Comparing plasma and skin imprint metabolic profiles in COVID-19 diagnosis and severity assessment.

As SARS-CoV-2 continues to produce new variants, the demand for diagnostics and a better understanding of COVID-19 remain key topics in healthcare. Skin manifestations have been widely reported in cases of COVID-19, but the mechanisms and markers of these symptoms are poorly described. In this cross-sectional study, 101 patients (64 COVID-19 positive patients and 37 controls) were enrolled between April and June 2020, during the first wave of COVID-19, in São Paulo, Brazil. Enrolled patients had skin imprints sampled non-invasively using silica plates; plasma samples were also collected. Samples were used for untargeted lipidomics/metabolomics through high-resolution mass spectrometry. We identified 558 molecular ions, with lipids comprising most of them. We found 245 plasma ions that were significant for COVID-19 diagnosis, compared to 61 from the skin imprints. Plasma samples outperformed skin imprints in distinguishing patients with COVID-19 from controls, with F1-scores of 91.9% and 84.3%, respectively. Skin imprints were excellent for assessing disease severity, exhibiting an F1-score of 93.5% when discriminating between patient hospitalization and home care statuses. Specifically, oleamide and linoleamide were the most discriminative biomarkers for identifying hospitalized patients through skin imprinting, and palmitic amides and N-acylethanolamine 18:0 were also identified as significant biomarkers. These observations underscore the importance of primary fatty acid amides and N-acylethanolamines in immunomodulatory processes and metabolic disorders. These findings confirm the potential utility of skin imprinting as a valuable non-invasive sampling method for COVID-19 screening; a method that may also be applied in the evaluation of other medical conditions. KEY MESSAGES: Skin imprints complement plasma in disease metabolomics. The annotated markers have a role in immunomodulation and metabolic diseases. Skin imprints outperformed plasma samples at assessing disease severity. Skin imprints have potential as non-invasive sampling strategy for COVID-19.

Influence of Physical Training after a Myocardial Infarction on Left Ventricular Contraction Mechanics. / Influência do Exercício Físico sobre a Mecânica de Contração do Ventrículo Esquerdo após Infarto do Miocárdio.

BACKGROUND: Exercise plays a positive role in the course of the ischemic heart disease, enhancing functional capacity and preventing ventricular remodeling. OBJECTIVE: To investigate the impact of exercise on left ventricular (LV) contraction mechanics after an uncomplicated acute myocardial infarction (AMI). METHODS: A total of 53 patients was included, 27 of whom were randomized to a supervised training program (TRAINING group), and 26 to a CONTROL group, who received usual recommendations on physical exercise after AMI. All patients underwent cardiopulmonary stress testing and a speckle tracking echocardiography to measure several parameters of LV contraction mechanics at one month and five months after AMI. A p value < 0.05 was considered statistically significant for the comparisons of the variables. RESULTS: No significant difference were found in the analysis of LV longitudinal, radial and circumferential strain parameters between groups after the training period. After the training program, analysis of torsional mechanics demonstrated a reduction in the LV basal rotation in the TRAINING group in comparison to the CONTROL group (5.9±2.3 vs. 7.5±2.9o; p=0.03), and in the basal rotational velocity (53.6±18.4 vs.68.8±22.1 º/s; p=0.01), twist velocity (127.4±32.2 vs. 149.9±35.9 º/s; p=0.02) and torsion (2.4±0.4 vs. 2.8±0.8 º/cm; p=0.02). CONCLUSIONS: Physical activity did not cause a significant improvement in LV longitudinal, radial and circumferential deformation parameters. However, the exercise had a significant impact on the LV torsional mechanics, consisting of a reduction in basal rotation, twist velocity, torsion and torsional velocity which can be interpreted as a ventricular "torsion reserve" in this population.

FUNDAMENTO: O exercício exerce um papel positivo na evolução da doença cardíaca isquêmica, melhorando a capacidade funcional e prevenindo o remodelamento ventricular. OBJETIVO: Investigar o impacto do exercício sobre a mecânica de contração do ventrículo esquerdo (VE) após um infarto agudo do miocárdio (IAM) não complicado. MÉTODOS: Um total de 53 pacientes foram incluídos e alocados aleatoriamente em um programa de treinamento supervisionado (grupo TREINO, n=27) ou em um grupo CONTROLE (n=26) que recebeu recomendações usuais sobre a prática de exercício físico após um IAM. Todos os pacientes realizaram um teste cardiopulmonar e um ecocardiograma com speckle tracking para medir vários parâmetros da mecânica de contração do VE em um mês e cinco meses após o IAM. Um valor de p <0,05 foi considerado para significância estatística nas comparações das variáveis. RESULTADOS: Não foram encontradas diferenças nas análises dos parâmetros de strain circunferencial, radial ou longitudinal do VE entre os grupos após o período de treinamento. Após o programa, a análise da mecânica de torção revelou uma redução na rotação basal do VE no grupo TREINO em comparação ao grupo CONTROLE (5,9±2,3 vs. 7,5±2.9o; p=0,03), bem como na velocidade rotacional basal (53,6±18,4 vs. 68,8± 22,1 º/s; p=0,01), velocidade de twist (127,4±32,2 vs. 149,9±35,9 º/s; p=0,02) e na torção (2,4±0,4 vs. 2,8±0, º/cm; p=0,02). CONCLUSÕES: A atividade física não causou melhora significativa nos parâmetros de deformação longitudinal, radial ou circunferencial do VE. No entanto, o exercício teve um impacto significativo sobre a mecânica de torção do VE, que consistiu em uma redução na rotação basal, na velocidade de twist, na torção, e na velocidade de torção, que pode ser interpretada como uma "reserva" de torção ventricular nessa população.

Effects of exercise on platelet reactivity after myocardial infarction: a randomized clinical trial.

Exercise training (ET) can lower platelet reactivity in patients with cardiovascular risk factors. However, the effects of ET on platelet reactivity in higher-risk patients is unknown. The aim of this study was to evaluate the effects of ET on platelet reactivity in patients with recent myocardial infarction (MI). Ninety patients were randomly assigned 1 month post-MI to the intervention (patients submitted to a supervised ET program) or control group. All patients were on dual antiplatelet therapy (DAPT). Platelet reactivity by VerifyNow-P2Y12 (measured by P2Y12 reaction units - PRUs) test was determined at baseline and at the end of 14 ± 2 weeks of follow-up at rest (primary endpoint), and multiplate electrode aggregometry (MEA) adenosine diphosphate (ADP) and aspirin (ASPI) tests were performed immediately before and after the maximal cardiopulmonary exercise test (CPET) at the same time points (secondary endpoints). Sixty-five patients (mean age 58.9 ± 10 years; 73.8% men; 60% ST elevation MI) completed follow-up (control group, n = 31; intervention group, n = 34). At the end of the follow-up, the mean platelet reactivity was 172.8 ± 68.9 PRUs and 166.9 ± 65.1 PRUs for the control and intervention groups, respectively (p = .72). Platelet reactivity was significantly increased after the CPET compared to rest at the beginning and at the end of the 14-week follow-up (among the intervention groups) by the MEA-ADP and MEA-ASPI tests (p < .01 for all analyses). In post-MI patients on DAPT, 14 weeks of supervised ET did not reduce platelet reactivity. Moreover, platelet reactivity was increased after high-intensity exercise (ClinicalTrials.gov: NCT02958657; https://clinicaltrials.gov/ct2/show/NCT02958657).

What is the context? Platelet reactivity is reduced after exercise training in healthy individuals and patients with cardiovascular risk factors, but the effect in higher-risk patients is unknown.High-intensity exercise in untrained individuals increases platelet reactivity. The effect of dual antiplatelet therapy in inhibiting exercise-induced hyperreactivity is poorly understood.What's new?Exercise training did not reduce platelet reactivity in post-myocardial infarction patients.High-intensity exercise increased platelet reactivity in post-myocardial infarction patients on dual antiplatelet therapy.Exercise training did not attenuate the exercise-induced increase in platelet reactivity.What's the impact?The study suggests that strenuous exercise, if indicated, should be applied carefully to patients with high risk of recurrent ischemic events, even if on optimal medical therapy and after being trained.

Influência do Exercício Físico sobre a Mecânica de Contração do Ventrículo Esquerdo após Infarto do Miocárdio / Influence of Physical Training after a Myocardial Infarction on Left Ventricular Contraction Mechanics

Resumo Fundamento O exercício exerce um papel positivo na evolução da doença cardíaca isquêmica, melhorando a capacidade funcional e prevenindo o remodelamento ventricular. Objetivo Investigar o impacto do exercício sobre a mecânica de contração do ventrículo esquerdo (VE) após um infarto agudo do miocárdio (IAM) não complicado. Métodos Um total de 53 pacientes foram incluídos e alocados aleatoriamente em um programa de treinamento supervisionado (grupo TREINO, n=27) ou em um grupo CONTROLE (n=26) que recebeu recomendações usuais sobre a prática de exercício físico após um IAM. Todos os pacientes realizaram um teste cardiopulmonar e um ecocardiograma com speckle tracking para medir vários parâmetros da mecânica de contração do VE em um mês e cinco meses após o IAM. Um valor de p <0,05 foi considerado para significância estatística nas comparações das variáveis. Resultados Não foram encontradas diferenças nas análises dos parâmetros de strain circunferencial, radial ou longitudinal do VE entre os grupos após o período de treinamento. Após o programa, a análise da mecânica de torção revelou uma redução na rotação basal do VE no grupo TREINO em comparação ao grupo CONTROLE (5,9±2,3 vs. 7,5±2.9o; p=0,03), bem como na velocidade rotacional basal (53,6±18,4 vs. 68,8± 22,1 º/s; p=0,01), velocidade de twist (127,4±32,2 vs. 149,9±35,9 º/s; p=0,02) e na torção (2,4±0,4 vs. 2,8±0, º/cm; p=0,02). Conclusões A atividade física não causou melhora significativa nos parâmetros de deformação longitudinal, radial ou circunferencial do VE. No entanto, o exercício teve um impacto significativo sobre a mecânica de torção do VE, que consistiu em uma redução na rotação basal, na velocidade de twist, na torção, e na velocidade de torção, que pode ser interpretada como uma "reserva" de torção ventricular nessa população.

Abstract Background Exercise plays a positive role in the course of the ischemic heart disease, enhancing functional capacity and preventing ventricular remodeling. Objective To investigate the impact of exercise on left ventricular (LV) contraction mechanics after an uncomplicated acute myocardial infarction (AMI). Methods A total of 53 patients was included, 27 of whom were randomized to a supervised training program (TRAINING group), and 26 to a CONTROL group, who received usual recommendations on physical exercise after AMI. All patients underwent cardiopulmonary stress testing and a speckle tracking echocardiography to measure several parameters of LV contraction mechanics at one month and five months after AMI. A p value < 0.05 was considered statistically significant for the comparisons of the variables. Results No significant difference were found in the analysis of LV longitudinal, radial and circumferential strain parameters between groups after the training period. After the training program, analysis of torsional mechanics demonstrated a reduction in the LV basal rotation in the TRAINING group in comparison to the CONTROL group (5.9±2.3 vs. 7.5±2.9o; p=0.03), and in the basal rotational velocity (53.6±18.4 vs.68.8±22.1 º/s; p=0.01), twist velocity (127.4±32.2 vs. 149.9±35.9 º/s; p=0.02) and torsion (2.4±0.4 vs. 2.8±0.8 º/cm; p=0.02). Conclusions Physical activity did not cause a significant improvement in LV longitudinal, radial and circumferential deformation parameters. However, the exercise had a significant impact on the LV torsional mechanics, consisting of a reduction in basal rotation, twist velocity, torsion and torsional velocity which can be interpreted as a ventricular "torsion reserve" in this population.

HDL proteome remodeling associates with COVID-19 severity.

BACKGROUND: Besides the well-accepted role in lipid metabolism, high-density lipoprotein (HDL) also seems to participate in host immune response against infectious diseases. OBJECTIVE: We used a quantitative proteomic approach to test the hypothesis that alterations in HDL proteome associate with severity of Coronavirus disease 2019 (COVID-19). METHODS: Based on clinical criteria, subjects (n=41) diagnosed with COVID-19 were divided into two groups: a group of subjects presenting mild symptoms and a second group displaying severe symptoms and requiring hospitalization. Using a proteomic approach, we quantified the levels of 29 proteins in HDL particles derived from these subjects. RESULTS: We showed that the levels of serum amyloid A 1 and 2 (SAA1 and SAA2, respectively), pulmonary surfactant-associated protein B (SFTPB), apolipoprotein F (APOF), and inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) were increased by more than 50% in hospitalized patients, independently of sex, HDL-C or triglycerides when comparing with subjects presenting only mild symptoms. Altered HDL proteins were able to classify COVID-19 subjects according to the severity of the disease (error rate 4.9%). Moreover, apolipoprotein M (APOM) in HDL was inversely associated with odds of death due to COVID-19 complications (odds ratio [OR] per 1-SD increase in APOM was 0.27, with 95% confidence interval [CI] of 0.07 to 0.72, P=0.007). CONCLUSION: Our results point to a profound inflammatory remodeling of HDL proteome tracking with severity of COVID-19 infection. They also raise the possibility that HDL particles could play an important role in infectious diseases.

Prognostic accuracy of MALDI-TOF mass spectrometric analysis of plasma in COVID-19.

SARS-CoV-2 infection poses a global health crisis. In parallel with the ongoing world effort to identify therapeutic solutions, there is a critical need for improvement in the prognosis of COVID-19. Here, we report plasma proteome fingerprinting that predict high (hospitalized) and low-risk (outpatients) cases of COVID-19 identified by a platform that combines machine learning with matrix-assisted laser desorption ionization mass spectrometry analysis. Sample preparation, MS, and data analysis parameters were optimized to achieve an overall accuracy of 92%, sensitivity of 93%, and specificity of 92% in dataset without feature selection. We identified two distinct regions in the MALDI-TOF profile belonging to the same proteoforms. A combination of SDS-PAGE and quantitative bottom-up proteomic analysis allowed the identification of intact and truncated forms of serum amyloid A-1 and A-2 proteins, both already described as biomarkers for viral infections in the acute phase. Unbiased discrimination of high- and low-risk COVID-19 patients using a technology that is currently in clinical use may have a prompt application in the noninvasive prognosis of COVID-19. Further validation will consolidate its clinical utility.

Covid-19 Automated Diagnosis and Risk Assessment through Metabolomics and Machine Learning.

COVID-19 is still placing a heavy health and financial burden worldwide. Impairment in patient screening and risk management plays a fundamental role on how governments and authorities are directing resources, planning reopening, as well as sanitary countermeasures, especially in regions where poverty is a major component in the equation. An efficient diagnostic method must be highly accurate, while having a cost-effective profile. We combined a machine learning-based algorithm with mass spectrometry to create an expeditious platform that discriminate COVID-19 in plasma samples within minutes, while also providing tools for risk assessment, to assist healthcare professionals in patient management and decision-making. A cross-sectional study enrolled 815 patients (442 COVID-19, 350 controls and 23 COVID-19 suspicious) from three Brazilian epicenters from April to July 2020. We were able to elect and identify 19 molecules related to the disease's pathophysiology and several discriminating features to patient's health-related outcomes. The method applied for COVID-19 diagnosis showed specificity >96% and sensitivity >83%, and specificity >80% and sensitivity >85% during risk assessment, both from blinded data. Our method introduced a new approach for COVID-19 screening, providing the indirect detection of infection through metabolites and contextualizing the findings with the disease's pathophysiology. The pairwise analysis of biomarkers brought robustness to the model developed using machine learning algorithms, transforming this screening approach in a tool with great potential for real-world application.

Insuficiência cardíaca com fração de ejeção preservada: Abordagem atual / Heart failure with preserved ejection fraction: Current Approach

A insuficiência cardíaca com fração de ejeção preservada é uma síndrome clínica caracterizada por sinais e sintomas de insuficiência cardíaca, fração de ejeção do ventrículo esquerdo dentro dos limites da normalidade e alteração da função diastólica do ventrículo esquerdo. A incidência vem crescendo e é mais frequente em pacientes idosos, mulheres, hipertensos e em portadores de fibrilação atrial. O prognóstico é algo melhor que pacientes com insuficiência cardíaca reduzida, porém ainda ruim...