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: Human SARS-CoV-2 infection can induce a wide spectrum of organ dysfunctions, including microvascular impairment [1]. S1 subunit of viral receptor-binding domain binds to the angiotensin-converting enzyme 2 receptor on endothelium and S2 subunit allows the virus to enter endothelial cells. The resulting breakdown of barrier integrity drives a cascade of infammatory and thrombotic events, that aggravate the course of COVID-19 together with other risk factors [2-4]. Up to date, a lower capillary density has been reported in several distinct body districts, using sublingual video microscopy, ocular optical coherence tomography angiography, skin functional laser Doppler perfusion imaging and nailfold videocapillaroscopy (NVC) [5-8]. NVC examination has been performed in adult COVID-19 patients, however, without a control group [8]. Objectives: To confrm the statistical signifcance of the reduction in capillary density per linear millimeter evaluated by NVC in comparison with primary Ray-naud's phenomenon (PRP) patients and control subjects (CNT) and to evaluate the impact of an aggressive therapy against COVID-19 on the sparing in the number of capillaries. Methods: Sixty-one COVID-19 survivors, thirty-one PRP patients and thirty CNT age and sex-matched underwent NVC analysis. Demographic and clinical data of COVID-19 survivors were collected with special regard to concomitant therapies, that included antivirals, antibiotics, anticoagulants and anti-infamma-tory/immunomodulant drugs (glucocorticoids, hydroxychloroquine, IL-6 receptor antagonist). COVID-19 survivors were divided in two subgroups according to the severity of the active infection: thirty-four survivors with past mild-moderate disease (either unneedy for oxygen supplementation or need for Venturi mask) and twenty-seven survivors with past severe disease (need for Continuous Positive Airways Pressure and/or mechanical ventilation). The same Rheumatologist performed NVC evaluations in all patients and controls, using an optical probe, equipped with a 200x magnifcation lens and connected to a picture analysis software (Videocap, DS Medica, Milan, Italy). Absolute capillary number per linear millimeter was counted. Results: COVID-19 survivors underwent NVC examination after a mean period of 126±53 days from the disease onset. Multivariate analysis showed differences in absolute capillary number per linear millimeter (p<0.001) after adjusting for age, sex, body mass index, comorbidities and concomitant drugs. The mean (± standard deviation) absolute nailfold capillary number per linear millimeter was signifcantly lower in severe (8.2±1.15) and mild-moderate (8.4±0.75) COVID-19 survivors than in both PRP (8.7±0.68) and CNT subjects (9.3±0.53) (p<0.001). The analysis of the impact of treatments on capillary density in the severe COVID-19 patients showed a positive trend (preservation of the capillary number) with antivirals (no: 7.8±1.53;yes: 8.5±0.64;p=0.35) and anti-IL-6 receptor antagonist administration (no: 7.8±1.36;yes: 8.6±0.74;p=0.16), while none of the other drugs was shown to be effective (glucocorticoids p = 0.46;antibiotics = 0.52;anticoagulants not evaluable as they were used in all COVID-19 patients). Conclusion: SARS-CoV-2 infection seems associated to a signifcant capillary loss as distinctive NVC feature and data concerning the comparison of capillary density pre COVID-19 and post COVID-19 are desirable to reinforce this observation. The positive trend in saving the number of capillaries induced by aggressive anti-infammatory therapies in COVID-19 survivors needs larger cohorts of 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.
ABSTRACT
Background: COVID-19 is a multifaceted condition with a wide range of clinical manifestations, including microvascular/endothelial dysfunction, that starts in the early phase of the disease and may become dramatically harmful in the late stage, causing a massive pro-thrombotic state. Nailfold videocapillaroscopy (NVC) is the most used tool to identify microvascular status in a large spectrum in a cohort of COVID-19 patients (no controls used) [2]. Objectives: To assess microvascular damage in recovered COVID-19 patients (range of 40-270 days from recovery) by considering the previous severity of the disease, and, as mandatory, the comparison with matched individuals suffering from primary Raynaud's phenomenon (PRP) and healthy volunteers (HV). Methods: NVC investigations were performed during standard clinical assessments in forty-four recovered COVID-19 patients (mean age 58±14 years, mean days from disease onset 129±54, mean days from disease recovery 106±52), twenty-two patients with PRP (mean age 60±15 years, mean years from disease onset 11±10) and twenty-two HV (mean age 60±14 years). COVID-19 patients were divided into two subgroups, according to the need of oxygen supplementation: twenty-two patients with severe lung involvement (need of Continuous Positive Airways Pressure and/or mechanical ventilation, mean age 57±12 years) vs twenty-two patients with mild-moderate lung involvement (need of Venturi mask or no need of oxygen supplementation, mean age 59±15 years). Clinical and demographic data of all the enrolled subjects were collected, during NVC examination. The following capillaroscopic parameters were evaluated: capillary number, dilated capillaries, giant capillaries, microhemorrhages, angiogenesis, disorganization of the microvascular array. A validated semiquantitative scoring (0-3) was adopted for NVC abnormalities [3-5]. Statistical analysis was carried out by non-parametric tests. Results: After COVID-19 recovery, no statistically significant difference was observed between COVID-19 patients and control groups of subjects concerning the score for the following NVC parameters: dilated capillaries, giant capillaries, disorganization of the microvascular array, angiogenesis. However, the capillary number per linear millimeter was significantly lower in COVID-19 patients (8.3±0.9) than in PRP (8.8±0.7, p=0.05) and HV (9.3±0.6, p<0.0001). Surprisingly, recovered COVID-19 patients showed significantly less microhemorrhages (score 0.4±0.3) than subjects of the other groups (PRP 0.6±0.5, p=0.01;HV 0.6±0.6, p=0.05). In particular, recovered patients who had more severe COVID-19 showed less microhemorrhages than patients with mild/moderate disease (score 0.18±0.4 vs 0.36±0.5), but this didn't reach the statistical significance (p=0.18). On the other hand, patients recovered from severe SARS-CoV-2 infection also showed higher rate of angiogenesis (0.18±0.4) than patients with mild/ moderate disease (no case, p=0.04). Conclusion: COVID-19 doesn't seem to significantly induce, in short-term, specific alterations in peripheral microvascular array as evaluated by NVC, despite the severity of the disease, except for a significant reduction of the absolute number of nailfold capillaries. The topic needs longer time of evaluation and larger number of COVID-19 recovered cases to also assess the role of concomitant therapies.
ABSTRACT
Backgrounds: Available data indicate that a large minority of patients with COVID-19 develop ARDS, and pulmonary fibrosis is a recognized sequela of ARDS. However, the long-term pulmonary consequences of COVID-19 remain speculative. The aim of this study is to evaluate risk factors, prevalence and characteristics of POST-COVID-19 interstitial lung changes, with the unique opportunity to evaluate radiologic and pathologic correlations using HRCT and transbronchial lung cryobiopsy specimens.Methods: Here we present the preliminary data on HRCT features of POST-COVID-19 ILD. Data were collected at the time of the first interim analysis (28/11/2020) of the PCOILS trial: a prospective, multicenter national study involving 12 Italian centers (Fig 1). We collected data of consecutively hospitalized patients at baseline and then at 6 (+/-1) months after hospital discharge. HRCT changes at 6 months involving more than 5% of the total lung volume were considered significant. Patients with significant HRCT changes will undergo BAL and/or cryobiopsy and a subsequent follow-up with HRCT and lung function evaluation at 12(+/-1) and 18 (+/-1) months.Results: At the time of the present interim analysis, 524 patients from 9 centers were enrolled (enrollment is still ongoing and will end on January 31st, 2021). Median age was 67 years (range 18-87), 330 were males (62.9%). HRCT changes were detected in 333 participants (63.5%), and in 219 (41.7%) were considered significant. 118 cases (22.5%) showed fibrotic changes including the following HRCT patterns: 7 (1.3%) probable UIP, 45 (8.5%) NSIP (with or without OP), 38 (7.2%) indeterminate, 28 (5.3%) fibrotic consolidations. Among the remaining 101 (19.2%) non fibrotic cases the radiologists described: 11 (2%) NSIP-OP, 15 (2.8%) indeterminate, 67 (12.7%) pure ground glass, 8 (1.5%) consolidations all suspected for lung cancer. Conclusions: This preliminary analysis confirms that after COVID-19 infection a large minority of patients develops interstitial lung changes mostly with NSIP-OP, indeterminate features or ground glass. The hypothesis that post-COVID-19 interstitial changes and interstitial lung diseases may share common risk factors, pathogenetic mechanisms and disease behaviour warrants further evaluations. .