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1.
Elife ; 102021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33752798

RESUMO

Numerous reports of vascular events after an initial recovery from COVID-19 form our impetus to investigate the impact of COVID-19 on vascular health of recovered patients. We found elevated levels of circulating endothelial cells (CECs), a biomarker of vascular injury, in COVID-19 convalescents compared to healthy controls. In particular, those with pre-existing conditions (e.g., hypertension, diabetes) had more pronounced endothelial activation hallmarks than non-COVID-19 patients with matched cardiovascular risk. Several proinflammatory and activated T lymphocyte-associated cytokines sustained from acute infection to recovery phase, which correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Notably, we found higher frequency of effector T cells in our COVID-19 convalescents compared to healthy controls. The activation markers detected on CECs mapped to counter receptors found primarily on cytotoxic CD8+ T cells, raising the possibility of cytotoxic effector cells targeting activated endothelial cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.


Assuntos
/complicações , Doenças Cardiovasculares/etiologia , Endotélio Vascular/patologia , Ativação Linfocitária , Adulto , Idoso , /patologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/patologia , Citocinas/imunologia , Células Endoteliais/imunologia , Células Endoteliais/patologia , Endotélio Vascular/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
2.
Med Clin North Am ; 105(2): 247-262, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33589100

RESUMO

Individuals with rheumatoid arthritis, systemic lupus erythematosus, or gout have increased risk of cardiovascular disease (CVD) compared with the general population. This risk relates to a combination of traditional cardiovascular risk factors and disease-specific factors. Screening for CVD is important because CVD contributes to significant morbidity and mortality. Management includes tight control of disease activity to reduce inflammation, but with care to minimize use of nonsteroidal anti-inflammatory drugs and prolonged courses of high-dose corticosteroids. Traditional cardiovascular risk factors should be managed with a combination of lifestyle interventions and pharmacotherapy. The decision to start antihypertensive and lipid-lowering therapy should be based on individual CVD risk.


Assuntos
Doenças Cardiovasculares , Doenças Reumáticas , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Serviços Preventivos de Saúde , Doenças Reumáticas/imunologia , Doenças Reumáticas/fisiopatologia , Doenças Reumáticas/terapia
3.
JCI Insight ; 6(6)2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33621211

RESUMO

Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multiparameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n = 20) or not hospitalized (n = 40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4+ T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4+ T cells and antibodies targeting the S1 domain of spike among subjects who were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2, which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19.


Assuntos
Anticorpos Antivirais/fisiologia , Linfócitos T CD4-Positivos/fisiologia , Hospitalização , Glicoproteína da Espícula de Coronavírus , Vírion , Adulto , Idoso , Anticorpos Neutralizantes/metabolismo , Anticorpos Neutralizantes/fisiologia , Anticorpos Antivirais/metabolismo , Linfócitos T CD4-Positivos/metabolismo , /imunologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/imunologia , Comorbidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Feminino , Humanos , Imunidade Humoral , Masculino , Pessoa de Meia-Idade , Nucleocapsídeo , Índice de Gravidade de Doença , Proteínas Virais , Adulto Jovem
4.
Arterioscler Thromb Vasc Biol ; 41(3): 1032-1046, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33380171

RESUMO

Innate immune cells can develop exacerbated immunologic response and long-term inflammatory phenotype following brief exposure to endogenous or exogenous insults, which leads to an altered response towards a second challenge after the return to a nonactivated state. This phenomenon is known as trained immunity (TI). TI is not only important for host defense and vaccine response but also for chronic inflammations such as cardiovascular and metabolic diseases such as atherosclerosis. TI can occur in innate immune cells such as monocytes/macrophages, natural killer cells, endothelial cells (ECs), and nonimmune cells, such as fibroblast. In this brief review, we analyze the significance of TI in ECs, which are also considered as innate immune cells in addition to macrophages. TI can be induced by a variety of stimuli, including lipopolysaccharides, BCG (bacillus Calmette-Guerin), and oxLDL (oxidized low-density lipoprotein), which are defined as risk factors for cardiovascular and metabolic diseases. Furthermore, TI in ECs is functional for inflammation effectiveness and transition to chronic inflammation. Rewiring of cellular metabolism of the trained cells takes place during induction of TI, including increased glycolysis, glutaminolysis, increased accumulation of tricarboxylic acid cycle metabolites and acetyl-coenzyme A production, as well as increased mevalonate synthesis. Subsequently, this leads to epigenetic remodeling, resulting in important changes in chromatin architecture that enables increased gene transcription and enhanced proinflammatory immune response. However, TI pathways and inflammatory pathways are separated to ensure memory stays when inflammation undergoes resolution. Additionally, reactive oxygen species play context-dependent roles in TI. Therefore, TI plays significant roles in EC and macrophage pathology and chronic inflammation. However, further characterization of TI in ECs and macrophages would provide novel insights into cardiovascular disease pathogenesis and new therapeutic targets. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Células Endoteliais/imunologia , Macrófagos/imunologia , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/imunologia , Citocinas/biossíntese , Metabolismo Energético , Epigênese Genética , Humanos , Imunidade Inata , Memória Imunológica , Infecções/etiologia , Infecções/imunologia , Inflamação/etiologia , Inflamação/imunologia , Doenças Metabólicas/etiologia , Doenças Metabólicas/imunologia , Redes e Vias Metabólicas/imunologia , Modelos Imunológicos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/imunologia , Fatores de Risco
6.
Med. clín (Ed. impr.) ; 155(6): 256-262, sept. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-195870

RESUMO

El reconocimiento de la aterogénesis como un proceso dinámico en vez de un depósito pasivo de colesterol ha subrayado la existencia de mecanismos inflamatorios claves. Así, la respuesta inmune, tanto innata como adaptativa, desempeña un papel importante en el inicio y la progresión de la aterosclerosis. Más recientemente, algunos estudios clínicos han sido diseñados para abordar el impacto de las estrategias de intervención antiinflamatoria en la reducción del riesgo de enfermedad cardiovascular más allá del control de los factores clásicos de riesgo. Por todo ello, revisamos en primer lugar la contribución fisiopatológica de la inflamación en la aterosclerosis y el efecto del tratamiento farmacológico hipolipidemiante en los marcadores de inflamación. A continuación, abordamos el efecto de los fármacos antiinflamatorios clásicos, de los tratamientos farmacológicos dirigidos a mediadores inflamatorios específicos y de las vacunas en la prevención cardiovascular


The recognition of atherogenesis as an active process rather than a passive cholesterol storage disease has underlined key inflammatory mechanisms. Hence, innate and adaptive immune responses play an important role in the onset and progression of atherosclerosis. More recently, some clinical studies were designed to address the impact of anti-inflammatory intervention strategies in reducing risk of cardiovascular disease beyond the management of classic risk factors. Therefore, we review first the pathophysiological contribution of inflammation to atherosclerosis and the effect of lipid-lowering drugs on inflammatory biomarkers. Next, we address the effect of classic anti-inflammatory drugs, pharmacological therapies targeting specific inflammatory mediators and vaccines in cardiovascular prevention


Assuntos
Humanos , Arteriosclerose/terapia , Inflamação/terapia , Imunoterapia/métodos , Progressão da Doença , Inflamação/fisiopatologia , Mediadores da Inflamação/uso terapêutico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Anticolesterolemiantes/uso terapêutico
7.
J Allergy Clin Immunol ; 146(4): 790-798, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32810517

RESUMO

BACKGROUND: There is inconclusive and controversial evidence of the association between allergic diseases and the risk of adverse clinical outcomes of coronavirus disease 2019 (COVID-19). OBJECTIVE: We sought to determine the association of allergic disorders with the likelihood of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test result and with clinical outcomes of COVID-19 (admission to intensive care unit, administration of invasive ventilation, and death). METHODS: A propensity-score-matched nationwide cohort study was performed in South Korea. Data obtained from the Health Insurance Review & Assessment Service of Korea from all adult patients (age, >20 years) who were tested for SARS-CoV-2 in South Korea between January 1, 2020, and May 15, 2020, were analyzed. The association of SARS-CoV-2 test positivity and allergic diseases in the entire cohort (n = 219,959) and the difference in clinical outcomes of COVID-19 were evaluated in patients with allergic diseases and SARS-CoV-2 positivity (n = 7,340). RESULTS: In the entire cohort, patients who underwent SARS-CoV-2 testing were evaluated to ascertain whether asthma and allergic rhinitis were associated with an increased likelihood of SARS-CoV-2 test positivity. After propensity score matching, we found that asthma and allergic rhinitis were associated with worse clinical outcomes of COVID-19 in patients with SARS-CoV-2 test positivity. Patients with nonallergic asthma had a greater risk of SARS-CoV-2 test positivity and worse clinical outcomes of COVID-19 than patients with allergic asthma. CONCLUSIONS: In a Korean nationwide cohort, allergic rhinitis and asthma, especially nonallergic asthma, confers a greater risk of susceptibility to SARS-CoV-2 infection and severe clinical outcomes of COVID-19.


Assuntos
Asma/complicações , Betacoronavirus/patogenicidade , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Dermatite Atópica/complicações , Complicações do Diabetes/diagnóstico , Pneumonia Viral/complicações , Rinite Alérgica/complicações , Adulto , Idoso , Asma/diagnóstico , Asma/imunologia , Asma/mortalidade , Betacoronavirus/imunologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/mortalidade , Técnicas de Laboratório Clínico , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Dermatite Atópica/mortalidade , Complicações do Diabetes/imunologia , Complicações do Diabetes/mortalidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/imunologia , Diabetes Mellitus/mortalidade , Suscetibilidade a Doenças , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Rinite Alérgica/mortalidade , Índice de Gravidade de Doença , Análise de Sobrevida
8.
Front Immunol ; 11: 1548, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733487

RESUMO

Background: The COVID-19 pandemic has been causing varying severities of illness. Some are asymptomatic and some develop severe disease leading to mortality across ages. This contrast triggered us explore the causes, with the background that a vaccine for effective immunization or a drug to tackle COVID-19 is not too close to reality. We have discussed strategies to combat COVID-19 through immune enhancement, using simple measures including nutritional supplements. Discussion: A literature search on mortality-related comorbid conditions was performed. For those conditions, we analyzed the pro-inflammatory cytokines, which could cause the draining of the immune reservoir. We also analyzed the immune markers necessary for the defense mechanism/immune surveillance against COVID-19, especially through simple means including immune enhancing nutritional supplement consumption, and we suggest strategies to combat COVID-19. Major comorbid conditions associated with increased mortality include cardiovascular disease (CVD), diabetes, being immunocompromised by cancer, and severe kidney disease with a senile immune system. Consumption of Aureobasidium pullulans strain (AFO-202) beta 1,3-1,6 glucan supported enhanced IL-8, sFAS macrophage activity, and NK cells' cytotoxicity, which are major defense mechanisms against viral infection. Conclusion: People with co-morbid conditions who are more prone to COVID-19-related deaths due to immune dysregulation are likely to benefit from consuming nutritional supplements that enhance the immune system. We recommend clinical studies to validate AFO-202 beta glucan in COVID-19 patients to prove its efficacy in overcoming a hyper-inflammation status, thus reducing the mortality, until a definite vaccine is made available.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Diabetes Mellitus/epidemiologia , Suplementos Nutricionais , Neoplasias/epidemiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Insuficiência Renal Crônica/epidemiologia , Actinobacteria/química , Biomarcadores/sangue , Doenças Cardiovasculares/imunologia , Comorbidade , Infecções por Coronavirus/dietoterapia , Infecções por Coronavirus/mortalidade , Citocinas/sangue , Diabetes Mellitus/imunologia , Humanos , Hospedeiro Imunocomprometido , Neoplasias/imunologia , Pandemias , Pneumonia Viral/dietoterapia , Pneumonia Viral/mortalidade , Insuficiência Renal Crônica/imunologia , beta-Glucanas/farmacologia , beta-Glucanas/uso terapêutico
9.
Clin Immunol ; 218: 108524, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32659373

RESUMO

The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4+ T cells significantly increased, while total lymphocytes and CD8+ T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4+ T cell differentiation.


Assuntos
Betacoronavirus/patogenicidade , Doenças Cardiovasculares/imunologia , Infecções por Coronavirus/imunologia , Diabetes Mellitus/imunologia , Imunidade Inata , Pneumopatias/imunologia , Neoplasias/imunologia , Pneumonia Viral/imunologia , Idoso , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/virologia , China/epidemiologia , Comorbidade , Convalescença , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Citocinas/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Feminino , Hospitalização , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Pneumopatias/epidemiologia , Pneumopatias/patologia , Pneumopatias/virologia , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/patologia , Subpopulações de Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Monócitos/virologia , Neoplasias/epidemiologia , Neoplasias/patologia , Neoplasias/virologia , Neutrófilos/imunologia , Neutrófilos/patologia , Neutrófilos/virologia , Pandemias , Alta do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Fatores de Tempo , Carga Viral/imunologia
10.
Nat Commun ; 11(1): 3766, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724076

RESUMO

Dipeptidyl peptidase-4 (DPP4) modulates inflammation by enzymatic cleavage of immunoregulatory peptides and through its soluble form (sDPP4) that directly engages immune cells. Here we examine whether reduction of DPP4 activity alters inflammation. Prolonged DPP4 inhibition increases plasma levels of sDPP4, and induces sDPP4 expression in lymphocyte-enriched organs in mice. Bone marrow transplantation experiments identify hematopoietic cells as the predominant source of plasma sDPP4 following catalytic DPP4 inhibition. Surprisingly, systemic DPP4 inhibition increases plasma levels of inflammatory markers in regular chow-fed but not in high fat-fed mice. Plasma levels of sDPP4 and biomarkers of inflammation are lower in metformin-treated subjects with type 2 diabetes (T2D) and cardiovascular disease, yet exhibit considerable inter-individual variation. Sitagliptin therapy for 12 months reduces DPP4 activity yet does not increase markers of inflammation or levels of sDPP4. Collectively our findings dissociate levels of DPP4 enzyme activity, sDPP4 and biomarkers of inflammation in mice and humans.


Assuntos
Doenças Cardiovasculares/imunologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptidil Peptidase 4/sangue , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Inflamação/imunologia , Idoso , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Dieta Aterogênica/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Dipeptidil Peptidase 4/imunologia , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Modelos Animais de Doenças , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Mediadores da Inflamação/análise , Mediadores da Inflamação/metabolismo , Masculino , Metformina/administração & dosagem , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/sangue , Isoformas de Proteínas/metabolismo , Fosfato de Sitagliptina/administração & dosagem , Fosfato de Sitagliptina/efeitos adversos
11.
Artigo em Inglês | MEDLINE | ID: mdl-32661006

RESUMO

To the best of our knowledge, there is no published study on the use of interferon ß-1a (IFN ß-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN ß-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN ß-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir). Each 44-µg/ml (12 million IU/ml) dose of interferon ß-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted of 39 patients who received only the national protocol medications. The primary outcome of the study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of intensive care unit stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects, and complications during the hospitalization. Between 29 February and 3 April 2020, 92 patients were recruited, and a total of 42 patients in the IFN group and 39 patients in the control group completed the study. As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively, P = 0.95). On day 14, 66.7% versus 43.6% of patients in the IFN group and the control group, respectively, were discharged (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.05 to 6.37). The 28-day overall mortality was significantly lower in the IFN than the control group (19% versus 43.6%, respectively, P = 0.015). Early administration significantly reduced mortality (OR, 13.5; 95% CI, 1.5 to 118). Although IFN did not change the time to reach the clinical response, adding it to the national protocol significantly increased discharge rate on day 14 and decreased 28-day mortality. (This study is in the Iranian Registry of Clinical Trials under identifier IRCT20100228003449N28.).


Assuntos
Antivirais/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Interferon beta-1a/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Adulto , Idoso , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/virologia , Comorbidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Dislipidemias/tratamento farmacológico , Dislipidemias/imunologia , Dislipidemias/mortalidade , Dislipidemias/virologia , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/mortalidade , Neoplasias/virologia , Pandemias , Segurança do Paciente , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Análise de Sobrevida , Resultado do Tratamento
13.
Expert Opin Pharmacother ; 21(13): 1617-1628, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32511034

RESUMO

INTRODUCTION: SLE is increasingly recognized as an important risk factor for cardiovascular disease. Premature CAD and several other cardiac manifestations are resulting in significant morbidity and premature death among young and older adults. There is a considerable unmet need for developing specific guidelines toward the primary and secondary prevention of cardiovascular disease in SLE patients. AREAS COVERED: The authors describe the prevalence of various cardiovascular manifestations, associated with traditional and lupus-specific risk factors. They summarize the evidence behind various nonpharmacological and pharmacological options such as cardiac medications, antimalarials, anti-inflammatory, and immunosuppressant medications. EXPERT OPINION: There is considerable literature claiming that the traditional Framingham score used to calculate the risk in the general population would not clearly predict the 10-year risk among SLE patients as they do not include lupus-specific risk factors such as accelerated inflammation, immunometabolic changes, thrombosis, vasospasm, vasculitis, and endothelial dysfunction into account. Identifying potential risk factors among SLE patients and treating hyperlipidemia regardless of their risk scores may be the first step in reducing mortality. Blocking lupus-specific inflammatory pathways by targeting validated biomarkers of pathogenesis has great future potential and more studies are needed on their cardiovascular benefits.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antimaláricos/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/imunologia , Humanos , Inflamação , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Prevalência , Fatores de Risco
14.
Artigo em Inglês | MEDLINE | ID: mdl-32571831

RESUMO

Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range [IQR], 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67]; hazard ratio [HR], 0.51 [95% confidence interval, 0.27 to 0.96]; P = 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 [95% confidence interval, 0.048 to 0.65]). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86]; odds ratio [OR], 0.880 [95% confidence interval, 0.449 to 1.726]; P = 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.


Assuntos
Antivirais/uso terapêutico , Azitromicina/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Interferons/uso terapêutico , Lopinavir/uso terapêutico , Metilprednisolona/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Idoso , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/virologia , Comorbidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Dislipidemias/tratamento farmacológico , Dislipidemias/imunologia , Dislipidemias/mortalidade , Dislipidemias/virologia , Feminino , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/mortalidade , Neoplasias/virologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Estudos Retrospectivos , Análise de Sobrevida
15.
PLoS Med ; 17(5): e1003115, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32379748

RESUMO

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is driven by multifaceted contributions of the immune system. However, the dysregulation of immune cells that leads to ASCVD is poorly understood. We determined the association of components of innate and adaptive immunity longitudinally with ASCVD, and assessed whether arterial calcifications play a role in this association. METHODS AND FINDINGS: Granulocyte (innate immunity) and lymphocyte (adaptive immunity) counts were determined 3 times (2002-2008, mean age 65.2 years; 2009-2013, mean age 69.0 years; and 2014-2015, mean age 78.5 years) in participants of the population-based Rotterdam Study without ASCVD at baseline. Participants were followed-up for ASCVD or death until 1 January 2015. A random sample of 2,366 underwent computed tomography at baseline to quantify arterial calcification volume in 4 vessel beds. We studied the association between immunity components with risk of ASCVD and assessed whether immunity components were related to arterial calcifications at baseline. Of 7,730 participants (59.4% women), 801 developed ASCVD during a median follow-up of 8.1 years. Having an increased granulocyte count increased ASCVD risk (adjusted hazard ratio for doubled granulocyte count [95% CI] = 1.78 [1.34-2.37], P < 0.001). Higher granulocyte counts were related to larger calcification volumes in all vessels, most prominently in the coronary arteries (mean difference in calcium volume [mm3] per SD increase in granulocyte count [95% CI] = 32.3 [9.9-54.7], P < 0.001). Respectively, the association between granulocyte count and incident coronary heart disease and stroke was partly mediated by coronary artery calcification (overall proportion mediated [95% CI] = 19.0% [-10% to 32.3%], P = 0.08) and intracranial artery calcification (14.9% [-10.9% to 19.1%], P = 0.05). A limitation of our study is that studying the etiology of ASCVD remains difficult within an epidemiological setting due to the limited availability of surrogates for innate and especially adaptive immunity. CONCLUSIONS: In this study, we found that an increased granulocyte count was associated with a higher risk of ASCVD in the general population. Moreover, higher levels of granulocytes were associated with larger volumes of arterial calcification. Arterial calcifications may explain a proportion of the link between granulocytes and ASCVD.


Assuntos
Imunidade Adaptativa/imunologia , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Imunidade Inata/imunologia , Idoso , Aterosclerose/imunologia , Doenças Cardiovasculares/imunologia , Vasos Coronários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia
16.
Clin Chim Acta ; 508: 110-114, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405080

RESUMO

BACKGROUND: We observe changes of the main lymphocyte subsets (CD16+CD56、CD19、CD3、CD4、and CD8) in COVID-19-infected patients and explore whether the changes are associated with disease severity. METHODS: One-hundred and fifty-four cases of COVID-19-infected patients were selected and divided into 3 groups (moderate group, severe group and critical group). The flow cytometry assay was performed to examine the numbers of lymphocyte subsets. RESULTS: CD3+, CD4+ and CD8 + T lymphocyte subsets were decreased in COVID-19-infected patients. Compared with the moderate group and the sever group, CD3+, CD4+ and CD8+ T cells in the critical group decreased greatly (P < 0.001, P = 0.005 or P = 0.001). CONCLUSIONS: Reduced CD3+, CD4+, CD8+ T lymphocyte counts may reflect the severity of the COVID-19. Monitoring T cell changes has important implications for the diagnosis and treatment of severe patients who may become critically ill.


Assuntos
Betacoronavirus/patogenicidade , Doenças Cardiovasculares/diagnóstico , Infecções por Coronavirus/diagnóstico , Diabetes Mellitus/diagnóstico , Pneumopatias/diagnóstico , Pneumonia Viral/diagnóstico , Subpopulações de Linfócitos T/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Complexo CD3/genética , Complexo CD3/imunologia , Antígenos CD4/genética , Antígenos CD4/imunologia , Antígenos CD8/genética , Antígenos CD8/imunologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus/imunologia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/fisiopatologia , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Pneumopatias/imunologia , Pneumopatias/mortalidade , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Seleção de Pacientes , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Prognóstico , Índice de Gravidade de Doença , Análise de Sobrevida , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia
19.
Am J Cardiol ; 125(12): 1920-1926, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32312493

RESUMO

Whether cardiovascular (CV) disease is associated with clinical outcomes in cancer patients receiving immunotherapy is unknown. We reviewed the Mayo Clinic database for all cancer patients who received an immune checkpoint inhibitor (ICI). Multivariate logistic regression analysis, survival analyses, and Cox proportional-hazards models were formulated. Between March, 2010 and July, 2019, 3,326 patients received ICI. Mean patient age was 63.5 years (range: 16 to 96 years). In a Cox proportional-hazards model, obesity (hazard ratio [HR] 0.65, 95% confidence level [CI] 0.55 to 0.77, p < 0.001) and hypercholesterolemia (HR 0.80, 95% CI 0.72 to 0.89, p < 0.001) were associated with lower all-cause mortality while hypertension (HR 1.32, 95% CI 1.17 to 1.49, p < 0.001) and smoking (HR 1.17, 95% CI 1.06 to 1.29, p = 0.002) were associated with higher overall mortality. Among patients with lung cancer, multivariable-adjusted hazard ratios for death from any cause for beta blocker users, as compared with patients who had never used a beta blocker, were 1.39 (95% CI 1.10 to 1.76, p = 0.006). A total of 80 patients (2.4%) experienced CV immune-related adverse events. Event-related morality for ICI-induced myocarditis was 41.7% (5/12). Multivariable-adjusted hazard ratios for ICI-induced myocarditis were 5.2 (95% CI 1.4 to 18.7, p = 0.01) for history of heart failure, 4.06 (95% CI 1.15 to 14.3, p = 0.03) for history of acute coronary syndrome, and 1.07 (per each 1-year increase, 95% CI 1.01 to 1.14, p = 0.02) for age. In conclusion, our study shows that CV factors are associated with clinical outcomes in cancer patients receiving ICI and could be used to predict mortality. In patients with lung cancer, pretreatment beta blocker use is associated with higher all-cause mortality. Three clinical factors-history of heart failure, history of acute coronary syndrome, and age greater than 80 years-help identify patients at higher risk of ICI-induced myocarditis who might benefit from more intensive cardiac surveillance.


Assuntos
Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/mortalidade , Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Doenças Cardiovasculares/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia
20.
Angiology ; 71(8): 689-697, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32292048

RESUMO

Current guidelines state that systemic inflammation, together with endothelial dysfunction, calcification, and hypercoagulability, predispose to premature atherosclerosis in patients with inflammatory bowel disease (IBD). We assessed whether IBD can affect aortic stiffness, a well-recognized vascular biomarker and an independent risk factor for cardiovascular (CV) disease (CVD) in several populations. Recent studies reported that aortic stiffness is increased in adults with IBD compared with matched controls. This association is dependent on inflammatory burden and disease duration, and is reduced by antitumor necrosis factor therapy. Considered together, current findings suggest that increased aortic stiffness is an extraintestinal manifestation of IBD. This is clinically relevant since measuring aortic stiffness in patients with IBD could improve risk assessment, especially in those without established CVD. Moreover, effective control of inflammation could lower CV risk in patients with IBD by reducing aortic stiffness. Further longitudinal studies are needed to better clarify (i) the relationship between disease duration and irreversible changes of the arterial wall, (ii) the clinical characteristics of patients with IBD that have an increased arterial stiffness at least in part reversible, and (iii) whether arterial stiffness is useful to evaluate the efficacy of immunosuppressive therapy.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Inflamatórias Intestinais/complicações , Rigidez Vascular , Animais , Anti-Inflamatórios/uso terapêutico , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Fatores de Risco , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Rigidez Vascular/efeitos dos fármacos
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