RESUMO
Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical Trial Registration: clinicaltrials.gov #NCT04992260.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Linfócitos T CD4-Positivos , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Citocinas/imunologia , Citocinas/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , SARS-CoV-2/imunologia , Vacinação , SeguimentosRESUMO
Introducción: El término MINOCA (Myocardial Infarction with Non-Obstructive Coronary Arteries) ha cobrado relevancia como diagnóstico de trabajo en el contexto de pacientes con sospecha de isquemia miocárdica y estudio coronario sin lesiones obstructivas. Objetivos: Describir las distintas etiologías y variables clínicas de pacientes con MINOCA hospitalizados en la unidad coronaria de nuestro centro (Hospital de la P Universalidad de Chile) Métodos: Estudio observacional retrospectivo en el que se realizó un análisis descriptivo de las variables estudiadas. Además, se analizó el uso de los métodos de imágenes complementarios y otras variables pronósticas. El seguimiento se realizó dentro del primer año posterior al evento. Resultados: El diagnóstico etiológico más frecuente de los pacientes con MINOCA fue el de miocardiopatía por estrés (MCE). Se incluyeron 55 pacientes, 55% de ellos mujeres. La edad promedio fue 57 años y la frecuencia de factores de riesgo cardiovascular clásicos (FRCV) fue baja. En los pacientes con MCE se observó menores niveles de troponina ultrasensible; mayores niveles de NT-proBNP y mayor mortalidad en comparación a otras etiologías. Conclusiones: El perfil de pacientes con MINOCA hospitalizados en nuestro centro correspondió predominantemente a mujeres postmenopáusicas con baja frecuencia de FRCV. La mortalidad de los pacientes con MINOCA se concentró en el grupo con MCE.
Background: MINOCA (acronym for "Myocardial Infarction with Non-Obstructive Coronary Arteries") is relevant as a working guide in the diagnosis of patients with suspicion of ischemia and absence of obstructive coronary artery disease. Aim: to describe the different causes and clinical variables in patients with MINOCA admitted to a coronary care unit of a University hospital in Santiago, Chile. Methods: this is an observational retrospective analysis of relevant clinical variables in 55 patients finally diagnosed as having MINOCA. Use of image based studies and characteristics related to prognosis were also analyzed. Follow up extended for one year after the event. Results: 55 patients were included, 55% of them women. Mean age was 57 years; presence of traditional risk factors for myocardial infarction was low. The most common eventual etiologic diagnosis was Stress Cardiomyopathy (SCM) in which lower levels of ultrasensitive troponin and higher levels of NT-proBNP were observed. Mortality in SCM was higher than that observed in other etiologies. Conclusion: MINOCA was more frequent in post menopausal women. Mortality was greater in patients with SMC.
Assuntos
Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Prognóstico , Troponina/análise , Estudos Retrospectivos , Análise de Variância , Peptídeo Natriurético Encefálico/análise , Tomografia de Coerência Óptica , Infarto do Miocárdio/etiologiaRESUMO
This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of ß-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.
Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Insuficiência Cardíaca , Síndrome Metabólica , Volume Sistólico , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Síndrome Metabólica/metabolismo , Síndrome Metabólica/tratamento farmacológico , Volume Sistólico/efeitos dos fármacos , Animais , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Obesidade/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológicoRESUMO
BACKGROUND: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. METHODS: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. FINDINGS: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. INTERPRETATION: Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. FUNDING: The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , COVID-19/prevenção & controle , Pandemias , SARS-CoV-2 , Vacinas de Produtos Inativados , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
Introduction: Booster doses of SARS-CoV-2 vaccines improve seroconversion rates in solid organ transplant recipients (SOTRs) but the impact of homologous and heterologous booster doses in neutralizing antibody (NAb) titers and their ability to interfere with the variant of concern Omicron are not well studied. Methods: We designed a prospective, open-label, observational clinical cohort study. 45 participants received two doses of BNT162b2 or CoronaVac (21-day or 28-day intervals, respectively) followed by a first and second booster with BNT162b2 (5-month apart each) and we analyzed the neutralizing antibody titers against SARSCoV-2 D614G (B.1 lineage) and Omicron (BA.1 lineage). Results: Our results show that SOTRs receiving an initial two-dose scheme of CoronaVac or BNT162b2 generate lower NAbs titers against the ancestral variant of SARS-CoV-2 when compared with healthy controls. Although these NAb titers were further decreased against the SARS-CoV-2 Omicron, a single BNT162b2 booster in both groups was sufficient to increase NAb titers against the variant of concern. More importantly, this effect was only observed in those participants responding to the first two shots but not in those not responding to the initial vaccination scheme. Discussion: The data provided here demonstrate the importance of monitoring antibody responses in immunocompromised subjects when planning booster vaccination programs in this risk group.
Assuntos
COVID-19 , Transplante de Órgãos , Humanos , Anticorpos Neutralizantes , Vacina BNT162 , Estudos de Coortes , Vacinas contra COVID-19 , Transplante de Órgãos/efeitos adversos , Estudos Prospectivos , SARS-CoV-2RESUMO
OBJECTIVE: Ideal cardiovascular health (CVH) was developed to promote CVH as a key component of primordial prevention. Mobile short message service (SMS) is useful for improving health behaviours. We aim to test the effectiveness of SMS intervention in women to improve CVH. METHODS: In a single-blinded, randomised, controlled study, 620 women, aged 35-70 years, without cardiovascular disease, were enrolled in SMS intervention versus no SMS. CVH metrics by self-report, and biochemical laboratory, anthropometric and blood pressure measurements were collected during home visits at baseline and 9 months. Women were categorised as having poor (0-2), intermediate (3-4) or ideal (5-7) CVH according to the number of ideal CVH metrics. Participants were randomised 1:1 to SMS intervention versus control. SMS was sent every 5-6 days for 9 months. The primary outcome was the difference in the proportion of women with ideal CVH between SMS and control groups at 9 months. Rates of intermediate CVH, poor CVH and each of the seven ideal CV health metrics at 9 months were key secondary endpoints. RESULTS: At 9 months, there was no significant difference between groups for the primary outcome (16.3% at baseline and 13.3% at 9 months, and 10.1% and 11.1%, in SMS and control groups, respectively, adjusted RR 1.0; 95% CI 0.6 to 1.6). Similarly, there were no significant differences between groups for the key secondary endpoints. SMS had an acceptance rate of 94.9%. CONCLUSIONS: Behavioural SMS intervention did not improve rates of ideal CVH in women, despite being feasible and well received. TRIAL REGISTRATION NUMBER: 6377.