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Background: Patients suffering from Post-Acute Sequelae of SARS CoV-2 (PASC) infection may benefit from a pulmonary rehabilitation program (PRP). However, patients respond differently to the protocols. Treatment selection based on sensitive endpoints remains arbitrary. Can quantitative CT play a role in providing a safe, effective PRP? Methods: Two patients admitted for PRP were tested. A low dose quantitative CT scan was taken. Functional respiratory imaging (FRI) was performed on the scans. FRI, Lung function and blood vessel analysis were used for clinical decision making in treatment protocol. Result(s): At visit 1, patient 1 showed a significant decrease in small blood vessel volume and increased volume for the larger vessels (fig 1). This vascular redistribution resulted in cardiac disturbances. Therefore, patient 1 was treated with corticosteroids. Patient 2 showed no deviations on the proportion of blood volume in vessels with a cross-sectional area between 1.25 and 5mm2 (BV5%) and enrolled in the PRP. Patients were re-evaluated after 3 months. Patient 1 improved significantly, recovered, and showed normalized results in BV5%. In Patient 2 V02max changed from 1728 to 2738 ml/min from 52% to 84% predicted. Conclusion(s): Vascular density endpoints as BV5% can be considered as identifier for selection of patient for a PRP in long-COVID, and potentially other pathologies. Once normalized, patients can safely enroll in a PRP.
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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.
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Purpose : The effects of COVID-19 on the retina have been debated since the start of the pandemic. This study aims to assess how COVID-19 may alter retinal microvasculature using wide-field swept-source optical coherence tomography angiography (WF SS-OCTA). Methods : This prospective, cross-sectional, observational study included patients with a positive COVID-19 polymerase chain reaction (PCR) test who underwent WF SS-OCTA imaging from August 2020 to November 2021. The mean days from PCR diagnosis to imaging was 175.6. Age-matched controls included healthy eyes and fellow eyes of retinal detachment, retinal tears, retinal artery occlusion, and retinal vein occlusion. Patients with diabetes, uncontrolled hypertension, retinal disease, prior retinal surgery, and a positive COVID-19 test >365 days before imaging were excluded. Vessel density (VD) and vessel skeletonized density (VSD) were calculated (Macular Density Algorithm v0.7.3.3, ARI Network) for the superficial capillary plexus (SCP), deep capillary plexus (DCP), and whole retina using 3x3, 6x6, and 12x12 mmscans centered on the fovea. A mixed-effect multivariate multilevel linear regression model was used to identify any difference between controls and COVID-19 groups. Results : 34 eyes of 29 patients with COVID-19 and 54 eyes of 45 controls were included. Generalized reductions in VD and VSD were seen in COVID-19 eyes compared to controls (Fig 1). Controlling for age, COVID-19 was associated with a statistically significant overall reduction in VD in the SCP and whole retina in 3x3 mmand DCP of 6x6 mm scans as well as decreased VSD in the DCP in 6x6 mm scans(Table 1). Looking at changes by region, COVID-19 eyes had significant reductions in superior sectors in VD across all scan sizes and layers except the whole retina in 6x6 mm scans, and in VSD across all scan sizes and layers except the SCP in 3x3 and 6x6 mm scans and whole retina in 6x6 mm scans. Additional region-specific reductions in VD and VSD were seen in the DCP in 6x6 and 12x12 mm scans, whole retina in 12x12 mmscans, and SCP in 12x12 mmscans. Conclusions : Patients with COVID-19 showed reduced VD and VSD compared to controls. This may indicate that there are some retinal microvasculature changes in patients with prior COVID-19 infection. (Figure Presented).
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Purpose : Long-COVID is assumed to have an autoimmune component. As a seropositivity of functional active autoantibodies against G-protein coupled receptors (GPCR-AAb) and an impaired retinal microcirculation, measured by OCT-angiography (OCT-A), was observed after COVID-19 infection, it was the aim of the present study to investigate the impact of GPCR-AAbs on retinal microcirculation in patients with LongCOVID. Methods : Seventy-six patients with Long-COVID (COVID-19 infection was confirmed by real time rt-PCR) were recruited. A seropositivity for GPCR-AAbs (Nociceptin-AAb, ß2-AAb, AT1-AAb, α1-AAb, MAS-AAb, M2-AAb, ETA-AAb) was analyzed by a specific rat cardiomyocyte bioassay in vitro. Macular (superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP)) and peripapillary vessel density (VD) were measured by OCT-A (Spectralis II, Heidelberg, Germany). VD analysis was done by the Erlangen-Angio tool, including an APSifyed and Bruch's membrane opening (BMO) based analysis. Data were analyzed by mixed model (SAS version 9.4). Gender and age were set as covariates. The study was approved by the local ethics committee and was done in accordance with the tenets of the Declaration of Helsinki. Informed consent was achieved. Results : All patients with Long-COVID showed a seropositivity for GPCR-AAbs (100%). Female patients with Long-COVID showed lower macular and peripapillary VD compared to men. A significant effect of a seropositivity of AT1-AAb on age-corrected least squares means (LS-means) overall VD of DCP ([CI: 0,25;6.07], p=0.03). A seropositivity of α1-AAb showed a significant effect on age-corrected LS-mean overall VD of SVP ([CI: 0.07;2.69], p=0.04), of DCP ([CI: 0.36;3.25], p=0.01), and of PH ([CI: 1.17;5.59], p=0.01), respectively. A seropositivity of MAS-AAb yielded a significant effect on age-corrected LS-mean overall VD of DH (CI: 1.48;6.07, p=0.001). A seropositivity of ß2-AAb has a significant effect on agecorrected LS-mean overall VD of MH (CI: 0,02;1,94, p=0.04). For those effects, the covariate age was significant in the type III tests (p<0.05), thus analysis was done considering this age-effect. Conclusions : As autoimmune mechanisms were reported to be involved in the pathogenesis of Long-COVID, we postulate that functional active GPCR-AAb may have an impact on retinal microcirculation, being a propable correlate to systemic disease.
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Purpose : OCTA is a non-invasive imaging technique for assessment of retino-choroidal vasculature. It allows for the quantitative assessment of retinal microvasculature. This study evaluates macular vessel density (VD), foveal avascular zone (FAZ) area, subfoveal choroidal thickness (SFCT) and retinal layer metrics by optical coherence tomography angiography (OCTA) in COVID-19 recovered patients. Additionally we studied the correlation of OCTA parameters with severity and duration of COVID-19 disease, steroid administration, and vaccination status. Methods : It is a case-control study of 180 patients. OCTA parameters namely-superficial and deep VD in various sectors-total, superior, inferior, central, inner, superior-inner, inferior-inner, full;superficial and deep FAZ area;SFCT: central subfield thickness (CST) were measured. Additionally, retinal layer metrics, including nerve fiber layer, ganglion cell layer-inner plexiform complex, inner nuclear layer, outer plexiform layer, and outer nuclear layer were compared between cases and controls. A correlation analysis of OCTA parameters was done with severity and duration of disease. Results : FAZ area (superficial and deep);retinal layer metrics including ganglion cell layer and inner plexiform layer, outer plexiform layer and outer nuclear layer showed significant reduction while there was a significant increase in SFCT in COVID-19 patients. Corticosteroid treatment resulted in significant decrease in VD. A positive correlation was elicited between FAZ area and disease duration;while VD correlated negatively with the duration of disease. Multivariate analysis showed significant relationship between superficial FAZ area, deep FAZ area and SFCT. Conclusions : OCTA showed alteration in retinal microvasculature and metrics in COVID-19 patients. Choroid being a highly vascular structure was also affected. There was a resultant alteration in FAZ area and SFCT. Moreover, thrombotic phenomenon associated with COVID could alter retinal layer metrics. Additionally, corticosteroids also appear to alter retinal microvasculature. This study could help understand the wide-spread thrombotic phenomenon often associated with COVID infection and predisposition for the same among specific patients.
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.