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1.
Clin Nucl Med ; 47(12): 1019-1025, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-2018388

ABSTRACT

PURPOSE: We quantified lung glycolytic metabolic activity, clinical symptoms and inflammation, coagulation, and endothelial activation biomarkers in 2019 coronavirus disease (COVID-19) pneumonia survivors. METHODS: Adults previously hospitalized with moderate to severe COVID-19 pneumonia were prospectively included. Subjects filled out a questionnaire on clinical consequences, underwent chest CT and 18 F-FDG PET/CT, and provided blood samples on the same day. Forty-five volunteers served as control subjects. Analysis of CT images and quantitative voxel-based analysis of PET/CT images were performed for both groups. 18 F-FDG uptake in the whole-lung volume and in high- and low-attenuation areas was calculated and normalized to liver values. Quantification of plasma markers of inflammation (interleukin 6), d -dimer, and endothelial cell activation (angiopoietins 1 and 2, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1) was also performed. RESULTS: We enrolled 53 COVID-19 survivors (62.3% were male; median age, 50 years). All survivors reported at least 1 persistent symptom, and 41.5% reported more than 6 symptoms. The mean lung density was greater in survivors than in control subjects, and more metabolic activity was observed in normal and dense lung areas, even months after symptom onset. Plasma proinflammatory, coagulation, and endothelial activation biomarker concentrations were also significantly higher in survivors. CONCLUSION: We observed more metabolic activity in areas of high and normal lung attenuation several months after moderate to severe COVID-19 pneumonia. In addition, plasma markers of thromboinflammation and endothelial activation persisted. These findings may have implications for our understanding of the in vivo pathogenesis and long-lasting effects of COVID-19 pneumonia.


Subject(s)
COVID-19 , Pneumonia , Thrombosis , Adult , Male , Humans , Middle Aged , Female , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography/methods , COVID-19/diagnostic imaging , Inflammation/diagnostic imaging , Lung/diagnostic imaging , Biomarkers , Survivors
2.
Lancet Digit Health ; 4(10): e705-e716, 2022 10.
Article in English | MEDLINE | ID: covidwho-2004681

ABSTRACT

BACKGROUND: Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19. METHODS: For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes. FINDINGS: Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43-6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17-3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [<6·99] C19-RS; hazard ratio [HR] 3·31 [95% CI 1·49-7·33], p=0·0033; and 2·58 [1·10-6·05], p=0·028), adjusted for clinical factors, biochemical biomarkers of inflammation and myocardial injury, and technical parameters. The adjusted HR for in-hospital mortality was 8·24 (95% CI 2·16-31·36, p=0·0019) in patients who received no dexamethasone treatment, but 2·27 (0·69-7·55, p=0·18) in those who received dexamethasone after the scan, suggesting that vascular inflammation might have been a therapeutic target of dexamethasone in COVID-19. Finally, C19-RS was strongly associated (r=0·61, p=0·00031) with a whole blood transcriptional module representing dysregulation of coagulation and platelet aggregation pathways. INTERPRETATION: Radiotranscriptomic analysis of CT angiography scans introduces a potentially powerful new platform for the development of non-invasive imaging biomarkers. Application of this platform in routine CT pulmonary angiography scans done in patients with COVID-19 produced the radiotranscriptomic signature C19-RS, a marker of cytokine-driven inflammation driving systemic activation of coagulation and responsible for adverse clinical outcomes, which predicts in-hospital mortality and might allow targeted therapy. FUNDING: Engineering and Physical Sciences Research Council, British Heart Foundation, Oxford BHF Centre of Research Excellence, Innovate UK, NIHR Oxford Biomedical Research Centre, Wellcome Trust, Onassis Foundation.


Subject(s)
COVID-19 , SARS-CoV-2 , Angiography , Artificial Intelligence , COVID-19/diagnostic imaging , Cytokines , Humans , Inflammation/diagnostic imaging , Prospective Studies , State Medicine , Tomography, X-Ray Computed
3.
J Transl Med ; 20(1): 98, 2022 02 21.
Article in English | MEDLINE | ID: covidwho-1703660

ABSTRACT

BACKGROUND: Frailty, determined by the Canadian Study of Health and Aging-Clinical Frailty Scale (CFS), is strongly associated with clinical outcomes including mortality in patients with COVID-19. However, the relationship between frailty and other recognised prognostic factors including age, nutritional status, obesity, sarcopenia and systemic inflammation is poorly understood. Therefore, the aim of this study was to examine the relationship between frailty and other prognostic domains, in patients admitted with COVID-19. METHODS: Patients who presented to our institutions between 1st April 2020-6th July 2020 with confirmed COVID-19 were assessed for inclusion. Data collected included general demographic details, clinicopathological variables, CFS admission assessment, Malnutrition Universal Screening Tool (MUST), CT-BC measurements and markers of systemic inflammation. RESULTS: 106 patients met the study inclusion criteria. The majority of patients were aged ≥ 70 years (67%), male (53%) and frail (scoring > 3 on the CFS, 72%). The majority of patients were not malnourished (MUST 0, 58%), had ≥ 1 co-morbidity (87%), were sarcopenic (low SMI, 80%) and had systemic inflammation (mGPS ≥ 1, 81%, NLR > 5, 55%). On multivariate binary logistics regression analysis, age (p < 0.01), COPD (p < 0.05) and NLR (p < 0.05) remained independently associated with frailty. On univariate binary logistics regression, NLR (p < 0.05) was significantly associated with 30-day mortality. CONCLUSION: Frailty was independently associated with age, co-morbidity, and systemic inflammation. The basis of the relationship between frailty and clinical outcomes in COVID-19 requires further study. Trial registration Registered with clinicaltrials.gov (NCT04484545).


Subject(s)
COVID-19 , Frailty , Aged , Body Composition , COVID-19/diagnostic imaging , COVID-19/epidemiology , Canada , Comorbidity , Female , Frailty/diagnostic imaging , Frailty/epidemiology , Humans , Inflammation/diagnostic imaging , Inflammation/epidemiology , Male , Nutritional Status , SARS-CoV-2 , Tomography, X-Ray Computed
4.
Semin Nucl Med ; 51(6): 633-645, 2021 11.
Article in English | MEDLINE | ID: covidwho-1300228

ABSTRACT

White blood cells activated by either a pathogen or as part of a systemic inflammatory disease are characterized by high energy consumption and are therefore taking up the glucose analogue PET tracer FDG avidly. It is therefore not surprising that a steadily growing body of research and clinical reports now supports the use of FDG PET/CT to diagnose a wide range of patients with non-oncological diseases. However, using FDG PET/CT in patients with infectious or inflammatory diseases has some limitations and potential pitfalls that are not necessarily as pronounced in oncology FDG PET/CT. Some of these limitations are of a general nature and related to the laborious acquisition of PET images in patients that are often acutely ill, whereas others are more disease-specific and related to the particular metabolism in some of the organs most commonly affected by infections or inflammatory disease. Both inflammatory and infectious diseases are characterized by a more diffuse and less pathognomonic pattern of FDG uptake than oncology FDG PET/CT and the affected organs also typically have some physiological FDG uptake. In addition, patients referred to PET/CT with suspected infection or inflammation are rarely treatment naïve and may have received varying doses of antibiotics, corticosteroids or other immune-modulating drugs at the time of their examination. Combined, this results in a higher rate of false positive FDG findings and also in some cases a lower sensitivity to detect active disease. In this review, we therefore discuss the limitations and pitfalls of FDG PET/CT to diagnose infections and inflammation taking these issues into consideration. Our review encompasses the most commonly encountered inflammatory and infectious diseases in head and neck, in the cardiovascular system, in the abdominal organs and in the musculoskeletal system. Finally, new developments in the field of PET/CT that may help overcome some of these limitations are briefly highlighted.


Subject(s)
Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Humans , Inflammation/diagnostic imaging , Positron-Emission Tomography
5.
Radiol Med ; 126(10): 1273-1281, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1305169

ABSTRACT

PURPOSE: The aim of the study was to prospectively evaluate the agreement between chest magnetic resonance imaging (MRI) and computed tomography (CT) and to assess the diagnostic performance of chest MRI relative to that of CT during the follow-up of patients recovered from coronavirus disease 2019. MATERIALS AND METHODS: Fifty-two patients underwent both follow-up chest CT and MRI scans, evaluated for ground-glass opacities (GGOs), consolidation, interlobular septal thickening, fibrosis, pleural indentation, vessel enlargement, bronchiolar ectasia, and changes compared to prior CT scans. DWI/ADC was evaluated for signal abnormalities suspicious for inflammation. Agreement between CT and MRI was assessed with Cohen's k and weighted k. Measures of diagnostic accuracy of MRI were calculated. RESULTS: The agreement between CT and MRI was almost perfect for consolidation (k = 1.00) and change from prior CT (k = 0.857); substantial for predominant pattern (k = 0.764) and interlobular septal thickening (k = 0.734); and poor for GGOs (k = 0.339), fibrosis (k = 0.224), pleural indentation (k = 0.231), and vessel enlargement (k = 0.339). Meanwhile, the sensitivity of MRI was high for GGOs (1.00), interlobular septal thickening (1.00), and consolidation (1.00) but poor for fibrotic changes (0.18), pleural indentation (0.23), and vessel enlargement (0.50) and the specificity was overall high. DWI was positive in 46.0% of cases. CONCLUSIONS: The agreement between MRI and CT was overall good. MRI was very sensitive for GGOs, consolidation and interlobular septal thickening and overall specific for most findings. DWI could be a reputable imaging biomarker of inflammatory activity.


Subject(s)
COVID-19/complications , Inflammation/diagnostic imaging , Inflammation/etiology , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Aged , COVID-19/physiopathology , Cohort Studies , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Inflammation/physiopathology , Lung/diagnostic imaging , Lung/physiopathology , Male , Middle Aged , Prospective Studies , Reproducibility of Results , SARS-CoV-2
6.
Pediatr Infect Dis J ; 40(2): e82-e83, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-968321

ABSTRACT

We report findings on abdominal imaging in critically ill children admitted with MIS-C. On sonography, hepatomegaly, nephromegaly, gallbladder wall edema, ascites, intestinal inflammation and mesenteric lymphadenopathy were seen, while CT showed fluid-filled small bowel loops, mural thickening of the terminal ileum, diffuse lymphadenopathy, and moderate ascites.


Subject(s)
Abdomen/diagnostic imaging , COVID-19/diagnostic imaging , Inflammation/diagnostic imaging , Adolescent , Ascites/diagnostic imaging , COVID-19/physiopathology , COVID-19/therapy , Child , Child, Preschool , Critical Illness , Female , Gallbladder Diseases/diagnostic imaging , Hepatomegaly/diagnostic imaging , Humans , Ileum/diagnostic imaging , Infant , Inflammation/drug therapy , Inflammation/physiopathology , Intestine, Small/diagnostic imaging , Kidney Diseases/diagnostic imaging , Lymphadenopathy/diagnostic imaging , Male , Mesenteric Lymphadenitis/diagnostic imaging , Mucocutaneous Lymph Node Syndrome/diagnostic imaging , SARS-CoV-2 , Ultrasonography
8.
Eur J Nucl Med Mol Imaging ; 48(1): 260-268, 2021 01.
Article in English | MEDLINE | ID: covidwho-670218

ABSTRACT

PURPOSE: [18F]-2-Fluoro-2-deoxy-D-glucose PET/CT (FDG PET/CT) is a sensitive and quantitative technic for detecting inflammatory process. Glucose uptake is correlated with an increased anaerobic glycolysis seen in activated inflammatory cells such as monocytes, lymphocytes, and granulocytes. The aim of the study was to assess the inflammatory status at the presumed peak of the inflammatory phase in non-critically ill patients requiring admission for COVID-19. METHODS: Patients admitted with COVID-19 were prospectively enrolled. FDG PET/CT was performed from day 6 to day 14 of the onset of symptoms. Depending on FDG PET/CT findings, patients' profiles were classified as "inflammatory" or "low inflammatory." FDG PET/CT data were compared with chest CT evolution and short-term clinical outcome. All inflammatory sites were reported to screen potential extra-pulmonary tropism. RESULTS: Thirteen patients were included. Maximum standardized uptake values ranged from 4.7 to 16.3 in lungs. All patients demonstrated increased mediastinal lymph nodes glucose uptake. Three patients (23%) presented mild nasopharyngeal, two patients (15%) bone marrow, and five patients (38%) splenic mild increase in glucose uptake. No patient had significant digestive focal or segmental glucose uptake. There was no significant physiological myocardial glucose uptake in all patients except one. There was no correlation between PET lung inflammatory status and chest CT evolution or short-term clinical outcome. CONCLUSION: Inflammatory process at the presumed peak of the inflammatory phase in COVID-19 patients is obvious in FDG PET/CT scans. Glucose uptake is heterogeneous and typically focused on lungs. TRIAL REGISTRATION: NCT04441489. Registered 22 June 2020 (retrospectively registered).


Subject(s)
COVID-19/diagnostic imaging , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Aged , Aged, 80 and over , COVID-19/classification , COVID-19/therapy , Female , Heart/diagnostic imaging , Humans , Inflammation/diagnostic imaging , Lung/diagnostic imaging , Lymph Nodes/diagnostic imaging , Male , Middle Aged , Treatment Outcome
9.
Med Hypotheses ; 144: 109885, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-382159

ABSTRACT

The recent outbreak of Covid-19 has represented a major challenge for the countries affected by the disease, not only in terms of loss of human life, economic downturn, and constraint on individual freedom, but also for the great pressure on the national health systems and hospitals. The 380 kDa virus has been a perfect storm, especially for those national health systems used to working with limited resources and high intensity rhythms, such as Italy. For the first time in the new century, a virtually unknown fast-spreading disease has caused a public health emergency thus forcing most countries to deal with an insurmountable logistic gap. Hence, every branch of Medicine, even though not directly involved in the treatment, has been called upon to provide its contribution to resolve the crisis. It is now becoming more apparent that Covid-19 is not solely a lung disease, but a complex systemic disease involving several organs and systems. This is due to an abnormal inflammatory response which eventually leads to multisystemic coagulopathy which mainly, but not uniquely, targets the lungs. Although the pathophysiology of this syndrome is still not fully understood, macrophages and their immune complex system seem to play a key role. It is not yet clear why some patients develop the violent immune response which results in pneumonitis while others do not. There are clues indicating that the systemic hyper-inflammation defined as macrophage activation syndrome (MAS), or cytokine storm, requires an increase in choline consumption to synthesize phosphatidylcholine and stimulate phagocytosis, organelle biogenesis, secretory functions, and endocytosis. 18F-Fluorocholine is a synthetic analog of the naturally occurring choline normally used for PET/CT imaging of prostate cancer patients. 18F-Fluorocholine could image and quantify the macrophage activity in pulmonary interstitial infiltrates of Covid-19 pneumonia. If the hypothesis is confirmed experimentally, 18F-Fluorocholine PET/CT could be used to in vivo image and quantify the degree of lung inflammation and potentially stratify the gravity of this disease.


Subject(s)
COVID-19/blood , COVID-19/diagnostic imaging , Inflammation/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Macrophages/metabolism , Choline/metabolism , Fluorodeoxyglucose F18 , Humans , Immune System , Lung Diseases, Interstitial/blood , Models, Theoretical , Positron-Emission Tomography , Tomography, X-Ray Computed
10.
Clin Hemorheol Microcirc ; 74(4): 353-361, 2020.
Article in English | MEDLINE | ID: covidwho-116593

ABSTRACT

In the hands of experienced examiners, the contrast enhanced sonography (CEUS) offers the possibility to analyze dynamic microcirculatory disturbances in real time dynamically without any risk for kidneys and thyroid gland even in severe progressing disease bedside. Based on severe COVID-19 infections, first experiences with abdominal CEUS examinations are presented. In the stage of an imminent organ failure with significantly reduced kidney and liver function, CEUS can be used to show a narrowing of the organ-supplying arteries, as well as a delayed capillary filling of vessels near the capsule, a regional reduced parenchymal perfusion or an inflammatory hyperemia with capillary hypercirculation. It is possible to quickly rule out organ infarction and to dynamically record the mesenteric arterial and venous blood flow.


Subject(s)
Abdomen/blood supply , Coronavirus Infections/diagnostic imaging , Microcirculation , Pneumonia, Viral/diagnostic imaging , Vascular Diseases/diagnostic imaging , Abdomen/diagnostic imaging , Aged , Betacoronavirus , COVID-19 , Contrast Media/chemistry , Female , Humans , Inflammation/diagnostic imaging , Kidney/diagnostic imaging , Liver/diagnostic imaging , Male , Middle Aged , Pandemics , Perfusion , Risk , SARS-CoV-2 , Thyroid Gland/diagnostic imaging , Ultrasonography
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