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1.
Sci Rep ; 11(1): 774, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436946

RESUMO

Population-level data have suggested that bacille Calmette-Guerin (BCG) vaccination may lessen the severity of Coronavirus Disease-19 (COVID-19) prompting clinical trials in this area. Some reports have demonstrated conflicting results. We performed a robust, ecologic analysis comparing COVID-19 related mortality (CRM) between strictly selected countries based on BCG vaccination program status utilizing publicly available databases and machine learning methods to define the association between active BCG vaccination programs and CRM. Validation was performed using linear regression and country-specific modeling. CRM was lower for the majority of countries with a BCG vaccination policy for at least the preceding 15 years (BCG15). CRM increased significantly for each increase in the percent population over age 65. A higher total population of a country and BCG15 were significantly associated with improved CRM. There was a consistent association between countries with a BCG vaccination for the preceding 15 years, but not other vaccination programs, and CRM. BCG vaccination programs continued to be associated with decreased CRM even for populations < 40 years old where CRM events are less frequent.


Assuntos
Vacina BCG/uso terapêutico , Vacinação/estatística & dados numéricos , /epidemiologia , Europa (Continente) , Humanos , República da Coreia , Aprendizado de Máquina não Supervisionado
2.
Immunobiology ; 226(1): 152052, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33418320

RESUMO

The century-old tuberculosis vaccine BCG has been the focus of renewed interest due to its well-documented ability to protect against various non-TB pathogens. Much of these broad spectrum protective effects are attributed to trained immunity, the epigenetic and metabolic reprogramming of innate immune cells. As BCG vaccine is safe, cheap, widely available, amendable to use as a recombinant vector, and immunogenic, it has immense potential for use as an immunotherapeutic agent for various conditions including autoimmune, allergic, neurodegenerative, and neoplastic diseases as well as a preventive measure against infectious agents. Of particular interest is the use of BCG vaccination to counteract the increasing prevalence of autoimmune and allergic conditions in industrialized countries attributable to reduced infectious burden as described by the 'hygiene hypothesis.' Furthermore, BCG vaccination has been proposed as a potential therapy to mitigate spread and disease burden of COVID-19 as a bridge to development of a specific vaccine and recombinant BCG expression vectors may prove useful for the introduction of SARS-CoV-2 antigens (rBCG-SARS-CoV-2) to induce long-term immunity. Understanding the immunomodulatory effects of BCG vaccine in these disease contexts is therefore critical. To that end, we review here BCG-induced immunomodulation focusing specifically on BCG-induced trained immunity and how it relates to the 'hygiene hypothesis' and COVID-19.


Assuntos
Vacina BCG/imunologia , Vacina BCG/uso terapêutico , /terapia , Hipótese da Higiene , Imunidade Inata , /virologia , Humanos , Imunomodulação
3.
Orv Hetil ; 162(4): 123-134, 2021 01 24.
Artigo em Húngaro | MEDLINE | ID: mdl-33486464

RESUMO

Összefoglaló. Bevezetés: A COVID-19-járvány az egész világon elterjedt. A járvány Európában való elso megjelenése során megfigyelheto volt, hogy a terjedés mértéke kisebb azokban az országokban, ahol a tuberkulózis elleni védekezésül kiterjedt BCG-vakcinációt végeznek. Célkituzés: A jelen munkában olyan összefüggéseket igyekeztünk feltárni, amelyek befolyásolták a járványterjedés paramétereit, különös figyelemmel a BCG-vakcinációs gyakorlatra. Módszerek: A világ összes olyan országára vonatkozóan, ahol megfelelo minoségu statisztikai adatok álltak rendelkezésünkre, vizsgáltuk a járvány terjedésének elso hullámát. A mozgóátlagolt járványgörbéken elemeztük a járvány idotartamát, a tetozés mértékét, a fertozöttek és a halálesetek egymillió lakosra vetített számát. Figyelembe vettük az országok gazdasági mutatóit (GDP, légi forgalom, a tengeri hajózás mértéke). Statisztikai analízis: A vizsgált paraméterek nem mutattak normális eloszlást, így nemparaméteres próbákkal (rangkorreláció, Kruskal-Wallis ANOVA) statisztikai kapcsolatot kerestünk a járványterjedés mértéke, a BCG-vakcináció és más paraméterek között. Eredmények: A járvány gyorsan elterjedt a világon, de mégis, február elso három hetében a terjedésben egy szünet volt megfigyelheto. A járványhullám Európában nagyjából egyszerre ért véget. A járvány által leginkább azok az országok érintettek, ahol nem alkalmaztak rendszeres BCG-vakcinációt, bár a képet bonyolítja, hogy ezek az országok gazdaságilag többnyire fejlettek. A halálozási rátában nem mutatkozott ilyen különbség. Következtetés: Statisztikailag igazolható tény, hogy a vakcinációt végzo országokból az elso hullám alatt kevesebb fertozöttet jelentettek; az ok-okozati összefüggés bizonytalan, hiszen az országok múltja, szokásai, társadalmi berendezkedése, gazdasági fejlettsége nem azonos. Eredményeink alátámasztják az összehasonlító kontaktkutatás fontosságát annak tisztázására, hogy a BCG-oltás hogyan befolyásolja az emberek vírussal szembeni érzékenységét, valamint a vírus terjesztésének, továbbadásának képességét. Orv Hetil. 2021; 162(4): 123-134. INTRODUCTION: The new type of coronavirus (SARS-CoV-2) epidemic is widespread throughout the world. During the outbreak of the pandemic in Europe it was revealed that the rate of spread was lower in countries where extensive BCG vaccination is used to protect against tuberculosis. OBJECTIVE: In the present work, we sought to explore relationships that influenced epidemic spreading parameters, with particular reference to BCG vaccination practice. METHODS: We examined the first wave of the spread of the epidemic for all countries in the world where adequate quality statistics were available. We analyzed the duration of the epidemic, the extent of the peak, the number of infected people, and the number of deaths per million inhabitants with the moving average of epidemic curves. We took into account the economic indicators of the countries (GDP, air traffic and extent of maritime shipping). STATISTICAL ANALYSIS: The examined parameters did not show a normal distribution, so we looked for a statistical relationship with non-parametric tests (rank correlation, Kruskal-Wallis ANOVA) between the extents of epidemic spread, BCG vaccination and other parameters. RESULTS: The epidemic spread rapidly around the world, but still, in the first three weeks of February, there was a pause in the spread. The first wave of epidemics ended roughly at the same time in Europe. Those countries are the most affected by the epidemic where regular BCG vaccination has not been used, although the picture is complicated by the fact that these countries are mostly economically developed. There was no such difference observable in the mortality rate. CONCLUSION: Although this work clearly demonstrates that during the first wave of the pandemic, fewer infections were reported worldwide in countries where BCG vaccination is obligatory, however, the causal relationship is uncertain, as the countries' past, customs, social organization and economic development are different. Our results support the necessity of comparative contact tracing to clarify how BCG vaccination affects people's susceptibility to this new type of coronavirus as well as their ability to spread and transmit the virus. Orv Hetil. 2021; 162(4): 123-134.


Assuntos
Vacina BCG/uso terapêutico , Pandemias , Saúde Global , Humanos
4.
Ned Tijdschr Geneeskd ; 1642020 10 07.
Artigo em Holandês | MEDLINE | ID: mdl-33331729

RESUMO

A number of clinical trials are currently underway worldwide to assess whether BCG, the old vaccine against tuberculosis, can protect against COVID-19 infection. In this Perspective, we briefly outline the background, the immunological mechanisms (in particular induction of 'innate immune memory' or 'trained immunity'), and further considerations for the potential future use of BCG against viral and other infections.


Assuntos
Vacina BCG , Reposicionamento de Medicamentos/métodos , Memória Imunológica/imunologia , Tuberculose/prevenção & controle , Vacina BCG/imunologia , Vacina BCG/uso terapêutico , /prevenção & controle , Humanos , Imunidade Inata/imunologia , Tuberculose/imunologia
6.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(11): 1044-1048, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33210600

RESUMO

The research and development of the coronavirus disease 2019 (COVID-19) vaccine is being carried out globally. Although vaccine research and development technology has made great progress, the possibility of obtaining a safe and effective vaccine that can control the global epidemic in a short period of time is still low due to the antibody-dependent enhancement effect (ADE) of the vaccine and the mutation of the virus. In the absence of specific treatment for COVID-19, finding other alternative protection schemes has become another treatment idea. Epidemiological studies have found that, in this COVID-19 epidemic, countries with long-term Bacillus Calmette-Guerin (BCG) vaccination policies have relatively less cases and lower mortality rates than countries without relevant policies. This phenomenon may be related to the "training immunity" effect of BCG. In order to further clarify the preventive and protective effects of BCG vaccine on SARS-CoV-2 infection, a number of clinical trials are underway.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , Ensaios Clínicos como Assunto , Humanos
7.
Sci Rep ; 10(1): 18377, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110184

RESUMO

The Bacillus Calmette-Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is thought to provide protection against non-TB infectious diseases. BCG vaccination has recently been proposed as a strategy to prevent infection with SARS-CoV-2 (CoV-2) to combat the COVID-19 outbreak, supported by its potential to boost innate immunity and initial epidemiological analyses which observed reduced severity of COVID-19 in countries with universal BCG vaccination policies. Seventeen clinical trials are currently registered to inform on the benefits of BCG vaccinations upon exposure to CoV-2. Numerous epidemiological analyses showed a correlation between incidence of COVID-19 and BCG vaccination policies. These studies were not systematically corrected for confounding variables. We observed that after correction for confounding variables, most notably testing rates, there was no association between BCG vaccination policy and COVD-19 spread rate or percent mortality. Moreover, we found variables describing co-morbidities, including cardiovascular death rate and smoking prevalence, were significantly associated COVID-19 spread rate and percent mortality, respectively. While reporting biases may confound our observations, our epidemiological findings do not provide evidence to correlate overall BCG vaccination policy with the spread of CoV-2 and its associated mortality.


Assuntos
Vacina BCG/administração & dosagem , Infecções por Coronavirus/epidemiologia , Vacinação em Massa/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Tuberculose/prevenção & controle , Vacina BCG/uso terapêutico , Correlação de Dados , Política de Saúde , Humanos , Pandemias
8.
Przegl Epidemiol ; 74(2): 290-302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33115218

RESUMO

THE AIM OF THE STUDY: Is to present the state of knowledge from April and May 2020 about the influence of Bacillus-Calmette-Guérin vaccination against tuberculosis on incidence and mortality due to COVID-19. MATERIAL AND METHODS: A review of the latest literature till 9 May 2020 has been made. PubMed and ResearchGate databases and WHO reports were used. RESULTS: Immunomodulatory properties of the tuberculosis vaccine which protects against severe cases of tuberculosis and partly against other infections are indicated, including viral and respiratory infections. The BCG vaccine induces heterologous immunity and trained innate immunity. It was noted that in countries which maintain obligatory BCG vaccination COVID-19 incidence and mortality are lower than in countries that have stopped or never introduced BCG as mandatory vaccination. Most analysis confirmed this relationship, but they indicated the possible impact of other factors, such as genetics in the population, the type of strain from BCG vaccine, the level of health care and the wealth of a nation, the structure of migration, co-morbidities and a policy of introducing social distance. CONCLUSIONS: At the moment, we do not have enough evidence to support or deny the hypothesis of COVID-19 reduction in incidence and mortality in countries maintaining obligatory BCG vaccination. Other factors that might affect the results should be considered in further analysis. The results of clinical trials will provide more reliable proofs than analysis of epidemiological data. WHO does not recommend BCG vaccination to prevent COVID-19 and recommends it to newborns from areas with a higher incidence of tuberculosis.


Assuntos
Imunidade Adaptativa , Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , Infecções por Coronavirus/imunologia , Humanos , Imunidade Inata , Pneumonia Viral/imunologia , Tuberculose/prevenção & controle
9.
Medicine (Baltimore) ; 99(35): e21930, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871933

RESUMO

BACKGROUND: This study will systematically assess the efficacy and safety of Bacillus Calmette-Guerin (BCG) for patients with bladder cancer (BC). METHODS: Literature searches will be performed in multiple electronic databases from inception to present: MEDLINE, EMBASE, CINAHL, Science Direct, Cochrane Library, Web of Science, and China National Knowledge Infrastructure. We will also examine grey literature through identifying conference proceedings, thesis, dissertations, and website of clinical trials registry. Two investigators will independently scan all citation titles, abstracts, and full-text studies. The study quality will be assessed by Cochrane Risk of Bias Tool. If possible, we will perform meta-analysis. Additional analyses will be carried out to test the potential sources of heterogeneity among included trials. RESULTS: The present study will summarize high quality trials on investigating the efficacy and safety of BCG for patients with BC. CONCLUSION: The results of this study will supply helpful evidence to determine whether BCG is effective or not for BC. STUDY REGISTRATION NUMBER: INPLASY202070042.


Assuntos
Vacina BCG/efeitos adversos , Vacina BCG/uso terapêutico , Revisões Sistemáticas como Assunto , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Kyobu Geka ; 73(8): 586-589, 2020 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-32879285

RESUMO

The patient was a 74-year-old male who had undergone intravesical Bacillus Calmette-Guérin(BCG) instillation therapy for bladder cancer. He visited our hospital with chief complaints of fever and abdominal pain. Abdominal aortic aneurysmal rupture and iliopsoas muscle abscess were confirmed by computed tomography( CT). We performed semi-emergency surgery, including replacement of the abdominal aorta with a synthetic graft, iliopsoas abscess debridement, and omentopexy. A rifampicin-bonded synthetic graft was used because of the possibility of tuberculous involvement after BCG instillation therapy. Examination of the tissues collected during surgery were positive for tuberculosis deoxyribonucleic acid (DNA) in a polymerase chain reaction (PCR), and showed multiple giant cell granulomas with caseous necrosis, which both strongly suggested involvement of tuberculosis. Therefore, 4 types of antituberculous drugs were administered for 40 days. This case shows that an infective aneurysm should be suspected when fever and abdominal pain develop after intravesical BCG instillation therapy.


Assuntos
Aneurisma da Aorta Abdominal , Ruptura Aórtica , Tuberculose , Neoplasias da Bexiga Urinária , Administração Intravesical , Idoso , Vacina BCG/uso terapêutico , Humanos , Masculino
11.
BMC Infect Dis ; 20(1): 708, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993546

RESUMO

BACKGROUND: Intravesical administration of Bacillus Calmette-Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy. CASE PRESENTATION: A 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident. CONCLUSIONS: We report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.


Assuntos
Antituberculosos/uso terapêutico , Vacina BCG/efeitos adversos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/etiologia , Esteroides/uso terapêutico , Exacerbação dos Sintomas , Administração Intravesical , Idoso , Autopsia , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Carcinoma in Situ/tratamento farmacológico , Carcinoma in Situ/prevenção & controle , Evolução Fatal , Humanos , Doenças Pulmonares Intersticiais/microbiologia , Masculino , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Mycobacterium bovis/genética , Resultados Negativos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Pulsoterapia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/prevenção & controle
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.
Rev Epidemiol Sante Publique ; 68(5): 302-305, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32948360

RESUMO

Following the onset of the global COVID-19 pandemic and the alerts issued by the World Health Organization, for several months attention has been focused on Africa as a potentially severely endangered continent. A sizable number of African countries, mainly low and middle income, suffer from limited available resources, especially in critical care, and COVID-19 is liable to overwhelm their already fragile health systems. To effectively manage what is shaping up as a multidimensional crisis, the challenge unquestionably goes beyond the necessary upgrading of public health infrastructures. It is also a matter of anticipating and taking timely action with regard to factors that may mitigate the propagation of SARS-CoV2 and thereby cushion the shock of the pandemic on the African continent. While some of these factors are largely unmanageable (climate, geography…), several others (socio-cultural, religious, audio-visual, and potentially political…) could be more or less effectively dealt with by African governments and populations.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , África/epidemiologia , Vacina BCG/uso terapêutico , Betacoronavirus/fisiologia , Clima , Infecções por Coronavirus/economia , Infecções por Coronavirus/terapia , Recursos em Saúde/organização & administração , Recursos em Saúde/estatística & dados numéricos , Recursos em Saúde/provisão & distribução , História do Século XX , História do Século XXI , Humanos , Controle de Infecções/economia , Controle de Infecções/história , Controle de Infecções/organização & administração , Controle de Infecções/normas , Pandemias/economia , Pandemias/estatística & dados numéricos , Pneumonia Viral/economia , Pneumonia Viral/terapia , Áreas de Pobreza , Papel Profissional , Saúde Pública/economia , Saúde Pública/história , Saúde Pública/estatística & dados numéricos , Mídias Sociais , Responsabilidade Social , Fatores Socioeconômicos , Organização Mundial da Saúde
15.
Cytokine Growth Factor Rev ; 54: 32-42, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747157

RESUMO

The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses including SARS-CoV and MERS-CoV, which can cause fatal lower respiratory tract infection. Likewise, SARS-CoV2 infection can be fatal as the disease advances to pneumonia, followed by acute respiratory distress syndrome (ARDS). The development of lethal clinical symptons is associated with an exaggerated production of inflammatory cytokines, referred to as the cytokine storm, is a consequence of a hyperactivated immune response aginst the infection. In this article, we discuss the pathogenic consequences of the cytokine storm and its relationship with COVID-19 associated risk factors. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 into a 'Cytokine Super Cyclone'. We also evaluate the antiviral immune responses provided by BCG vaccination and the potential role of 'trained immunity' in early protection against SARS-CoV2.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/sangue , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Diabetes Mellitus/patologia , Humanos , Hipertensão/patologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Mycobacterium bovis/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Vacinação
16.
Mol Cancer Ther ; 19(9): 1930-1942, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32737155

RESUMO

Although intravesical bacillus Calmette-Guérin (BCG) immunotherapy has been the gold standard for nonsurgical management of non-muscle-invasive bladder cancer, a considerable number of patients exhibit resistance to the adjuvant treatment with unexplained mechanisms. This study aimed to investigate whether and how androgen receptor (AR) signals modulate BCG cytotoxicity in bladder cancer. AR knockdown or overexpression in bladder cancer lines resulted in induction or reduction, respectively, in intracellular BCG quantity and its cytotoxic activity. Microarray screening identified Rab27b, a small GTPase known to mediate bacterial exocytosis, which was upregulated in BCG-resistant cells and downregulated in AR-shRNA cells. Knockdown of Rab27b, or its effector SYTL3, or overexpression of Rab27b also induced or reduced, respectively, BCG quantity and cytotoxicity. In addition, treatment with GW4869, which was previously shown to inhibit Rab27b-dependent secretion, induced them and reduced Rab27b expression in bladder cancer cells. Meanwhile, AR expression was upregulated in BCG-resistant lines, compared with respective controls. In a mouse orthotopic xenograft model, Rab27b/SYTL3 knockdown or GW4869 treatment enhanced the amount of BCG within tumors and its suppressive effect on tumor growth. Moreover, in non-muscle-invasive bladder cancer specimens from patients subsequently undergoing BCG therapy, positivity of AR/Rab27b expression was associated with significantly higher risks of tumor recurrence. AR activation thus correlates with resistance to BCG treatment, presumably via upregulating Rab27b expression. Mechanistically, it is suggested that BCG elimination from urothelial cells is induced by Rab27b/SYTL3-mediated exocytosis. Accordingly, Rab27b inactivation, potentially via antiandrogenic drugs and/or exocytosis inhibition are anticipated to sensitize the efficacy of BCG therapy, especially in patients with BCG-refractory AR/Rab27b-positive bladder cancer.


Assuntos
Vacina BCG/uso terapêutico , Exocitose/efeitos dos fármacos , Imunoterapia/métodos , Receptores Androgênicos/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Proteínas rab de Ligação ao GTP/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Vacina BCG/farmacologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Transdução de Sinais
17.
Cell Immunol ; 356: 104187, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32745670

RESUMO

Mycobacterium bovis BCG, a live attenuated tuberculosis vaccine offers protection against disseminated TB in children. BCG exhibits heterologous protective effects against unrelated infections and reduces infant mortality due to non-mycobacterial infections. Recent reports have suggested that BCG vaccination might have protective effects against COVID-19, however it is highly unlikely that BCG vaccine in its current form can offer complete protection against SARS-CoV-2 infection due to the lack of specific immunity. Nonetheless, recombinant BCG strains expressing antigens of SARS-CoV-2 may offer protection against COVID-19 due to the activation of innate as well as specific adaptive immune response. Further proven safety records of BCG in humans, its adjuvant activity and low cost manufacturing makes it a frontrunner in the vaccine development to stop this pandemic. In this review we discuss about the heterologous effects of BCG, induction of trained immunity and its implication in development of a potential vaccine against COVID-19 pandemic.


Assuntos
Vacina BCG/uso terapêutico , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Betacoronavirus , Humanos , Imunidade Inata , Memória Imunológica , Vacinas Atenuadas/uso terapêutico
18.
Cochrane Database Syst Rev ; 8: CD004834, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853410

RESUMO

BACKGROUND: On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009. OBJECTIVES: To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML). SEARCH METHODS: We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome. MAIN RESULTS: We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.


Assuntos
Leishmaniose Cutânea/terapia , Administração Oral , Adulto , Antiprotozoários/administração & dosagem , Antiprotozoários/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Vacina BCG/uso terapêutico , Feminino , Humanos , Hipertermia Induzida , Imunocompetência , Injeções Intramusculares , Injeções Intravenosas , Interferon gama/uso terapêutico , Vacinas contra Leishmaniose/uso terapêutico , Leishmaniose Mucocutânea/terapia , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Pentoxifilina/administração & dosagem , Pentoxifilina/efeitos adversos , Fosforilcolina/administração & dosagem , Fosforilcolina/efeitos adversos , Fosforilcolina/análogos & derivados , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Brasília; s.n; 8 ago. 2020.
Não convencional em Português | LILACS, BRISA/RedTESA, PIE | ID: biblio-1117974

RESUMO

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 16 artigos e 4 protocolos.


Assuntos
Humanos , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Ozônio/uso terapêutico , Avaliação da Tecnologia Biomédica , Imunoglobulinas/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Vacina BCG/uso terapêutico , Estudos Transversais , Estudos de Coortes , Corticosteroides/uso terapêutico , Ritonavir/uso terapêutico , Combinação de Medicamentos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Células-Tronco Mesenquimais , Lopinavir/uso terapêutico , Darunavir/uso terapêutico , Hidroxicloroquina/uso terapêutico
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