Risultati per: Diagnosi di COVID-19: dal sospetto alla conferma

Background
Early in the COVID-19 pandemic, numerous clinical trials were initiated. Although concerns were raised regarding the quality of the trials, the eventual research output yielded from the trials remains unknown. The objective of this study was to include all clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic and assess if and where their results had been reported, their completion and discontinuation rates, achieved enrolment and changes made to the primary outcome after trial registration.

Methods
We included all interventional studies related to COVID-19 first registered on ClinicalTrials.gov between 1 January 2020 and 1 July 2020. We systematically searched for trial results, reported through 15 May 2023, in scientific publications, preprints and ClinicalTrials.gov. We assessed the achieved trial enrolment, trial discontinuation (reaching

Objectives
To examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.

Design
A population-based longitudinal cohort study using real-time user data.

Setting
35 specialised long COVID clinics in the UK.

Participants
4087 adults diagnosed with long COVID in primary or secondary care deemed suitable for rehabilitation and registered in the Living With Covid Recovery (LWCR) programme between 4 August 2020 and 5 August 2022.

Main outcome measures
Generalised linear mixed models were fitted to estimate trajectories of functional limitations, using the Work and Social Adjustment Scale (WSAS); scores of ≥20 indicate moderately severe limitations. Other outcomes included fatigue using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) reversed score (scores of ≥22 indicate impairment), HRQL using the EQ-5D-5L, and long COVID-related societal costs, encompassing healthcare costs and productivity losses.

Results
The mean WSAS score at 6 months after registration in the LWCR was 19.1 (95% CI 18.6, 19.6), with 46% of the participants (95% CI 40.3%, 52.4%) reporting a WSAS score above 20 (moderately severe or worse impairment). The mean change in the WSAS score over the 6-month period was –0.86 (95% CI –1.32, –0.41). The mean reversed FACIT-F score at 6 months was 29.1 (95% CI 22.7, 35.5) compared with 32.0 (95% CI 31.7, 32.3) at baseline. The mean EQ-5D-5L score remained relatively constant between baseline (0.63, 95% CI 0.62, 0.64) and 6 months (0.64, 95% CI 0.59, 0.69). The monthly societal cost per patient related to long COVID at 6 months was £931, mostly driven by the costs associated with working days lost.

Conclusions
Individuals referred to long COVID clinics in the UK reported small improvements in functional limitations, fatigue, HRQL and ability to work within 6 months of registering in the LWCR programme.

New England Journal of Medicine, Volume 391, Issue 19, Page 1860-1862, November 14, 2024.

This Viewpoint summarizes the factors contributing to increased risk of severe outcomes and hospitalization associated with COVID-19 among older adults, stresses the importance of assessing COVID-19 risk before infection occurs, calls for all immunocompromised older adults to be considered for COVID-19 treatment, and details 3 recommended COVID-19 therapies.

Annals of Internal Medicine, Ahead of Print.

Circulation, Volume 150, Issue Suppl_1, Page A4143985-A4143985, November 12, 2024. Introduction:Endothelial dysfunction can trigger the development and progression of cardiovascular disease. We hypothesize that cardiovascular PASC is induced by persistent endothelial dysfunction mediated via asymmetric-dimethylarginine (ADMA, the endogenous inhibitor of endothelial nitric oxide synthase). ADMA levels rise in response to viral infections, but it is usually degraded by the enzyme DDAH1, which is inhibited by chronic inflammation and oxidative stress. This study aims to determine whether cardiovascular PASC is associated with endothelial dysfunction and to clarify the role of ADMA in this relationship.Methods:We recruited subjects who had been previously infected and developed cardiovascular symptoms (PASC+), those who had been infected but did not have PASC (PASC-), and those who had never been infected (controls) (n=20 each). Groups were matched for age, sex, and BMI and underwent blood draws and fat biopsies. Vascular function was assessedin-vivovia ultrasound imaging andex-vivoin fat-isolated arterioles.Results:Compared to PASC- and controls, PASC+ subjects exhibited 80% higher serum levels of ADMA and 40% reduced nitric oxide levels. DDAH1 activity was elevated in the PASC+, suggesting a compensatory mechanism for the elevated ADMA levels. However, PASC+ obese subjects exhibited substantially lower DDAH1 activity than non-obese subjects, which was associated with lower insulin sensitivity and higher ADMA levels. Compared to the other two groups, the PASC+ group exhibited lower brachial artery vasoreactivity, while nitroglycerin-induced dilation did not differ statistically, suggesting impaired endothelial function. In the PASC+ group, microvascular recruitment in response to reactive hyperemia was diminished, as was the ex vivo measured flow-induced arteriolar dilation and NO generation. Left ventricle (LV) dysfunction was observed in 80% of the PASC+ group, as opposed to 5% of the PASC- and controls. The LV ejection fraction and global longitudinal strain (GLS) were substantially reduced in the PASC+ group, which was correlated with higher ADMA, C-reactive protein, and troponin-1, as well as lower NO and vascular function. Obese PASC+ subjects had the highest ADMA and the lowest endothelial-dependent vasodilation and insulin sensitivity.Conclusion:Cardiovascular PASC symptoms are related to persistent endothelial dysfunction and elevated ADMA levels, which may be further exacerbated by obesity and reduced DDAH1 activity.

Circulation, Volume 150, Issue Suppl_1, Page A4140585-A4140585, November 12, 2024. Introduction:Stroke-related mortality poses significant challenges in the US. Increased at-home deaths since COVID-19 pandemic prompted changes in the provision of end-of-life care.Question:What were the settings of stroke deaths in the US during COVID-19 pandemic?Methods:Decedent-level mortality data from death certificates in CDC repository were obtained for the year 2020 (pandemic) and 2019 (comparison). Demographic data include age, sex, race/ethnicity, education, marital status, and place of stroke death, including inpatient, outpatient/emergency room (ER), hospice/nursing facilities (H/NF), and at-home. Multivariable logistic regression models assessed demographic impact on stroke mortality by place-of-death, yielding odds ratios (OR) with significance threshold of p65 years were more likely to die in H/NF (OR 10.05, p

Circulation, Volume 150, Issue Suppl_1, Page A4145096-A4145096, November 12, 2024. Introduction:Postural orthostatic tachycardia syndrome (POTS) and Inappropriate sinus tachycardia (IST) are common manifestations of cardiovascular dysautonomia (CVAD) in patients with post-COVID-19 syndrome. Studies regarding differences between post-COVID-19 POTS and post-COVID-19 IST have been sparse and based on small patient series.Aims:To examine clinical differences between POTS and IST in patients with post-COVID-19 syndrome.Methods:A cross-sectional observational study based on a dataset of patients diagnosed with post-COVID-19 syndrome and POTS/IST, at Karolinska University Hospital, Stockholm in 2020-2023, was performed. Data was retrieved using patients’ medical records. ANOVA, chi-square tests and Fisher’s exact tests were used for analysis.Results:A total of 200 patients diagnosed with post-COVID POTS/IST (ICD-10 codes, I.498 + U.099) were included (female, 85%) and divided into a POTS-group (n=110) and IST-group (n=90). Sixty-one patients (31%) met the diagnostic criteria of both and were included in the IST-group. The mean ages were 38 years for the POTS-group and 42 years for the IST-group (p=0.027). Hypertension was more common within the IST-group (p

Circulation, Volume 150, Issue Suppl_1, Page A4145209-A4145209, November 12, 2024. Background:Acute decompensated heart failure accounts for an increasing proportion of hospitalizations in the United States and is linked to high readmission and 30-day mortality rates. Prior studies suggest up to 17% mortality rate within 30 days for patients admitted with heart failure.Research Questions/Hypothesis:We present an analysis characterizing patients who experienced mortality within 30 days of admission at a large safety net hospital following the COVID-19 pandemic.Methods/Approach:A retrospective review was conducted for all heart failure admissions of patients >18 years of age admitted to the coronary care unit (CCU) at Los Angeles General Medical Center from January to December 2021 after the peak of the COVID-19 pandemic. Demographics, insurance information, drug use, medication use, heart failure etiology, and CCU interventions were indexed. The primary outcome was all-cause mortality.Results/Data:172 patients were identified during the study period. 10% of patients died within 30 days of admission, of which 94% died during the same admission. Of patients who died during index admission, 88% had heart failure with reduced EF. None of these patients were on all four pillars of guideline-directed medical therapy (GDMT), with 33% on one or no GDMT medications.There was not a statistically significant difference in mortality rate when comparing those with active stimulant use 5/60 (8%) to those without active illicit drug use 12/112 (11%) (RR 0.79, 95% CI, p= 0.64).9/17 (53%) patients died of refractory cardiogenic shock, 5/17 (29%) were found in cardiopulmonary arrest of unknown etiology while undergoing treatment for acute decompensated heart failure. Two patients (12%) died of septic shock while 1/17 (5%) died of hemorrhagic shock related to chronic liver disease.Conclusion(s)The COVID-19 pandemic exacerbated significant healthcare inequalities, especially for urban underserved populations leading to late presentations of disease and worse outcomes, however, based on our data the overall inpatient mortality rate remained largely similar to pre-pandemic values.

Circulation, Volume 150, Issue Suppl_1, Page A4142935-A4142935, November 12, 2024. Background.Post-COVID syndrome is related to a multisystem disorder that affects in part the cardiovascular system. This disease involves symptoms, and conditions that continue or develop after acute COVID-19. SARS-CoV-2 infection of immune and endothelial cells are associated with NETosis, microthrombosis and endothelial dysfunction that could persist several weeks after acute phase of infection. Damaged endothelial cells can expose the vessel pro-coagulant area leading to platelet and neutrophil clumps. Increased levels of circulating endothelial cells (CECs) have been described as biomarkers for cardiovascular diseases. Therefore, we hypothesize that CECs and microthrombosis are potential biomarkers of vascular dysfunction in Long COVID.Methods.A cross-sectional study was conducted at the Miami VA long COVID clinic. Long COVID cases and controls were recruited according to WHO definition for long COVID. A total of 23 patients and 7 controls were included in this study. Blood samples were collected in Heparin and Sodium Citrate tubes. Cell immunophenotyping and NETosis markers (MPO) were quantified on a Cytek Aurora spectral flow cytometer system. Microclots (CD62P+PAC-1+) and platelet response were assessed by flow cytometry and response to Adenosine di-phosphate (ADP), respectively. A ttest was used for statistical analysis. Differences were considered significant when p < 0.05.Results.The age and gender were similar between cases and controls while their symptom score was significantly different. There was a significant increase in the number of CECs (CD31+CD309+CD45-CD133-) in Long COVID cases. MPO expression in neutrophils (CD11b+CD66b+CD15+) and classical monocytes (CD14+CD16-) was significantly higher in Long COVID. Microclots were significantly elevated, and the platelet aggregation response was dysregulated in Long COVID.Conclusions.CECs and microthrombosis including NETosis are present in Long COVID and may serve as potential biomarkers or causative mechanisms for vascular dysfunction.

Circulation, Volume 150, Issue Suppl_1, Page A4140201-A4140201, November 12, 2024. Introduction:While implantable cardiac defibrillators (ICD) decrease sudden cardiac death, disparities in ICD use remain. The COVID-19 pandemic created strains on the US healthcare system that may have exacerbated these disparities.Methods:Using the US NCDR registry of primary and secondary prevention ICD implants, we compared sex, racial and ethnic disparities for 239,014 patients, aged 19-90 years, grouped into three time intervals from 2016 to 2022: Pre-COVID, COVID and Post-COVID. Centers without consistent reporting were excluded, as were patients with incomplete sex, race or ethnicity data. ICD implantation rates were compared using a Poisson regression model with interaction tests for sex, race and ethnicity by time window to see if disparities changed within this period. Implant rates by indication were also assessed.Results:Overall ICD implants decreased over the study period (Figure 1) with an average monthly rate of 3271 in the first three months of 2016 declining to 2334 in the last three months of 2022 (p=0.017). Disparities in ICD implantation for women, racial and ethnic minorities were observed pre-COVID and persisted (Table 1). Average ICD implant rates during these time periods varied by race with predominance in White patients. While gaps in ICD implant persisted, the disparities did not worsen during COVID-19 by sex, race or ethnicity (p-value for interactions were 0.79; 0.47; and 0.095, respectively). There was a more significant decrease in primary prevention ICD compared to secondary prevention ICD (p

Circulation, Volume 150, Issue Suppl_1, Page A4148010-A4148010, November 12, 2024. Background:Severe COVID-19 infection has been associated with acute respiratory distress syndrome (ARDS) and right ventricular (RV) dysfunction. In this study, we report associations between echocardiographic findings and laboratory markers that portend RV failure in patients with ARDS secondary to COVID-19 infection on ECMO.Methods:A single-center study was conducted in the cardiovascular ICU of our institute. A retrospective chart review was performed on 41 patients with COVID-19 on ECMO between March and October 2020. Twenty-two patients had transthoracic echocardiograms (TTE) completed while on ECMO (VV-ECMO = 19, VA-ECMO = 3). Echocardiograms (echo) were obtained pre-cannulation, during ECMO, and post-ECMO decannulation. RV parameters analyzed included tricuspid annular plane systolic excursion (TAPSE), basal diastolic RV diameter, right ventricular fractional area of change (RV FAC), and S’. Laboratory values including BNP, CRP, D-dimer, ferritin, fibrinogen, lactate and troponin were analyzed for correlation with echo findings.Results:TAPSE was significantly lower in deceased patients (1.9± 0.4cm vs 1.3±0.6 cm, P< 0.05). RV FAC and S’ were also lower in the deceased group. TAPSE while on ECMO showed a positive association with peak D-dimer levels in survivors and a negative association in deceased patients. Peri-ECMO fibrinogen and CRP levels were negatively associated with TAPSE in survivors while fibrinogen showed positive association in deceased patients. LDH peak, fibrinogen initial and lactate peak were higher in the deceased[ZQ1] group. There is a trend of increased RV basal diameter in the deceased group (3.9±0.9 vs 4.2±0.9 cm). Last troponin levels were negatively associated with basal diastolic RV diameter while on ECMO in deceased patients.Conclusion:Preservation of RV longitudinal contractility, as reflected by TAPSE, may play an important role in the survival of COVID-19 patients on ECMO. Laboratory markers such as LDH, D-dimer, fibrinogen and lactate may have prognostic value in predicting RV failure. Further studies are required to determine if early initiation of therapies to improve RV systolic function in COVID-19 ECMO patients with ARDS improves outcomes.

Circulation, Volume 150, Issue Suppl_1, Page A4117883-A4117883, November 12, 2024. Introduction/Background:Cardiovascular symptoms appear in a high proportion of patients in the few months following a severe SARS-CoV-2 infection. Non-invasive methods to predict disease severity could help personalizing healthcare and reducing the occurrence of these symptoms.Research Questions/Hypothesis:We hypothesized that blood long noncoding RNAs (lncRNAs) and machine learning (ML) could help predict COVID-19 severity.Goals/Aims:To develop a model based on lncRNAs and ML for predicting COVID-19 severity.Methods/Approach:Expression data of 2906 lncRNAs were obtained by targeted sequencing in plasma samples collected at baseline from four independent cohorts, totaling 564 COVID-19 patients. Patients were aged 18+ and were recruited from 2020 to 2023 in the PrediCOVID cohort (n=162; Luxembourg), the COVID19_OMICS-COVIRNA cohort (n=100, Italy), the TOCOVID cohort (n=233, Spain), and the MiRCOVID cohort (n=69, Germany). The study complied with the Declaration of Helsinki. Cohorts were approved by ethics committees and patients signed an informed consent.Results/Data:After data curation and pre-processing, 463 complete datasets were included in further analysis, representing 101 severe patients (in-hospital death or ICU admission) and 362 stable patients (no hospital admission or hospital admission but not ICU). Feature selection with Boruta, a random forest-based method, identified age and five lncRNAs (LINC01088-201, FGDP-AS1, LINC01088-209, AKAP13, and a novel lncRNA) associated with disease severity, which were used to build predictive models using six ML algorithms. A naïve Bayes model based on age and five lncRNAs predicted disease severity with an AUC of 0.875 [0.868-0.881] and an accuracy of 0.783 [0.775-0.791].Conclusion:We developed a ML model including age and five lncRNAs predicting COVID-19 severity. This model could help improve patients’ management and cardiovascular outcomes.