Lung Ultrasound in the Diagnosis of COVID-19 Pneumonia: Not Always and Not Only What Is COVID-19 "Glitters".

Background: In the current coronavirus disease-2019 (COVID-19) pandemic, lung ultrasound (LUS) has been extensively employed to evaluate lung involvement and proposed as a useful screening tool for early diagnosis in the emergency department (ED), prehospitalization triage, and treatment monitoring of COVID-19 pneumonia. However, the actual effectiveness of LUS in characterizing lung involvement in COVID-19 is still unclear. Our aim was to evaluate LUS diagnostic performance in assessing or ruling out COVID-19 pneumonia when compared with chest CT (gold standard) in a population of SARS-CoV-2-infected patients. Methods: A total of 260 consecutive RT-PCR confirmed SARS-CoV-2-infected patients were included in the study. All the patients underwent both chest CT scan and concurrent LUS at admission, within the first 6-12 h of hospital stay. Results: Chest CT scan was considered positive when showing a "typical" or "indeterminate" pattern for COVID-19, according to the RSNA classification system. Disease prevalence for COVID-19 pneumonia was 90.77%. LUS demonstrated a sensitivity of 56.78% in detecting lung alteration. The concordance rate for the assessment of abnormalities by both methods increased in the case of peripheral distribution and middle-lower lung location of lesions and in cases of more severe lung involvement. A total of nine patients had a "false-positive" LUS examination. Alternative diagnosis included chronic heart disease (six cases), bronchiectasis (two cases), and subpleural emphysema (one case). LUS specificity was 62.50%. Collateral findings indicative of overlapping conditions at chest CT were recorded also in patients with COVID-19 pneumonia and appeared distributed with increasing frequency passing from the group with mild disease (17 cases) to that with severe disease (40 cases). Conclusions: LUS does not seem to be an adequate tool for screening purposes in the ED, due to the risk of missing some lesions and/or to underestimate the actual extent of the disease. Furthermore, the not specificity of LUS implies the possibility to erroneously classify pre-existing or overlapping conditions as COVID-19 pneumonia. It seems more safe to integrate a positive LUS examination with clinical, epidemiological, laboratory, and radiologic findings to suggest a "virosis." Viral testing confirmation is always required.

Pycnogenol®-Centellicum® supplementation improves lung fibrosis and post-COVID-19 lung healing.

BACKGROUND: The aim of this study was to evaluate the combination of Pycnogenol® (150 mg/day) (Horphag Research, London, UK) and Centella asiatica (Centellicum® 3×225 mg/day; Horphag Research) (PY-CE) for 8 months in subjects with sequelae of idiopathic interstitial pneumonia (IIP). Recently, post-COVID-19 lung disease is emerging with large numbers of patients left with chronic lung conditions. Considering the antifibrotic activity of the combination PY-CE, we also tested this supplementary management in post-COVID-19 lung patients. METHODS: Nineteen subjects with idiopathic interstitial pneumonia (IIP) were included in the study. High Resolution CT scans at inclusion confirmed the presence of lung fibrosis: 10 patients were treated with the Pycnogenol® Centellicum® combination and 9 subjects with standard management (SM) served as controls. Oxidative stress that was very high in all subjects at inclusion, decreased significantly in the supplement group (P<0.05). The Karnofsky Performance Scale Index significantly improved in the supplement group in comparison with controls (P<0.05). The symptoms (fatigue, muscular pain, dyspnea) were significantly lower after 8 months in supplemented patients (P<0.05) as compared with controls. RESULTS: At the end of the study, the small cystic lesions (honeycombing) and traction bronchiectasis were stable or in partial regression in 4 subjects in the supplemented group (vs. none in the control group) with a significant improvement in tissue edema in the supplemented subjects. On ultrasound lung scans the white (more echogenic) fibrotic component at inclusion was 18.5±2.2% in the images in controls vs. 19.4±2.7% in the supplement group. At the end of the study, there was no improvement in controls (18.9±2.5%) vs. a significant improvement in supplemented subjects (16.2±2.1%; P<0.05). In addition, 18 subjects with post-COVID-19 lung disease were included in the study; 10 patients were treated with the Pycnogenol® Centellicum® combination and evaluated after 4 weeks; 8 patients served as controls. Preliminary results show that symptoms associated with post-COVID-19 lung disease after 4 weeks were significantly improved with the supplement combination (P<0.05). Oxidative stress and the Karnofsky Performance Scale Index were significantly improved in the supplements group as compared with controls (P<0.05). CONCLUSIONS: According to these observations, Pycnogenol® controls and decreases edema and Centellicum® by modulating the apposition of collagen, slows down the development of irregular cicatrization, the keloidal scarring and fibrosis. More time is needed to evaluate this effect in a larger number of post-COVID-19 patients with lung disease. This disease has affected millions of subjects worldwide, leaving severe consequences. Pycnogenol® and Centellicum® may improve the residual clinical picture in post-COVID-19 lung disease (PCL) patients and may reduce the number of subjects evolving into lung fibrosis. The evolution from edema to fibrosis seems to be slower or attenuated with this supplement combination both in Idiopathic pulmonary fibrosis (IPF) and in PCL patients.

Preventive effects of Pycnogenol® on cardiovascular risk factors (including endothelial function) and microcirculation in subjects recovering from coronavirus disease 2019 (COVID-19).

BACKGROUND: The aim of this open supplement study was to evaluate the effects of Pycnogenol® in comparison with controls on symptoms of post-COVID-19 syndrome and in improving endothelial function, microcirculation, inflammatory markers and oxidative stress over 3 months in symptomatic subjects recovering from COVID-19. METHODS: Sixty subjects recovering from symptomatic COVID-19 were included. One group of 30 followed a standard recovery management while 30 comparable subjects received a supplement of 150 mg Pycnogenol® daily (in 3 doses of 50 mg) in addition to standard management. RESULTS: Two groups of selected subjects were comparable at baseline. The groups progressively improved both with the SM (standard management) and with the SM in combination with the supplement. Patients, supplemented with Pycnogenol® showed significantly better improvement compared to the control group patients. No side effects from the supplementation were observed; tolerability was optimal. The progressive evolution over time was visible in all target measurements. Physiological tests: endothelial function, low in all subjects at inclusion was assessed by flow mediated dilation (FMD) and finger reactive hyperemia in the microcirculation (laser Doppler measurements) after the release of an occluding suprasystolic cuff. It was significantly improved in the Pycnogenol® group after one month and after 3 months (P<0.05 vs. controls). The rate of ankle swelling (RAS) by strain gauge decreased significantly in the supplemented group (P<0.05) in comparison with controls showing an improvement of the capillary filtration rate. At inclusion, the kidney cortical flow velocity indicated a decrease in perfusion (lower systolic and diastolic flow velocity) in all patients. Kidney cortical flow velocity increased significantly with the supplement (P<0.05) in comparison with controls with improvement in systolic velocity and in diastolic component. High sensitivity CRP (hs-CRP) and Il-6 plasma levels decreased progressively over 3 months with a significant more pronounced decrease in the supplement group (P<0.05). The number of patients with normal plasma IL-6 levels at the end of the study was higher (P<0.05) with the supplement. ESR followed the same pattern with a progressive and a more significant decrease in the supplemented subjects (P<0.02). Oxidative stress decreased significantly in the supplemented group (P<0.05) compared with the control group. Systolic blood pressure was significantly lower in the supplemented group (P<0.05) at the end of the study. Finally, the scores of Quality-of-life, mood and fatigue questionnaire and the Karnofsky Scale Performance Index significantly improved in the supplement group (P<0.05) compared to controls after 1 and 3 months. All other blood parameters (including platelets and clotting factors) were within normal values at the end of the study. CONCLUSIONS: In conclusion, Pycnogenol® may offer a significant option for managing some of the signs and symptoms associated with post-COVID-19 syndrome. This pilot evaluation offers some potential rationale for the use of Pycnogenol® in this condition that will have significant importance in the coming years.

Low Sensitivity of Admission Lung US Compared to Chest CT for Diagnosis of Lung Involvement in a Cohort of 82 Patients with COVID-19 Pneumonia.

Background and Objectives: The potential role of lung ultrasound (LUS) in characterizing lung involvement in Coronavirus disease 2019 (COVID-19) is still debated. The aim of the study was to estimate sensitivity of admission LUS for the detection of SARS-CoV-2 lung involvement using Chest-CT (Computed Tomography) as reference standard in order to assess LUS usefulness in ruling out COVID-19 pneumonia in the Emergency Department (ED). Methods: Eighty-two patients with confirmed COVID-19 and signs of lung involvement on Chest-CT were consecutively admitted to our hospital and recruited in the study. Chest-CT and LUS examination were concurrently performed within the first 6-12h from admission. Sensitivity of LUS was calculated using CT findings as a reference standard. Results: Global LUS sensitivity in detecting COVID-19 pulmonary lesions was 52%. LUS sensitivity ranged from 8% in case of focal and sporadic ground-glass opacities (mild disease), to 52% for a crazy-paving pattern (moderate disease) and up to 100% in case of extensive subpleural consolidations (severe disease), although LUS was not always able to detect all the consolidations assessed at Chest-CT. LUS sensitivity was higher in detecting a typical Chest-CT pattern (60%) and abnormalities showing a middle-lower zone predominance (79%). Conclusions: As admission LUS may result falsely negative in most cases, it should not be considered as a reliable imaging tool in ruling out COVID-19 pneumonia in patients presenting in ED. It may at least represent an expanded clinical evaluation that needs integration with other diagnostic tests (e.g., nasopharyngeal swab, Chest-CT).

Coronavirus Disease 2019 (COVID-19) in Italy: Double Reading of Chest CT Examination.

To assess the performance of the second reading of chest compute tomography (CT) examinations by expert radiologists in patients with discordance between the reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test for COVID-19 viral pneumonia and the CT report. Three hundred and seventy-eight patients were included in this retrospective study (121 women and 257 men; 71 years median age, with a range of 29-93 years) and subjected to RT-PCR tests for suspicious COVID-19 infection. All patients were subjected to CT examination in order to evaluate the pulmonary disease involvement by COVID-19. CT images were reviewed first by two radiologists who identified COVID-19 typical CT patterns and then reanalyzed by another two radiologists using a CT structured report for COVID-19 diagnosis. Weighted к values were used to evaluate the inter-reader agreement. The median temporal window between RT-PCRs execution and CT scan was zero days with a range of (-9,11) days. The RT-PCR test was positive in 328/378 (86.8%). Discordance between RT-PCR and CT findings for viral pneumonia was revealed in 60 cases. The second reading changed the CT diagnosis in 16/60 (26.7%) cases contributing to an increase the concordance with the RT-PCR. Among these 60 cases, eight were false negative with positive RT-PCR, and 36 were false positive with negative RT-PCR. Sensitivity, specificity, positive predictive value and negative predictive value of CT were respectively of 97.3%, 53.8%, 89.0%, and 88.4%. Double reading of CT scans and expert second readers could increase the diagnostic confidence of radiological interpretation in COVID-19 patients.

COVID-19 pneumonia: computer-aided quantification of healthy lung parenchyma, emphysema, ground glass and consolidation on chest computed tomography (CT).

OBJECTIVE: To calculate by means of a computer-aided tool the volumes of healthy residual lung parenchyma, of emphysema, of ground glass opacity (GGO) and of consolidation on chest computed tomography (CT) in patients with suspected viral pneumonia by COVID-19. MATERIALS AND METHODS: This study included 116 patients that for suspected COVID-19 infection were subjected to the reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test. A computer-aided tool was used to calculate on chest CT images healthy residual lung parenchyma, emphysema, GGO and consolidation volumes for both right and left lung. Expert radiologists, in consensus, assessed the CT images using a structured report and attributed a radiological severity score at the disease pulmonary involvement using a scale of five levels. Nonparametric test was performed to assess differences statistically significant among groups. RESULTS: GGO was the most represented feature in suspected CT by COVID-19 infection; it is present in 102/109 (93.6%) patients with a volume percentage value of 19.50% and a median value of 0.64 L, while the emphysema and consolidation volumes were low (0.01 L and 0.03 L, respectively). Among quantified volume, only GGO volume had a difference statistically significant between the group of patients with suspected versus non-suspected CT for COVID-19 (p < < 0.01). There were differences statistically significant among the groups based on radiological severity score in terms of healthy residual parenchyma volume, of GGO volume and of consolidations volume (p < < 0.001). CONCLUSION: We demonstrated that, using a computer-aided tool, the COVID-19 pneumonia was mirrored with a percentage median value of GGO of 19.50% and that only GGO volume had a difference significant between the patients with suspected or non-suspected CT for COVID-19 infection.

Coronavirus disease 2019 (COVID-19) in Italy: features on chest computed tomography using a structured report system.

To assess the use of a structured report in the Chest Computed Tomography (CT) reporting of patients with suspicious viral pneumonia by COVID-19 and the evaluation of the main CT patterns. This study included 134 patients (43 women and 91 men; 68.8 years of mean age, range 29-93 years) with suspicious COVID-19 viral infection evaluated by reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test. All patients underwent CT examinations at the time of admission. CT images were reviewed by two radiologists who identified COVID-19 CT patterns using a structured reports. Temporal difference mean value between RT-PCRs and CT scan was 0.18 days ± 2.0 days. CT findings were positive for viral pneumonia in 94.0% patients while COVID-19 was diagnosed at RT-PCR in 77.6% patients. Time mean value to complete the structured report by radiologist was 8.5 min ± 2.4 min. The disease on chest CT predominantly affected multiple lobes and the main CT feature was ground glass opacity (GGO) with or without consolidation (96.8%). GGO was predominantly bilateral (89.3%), peripheral (80.3%), multifocal/patching (70.5%). Consolidation disease was predominantly bilateral (83.9%) with prevalent peripheral (87.1%) and segmental (47.3%) distribution. Additional CT signs were the crazy-paving pattern in 75.4% of patients, the septal thickening in 37.3% of patients, the air bronchogram sign in 39.7% and the "reversed halo" sign in 23.8%. Less frequent characteristics at CT regard discrete pulmonary nodules, increased trunk diameter of the pulmonary artery, pleural effusion and pericardium effusion (7.9%, 6.3%, 14.3% and 16.7%, respectively). Barotrauma sign was absent in all the patients. High percentage (54.8%) of the patients had mediastinal lymphadenopathy. Using a Chest CT structured report, with a standardized language, we identified that the cardinal hallmarks of COVID-19 infection were bilateral, peripheral and multifocal/patching GGO and bilateral consolidation with peripheral and segmental distribution.

Chest CT Computerized Aided Quantification of PNEUMONIA Lesions in COVID-19 Infection: A Comparison among Three Commercial Software

Purpose: To compare different commercial software in the quantification of Pneumonia Lesions in COVID-19 infection and to stratify the patients based on the disease severity using on chest computed tomography (CT) images. Materials and methods: We retrospectively examined 162 patients with confirmed COVID-19 infection by reverse transcriptase-polymerase chain reaction (RT-PCR) test. All cases were evaluated separately by radiologists (visually) and by using three computer software programs: (1) Thoracic VCAR software, GE Healthcare, United States;(2) Myrian, Intrasense, France;(3) InferRead, InferVision Europe, Wiesbaden, Germany. The degree of lesions was visually scored by the radiologist using a score on 5 levels (none, mild, moderate, severe, and critic). The parameters obtained using the computer tools included healthy residual lung parenchyma, ground-glass opacity area, and consolidation volume. Intraclass coefficient (ICC), Spearman correlation analysis, and non-parametric tests were performed. Results: Thoracic VCAR software was not able to perform volumes segmentation in 26/162 (16.0%) cases, Myrian software in 12/162 (7.4%) patients while InferRead software in 61/162 (37.7%) patients. A great variability (ICC ranged for 0.17 to 0.51) was detected among the quantitative measurements of the residual healthy lung parenchyma volume, GGO, and consolidations volumes calculated by different computer tools. The overall radiological severity score was moderately correlated with the residual healthy lung parenchyma volume obtained by ThoracicVCAR or Myrian software, with the GGO area obtained by the ThoracicVCAR tool and with consolidation volume obtained by Myrian software. Quantified volumes by InferRead software had a low correlation with the overall radiological severity score. Conclusions: Computer-aided pneumonia quantification could be an easy and feasible way to stratify COVID-19 cases according to severity;however, a great variability among quantitative measurements provided by computer tools should be considered.

Coronavirus Disease 2019 (COVID-19) in Italy: Double reading of chest CT examination (preprint)

OBJECTIVETo assess the performance of the second reading of chest Compute Tomography (CT) examinations by expert radiologists in patients with discordance between the reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test for COVID-19 viral pneumonia and the first CT report.MATERIALS AND METHODS.Three hundred seventy-heigth patients were included in this retrospective study (121 women and 257 men; 71 years of median age - range, 29–93 years) subjected to RT-PCR test for suspicious COVID-19 infection. All patients were subjected to CT examination in order to evaluate the pulmonary disease involvement by COVID-19. CT images were reviewed first by two radiologists who identified COVID-19 typical CT patterns and then reanalyzed by anoter two radiologists using a CT structured report for COVID-19 diagnosis.RESULTS.The median temporal window between RT-PCRs execution and CT scan was 0 days with a range of [-9, 11] days. RT-PCR test was resulted positive in 328/378 (86.8%). Discordance between RT-PCR and CT findings for viral pneumonia was revealed in 60 cases. The second reading changed the CT diagnosis in 16/60 (26.7%) cases contributing to increase the concordance with the RT-PCR. Among these 60 cases, 8 were false negative with positive RT-PCR, and 36 were false positive with negative RT-PCR. Sensitivity, specificity, positive predictive value and negative predictive value of CT were respectively of 97.3%, 53.8%, 89.0%, and 88.4%.CONCLUSION.Double reading of CT could increase the diagnostic confidence of radiological interpretation in COVID-19 patients. Using expert second readers could reduce the rate of discrepant cases between RT-PCR results and CT diagnosis for COVID-19 viral pneumonia.

Coronavirus Disease 2019 (COVID-19) in Italy: features on Chest Computed Tomography using a structured report system (preprint)

OBJECTIVE. To assess the use of a structured report system in the Chest Computed Tomography (CT) reporting of patients with suspicious viral pneumonia by COVID-19 and the evaluation of the main CT patterns.MATERIALS AND METHODS. This study included 134 patients (43 women and 91 men; 68.8 years of mean age, range 29-93 years) with suspicious COVID-19 viral infection evaluated by reverse transcription real-time fluorescence polymerase chain reaction (RT-PCR) test. All patients underwent CT examinations at the time of admission. CT images were reviewed by two radiologists who identified COVID-19 CT patterns using a structured reports.RESULTS. Temporal difference mean value between RT-PCRs and CT scan was 0.18 days ±2.0 days. CT findings were positive for viral pneumonia in 94.0% patients while COVID-19 was diagnosed at RT-PCR in 77.6% patients. Mean value of time for radiologist to complete the structured report was 8.5 min±2.4 min. The disease on chest CT predominantly affected multiple lobes and the main CT feature was GGOs with or without consolidation (96.8%). GGOs was predominantly bilateral (89.3%), peripheral (80.3%), multifocal/patching (70.5%). Consolidation disease was predominantly bilateral (83.9%) with prevalent peripheral (87.1%) and segmental (47.3%) distribution. Additional CT signs were the crazy-paving pattern in 75.4% of patients, the septal thickening in 37.3% of patients, the air bronchogram sign in 39.7% and the “reversed halo” sign in 23.8%. Less frequent characteristics at CT regard discrete pulmonary nodules, increased trunk diameter of the pulmonary artery, pleural effusion and pericardium effusion (7.9%, 6.3%, 14.3% and 16.7%, respectively). Barotrauma sign was absent in all the patients. High percentage (54.8%) of the patients had mediastinal lymphadenopathy.CONCLUSION. Using a Chest CT structured report, with a standardized language, we identified that the cardinal hallmarks of COVID-19 infection were bilateral, peripheral and multifocal/patching ground-glass opacities and bilateral consolidations with peripheral and segmental distribution.