RESUMO
Immune response dysregulation plays a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. In this study, we evaluated immune and endothelial blood cell profiles of patients with coronavirus disease 2019 (COVID-19) to determine critical differences between those with mild, moderate, or severe COVID-19 using spectral flow cytometry. We examined a suite of immune phenotypes, including monocytes, T cells, NK cells, B cells, endothelial cells, and neutrophils, alongside surface and intracellular markers of activation. Our results showed progressive lymphopenia and depletion of T cell subsets (CD3+, CD4+, and CD8+) in patients with severe disease and a significant increase in the CD56+CD14+Ki67+IFN-γ+ monocyte population in patients with moderate and severe COVID-19 that has not been previously described. Enhanced circulating endothelial cells (CD45-CD31+CD34+CD146+), circulating endothelial progenitors (CD45-CD31+CD34+/-CD146-), and neutrophils (CD11b+CD66b+) were coevaluated for COVID-19 severity. Spearman correlation analysis demonstrated the synergism among age, obesity, and hypertension with upregulated CD56+ monocytes, endothelial cells, and decreased T cells that lead to severe outcomes of SARS-CoV-2 infection. Circulating monocytes and endothelial cells may represent important cellular markers for monitoring postacute sequelae and impacts of SARS-CoV-2 infection during convalescence and for their role in immune host defense in high-risk adults after vaccination.
Assuntos
COVID-19/imunologia , Células Endoteliais/imunologia , Monócitos/imunologia , SARS-CoV-2 , Adolescente , Adulto , Fatores Etários , Idoso , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Biomarcadores , Antígeno CD56/análise , COVID-19/sangue , COVID-19/epidemiologia , Criança , Comorbidade , Células Endoteliais/química , Feminino , Citometria de Fluxo , Humanos , Hipertensão/epidemiologia , Hipertensão/imunologia , Imunofenotipagem , Ativação Linfocitária , Subpopulações de Linfócitos/imunologia , Linfopenia/etiologia , Linfopenia/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/química , Neutrófilos/imunologia , Obesidade/epidemiologia , Obesidade/imunologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto JovemRESUMO
BACKGROUND & AIMS: Obesity is associated with low grade systemic inflammation and insulin resistance. Although metabolic and immunological changes may contribute to the increased risk for COVID-19 mortality in obese, little is known about the impact of obesity in the lungs of patients with COVID-19. METHODS: We analyzed gene expression profiles of autopsy lungs of a cohort of 14 COVID-19 patients and 4 control individuals. Patients were divided into 3 groups according to their comorbidities: hypertension, type 2 diabetes (T2D) and obesity. We then identified the molecular alterations associated with these comorbidities in COVID-19 patients. RESULTS: Patients with only hypertension showed higher levels of inflammatory genes and B-cell related genes when compared to those with T2D and obesity. However, the levels of IFN-gamma, IL22, and CD274 (a ligand that binds to receptor PD1) were higher in COVID-19 patients with T2D and obesity. Several metabolic- and immune-associated genes such as G6PD, LCK and IL10 were significantly induced in the lungs of the obese group. CONCLUSION: Our findings suggest that SARS-CoV-2 infection in the lungs may exacerbate the immune response and chronic condition in obese COVID-19 patients.
Assuntos
COVID-19/complicações , COVID-19/genética , Expressão Gênica/genética , Pulmão/imunologia , Obesidade/complicações , Obesidade/genética , Autopsia , COVID-19/imunologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Humanos , Hipertensão/complicações , Hipertensão/genética , Hipertensão/imunologia , Obesidade/imunologia , SARS-CoV-2RESUMO
The SARS-CoV-2 virus has emerged and rapidly evolved into a current global pandemic. Although bacterial and fungal coinfections have been associated with COVID-19, little is known about parasitic infection. We report a case of a COVID-19 patient who developed disseminated strongyloidiasis following treatment with high-dose corticosteroids and tocilizumab. Screening for Strongyloides infection should be pursued in individuals with COVID-19 who originate from endemic regions before initiating immunosuppressive therapy.
Assuntos
Infecções por Coronavirus/parasitologia , Diabetes Mellitus/parasitologia , Hipertensão/parasitologia , Doenças do Sistema Nervoso Periférico/parasitologia , Pneumonia Viral/parasitologia , Strongyloides stercoralis/patogenicidade , Estrongiloidíase/parasitologia , Corticosteroides/administração & dosagem , Idoso , Animais , Anti-Helmínticos/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Betacoronavirus/patogenicidade , COVID-19 , Coinfecção , Connecticut , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/imunologia , Diabetes Mellitus/virologia , Equador , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Hipertensão/virologia , Fatores Imunológicos/administração & dosagem , Masculino , Pandemias , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , SARS-CoV-2 , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/imunologia , Estrongiloidíase/virologiaRESUMO
BACKGROUND AND AIMS: The outbreak of the new coronavirus, SARS-CoV-2, causes a respiratory disease and individuals with pre-existing cardiometabolic disorders display worse prognosis through the infection course. The aim of this minireview is to present epidemiological data related to metabolic comorbidities in association with the SARS-CoV-2. METHODS: This is a narrative mini-review with Pubmed search until April 23, 2020 using the keywords COVID-19, SARS-CoV-2, treatment of coronavirus and following terms: diabetes mellitus, obesity, arterial hypertension, ACE-inhibitors, cytokine storm, immune response and vitamin D. RESULTS: Studies indicate that obese individuals are more likely to develop infections, and that adipose tissue serves as a pathogen reservoir. In diabetic individuals higher rate of inflammatory processes is seen due to constant glucose recognition by C type lectin receptors. Hypertensive individuals, usually grouped with other conditions, are treated with drugs to reduce blood pressure mostly through ACEi and ARB, that leads to increased ACE2 expression, used by SARS-CoV-2 for human's cell entry. Until now, the studies have shown that individuals with those conditions and affected by COVID-19 present an uncontrolled release of pro-inflammatory cytokines and an unbalanced immune response, leading to the cytokine storm phenomenon. Vitamin D is highlighted as a potential therapeutic target, because in addition to acting on the immune system, it plays an important role in the control of cardiometabolic diseases. CONCLUSION: Currently, since there is no proven and effective antiviral therapy for SARS-CoV-2, the efforts should focus on controlling inflammatory response and reduce the risks of associated complications.
Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/fisiopatologia , Hipertensão/imunologia , Obesidade/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Inibidores da Enzima Conversora de Angiotensina , COVID-19 , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/terapia , Humanos , Hipertensão/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , SARS-CoV-2 , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/fisiopatologia , Tratamento Farmacológico da COVID-19RESUMO
Malaria etiologies with pathophysiological similarities to hypertension currently constitute a major subject of research. The malaria-high blood pressure hypothesis is strongly supported by observations of the increasing incidence of hypertension in malaria-endemic, low- and middle-income countries with poor socioeconomic conditions, particularly in sub-Saharan African countries. Malnutrition and low birth weight with persistent symptomatic malaria presentations in pregnancy correlate strongly with the development of preeclampsia, gestational hypertension and subsequent hypertension in adult life. Evidence suggest that the link between malaria infection and high blood pressure involves interactions between malaria parasites and erythrocytes, the inflammatory process, effects of the infection during pregnancy; effects on renal and vascular functions as well as effects in sickle cell disease. Possible mechanisms which provide justification for the malaria-high blood pressure hypothesis include the following: endothelial dysfunction (reduced nitric oxide (NO) levels), impaired release of local neurotransmitters and cytokines, decrease in vascular smooth muscle cell viability and/or alterations in cellular calcium signaling leading to enhanced vascular reactivity, remodeling, and cardiomyopathies, deranged homeostasis through dehydration, elevated intracellular mediators and proinflammatory cytokine responses, possible genetic regulations, activation of the renin-angiotensin-aldosterone system mechanisms and renal derangements, severe anemia and hemolysis, renal failure, and end organ damage. Two key mediators of the malaria-high blood pressure association are: endothelial dysfunction (reduced NO) and increased angiotensin-converting enzyme activity/angiotensin II levels. Sickle cell disease is associated with protection against malaria infection and reduced blood pressure. In this review, we present the state of knowledge about the malaria-blood pressure hypothesis and suggest insights for future studies.
Assuntos
Endotélio/fisiopatologia , Hipertensão/fisiopatologia , Malária/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Angiotensina II/metabolismo , Sinalização do Cálcio , Sobrevivência Celular , Citocinas/metabolismo , Países em Desenvolvimento , Endotélio/metabolismo , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/imunologia , Hipertensão/metabolismo , Hipertensão Induzida pela Gravidez/epidemiologia , Inflamação/imunologia , Inflamação/metabolismo , Malária/epidemiologia , Malária/imunologia , Malária/metabolismo , Músculo Liso Vascular , Miócitos de Músculo Liso/metabolismo , Neurotransmissores/metabolismo , Óxido Nítrico/metabolismo , Peptidil Dipeptidase A/metabolismo , Pré-Eclâmpsia/epidemiologia , GravidezRESUMO
PURPOSE OF REVIEW: To gather data from studies evaluating the pro-inflammatory profile of individuals with resistant hypertension (RH), and bring a clinical update of new and potential complementary therapies to treat inflammation in RH. RECENT FINDINGS: Increases in pro-inflammatory cytokines are related to elevated blood pressure and target organ damage in RH patients. Clinical and experimental studies have shown that some biological therapies, especially TNF-α inhibitors, regulated pro- and anti-inflammatory cytokines associated with improvements in clinical outcomes, although they are not yet reported in RH. New emerging therapies to treat inflammation in RH, although promising, are still hypotheses that have not been scientifically confirmed in clinical trials. For this reason, inflammation-target treatments, such as the TNF-α and IL-6 inhibitors, should be encouraged for testing as complementary therapies in RH in order to elucidate their potential benefits.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Citocinas/imunologia , Hipertensão/tratamento farmacológico , Hipertensão/imunologia , Inflamação/imunologia , Citocinas/sangue , Humanos , Hipertensão/sangue , Inflamação/sangue , Inflamação/tratamento farmacológicoRESUMO
Type 2 diabetes mellitus (DM2) is strongly associated with other comorbidities such as obesity, atherosclerosis, and hypertension. Obesity is associated with sustained low-grade inflammatory response due to the production of proinflammatory cytokines. This inflammatory process promotes the differentiation of some myeloid cells, including myeloid-derived suppressor cells (MDSCs). In this study, two groups of individuals were included: DM2 patients and non-DM2 individuals with similar characteristics. Immunolabeling of CD15+ CD14- and CD33+ HLA-DR-/low was performed from whole peripheral blood, and samples were analyzed by flow cytometry, and frequencies of MDSCs and the relationship of these with clinical variables, cytokine profile (measured by cytometric bead array), and anthropometric variables were analyzed. The frequency of CD33+ HLA-DR-/low MDSCs (that produce IL-10 and TGF-ß, according to an intracellular detection) is higher in patients with DM2 (P < 0.05), and there is a positive correlation between the frequency of CD15+ CD14- and CD33+ HLA-DR-/low MDSC phenotypes. DM2 patients have an increased concentration of serum IL-5 (P < 0.05). Also, a negative correlation between the frequency of CD15+ CD14- MDSCs and LDL cholesterol was found. Our group of DM2 patients have an increased frequency of mononuclear MDSC CD33+ HLA-DR-/low that produce TGF-ß and IL-10. These cytokines have been associated with immune modulation and reduced T cell responses. DM2 and non-DM2 subjects show a similar cytokine profile, but the DM2 patients have an increased concentration of IL-5.
Assuntos
Diabetes Mellitus Tipo 2/imunologia , Hipertensão/imunologia , Células Supressoras Mieloides/imunologia , Adulto , Feminino , Antígenos HLA-DR/análise , Humanos , Interleucina-10/biossíntese , Interleucina-5/sangue , Masculino , Pessoa de Meia-Idade , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/análise , Fator de Crescimento Transformador beta/biossínteseAssuntos
Pressão Sanguínea/genética , Hipertensão/genética , Polimorfismo de Nucleotídeo Único , Pressão Sanguínea/imunologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/imunologia , Hipertensão/fisiopatologia , Fenótipo , Prognóstico , Medição de Risco , Fatores de RiscoRESUMO
Chronic Chagas heart disease (CCHD affects about 30% of patients with chronic Chagas disease (CCD). Systemic arterial hypertension (SAH) afflicts about 25% of patients with CCD. The association of CCHD with SAH (CCHD-SAH) predisposes patients to develop chronic heart failure. The role of cytokines in disease progression in patients with CCHD-SAH is unknown. Accordingly, the aim of this study was to evaluate the plasma levels of cytokines expressing the Th1, Th2, Th17 pattern, as well as Treg cytokines, TNF-alpha, IL-1ß, IL-8, IL-7 in patients with SAH-CCHD to get insight into the immunomodulation process in patients with this condition. Fifteen patients with CCHD, 22 patients with CCHD-SAH, and 28 controls were studied. All patients underwent history-taking, physical examination, 12-lead resting ECG, chest X-ray, and Doppler-echocardiogram. Ten of 15 (66%) patients with CCHD, and 16 of 22 (73%) patients with CCHD-SAH had decreased left ventricular ejection fraction (p > 0.05). Cytokines levels were performed on plasma samples using the ELISA method. Overall, proinflammatory, anti-inflammatory, and regulatory cytokine levels were increased in patients with CCHD-SAH in comparison to patients with CCHD and controls. However, such a difference was higher regarding IL-2, IL-5, IL-17, IL-12, and TNF-alpha cytokine levels, respectively. Cytokine levels were higher in CCHD patients in comparison to controls. Patients with CCHD-SAH have increased plasma levels of pro-inflammatory, anti-inflammatory, and regulatory cytokines in comparison with CCHD patients, thus suggesting a higher level of immunomodulation in patients with CCHD-SAH.
Assuntos
Cardiomiopatia Chagásica/imunologia , Citocinas/metabolismo , Hipertensão/imunologia , Linfócitos T Reguladores/metabolismo , Células Th1/metabolismo , Células Th17/metabolismo , Células Th2/metabolismo , Biomarcadores/metabolismo , Cardiomiopatia Chagásica/metabolismo , Doença Crônica , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hipertensão/metabolismo , Masculino , Pessoa de Meia-Idade , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologiaRESUMO
Arterial hypertension represents a serious public health problem, being a major cause of morbidity and mortality worldwide. The availability of many antihypertensive therapeutic strategies still fails to adequately treat around 20% of hypertensive patients, who are considered resistant to conventional treatment. In the pathogenesis of hypertension, immune system mechanisms are activated and both the innate and adaptive immune responses play a crucial role. However, what, when and how the immune system is triggered during hypertension development is still largely undefined. In this context, this review highlights scientific advances in the manipulation of the immune system in order to attenuate hypertension and end-organ damage. Here, we discuss the potential use of immunosuppressants and immunomodulators as pharmacological tools to control the activation of the immune system, by non-specific and specific mechanisms, to treat hypertension and improve end-organ damage. Nevertheless, more clinical trials should be performed with these drugs to establish their therapeutic efficacy, safety and risk-benefit ratio in hypertensive conditions. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.