rates for upper, middle, and lower fields were calculated in order to compute their ratio with total lung counts (UTR, MTR, and LTR, respectively) for both right and left lungs (RL and LL, respectively). CT images were analyzed using a semi-automated segmentation algorithm of 3D Slicer ( http://www.slicer.org), obtaining total, infiltrated and blood vessels' volumes, in order to calculate the infiltration rate (IR) and vascular density (VD). White blood cells, platelets, PT, INR, PTT, fibrinogen, and D-dimer of 15/24 POST-COVID patients were also collected from blood tests performed before the lung perfusion scintigraphy. Results: POST-COVID patients with persistent dyspnea showed reduced LTR (RL 22.4% ± 6.6%;LL 24.7% ± 3.1%) and higher MTR (RL 55.2% ± 5.2%;LL 49.1% ± 3.3%) compared to non- COVID patients (RL-LTR 29.6% ± 6.0%, p<0.0001;LL-LTR 28.3% ± 4.6%, p = 0.001;RL-MTR 47.3% ± 4.2%, p<0.0001;LL-MTR 47.3% ± 3.0%, p = 0.036), while UTR resulted bilaterally superimposable between the two groups. Similar IR and VD values at CT imaging were documented bilaterally in both groups. In POSTCOVID patients, no significant correlations between lung perfusion scintigraphy and CT findings were observed. Correlation analysis indicated D-dimer levels as associated with UTR (Pearson's r = 0.664;p = 0.007) and MTR (Pearson's r = - 0.555;p = 0.032), while no parameter significantly associated with LTR was observed. Conclusions: Lung perfusion scintigraphy can reveal reduced perfusion rates of lower pulmonary fields in POST-COVID patients with persistent dyspnea in the absence of pulmonary embolism, independently from CT abnormalities, infection duration and coagulation biomarkers. Although mechanisms underlying these findings need to be supported by pathological lung tissue examination, lung nonthrombotic microvascular and endothelial dysfunction may be involved.