Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 9.730
Filtrar
1.
J Transl Med ; 19(1): 32, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413422

RESUMO

BACKGROUND: Although it is becoming evident that individual's immune system has a decisive influence on SARS-CoV-2 disease progression, pathogenesis is largely unknown. In this study, we aimed to profile the host transcriptome of COVID-19 patients from nasopharyngeal samples along with virus genomic features isolated from respective host, and a comparative analyses of differential host responses in various SARS-CoV-2 infection systems. RESULTS: Unique and rare missense mutations in 3C-like protease observed in all of our reported isolates. Functional enrichment analyses exhibited that the host induced responses are mediated by innate immunity, interferon, and cytokine stimulation. Surprisingly, induction of apoptosis, phagosome, antigen presentation, hypoxia response was lacking within these patients. Upregulation of immune and cytokine signaling genes such as CCL4, TNFA, IL6, IL1A, CCL2, CXCL2, IFN, and CCR1 were observed in lungs. Lungs lacked the overexpression of ACE2 as suspected, however, high ACE2 but low DPP4 expression was observed in nasopharyngeal cells. Interestingly, directly or indirectly, viral proteins specially non-structural protein mediated overexpression of integrins such as ITGAV, ITGA6, ITGB7, ITGB3, ITGA2B, ITGA5, ITGA6, ITGA9, ITGA4, ITGAE, and ITGA8 in lungs compared to nasopharyngeal samples suggesting the possible way of enhanced invasion. Furthermore, we found comparatively highly expressed transcription factors such as CBP, CEBP, NFAT, ATF3, GATA6, HDAC2, TCF12 which have pivotal roles in lung injury. CONCLUSIONS: Even though this study incorporates a limited number of cases, our data will provide valuable insights in developing potential studies to elucidate the differential host responses on the viral pathogenesis in COVID-19, and incorporation of further data will enrich the search of an effective therapeutics.


Assuntos
/genética , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , /imunologia , Adulto , Idoso de 80 Anos ou mais , /genética , Citocinas/genética , Feminino , Variação Genética , Humanos , Imunidade Inata/genética , Integrinas/genética , Pulmão/imunologia , Masculino , Pessoa de Meia-Idade , Modelos Imunológicos , Mutação de Sentido Incorreto , Nasofaringe/imunologia , Nasofaringe/virologia , Pandemias , RNA-Seq , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Transcriptoma , Pesquisa Médica Translacional
2.
Biomed Pharmacother ; 133: 110825, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378989

RESUMO

BACKGROUND: Since December 2019, COVID-19 has spread to almost every corner of the world. In theory, tocilizumab and favipiravir are considered to be reliable drugs for the treatment of COVID-19 with elevated IL-6. We aimed to assess the efficacy and safety of tocilizumab combined with favipiravir in patients with COVID-19. METHODS: This was a multicenter trial in adults with COVID-19. Patients were randomly assigned (3:1:1) to a 14-day combination of favipiravir combined with tocilizumab (combination group), favipiravir, and tocilizumab. The primary outcome was the cumulative lung lesion remission rate (lung CT examination indicated absorption of lung inflammation). RESULTS: Between Feb 2 and March 15, 2020, 26 patients were recruited; 14 were randomly assigned to the combination group, 7 were assigned to the favipiravir group and 5 were assigned to the tocilizumab group. The cumulative lung lesion remission rate at day 14 was significantly higher in combination group as compared with favipiravir group (P = 0.019, HR 2.66 95 % CI [1.08-6.53]). And there was also a significant difference between tocilizumab and favipivavir (P = 0.034, HR 3.16, 95 % CI 0.62-16.10). In addition, there was no significant difference between the combination group and the tocilizumab group (P = 0.575, HR 1.28 95 %CI 0.39-4.23). Furthermore, combined therapy can also significantly relieve clinical symptoms and help blood routine to return to normal. No serious adverse events were reported. CONCLUSION: Tocilizumab combined with or without favipiravir can effectively improve the pulmonary inflammation of COVID-19 patients and inhibit the deterioration of the disease.


Assuntos
Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Pirazinas/uso terapêutico , /efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Amidas/administração & dosagem , Amidas/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , /patologia , Quimioterapia Combinada , Feminino , Humanos , Interleucina-6/sangue , Estimativa de Kaplan-Meier , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Modelos Imunológicos , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Receptores de Interleucina-6/antagonistas & inibidores , Respiração Artificial/estatística & dados numéricos , Tamanho da Amostra , Resultado do Tratamento
3.
Can J Microbiol ; 67(1): 23-28, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32640169

RESUMO

Understanding the pathogenesis of certain viral agents is essential for developing new treatments and obtaining a clinical cure. With the onset of the new coronavirus (SARS-CoV-2) pandemic in the beginning of 2020, a rush to conduct studies and develop drugs has led to the publication of articles that seek to address knowledge gaps and contribute to the global scientific research community. There are still no reports on the infectivity or repercussions of SARS-CoV-2 infection on the central lymphoid organ, the thymus, nor on thymocytes or thymic epithelial cells. In this brief review, we present a hypothesis about lymphopenia observed in SARS patients and the probable pathological changes that the thymus may undergo due to this new virus.


Assuntos
/complicações , Linfopenia/complicações , Timo/virologia , Animais , Humanos , Linfopenia/imunologia , Linfopenia/virologia , Camundongos , Modelos Imunológicos , Pandemias , Timo/imunologia
4.
PLoS Comput Biol ; 16(12): e1008451, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33347439

RESUMO

Simulations of tissue-specific effects of primary acute viral infections like COVID-19 are essential for understanding disease outcomes and optimizing therapies. Such simulations need to support continuous updating in response to rapid advances in understanding of infection mechanisms, and parallel development of components by multiple groups. We present an open-source platform for multiscale spatiotemporal simulation of an epithelial tissue, viral infection, cellular immune response and tissue damage, specifically designed to be modular and extensible to support continuous updating and parallel development. The base simulation of a simplified patch of epithelial tissue and immune response exhibits distinct patterns of infection dynamics from widespread infection, to recurrence, to clearance. Slower viral internalization and faster immune-cell recruitment slow infection and promote containment. Because antiviral drugs can have side effects and show reduced clinical effectiveness when given later during infection, we studied the effects on progression of treatment potency and time-of-first treatment after infection. In simulations, even a low potency therapy with a drug which reduces the replication rate of viral RNA greatly decreases the total tissue damage and virus burden when given near the beginning of infection. Many combinations of dosage and treatment time lead to stochastic outcomes, with some simulation replicas showing clearance or control (treatment success), while others show rapid infection of all epithelial cells (treatment failure). Thus, while a high potency therapy usually is less effective when given later, treatments at late times are occasionally effective. We illustrate how to extend the platform to model specific virus types (e.g., hepatitis C) and add additional cellular mechanisms (tissue recovery and variable cell susceptibility to infection), using our software modules and publicly-available software repository.


Assuntos
Biologia Computacional/métodos , Epitélio , Modelos Imunológicos , Viroses , Antivirais/uso terapêutico , Simulação por Computador , Epitélio/imunologia , Epitélio/virologia , Hepacivirus/imunologia , Hepatite C/tratamento farmacológico , Hepatite C/imunologia , Humanos , Viroses/tratamento farmacológico , Viroses/imunologia
5.
Sci China Life Sci ; 63(12): 1833-1849, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33355886

RESUMO

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients' outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.


Assuntos
Anticorpos Antivirais/biossíntese , /imunologia , /imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/biossíntese , Anticorpos Neutralizantes/uso terapêutico , Infecções Assintomáticas , /isolamento & purificação , China , Desenvolvimento de Medicamentos/tendências , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunidade Humoral , Imunização Passiva , Imunoglobulinas Intravenosas/uso terapêutico , Modelos Imunológicos , Pandemias , /prevenção & controle , Soroconversão
6.
Med Hypotheses ; 144: 110208, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254515

RESUMO

Prolactin (PRL), the well-known lactogenic hormone, plays a crucial role in immune function given the fact that long term hypoprolactinemia (serum prolactin level below normal) can even lead to death from opportunistic infection. High blood PRL level is known to provide an immunological advantage in many pathological conditions (with some exceptions like autoimmune diseases) and women, because of their higher blood PRL level, get an advantage in this regard. It has been reported that by controlled enhancement of blood PRL level (within the physiological limit and in some cases a little elevated above the normal to induce mild hyperprolactinemia) using dopamine antagonists such immune-stimulatory advantage can led to survival of the patients in many critical conditions. Here it is hypothesized that through controlled augmentation of blood PRL level using dopamine antagonists like domperidone/metoclopramide, which are commonly used drugs for the treatment of nausea and vomiting, both innate and adaptive immunity can be boosted to evade or tone down COVID-19. The hypothesis is strengthened from the fact that at least seven little-understood salient observations in coronavirus patients can apparently be explained by considering the role of enhanced PRL in line with the proposed hypothesis and hence, clinical trials (both therapeutic and prophylactic) on the role of enhanced PRL on the course and outcome of coronavirus patients should be conducted accordingly.


Assuntos
Antieméticos/uso terapêutico , Antivirais/uso terapêutico , /imunologia , Reposicionamento de Medicamentos , Fatores Imunológicos/uso terapêutico , Prolactina/uso terapêutico , Imunidade Adaptativa/efeitos dos fármacos , Adulto , Criança , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Masculino , Modelos Imunológicos , Pandemias , Prolactina/sangue , Prolactina/imunologia
7.
Mediators Inflamm ; 2020: 8829674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33343232

RESUMO

Coronavirus disease 2019 (COVID-19) is a virus-induced respiratory disease that may progress to acute respiratory distress syndrome (ARDS) and is triggered by immunopathological mechanisms that cause excessive inflammation and leukocyte dysfunction. Neutrophils play a critical function in the clearance of bacteria with specific mechanisms to combat viruses. The aim of this review is to highlight the current advances in the pathways of neutrophilic inflammation against viral infection over the past ten years, focusing on the production of neutrophil extracellular traps (NETs) and its impact on severe lung diseases, such as COVID-19. We focused on studies regarding hyperinflammation, cytokine storms, neutrophil function, and viral infections. We discuss how the neutrophil's role could influence COVID-19 symptoms in the interaction between hyperinflammation (overproduction of NETs and cytokines) and the clearance function of neutrophils to eliminate the viral infection. We also propose a more in-depth investigation into the neutrophil response mechanism targeting NETosis in the different phases of COVID-19.


Assuntos
/imunologia , Inflamação/imunologia , Neutrófilos/imunologia , /complicações , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Armadilhas Extracelulares/imunologia , Armadilhas Extracelulares/virologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunidade Inata , Inflamação/etiologia , Inflamação/virologia , Mediadores da Inflamação/imunologia , Pulmão/imunologia , Pulmão/virologia , Modelos Imunológicos , Neutrófilos/virologia , Pandemias , /imunologia , /imunologia , /patogenicidade
8.
Med Hypotheses ; 144: 110202, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254510

RESUMO

Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-2, and generation of anti-viral immunity. Coronaviruses evolved strategies to dampen the host immunity. Herein, we discuss the potential use of TLR7 agonists in the early stages of COVID-19 treatment.


Assuntos
Antivirais/uso terapêutico , Imiquimode/uso terapêutico , Receptor 7 Toll-Like/agonistas , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Antivirais/administração & dosagem , Humanos , Imiquimode/administração & dosagem , Imunidade Inata/efeitos dos fármacos , Modelos Imunológicos , Pandemias , Creme para a Pele
9.
BMC Bioinformatics ; 21(Suppl 17): 527, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33308153

RESUMO

BACKGROUND: SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. RESULTS: We present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2. CONCLUSIONS: In silico trials are showing to be powerful weapons in predicting immune responses of potential candidate vaccines. Here, UISS has been extended to be used as an in silico trial platform to speed-up and drive the discovery pipeline of vaccine against SARS-CoV-2.


Assuntos
Modelos Imunológicos , Software , /imunologia , Biologia Computacional/métodos , Simulação por Computador , Humanos
11.
PLoS One ; 15(11): e0242649, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33253212

RESUMO

OBJECTIVE: To reconstruct the transmission trajectory of SARS-CoV-2 and analyze the effects of control measures in China. METHODS: Python 3.7.1 was used to write a SEIR class to model the epidemic procedure and proportional estimation method to estimate the initial true infected number. The epidemic area in China was divided into three parts, Wuhan city, Hubei province (except Wuhan) and China (except Hubei) based on the different transmission pattern. A testing capacity limitation factor for medical resources was imposed to model the number of infected but not quarantined individuals. Baidu migration data were used to assess the number of infected individuals who migrated from Wuhan to other areas. RESULTS: Basic reproduction number, R0, was 3.6 before the city was lockdown on Jan 23, 2020. The actual infected number the model predicted was 4508 in Wuhan before Jan 23, 2020. By January 22 2020, it was estimated that 1764 infected cases migrated from Wuhan to other cities in Hubei province. Effective reproductive number, R, gradually decreased from 3.6 (Wuhan), 3.4 (Hubei except Wuhan,) and 3.3 (China except Hubei) in stage 1 (from Dec 08, 2019 to Jan 22, 2020) to 0.67 (Wuhan), 0.59 (Hubei except Wuhan) and 0.63 (China except Hubei) respectively. Especially after January 23, 2020 when Wuhan City was closed, the infected number showed a turning point in Wuhan. By early April, there would be 42073 (95% confidence interval, 41673 to 42475), 21342 (95% confidence interval, 21057 to 21629) and 13384 (95% confidence interval, 13158 to 13612) infected cases in Wuhan, Hubei (except Wuhan) and China (except Hubei), respectively. CONCLUSION: A series of control measures in China have effectively prevented the spread of COVID-19, and the epidemic should be under control in early April with very few new cases occasionally reported.


Assuntos
Número Básico de Reprodução , /transmissão , /epidemiologia , China/epidemiologia , Humanos , Modelos Imunológicos , Pandemias , Quarentena
12.
Mol Med ; 26(1): 103, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33167852

RESUMO

The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Pneumonia Viral/imunologia , Animais , Bradicinina/metabolismo , Humanos , Calicreínas/metabolismo , Modelos Imunológicos , Pandemias , Sistema Renina-Angiotensina
13.
Trends Mol Med ; 26(12): 1078-1085, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33051104

RESUMO

An unbridled host immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to underlie severe cases of the disease and has been labeled a 'cytokine storm syndrome' (CSS). Here, we emphasize that categorization of syndromes triggered by a completely novel pathogen based on other seemingly similar, but potentially distinct, known entities is an inherently risky endeavor.


Assuntos
/complicações , Síndrome da Liberação de Citocina/etiologia , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Adolescente , /imunologia , Criança , Pré-Escolar , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Citocinas/sangue , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Modelos Imunológicos , Pandemias , /patogenicidade , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Adulto Jovem
14.
Euro Surveill ; 25(42)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33094713

RESUMO

BackgroundThe progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.AimOur objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.MethodsA pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study comprised samples from 3,500 blood donors collected in Scotland between 17 March and 18 May 2020. Controls were collected from 100 donors in Scotland during 2019.ResultsAll samples collected on 17 March 2020 (n = 500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in six of 500 donors from 23 to 26 March. The number of samples containing neutralising antibodies did not significantly rise after 5-6 April until the end of the study on 18 May. We found that infections were concentrated in certain postcodes, indicating that outbreaks of infection were extremely localised. In contrast, other areas remained comparatively untouched by the epidemic.ConclusionAlthough blood donors are not representative of the overall population, we demonstrated that serosurveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic such as the SARS-CoV-2 outbreak.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Doadores de Sangue , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Vigilância da População , Adulto , Análise por Conglomerados , Infecções por Coronavirus/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Geografia Médica , Humanos , Concentração Inibidora 50 , Masculino , Modelos Imunológicos , Testes de Neutralização , Pneumonia Viral/sangue , Prevalência , Escócia/epidemiologia , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , População Urbana
15.
Nat Commun ; 11(1): 5439, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116132

RESUMO

Oncogenic KRAS mutations are the most frequent mutations in human cancer, but most difficult to target. While sustained proliferation caused by oncogenic KRAS-downstream signalling is a main driver of carcinogenesis, there is increasing evidence that it also mediates autocrine effects and crosstalk with the tumour microenvironment (TME). Here, we discuss recent reports connecting KRAS mutations with tumour-promoting inflammation and immune modulation caused by KRAS that leads to immune escape in the TME. We discuss the preclinical work on KRAS-induced inflammation and immune modulation in the context of currently ongoing clinical trials targeting cancer entities that carry KRAS mutations and strategies to overcome the oncogene-induced effects on the immune system.


Assuntos
Carcinogênese/genética , Carcinogênese/imunologia , Imunomodulação/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/imunologia , Animais , Humanos , Inflamação/genética , Inflamação/imunologia , Camundongos , Modelos Imunológicos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Pesquisa Médica Translacional
17.
Transfus Clin Biol ; 27(4): 253-258, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32987167

RESUMO

BACKGROUND: Novel coronavirus disease-19 (COVID-19) has spread worldwide, and to date presence of the virus has been recorded in 215 countries contributing 0.43 million of death. The role of blood groups in susceptibility/resistance to various infectious diseases has been reported. However, the association of blood groups with susceptibility to COVID-19 infections or related death are limited. In the present report, we performed an epidemiological investigation in the Indian population to decipher the importance of blood groups concerning susceptibility or mortality in COVID-19 infection. MATERIALS AND METHODS: Data on COVID-19 infection and mortality was obtained from the website of the Government of India. Prevalence of ABO blood groups in different states and union territories of India were searched using different databases such as PubMed and Google Scholar. Relevant articles were downloaded, and data were extracted. Spearman's rank coefficient analysis was employed to study the correlation between blood group frequencies and COVID-19 infection or mortality rate. RESULTS: A significant inverse correlation was observed between the frequency of O blood group and the COVID-19 mortality rate (Spearman r=-0.36, P=0.03), indicating a possible protective role of O blood group against COVID-19 related death. In contrast, the prevalence of blood group B was positively correlated with COVID-19 death/million (Spearman r=0.67, P<0.0001), suggesting B blood type as a deleterious factor in COVID-19 infection. CONCLUSIONS: ABO blood group system is associated with poor prognosis of COVID-19 infection. Blood group O may protects, and subjects with blood type B could be susceptible to COVID-19 mortality. However, further studies on COVID-19 infected patients in different population are required to validate our findings.


Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Betacoronavirus , Infecções por Coronavirus/genética , Pneumonia Viral/genética , Infecções por Coronavirus/sangue , Infecções por Coronavirus/etnologia , Infecções por Coronavirus/mortalidade , Grupos Étnicos/genética , Frequência do Gene , Predisposição Genética para Doença , Geografia Médica , Humanos , Índia/epidemiologia , Modelos Imunológicos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/etnologia , Pneumonia Viral/mortalidade , Prognóstico , Seleção Genética
18.
J Exp Med ; 217(10)2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32910820

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) is an unprecedented global health crisis. Tissue and peripheral blood analysis indicate profound, aberrant myeloid cell activation, cytokine storm, and lymphopenia, with unknown immunopathological mechanisms. Spatiotemporal control of the quality and quantity of the antiviral immune responses involves synchronized cellular and molecular cascades and cross-talk between innate and adaptive immunity. Dysregulated responses in immunity, such as at the stages of immune sensing, alarming, polarization, and resolution, may contribute to disease pathology. Herein, we approach SARS-CoV-2 through an immunomodulatory lens, discussing possible mechanisms of the asynchronized antiviral immune response and proposing potential therapeutic strategies to correct the dysregulation.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Imunoterapia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Betacoronavirus/fisiologia , Humanos , Imunidade , Modelos Imunológicos , Pandemias , Internalização do Vírus
19.
J Int Med Res ; 48(9): 300060520958594, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32962495

RESUMO

OBJECTIVE: Coronavirus disease 2019 (COVID-19) shows a wide range of severity, ranging from an asymptomatic presentation to a severe illness requiring intensive care unit admission. Identification of a strategy to manage the severity of this disease will not only help to reduce its case fatality but also help to remove some of the burden from the already overwhelmed health care systems. While successful management of symptoms in general is important, identifying measures to modify the severity of the illness is a key factor in the fight against this pandemic. METHODS: This paper presents a short literature review to suggest a new treatment modality for COVID-19. RESULTS: COVID-19 is less severe and rarely fatal in children than in adults, which could be caused by greater fluctuations of plasma epinephrine in children. Our literature survey endorses this hypothesis according to both the epidemiological and immunological findings. CONCLUSION: Application of epinephrine pulses with a specific amplitude may be considered an intervention to minimize the severity of COVID-19.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Ritmo Circadiano/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Epinefrina/uso terapêutico , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Adulto , Fatores Etários , Doenças Assintomáticas , Biomarcadores/sangue , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Criança , Ritmo Circadiano/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Esquema de Medicação , Epinefrina/sangue , Epinefrina/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Modelos Imunológicos , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Prognóstico , Índice de Gravidade de Doença
20.
Nat Microbiol ; 5(10): 1185-1191, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32908214

RESUMO

Antibody-based drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being expedited through preclinical and clinical development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clinical safety risks related to ADE, resulting in failed vaccine trials. Here, we describe key ADE mechanisms and discuss mitigation strategies for SARS-CoV-2 vaccines and therapies in development. We also outline recently published data to evaluate the risks and opportunities for antibody-based protection against SARS-CoV-2.


Assuntos
Anticorpos Facilitadores , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Vacinas Virais/efeitos adversos , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , Anticorpos Facilitadores/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Humanos , Imunização Passiva/efeitos adversos , Técnicas In Vitro , Modelos Imunológicos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Doenças Respiratórias/etiologia , Doenças Respiratórias/imunologia , Fatores de Risco , Segurança , Vacinas Virais/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA