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1.
Rev. esp. geriatr. gerontol. (Ed. impr.) ; 55(5): 286-288, sept.-oct. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-192478

RESUMO

INTRODUCCIÓN: El síndrome de tormenta de citoquinas (STC) es una complicación muy grave de los pacientes con infección por SARS-CoV-2. El tratamiento y la evolución no están bien definidos. Nuestro objetivo es describir sus características clínicas, los tratamientos empleados y su evolución clínica. PACIENTES Y MÉTODO: Estudio retrospectivo observacional de pacientes consecutivos ingresados en el período comprendido entre el 23 de marzo y el 12 de abril de 2020 con infección por SARS-CoV-2 confirmada, con neumonía por estudio radiológico o tomografía de tórax, que cumplían criterios de STC y que recibieron tratamiento. Clasificamos a los pacientes en los que recibieron solo pulsos de glucocorticoides (GC), o pulsos de GC y tocilizumab. Determinamos niveles séricos de ferritina, PCR y dímeros-D. La variable final fue la supervivencia. RESULTADOS: Veintiún pacientes con una edad de 83 años (80-88 años). La ferritina media fue de 1.056 microg/L (317-3.553), la PCR de 115,8mg/dL (22-306) y los dímeros-D de 2,9mg/L (0,45-17,5). Todos los pacientes recibieron pulsos de GC y en 2 casos simultáneamente tocilizumab. El tiempo medio de seguimiento fue de 13,7 días (8-21). La mortalidad global fue del 38,1% (8/21pacientes). Los 2 pacientes que recibieron tocilizumab fallecieron. Los fallecidos presentaron niveles significativamente más elevados de ferritina (1.254 vs. 925microg/L; p = 0,045) y PCR (197,6 vs. 76mg/dL; p = 0,007). Al final del seguimiento se observó una disminución en los parámetros bioquímicos con ferritina de 727microg/L, PCR de 27mg/dl y dímeros-D de 1,18mg/L. En 13/21 pacientes (61,9%) el STC se controló sin necesidad de añadir otros tratamientos. CONCLUSIONES: La mortalidad del STC por SARS-CoV-2 es alta a pesar del tratamiento. Una mayor respuesta inflamatoria se asoció con una mayor mortalidad. Aunque parece que el uso precoz de pulsos de GC puede controlarlo, pudiendo disminuir la necesidad de uso de otros tratamientos, con el diseño del estudio y sus limitaciones, no se puede establecer esta conclusión


INTRODUCTION: Cytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defiREVned. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution. PATIENTS AND METHOD: Retrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival. RESULTS: 21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8mg/dL (22-306) and D-dimers 2.9m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925microg/L; P=.045) and CRP (197.6 vs. 76mg / dL; P=.007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727microg/L, CRP of 27mg/dl and D-dimers of 1.18mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments. CONCLUSIONS: STC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished


Assuntos
Humanos , Masculino , Feminino , Idoso de 80 Anos ou mais , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Vírus da SARS/patogenicidade , Citocinas/efeitos adversos , Inflamação/fisiopatologia , Glucocorticoides/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos Retrospectivos , Infecções por Coronavirus/epidemiologia , Epidemias , Mediadores da Inflamação/imunologia , Inflamação/imunologia , Ferritinas/efeitos dos fármacos , Linfo-Histiocitose Hemofagocítica/imunologia
2.
Anatol J Cardiol ; 24(4): 224-234, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33001051

RESUMO

Coronavirus disease 2019 (COVID-19) caused by 'Severe Acute Respiratory Syndrome Coronavirus-2' (SARS-CoV-2) infection emerged in Wuhan, a city of China, and spread to the entire planet in early 2020. The virus enters the respiratory tract cells and other tissues via ACE2 receptors. Approximately 20% of infected subjects develop severe or critical disease. A cytokine storm leads to over inflammation and thrombotic events. The most common clinical presentation in COVID-19 is pneumonia, typically characterized by bilateral, peripheral, and patchy infiltrations in the lungs. However multi-systemic involvement including peripheral thromboembolic skin lesions, central nervous, gastrointestinal, circulatory, and urinary systems are reported. The disease has a higher mortality compared to other viral agents causing pneumonia and unfortunately, no approved specific therapy, nor vaccine has yet been discovered. Several clinical trials are ongoing with hydroxychloroquine, remdesivir, favipiravir, and low molecular weight heparins. This comprehensive review aimed to summarize coagulation abnormalities reported in COVID-19, discuss the thrombosis, and inflammation-driven background of the disease, emphasize the impact of thrombotic and inflammatory processes on the progression and prognosis of COVID-19, and to provide evidence-based therapeutic guidance, especially from antithrombotic and anti-inflammatory perspectives.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Inflamação/virologia , Pneumonia Viral/complicações , Trombose/virologia , Transtornos da Coagulação Sanguínea/terapia , Transtornos da Coagulação Sanguínea/virologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Transtornos Hemostáticos/virologia , Humanos , Imunomodulação/fisiologia , Inflamação/terapia , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Prognóstico , Trombose/terapia
3.
Cells ; 9(10)2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003471

RESUMO

COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host-pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.


Assuntos
Infecções por Coronavirus/sangue , Células Dendríticas/imunologia , Monócitos/imunologia , Neutrófilos/imunologia , Pneumonia Viral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Células Cultivadas , Infecções por Coronavirus/imunologia , Citocinas/genética , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia
4.
Mediators Inflamm ; 2020: 8198963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029105

RESUMO

The novel coronavirus is not only causing respiratory problems, but it may also damage the heart, kidneys, liver, and other organs; in Wuhan, 14 to 30% of COVID-19 patients have lost their kidney function and now require either dialysis or kidney transplants. The novel coronavirus gains entry into humans by targeting the ACE2 receptor that found on lung cells, which destroy human lungs through cytokine storms, and this leads to hyperinflammation, forcing the immune cells to destroy healthy cells. This is why some COVID-19 patients need intensive care. The inflammatory chemicals released during COVID-19 infection cause the liver to produce proteins that defend the body from infections. However, these proteins can cause blood clotting, which can clog blood vessels in the heart and other organs; as a result, the organs are deprived of oxygen and nutrients which could ultimately lead to multiorgan failure and consequent progression to acute lung injury, acute respiratory distress syndrome, and often death. However, there are novel protein modification tools called the QTY code, which are similar in their structure to antibodies, which could provide a solution to excess cytokines. These synthetic proteins can be injected into the body to bind the excess cytokines created by the cytokine storm; this will eventually remove the excessive cytokines and inhibit the severe symptoms caused by the COVID-19 infection. In this review, we will focus on cytokine storm in COVID-19 patients, their impact on the body organs, and the potential treatment by QTY code-designed detergent-free chemokine receptors.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/terapia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Receptores de Quimiocinas/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/imunologia , Citocinas/antagonistas & inibidores , Desenho de Fármacos , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/imunologia , Modelos Moleculares , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/terapia , Pandemias , Pneumonia Viral/terapia , Engenharia de Proteínas , Modificação Traducional de Proteínas , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo
6.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(8. Vyp. 2): 58-64, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33016678

RESUMO

The pandemic caused by the SARS-CoV-2 virus (COVID-19) made it necessary to evaluate in more detail the processes of neuroinflammation as an integral component of the pathogenesis of viral infection. The acute neuroinflammatory response includes the activation of resident tissue macrophages in the CNS and the subsequent release of various cytokines and chemokines, which probably activates oxidative stress, causing long-term neuronal damage. This makes urgent the search for drugs with indirect anti-inflammatory effects with proven effectiveness. From this point of view, it is worth further studying the treatment of patients with COVID-19 with dipyridamole, which, with its antiviral activity and anti-inflammatory effect, inhibiting acute inflammation and progressive fibrosis, is the drug of choice, especially for patients with early signs of elevated D-dimer concentrations and pronounced clinical symptoms of microangiopathy.


Assuntos
Infecções por Coronavirus , Inflamação , Doenças do Sistema Nervoso , Pandemias , Pneumonia Viral , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Betacoronavirus , Citocinas , Humanos , Doenças do Sistema Nervoso/virologia
7.
Front Immunol ; 11: 565521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013930

RESUMO

Neurological disorders caused by neuroviral infections are an obvious pathogenic manifestation. However, non-neurotropic viruses or peripheral viral infections pose a considerable challenge as their neuropathological manifestations do not emerge because of primary infection. Their secondary or bystander pathologies develop much later, like a syndrome, during and after the recovery of patients from the primary disease. Massive inflammation caused by peripheral viral infections can trigger multiple neurological anomalies. These neurological damages may range from a general cognitive and motor dysfunction up to a wide spectrum of CNS anomalies, such as Acute Necrotizing Hemorrhagic Encephalopathy, Guillain-Barré syndrome, Encephalitis, Meningitis, anxiety, and other audio-visual disabilities. Peripheral viruses like Measles virus, Enteroviruses, Influenza viruses (HIN1 series), SARS-CoV-1, MERS-CoV, and, recently, SARS-CoV-2 are reported to cause various neurological manifestations in patients and are proven to be neuropathogenic even in cellular and animal model systems. This review presents a comprehensive picture of CNS susceptibilities toward these peripheral viral infections and explains some common underlying themes of their neuropathology in the human brain.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Inflamação Neurogênica/complicações , Inflamação Neurogênica/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/complicações , Animais , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/virologia , Infecções por Coronavirus/virologia , Citocinas/sangue , Modelos Animais de Doenças , Humanos , Microglia/imunologia , Microglia/virologia , Inflamação Neurogênica/virologia , Pandemias , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia
8.
Acta Med Indones ; 52(3): 306-313, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33020343

RESUMO

Cytokine storm in COVID-19 infection is an excessive immune response to external stimuli where the pathogenesis is complex. The disease progresses rapidly and the mortality is high. Certain evidence shows that the severe deterioration of some patients has been closely related to the strong upregulation of cytokine production in SARS-Co-V2 induced pneumonia with an associated cytokine storm syndrome. Identification of existing approaved therapy with proven safety profile to treat hyperinflammation is critical unmet need in order to reduce COVID-19 associated mortality. To date, no specific therapeutic drugs are available to treat COVID-19 infection. Preliminary studies have shown that immune-modulatory or immune suppressive treatments might be considered as treatment choices for COVID-19, particularly in severe disease. This article review the pathogenesis and treatment strategies of COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Citocinas/sangue , Gerenciamento Clínico , Imunidade Inata , Pandemias , Pneumonia Viral/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Citocinas/imunologia , Humanos , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia
9.
Signal Transduct Target Ther ; 5(1): 221, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024073
10.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(5): 821-827, 2020 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-33047714

RESUMO

OBJECTIVE: To evaluate the sub-acute oral effect of titanium dioxide (TiO2) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats. METHODS: Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO2 nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats. RESULTS: Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO2 gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed. CONCLUSION: TiO2 nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO2 nanoparticles, followed by intestine, blood, and colon in sequence.


Assuntos
Antioxidantes , Nanopartículas , Animais , Biomarcadores , Citocinas , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Titânio
11.
Crit Care ; 24(1): 605, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046113

RESUMO

BACKGROUND: Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19. AIM: Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties. METHODS: An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events. RESULTS: The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime (p < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h (p = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime (p < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p = 0.001). Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement. CONCLUSIONS: EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.


Assuntos
Infecções por Coronavirus/terapia , Citocinas/sangue , Hemodiafiltração/instrumentação , Hemodiafiltração/métodos , Pneumonia Viral/terapia , Infecções por Coronavirus/sangue , Humanos , Unidades de Terapia Intensiva , Pandemias , Projetos Piloto , Pneumonia Viral/sangue , Estudos Prospectivos , Resultado do Tratamento
12.
Med Hypotheses ; 143: 110201, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33017909

RESUMO

COVID-19 initially an epidemic caused by SARS-CoV-2 has turned out to be a life- threatening global pandemic with increased morbidity and mortality. The presence of cytokine storm has been linked with the pathogenesis of severe lung injury as evinced in COVID-19. Aquaporins (AQPs) are molecular water channels, facilitating water transport across the cell membrane in response to osmotic gradients. Impairment in alveolar fluid clearance due to altered functional expression of respiratory AQPs highlight their pathophysiological significance in pulmonary edema associated respiratory illness. Therefore, we hypothesize that targeted modulation of AQPs in lungs in the intervening period of time, could diminish the dreadful effects of inflammation- induced comorbidity in COVID-19.


Assuntos
Aquaporinas/metabolismo , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Edema Pulmonar/tratamento farmacológico , Animais , Betacoronavirus , Transporte Biológico , Comorbidade , Citocinas/metabolismo , Humanos , Inflamação , Pulmão/imunologia , Pulmão/virologia , Camundongos , Pandemias
13.
Can Respir J ; 2020: 1401053, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32934758

RESUMO

Background: The threat of contagious infectious diseases is constantly evolving as demographic explosion, travel globalization, and changes in human lifestyle increase the risk of spreading pathogens, leading to accelerated changes in disease landscape. Of particular interest is the aftermath of superimposing viral epidemics (especially SARS-CoV-2) over long-standing diseases, such as tuberculosis (TB), which remains a significant disease for public health worldwide and especially in emerging economies. Methods and Results: The PubMed electronic database was systematically searched for relevant articles linking TB, influenza, and SARS-CoV viruses and subsequently assessed eligibility according to inclusion criteria. Using a data mining approach, we also queried the COVID-19 Open Research Dataset (CORD-19). We aimed to answer the following questions: What can be learned from other coronavirus outbreaks (focusing on TB patients)? Is coinfection (TB and SARS-CoV-2) more severe? Is there a vaccine for SARS-CoV-2? How does the TB vaccine affect COVID-19? How does one diagnosis affect the other? Discussions. Few essential elements about TB and SARS-CoV coinfections were discussed. First, lessons from past outbreaks (other coronaviruses) and influenza pandemic/seasonal outbreaks have taught the importance of infection control to avoid the severe impact on TB patients. Second, although challenging due to data scarcity, investigating the pathological pathways linking TB and SARS-CoV-2 leads to the idea that their coexistence might yield a more severe clinical evolution. Finally, we addressed the issues of vaccination and diagnostic reliability in the context of coinfection. Conclusions: Because viral respiratory infections and TB impede the host's immune responses, it can be assumed that their lethal synergism may contribute to more severe clinical evolution. Despite the rapidly growing number of cases, the data needed to predict the impact of the COVID-19 pandemic on patients with latent TB and TB sequelae still lies ahead. The trial is registered with NCT04327206, NCT01829490, and NCT04121494.


Assuntos
Coinfecção/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Tuberculose/epidemiologia , Vacina BCG/uso terapêutico , Betacoronavirus , Técnicas de Laboratório Clínico , Coinfecção/imunologia , Coinfecção/fisiopatologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Citocinas/imunologia , Erros de Diagnóstico , Surtos de Doenças , Humanos , Influenza Humana/epidemiologia , Influenza Humana/fisiopatologia , Coronavírus da Síndrome Respiratória do Oriente Médio , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Vírus da SARS , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/fisiopatologia , Índice de Gravidade de Doença , Tuberculose/imunologia , Tuberculose/fisiopatologia , Tuberculose/prevenção & controle
14.
Yonsei Med J ; 61(9): 789-796, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882763

RESUMO

PURPOSE: The prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea. MATERIALS AND METHODS: Pulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed. RESULTS: Statistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95-100%). CONCLUSION: Our data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic.


Assuntos
Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Antígenos de Bactérias/sangue , Antígenos de Bactérias/genética , Antígenos de Superfície/sangue , Antígenos de Superfície/genética , Proteínas de Bactérias , Pequim , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/metabolismo , República da Coreia , Sensibilidade e Especificidade
15.
J Korean Med Sci ; 35(35): e324, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32893524

RESUMO

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic infection associated with high morbidity and mortality. The Korean city of Daegu endured the first large COVID-19 outbreak outside of China. Since the report of the first confirmed case in Daegu on February 18, 2020, a total of 6,880 patients have been reported until May 29, 2020. We experienced five patients with ischemic stroke and COVID-19 during this period in four tertiary hospitals in Daegu. The D-dimer levels were high in all three patients in whom D-dimer blood testing was performed. Multiple embolic infarctions were observed in three patients and suspected in one. The mean time from stroke symptom onset to emergency room arrival was 22 hours. As a result, acute treatment for ischemic stroke was delayed. The present case series report raises the possibility that the coronavirus responsible for COVID-19 causes or worsens stroke, perhaps by inducing inflammation. The control of COVID-19 is very important; however, early and proper management of stroke should not be neglected during the epidemic.


Assuntos
Infecções por Coronavirus/patologia , Citocinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Pneumonia Viral/patologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Serviços Médicos de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , República da Coreia/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Tromboembolia/patologia , Terapia Trombolítica/métodos , Tempo para o Tratamento
16.
Urologiia ; (4): 36-44, 2020 Sep.
Artigo em Russo | MEDLINE | ID: mdl-32897012

RESUMO

PURPOSE: Assessment of the severity of immunological disorders in patients with hlamydia trachomatis (CT) infection and the effectiveness of antibacterial therapy in combination with systemic enzyme therapy for the eradication of pathogenic pathogen and correction of detected violations of the immune system. MATERIALS AND METHODS: 84 patients with identified CT infection were divided into 2 clinical groups: group 1 (42 people) received antibiotic therapy with doxycycline monohydrate for 10 days, 100 mg 2 times a day (the first dose of 200 mg) at regular intervals (daily dose of 200 mg, course - 2.0 g.) in combination with phlogenzyme, 3 tablets 2 times a day within 14 days. The second clinical group (42 people) received only doxycycline monohydrate therapy at the same doses as in the first clinical group. In all patients with CT infection (84 people) and in the control group (32 practically healthy people), the activity of immune reac-tions in the body was additionally assessed by the level of cytokines (-INF, IL-1, IL-4, IL-6), circulating immune complexes (CIC), lactoferrin (LF) and 2-macroglobulin in blood serum. RESULTS: The level of CEC in the blood serum of patients with CT infection is significantly higher than the standard indicators (by 1.83 times) compared with the indicators of the control group (106.1+/-5.12 conventional units versus 57.8+/-3.39 conventional units, p<0.05). The level of -IFN in the blood serum of patients with CT infection is 1.64 times lower than in the control (28.9+/-4.15 pkg / ml and 47.3+/-4.26 pkg / ml, p<0.05), and indicators of IL-1 in blood serum - 3.12 times higher; the level of IL-6 is 2.13 times higher (p<0.001); the level of IL-4 is 1.65 times higher (p<0.05). The Lf level in patients with CT infection exceeded 2.37 times the indicator in the control group (1742.0+/-112.15 ng / ml and 732.1+/-36.11 ng / ml, p<0.001), 2-macroglobulin - in 1, 36 times (2.59 - 0.21 mg/l and 1.9 - 0.47 mg / l, p<0.001). The efficiency of clinical and microbiological cure in patients with CT infection, who received complex therapy with doxycycline monohydrate and phlogenzyme, was 97.6%. With monotherapy (doxycycline monohydrate), the effectiveness of clinical and microbiological cure was significantly lower - 78.6%, statistically significant (OR=11.2; 95% CI 1.3-247.9; p=0.007). The fact of a decrease in the activity of Th-2 type of the cellular link of immunity in patients with CT infection receiving systemic enzyme therapy drug was established. DISCUSSION: One of the pathogenetic mechanisms of CT infection is an imbalance in the cytokine profile, which manifests itself in an increase in the level of cytokines of the Th-2 (IL-6) type and a decrease in the Th-1 (-IFN) type. With the predominant production of pro-inflammatory cytokines (IL-1, IL-6), the dynamics of CT infection becomes chronic. A decrease in the reserve capacity of the proteolytic enzyme system during CT infection with a subsequent increase in the level of 2-macroglobulins in the blood contributes to the dysregulation of local inflammation processes and the formation of immune disorders. With a long course of CT infection, it is most advisable to use (as a basic pathogenetic therapy) systemic enzyme therapy (phlogenzyme). The effect of systemic enzyme therapy on immune responses in C. trachomatis enhances the activity of the Th-1 type of cytokines (-IFN) and a decrease in the level of 2-macroglobulins and pro-inflammatory cytokines (IL-1, IL-6) in the blood. Systemic enzyme therapy can significantly increase the effectiveness of antibiotic therapy and reduce the risk of side effects. CONCLUSION: The theoretical argumentation of the pathophysiological mechanisms of disorders in the interaction of the most important functional systems made it possible to substantiate new conceptual approaches to the therapy of CT infection, taking into account the level and specific disorders in the universal systems of homeostasis regulation. In particular, a pathophysiological basis has been provided to substantiate the advisability of combining antibacterial therapy with systemic enzyme therapy drugs to correct systemic immunological disorders in patients with CT infection.


Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Citocinas , Doxiciclina , Terapia Enzimática , Humanos
17.
J Exp Med ; 217(12)2020 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-32886755

RESUMO

COVID-19 includes lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors involved in COVID-19-driven ARDS are poorly understood. Here, in blood and airways of severe COVID-19 patients, we serially analyzed unconventional T cells, a heterogeneous class of T lymphocytes (MAIT, γδT, and iNKT cells) with potent antimicrobial and regulatory functions. Circulating unconventional T cells of COVID-19 patients presented with a profound and persistent phenotypic alteration. In the airways, highly activated unconventional T cells were detected, suggesting a potential contribution in the regulation of local inflammation. Finally, expression of the CD69 activation marker on blood iNKT and MAIT cells of COVID-19 patients on admission was predictive of clinical course and disease severity. Thus, COVID-19 patients present with an altered unconventional T cell biology, and further investigations will be required to precisely assess their functions during SARS-CoV-2-driven ARDS.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Células T Invariáveis Associadas à Mucosa/metabolismo , Células T Matadoras Naturais/metabolismo , Fenótipo , Pneumonia Viral/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Síndrome do Desconforto Respiratório do Adulto/imunologia , Idoso , Antígenos CD/sangue , Antígenos de Diferenciação de Linfócitos T/sangue , Células Cultivadas , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Feminino , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Lectinas Tipo C/sangue , Masculino , Pessoa de Meia-Idade , Células T Invariáveis Associadas à Mucosa/imunologia , Células T Matadoras Naturais/imunologia , Pandemias , Pneumonia Viral/virologia , Prognóstico , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Adulto/virologia , Índice de Gravidade de Doença
18.
Front Immunol ; 11: 1844, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903555

RESUMO

With the onset of the global pandemic in 2020 of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), there has been increasing research activity around certain disease-modifying drugs that are used for the management of inflammatory disorders such as rheumatoid arthritis, spondyloarthrosis, psoriatic arthritis, systemic lupus erythematosus, and inflammatory bowel disease for managing coronavirus symptoms. In the conditions mentioned, many people are on long-term treatment with agents including hydroxychloroquine, tumor necrosis factor alpha (TNFα) inhibitor drugs, other biologic agents such as monoclonal antibodies to IL-6 and Janus kinase inhibitors including baricitinib and tofacitinib, which are used to control inflammatory responses in their respective auto-immune condition. There is emerging data that immunomodulatory drugs could be protective at reducing certain features of SARS-CoV-2 and improving recovery. In addition, it is important to understand if subjects being treated with the immunomodulatory agents described have a less severe SARS-CoV-2 infection, as they are deemed some protection from their immunomodulatory treatment, or if they develop infections similar to non-immunocompromised patients. There is a huge unmet clinical need to advise patients responsibly about whether they should remain on their immunomodulatory treatment or not in light of Covid-19 infection. In this article we will discuss potential treatment options for SARS-CoV-2 using immunomodulatory drugs and at what stage of the condition they may be beneficial. Viable treatment options during the global coronavirus pandemic are a much-needed and an intensely active area of research.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Imunomodulação/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colchicina/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas/sangue , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores
20.
Eur Rev Med Pharmacol Sci ; 24(17): 9169-9171, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32965010

RESUMO

NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome has recently become an intriguing target of several chronic and viral diseases. Here, we argue that targeting NLRP3 inflammasome could be a strategy to prevent cardiovascular outcomes [fulminant myocarditis, heart failure, venous thromboembolism (VTE)] and acute respiratory distress syndrome (ARDS) in patients with SARS-CoV-2 infection. We discuss the rationale for NLRP3 targeting in clinical trials as an effective therapeutic strategy aimed to improve prognosis of COVID-19, analyzing the potential of two therapeutic options (tranilast and OLT1177) currently available in clinical practice.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Infecções por Coronavirus/diagnóstico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pneumonia Viral/diagnóstico , Betacoronavirus/isolamento & purificação , Ensaios Clínicos como Assunto , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Inflamassomos/metabolismo , Miocardite/prevenção & controle , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Nitrilos/uso terapêutico , Pandemias , Pneumonia Viral/virologia , Prognóstico , Tromboembolia Venosa/prevenção & controle , ortoaminobenzoatos/uso terapêutico
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