Advanced Imaging Supports the Mechanistic Role of Autoimmunity and Plaque Rupture in COVID-19 Heart Involvement.

The cardiovascular system is frequently affected by coronavirus disease-19 (COVID-19), particularly in hospitalized cases, and these manifestations are associated with a worse prognosis. Most commonly, heart involvement is represented by myocarditis, myocardial infarction, and pulmonary embolism, while arrhythmias, heart valve damage, and pericarditis are less frequent. While the clinical suspicion is necessary for a prompt disease recognition, imaging allows the early detection of cardiovascular complications in patients with COVID-19. The combination of cardiothoracic approaches has been proposed for advanced imaging techniques, i.e., CT scan and MRI, for a simultaneous evaluation of cardiovascular structures, pulmonary arteries, and lung parenchyma. Several mechanisms have been proposed to explain the cardiovascular injury, and among these, it is established that the host immune system is responsible for the aberrant response characterizing severe COVID-19 and inducing organ-specific injury. We illustrate novel evidence to support the hypothesis that molecular mimicry may be the immunological mechanism for myocarditis in COVID-19. The present article provides a comprehensive review of the available evidence of the immune mechanisms of the COVID-19 cardiovascular injury and the imaging tools to be used in the diagnostic workup. As some of these techniques cannot be implemented for general screening of all cases, we critically discuss the need to maximize the sustainability and the specificity of the proposed tests while illustrating the findings of some paradigmatic cases.

COVID-19 vaccination, implications for PET/CT image interpretation and future perspectives.

Introduction: The present paper aims to systematically review the literature on COVID-19 vaccine-related findings in patients undergoing PET/CT. Methods: The search algorithms included the following combination of terms: "PET" OR "positron emission tomography" AND "COVID"; "PET" OR "positron emission tomography" AND "COVID" AND "vaccination"; "PET" OR "positron emission tomography" AND "COVID", AND "autoimmune". Results: We selected 17 articles which were assessed for quality and included in the systematic analysis. The most frequent vaccine-related signs on PET/CT were the deltoid [18F]FDG uptake and axillary hypermetabolic lymph nodes, which were described in 8-71% and 7-90% of the patients, respectively. Similarly, frequency of these findings using other tracers than [18F]FDG was greatly variable. This large variability was related to the variability in time elapsed between vaccination and PET/CT, and the criteria used to define positivity. In addition, vaccine-related findings were detected more frequently in young and immunocompetent patients than in elderly and immunocompromised ones. Discussion: Therefore, awareness on vaccination status (timing, patient characteristics, and concurrent therapies) and knowledge on patterns of radiopharmaceutical uptake are necessary to properly interpret PET/CT findings.

COVID-19 vaccination, implications for PET/CT image interpretation and future perspectives

Introduction The present paper aims to systematically review the literature on COVID-19 vaccine-related findings in patients undergoing PET/CT. Methods The search algorithms included the following combination of terms: “PET” OR “positron emission tomography” AND “COVID”;“PET” OR “positron emission tomography” AND “COVID” AND “vaccination”;“PET” OR “positron emission tomography” AND “COVID”, AND “autoimmune”. Results We selected 17 articles which were assessed for quality and included in the systematic analysis. The most frequent vaccine-related signs on PET/CT were the deltoid [18F]FDG uptake and axillary hypermetabolic lymph nodes, which were described in 8–71% and 7–90% of the patients, respectively. Similarly, frequency of these findings using other tracers than [18F]FDG was greatly variable. This large variability was related to the variability in time elapsed between vaccination and PET/CT, and the criteria used to define positivity. In addition, vaccine-related findings were detected more frequently in young and immunocompetent patients than in elderly and immunocompromised ones. Discussion Therefore, awareness on vaccination status (timing, patient characteristics, and concurrent therapies) and knowledge on patterns of radiopharmaceutical uptake are necessary to properly interpret PET/CT findings.

Factors Affecting Citizen Trust and Public Engagement Relating to the Generation and Use of Real-World Evidence in Healthcare.

The potential for the use of real-world data (RWD) to generate real-world evidence (RWE) that can inform clinical decision-making and health policy is increasingly recognized, albeit with hesitancy in some circles. If used appropriately, the rapidly expanding wealth of health data could improve healthcare research, delivery of care, and patient outcomes. However, this depends on two key factors: (1) building structures that increase the confidence and willingness of European Union (EU) citizens to permit the collection and use of their data, and (2) development of EU health policy to support and shape data collection infrastructures, methodologies, transmission, and use. The great potential for use of RWE in healthcare improvement merits careful exploration of the drivers of, and challenges preventing, efficient RWD curation. Literature-based research was performed to identify relevant themes and discussion topics for two sets of expert panels, organized by the European Alliance for Personalised Medicine. These expert panels discussed steps that would enable a gradual but steady growth in the quantity, quality, and beneficial deployment of RWE. Participants were selected to provide insight based on their professional medical, economic, patient, industry, or governmental experience. Here, we propose a framework that addresses public trust and access to data, cross-border governance, alignment of evidence frameworks, and demonstrable improvements in healthcare decisions. We also discuss key case studies that support these recommendations, in accordance with the discussions at the expert panels.

Prognostic findings for ICU admission in patients with COVID-19 pneumonia: baseline and follow-up chest CT and the added value of artificial intelligence.

Infection with SARS-CoV-2 has dominated discussion and caused global healthcare and economic crisis over the past 18 months. Coronavirus disease 19 (COVID-19) causes mild-to-moderate symptoms in most individuals. However, rapid deterioration to severe disease with or without acute respiratory distress syndrome (ARDS) can occur within 1-2 weeks from the onset of symptoms in a proportion of patients. Early identification by risk stratifying such patients who are at risk of severe complications of COVID-19 is of great clinical importance. Computed tomography (CT) is widely available and offers the potential for fast triage, robust, rapid, and minimally invasive diagnosis: Ground glass opacities (GGO), crazy-paving pattern (GGO with superimposed septal thickening), and consolidation are the most common chest CT findings in COVID pneumonia. There is growing interest in the prognostic value of baseline chest CT since an early risk stratification of patients with COVID-19 would allow for better resource allocation and could help improve outcomes. Recent studies have demonstrated the utility of baseline chest CT to predict intensive care unit (ICU) admission in patients with COVID-19. Furthermore, developments and progress integrating artificial intelligence (AI) with computer-aided design (CAD) software for diagnostic imaging allow for objective, unbiased, and rapid assessment of CT images.

In-hospital prognostic role of coronary atherosclerotic burden in COVID-19 patients.

AIMS: Currently, there are few available data regarding a possible role for subclinical atherosclerosis as a risk factor for mortality in Coronavirus Disease 19 (COVID-19) patients. We used coronary artery calcium (CAC) score derived from chest computed tomography (CT) scan to assess the in-hospital prognostic role of CAC in patients affected by COVID-19 pneumonia. METHODS: Electronic medical records of patients with confirmed diagnosis of COVID-19 were retrospectively reviewed. Patients with known coronary artery disease (CAD) were excluded. A CAC score was calculated for each patient and was used to categorize them into one of four groups: 0, 1-299, 300-999 and at least 1000. The primary endpoint was in-hospital mortality for any cause. RESULTS: The final population consisted of 282 patients. Fifty-seven patients (20%) died over a follow-up time of 40 days. The presence of CAC was detected in 144 patients (51%). Higher CAC score values were observed in nonsurvivors [median: 87, interquartile range (IQR): 0.0-836] compared with survivors (median: 0, IQR: 0.0-136). The mortality rate in patients with a CAC score of at least 1000 was significantly higher than in patients without coronary calcifications (50 vs. 11%) and CAC score 1-299 (50 vs. 23%), P < 0.05. After adjusting for clinical variables, the presence of any CAC categories was not an independent predictor of mortality; however, a trend for increased risk of mortality was observed in patients with CAC of at least 1000. CONCLUSION: The correlation between CAC score and COVID-19 is fascinating and under-explored. However, in multivariable analysis, the CAC score did not show an additional value over more robust clinical variables in predicting in-hospital mortality. Only patients with the highest atherosclerotic burden (CAC ≥1000) could represent a high-risk population, similarly to patients with known CAD.

Long COVID hallmarks on [18F]FDG-PET/CT: a case-control study.

PURPOSE: The present study hypothesised that whole-body [18F]FDG-PET/CT might provide insight into the pathophysiology of long COVID. METHODS: We prospectively enrolled 13 adult long COVID patients who complained for at least one persistent symptom for >30 days after infection recovery. A group of 26 melanoma patients with negative PET/CT matched for sex/age was used as controls (2:1 control to case ratio). Qualitative and semi-quantitative analysis of whole-body images was performed. Fisher exact and Mann-Whitney tests were applied to test differences between the two groups. Voxel-based analysis was performed to compare brain metabolism in cases and controls. Cases were further grouped according to prevalent symptoms and analysed accordingly. RESULTS: In 4/13 long COVID patients, CT images showed lung abnormalities presenting mild [18F]FDG uptake. Many healthy organs/parenchyma SUVs and SUV ratios significantly differed between the two groups (p ≤ 0.05). Long COVID patients exhibited brain hypometabolism in the right parahippocampal gyrus and thalamus (uncorrected p < 0.001 at voxel level). Specific area(s) of hypometabolism characterised patients with persistent anosmia/ageusia, fatigue, and vascular uptake (uncorrected p < 0.005 at voxel level). CONCLUSION: [18F]FDG PET/CT acknowledged the multi-organ nature of long COVID, supporting the hypothesis of underlying systemic inflammation. Whole-body images showed increased [18F]FDG uptake in several "target" and "non-target" tissues. We found a typical pattern of brain hypometabolism associated with persistent complaints at the PET time, suggesting a different temporal sequence for brain and whole-body inflammatory changes. This evidence underlined the potential value of whole-body [18F]FDG PET in disclosing the pathophysiology of long COVID.

The Impact of COVID-19 on Nuclear Medicine in Europe.

The COVID-19 pandemic has profoundly changed hospital activities, including nuclear medicine (NM) practice. This review aimed to determine and describe the impact of COVID-19 on NM in Europe and critically discuss actions and strategies applied to face the pandemic. A literature search for relevant articles was performed on PubMed, covering COVID-19 studies published up until January 21, 2021. The findings were summarized according to general and specific activities within the NM departments. The pandemic strongly challenged NM departments: a reduction in the workforce has been experienced in almost every center in Europe due to personnel diagnosed with COVID-19 and other reasons related to the coronavirus. NM departments introduced procedures to limit COVID-19 transmission, including environmental and personal hygiene, social distancing, rescheduling of non-high-priority procedures, the correct use of personal protective equipment, and prompt identification of suspect COVID-19 cases. A proportion of the departments experienced a delay in radiopharmaceuticals supply or technical assistance during the pandemic. Furthermore, the pandemic resulted in a significant reduction of diagnostic and therapeutic NM procedures, as well as a reduced level of care for patients affected by diseases other than COVID-19, such as cancer or acute cardiovascular disease. Telemedicine services have been set up to maintain medical assistance for patients. COVID-19 pandemic has reshaped human work resources, patient's diagnostic and therapeutic management, operative models, radiopharmaceutical supplies, teaching, training and research of NM departments. Limits of availability of resources emerged. Nonetheless, we have to provide continuity in care, especially for fragile patients, maintaining infection control measures. Challenges that have been faced should reshape our vision and get us prepared for the future.

Short-term health-related quality of life, physical function and psychological consequences of severe COVID-19.

BACKGROUND: Survivors of severe COVID-19 are at risk of impaired health-related quality of life (HRQoL) and persistent physical and psychological disability after ICU and hospital discharge. The subsequent social burden is a major concern. We aimed to assess the short-term HRQoL, physical function and prevalence of post-traumatic stress symptoms of invasively mechanically ventilated COVID-19 patients treated in our ICU. METHODS: Prospective, observational cohort study in a follow-up clinic. Patients completed a 6-min walking test (6MWT) to assess their cardio-pulmonary function around 2 months (early follow-up) from hospital discharge, the EQ-5D-5L questionnaire for quality of life assessment around 2 months and at 6 months from hospital discharge and an anonymous web-based Impact of Event Scale-Revised (IES-R) questionnaire for Post-Traumatic Stress symptoms at 2 months. RESULTS: 47 patients attended our follow-up program, mean age 59 ± 10 years, median pre-morbid Clinical Frailty Scale (CFS) 2 [2-3]. The median distance walked in 6 min was 470 [406-516] m, 83 [67-99]% of the predicted value. Overall 1 out 3 patients and 4/18 (22%) among those with a good functional baseline prior to COVID-19 (CFS of 1 or 2) had lower (84%) than predicted 6MWT. EQ-5D-5L quality of life VAS was 80 [70-90] out of 100 at early follow-up with a slight improvement to 85 [77.5-90] at 6 months. Mobility, self-care and usual activities improved between the two timepoints, while pain/discomfort and depression/anxiety did not improve or got worse. The IES-R total score was greater than the threshold for concern of 1.6 in 27/41(66%) respondents. CONCLUSIONS: Patients recovering from severe COVID-19 requiring invasive mechanical ventilation surviving hospital discharge present with early mild to moderate functional impairment, mildly reduced quality of life from hospital discharge with an overall improvement of mobility, self-care and the ability of performing usual activities, while a worsening of pain and depression/anxiety symptoms at 6 months and a large proportion of symptoms of post-traumatic distress soon after hospital discharge.

Volume-of-Interest Aware Deep Neural Networks for Rapid Chest CT-Based COVID-19 Patient Risk Assessment.

Since December 2019, the world has been devastated by the Coronavirus Disease 2019 (COVID-19) pandemic. Emergency Departments have been experiencing situations of urgency where clinical experts, without long experience and mature means in the fight against COVID-19, have to rapidly decide the most proper patient treatment. In this context, we introduce an artificially intelligent tool for effective and efficient Computed Tomography (CT)-based risk assessment to improve treatment and patient care. In this paper, we introduce a data-driven approach built on top of volume-of-interest aware deep neural networks for automatic COVID-19 patient risk assessment (discharged, hospitalized, intensive care unit) based on lung infection quantization through segmentation and, subsequently, CT classification. We tackle the high and varying dimensionality of the CT input by detecting and analyzing only a sub-volume of the CT, the Volume-of-Interest (VoI). Differently from recent strategies that consider infected CT slices without requiring any spatial coherency between them, or use the whole lung volume by applying abrupt and lossy volume down-sampling, we assess only the "most infected volume" composed of slices at its original spatial resolution. To achieve the above, we create, present and publish a new labeled and annotated CT dataset with 626 CT samples from COVID-19 patients. The comparison against such strategies proves the effectiveness of our VoI-based approach. We achieve remarkable performance on patient risk assessment evaluated on balanced data by reaching 88.88%, 89.77%, 94.73% and 88.88% accuracy, sensitivity, specificity and F1-score, respectively.

Vasculitis changes in COVID-19 survivors with persistent symptoms: an [18F]FDG-PET/CT study.

PURPOSE: Several patients experience unexplained persistent symptoms after SARS-CoV-2 recovering. We aimed at evaluating if 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was able to demonstrate a persistent inflammatory process. METHODS: Recovered adult COVID-19 patients, who complained unexplained persisting symptoms for more than 30 days during the follow-up visits, were invited to participate in the study. Patients fulfilling inclusion criteria were imaged by [18F]FDG positron emission tomography/computed tomography ([18F]FDG-PET/CT). Whole-body [18F]FDG-PET/CT, performed according to good clinical practice, was qualitatively (comparison with background/liver) and semi-quantitatively (target-to-blood pool ratio calculated as average SUVmax artery/average SUVmean inferior vena cava) analyzed. Negative follow-up [18F]FDG-PET/CT images of oncologic patients matched for age/sex served as controls. Mann-Whitney test was used to test differences between groups. SPSS version 26 was used for analyses. RESULTS: Ten recovered SARS-CoV-2 patients (seven male and three females, median age 52 years, range 46-80) with persisting symptoms were enrolled in the study. Common findings at visual analysis were increased [18F]FDG uptake in bone marrow and blood vessels (8/10 and 6/10 cases, respectively). [18F]FDG uptake in bone marrow did not differ between cases and controls (p = 0.16). The total vascular score was similar in the two groups (p = 0.95). The target-to-blood pool ratio resulted higher in recovered SARS-CoV-2 patients than in controls. CONCLUSION: Although the total vascular score was similar in the two groups, the target-to-blood pool ratio was significantly higher in three vascular regions (thoracic aorta, right iliac artery, and femoral arteries) in the recovered COVID-19 cohort than in controls, suggesting that SARS-CoV-2 induces vascular inflammation, which may be responsible for persisting symptoms.

Global Issues of Radiopharmaceutical Access and Availability: A Nuclear Medicine Global Initiative Project.

The Nuclear Medicine Global Initiative was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging by supporting the practice and application of nuclear medicine. The first project focused on standardization of administered activities in pediatric nuclear medicine and resulted in 2 articles. For its second project the Nuclear Medicine Global Initiative chose to explore issues impacting on access and availability of radiopharmaceuticals around the world. Methods: Information was obtained by survey responses from 35 countries on available radioisotopes, radiopharmaceuticals, and kits for diagnostic and therapeutic use. Issues impacting on access and availability of radiopharmaceuticals in individual countries were also identified. Results: Detailed information on radiopharmaceuticals used in each country, and sources of supply, was evaluated. Responses highlighted problems in access, particularly due to the reliance on a sole provider, regulatory issues, and reimbursement, as well as issues of facilities and workforce, particularly in low- and middle-income countries. Conclusion: Strategies to address access and availability of radiopharmaceuticals are outlined, to enable timely and equitable patient access to nuclear medicine procedures worldwide. In the face of disruptions to global supply chains by the coronavirus disease 2019 outbreak, renewed focus on ensuring a reliable supply of radiopharmaceuticals is a major priority for nuclear medicine practice globally.

Chest CT in patients with a moderate or high pretest probability of COVID-19 and negative swab.

OBJECTIVES: We aimed to assess the diagnostic performance of CT in patients with a negative first RT-PCR testing and to identify typical features of COVID-19 pneumonia that can guide diagnosis in this case. METHODS: Patients suspected of COVID-19 with a negative first RT-PCR testing were retrospectively revalued after undergoing CT. CT was reviewed by two radiologists and classified as suspected COVID-19 pneumonia, non-COVID-19 pneumonia or negative. The performance of both first RT-PCR result and CT was evaluated by using sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) and by using the second RT-PCR test as the reference standard. CT findings for confirmed COVID-19 positive or negative were compared by using the Pearson chi-squared test (P values < 0.05) RESULTS: Totally, 337 patients suspected of COVID-19 underwent CT and nasopharyngeal swabs in March 2020. Eighty-seven out of 337 patients had a negative first RT-PCR result; of these, 68 repeated RT-PCR testing and were included in the study. The first RT-PCR test showed SE 0, SP = 100%, PPV = NaN, NPV = 70%, AUC = 50%, and CT showed SE = 70% SP = 79%, PPV = 86%, NPV = 76%, AUC = 75%. The most relevant CT variables were ground glass opacity more than 50% and peripheral and/or perihilar distribution. DISCUSSION: Negative RT-PCR test but positive CT features should be highly suggestive of COVID-19 in a cluster or community transmission scenarios, and the second RT-PCR test should be promptly requested to confirm the final diagnosis.