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1.
Cells ; 9(10)2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32998369

RESUMO

The vitamin K-dependent factors protein S (PROS1) and growth-arrest-specific gene 6 (GAS6) and their tyrosine kinase receptors TYRO3, AXL, and MERTK, the TAM subfamily of receptor tyrosine kinases (RTK), are key regulators of inflammation and vascular response to damage. TAM signaling, which has largely studied in the immune system and in cancer, has been involved in coagulation-related pathologies. Because of these established biological functions, the GAS6-PROS1/TAM system is postulated to play an important role in SARS-CoV-2 infection and progression complications. The participation of the TAM system in vascular function and pathology has been previously reported. However, in the context of COVID-19, the role of TAMs could provide new clues in virus-host interplay with important consequences in the way that we understand this pathology. From the viral mimicry used by SARS-CoV-2 to infect cells, to the immunothrombosis that is associated with respiratory failure in COVID-19 patients, TAM signaling seems to be involved at different stages of the disease. TAM targeting is becoming an interesting biomedical strategy, which is useful for COVID-19 treatment now, but also for other viral and inflammatory diseases in the future.


Assuntos
Infecções por Coronavirus/complicações , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pneumonia Viral/complicações , Proteína S/metabolismo , Trombose/etiologia , Imunidade Adaptativa , Animais , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Hemostasia , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Trombose/sangue , Trombose/imunologia , c-Mer Tirosina Quinase/metabolismo
2.
Oxid Med Cell Longev ; 2020: 6401341, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014275

RESUMO

Human SARS-CoV-2 infection is characterized by a high mortality rate due to some patients developing a large innate immune response associated with a cytokine storm and acute respiratory distress syndrome (ARDS). This is characterized at the molecular level by decreased energy metabolism, altered redox state, oxidative damage, and cell death. Therapies that increase levels of (R)-beta-hydroxybutyrate (R-BHB), such as the ketogenic diet or consuming exogenous ketones, should restore altered energy metabolism and redox state. R-BHB activates anti-inflammatory GPR109A signaling and inhibits the NLRP3 inflammasome and histone deacetylases, while a ketogenic diet has been shown to protect mice from influenza virus infection through a protective γδ T cell response and by increasing electron transport chain gene expression to restore energy metabolism. During a virus-induced cytokine storm, metabolic flexibility is compromised due to increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that damage, downregulate, or inactivate many enzymes of central metabolism including the pyruvate dehydrogenase complex (PDC). This leads to an energy and redox crisis that decreases B and T cell proliferation and results in increased cytokine production and cell death. It is hypothesized that a moderately high-fat diet together with exogenous ketone supplementation at the first signs of respiratory distress will increase mitochondrial metabolism by bypassing the block at PDC. R-BHB-mediated restoration of nucleotide coenzyme ratios and redox state should decrease ROS and RNS to blunt the innate immune response and the associated cytokine storm, allowing the proliferation of cells responsible for adaptive immunity. Limitations of the proposed therapy include the following: it is unknown if human immune and lung cell functions are enhanced by ketosis, the risk of ketoacidosis must be assessed prior to initiating treatment, and permissive dietary fat and carbohydrate levels for exogenous ketones to boost immune function are not yet established. The third limitation could be addressed by studies with influenza-infected mice. A clinical study is warranted where COVID-19 patients consume a permissive diet combined with ketone ester to raise blood ketone levels to 1 to 2 mM with measured outcomes of symptom severity, length of infection, and case fatality rate.


Assuntos
Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/terapia , Dieta Cetogênica/métodos , Cetonas/administração & dosagem , Pneumonia Viral/terapia , Ácido 3-Hidroxibutírico/metabolismo , Imunidade Adaptativa , Animais , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/metabolismo , Metabolismo Energético , Humanos , Imunidade Inata , Cetonas/metabolismo , Oxirredução , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo
4.
Artigo em Russo | MEDLINE | ID: mdl-32929928

RESUMO

OBJECTIVE: To determine factors of innate and acquired immunity in adaptation disorders with a predominance of asthenic or anxiety-depressive syndrome. MATERIAL AND METHODS: Twenty-five patients with ICD-10 diagnosis of «Adaptation Disorders¼ (F43.2), including 9 with asthenic syndrome and 16 with anxiety-depressive syndrome, were examined. The control group consisted of 23 healthy individuals. The relative number of lymphocyte phenotypes was determined by flow cytometry; the concentration of IgM, IgG, IgA, aAB to S100b and MBP - by ELISA; CIC level - by the method of selective precipitation with PEG-6000; phagocytic activity of neutrophils by a test system with melamine-formaldehyde latex; activities of leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) by a spectrophotometric method. RESULTS: There were significant changes in the parameters of acquired immunity in the group with asthenic syndrome and those of innate immunity in the group with anxiety-depressive syndrome. An increase in α1-PI activity, in the total number of significant correlations between different immunological parameters, in the involvement of α1-PI in integration of acquired and innate immunity were observed in the anxiety-depressive group compared with the asthenic group. CONCLUSIONS: The peculiarities of stress response in patients with leading anxiety-depressive syndrome are the high activity of α1-PI, which, along with the strengthening of correlation intersystem associations and the involvement of this protein in the integration of acquired and innate immunity, allows us to consider α1-PI as a criterion that improves the accuracy of diagnosis of the nature of the course of adaptation disorders.


Assuntos
Imunidade Adaptativa , Elastase de Leucócito , Astenia , Humanos , Imunidade Inata , alfa 1-Antitripsina
5.
S Afr Med J ; 110(9): 837-841, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32880263

RESUMO

The potential role for serological tests in the current COVID-19 pandemic has generated very considerable recent interest across many sectors worldwide, inter alia pathologists seeking additional weapons for their armoury of diagnostic tests; epidemiologists seeking tools to gain seroprevalence data that will inform improved models of the spread of disease; research scientists seeking tools to study the natural history of COVID-19 disease; vaccine developers seeking tools to assess vaccine efficacy in clinical trials; and companies and governments seeking tools to aid return-to-work decision-making. However, much of the local debate to date has centred on questions surrounding whether regulatory approval processes are limiting access to serological tests, and has not paused to consider the intrinsically limiting impact of underlying fundamental biology and immunology on where and how different COVID-19 serological tests can usefully be deployed in the response to the current pandemic. We review, from an immunological perspective, recent experimental evidence on the time-dependency of adaptive immune responses following SARS-CoV-2 infection and the impact of this on the sensitivity and specificity of COVID-19 antibody tests made at different time points post infection. We interpret this scientific evidence in terms of mooted clinical applications for current COVID-19 antibody tests in identifying acute infections, in confirming recent or past infections at the individual and population level, and in detecting re-infection and protective immunity. We conclude with guidance on where current COVID-19 antibody tests can make a genuine impact in the pandemic.


Assuntos
Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Humanos , Pandemias , Pneumonia Viral/imunologia , Sensibilidade e Especificidade , Fatores de Tempo
6.
Sci Rep ; 10(1): 14991, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929138

RESUMO

Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the innate and adaptive immune response to the SARS-CoV-2 virus or to a related vaccine. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the notable exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight of the S trimer (17% for the HEK293 glycoform) they shield approximately 40% of the protein surface.


Assuntos
Betacoronavirus/metabolismo , Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Polissacarídeos/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Imunidade Adaptativa , Sequência de Aminoácidos , Anticorpos Neutralizantes/imunologia , Complexo Antígeno-Anticorpo , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Sítios de Ligação , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Glicosilação , Células HEK293 , Antígenos HLA/metabolismo , Humanos , Imunidade Inata , Simulação de Dinâmica Molecular , Pandemias , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ligação Proteica , Estrutura Terciária de Proteína , Alinhamento de Sequência , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
8.
Front Immunol ; 11: 2147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983176

RESUMO

The novel severe acute respiratory syndrome coronavirus 2, the cause of the coronavirus disease 2019 (COVID-19) pandemic, has ravaged the world, with over 22 million total cases and over 770,000 deaths worldwide as of August 18, 2020. While the elderly are most severely affected, implicating an age bias, a striking factor in the demographics of this deadly disease is the gender bias, with higher numbers of cases, greater disease severity, and higher death rates among men than women across the lifespan. While pre-existing comorbidities and social, behavioral, and lifestyle factors contribute to this bias, biological factors underlying the host immune response may be crucial contributors. Women mount stronger immune responses to infections and vaccinations and outlive men. Sex-based biological factors underlying the immune response are therefore important determinants of susceptibility to infections, disease outcomes, and mortality. Despite this, gender is a profoundly understudied and often overlooked variable in research related to the immune response and infectious diseases, and it is largely ignored in drug and vaccine clinical trials. Understanding these factors will not only help better understand the pathogenesis of COVID-19, but it will also guide the design of effective therapies and vaccine strategies for gender-based personalized medicine. This review focuses on sex-based differences in genes, sex hormones, and the microbiome underlying the host immune response and their relevance to infections with a focus on coronaviruses.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Interações Hospedeiro-Patógeno/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Imunidade Adaptativa/genética , Infecções por Coronavirus/virologia , Feminino , Predisposição Genética para Doença , Hormônios Esteroides Gonadais/imunologia , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata/genética , Masculino , Microbiota/imunologia , Pandemias , Pneumonia Viral/virologia , Fatores Sexuais
9.
Sci Immunol ; 5(51)2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887844

RESUMO

E2A specifies adaptive immunity by instructing large-scale topological changes for Rag gene super-enhancer formation (see the related Research Article by Miyazaki et al.).


Assuntos
Cromatina , Fatores de Transcrição , Imunidade Adaptativa , Linfócitos B , Regulação da Expressão Gênica
10.
Monaldi Arch Chest Dis ; 90(4)2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945643

RESUMO

Novel coronavirus disease (COVID-19) has affected nearly 7 million individuals and claimed more than 0.4 million lives to date. There are several reports of gender differences related to infection and death due to COVID-19. This raises important questions such as "Whether there are differences based on gender in risk and severity of infection or mortality rate?" and "What are the biological explanation and mechanisms underlying these differences?" Emerging evidences have proposed sex-based immunological, genetic, and hormonal differences to explain this ambiguity. Besides biological differences, women have also faced social inequities and economic hardships due to this pandemic. Several recent studies have shown that independent of age males are at higher risk for severity and mortality in COVID-19 patients. Although susceptibility to SARS-CoV-2 was found to be similar across both genders in several disease cohorts, a disproportionate death ratio in men can be partly explained by the higher burden of pre-existing diseases and occupational exposures among men. At immunological point of view, females can engage a more active immune response, which may protect them and counter infectious diseases as compared to men. This attribute of better immune responses towards pathogens is thought to be due to high estrogen levels in females. Here we review the current knowledge about sex differences in susceptibility, the severity of infection and mortality, host immune responses, and the role of sex hormones in COVID-19 disease.


Assuntos
Imunidade Adaptativa/imunologia , Infecções por Coronavirus/imunologia , Estrogênios/imunologia , Imunidade Inata/imunologia , Pneumonia Viral/imunologia , Testosterona/imunologia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Mortalidade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Índice de Gravidade de Doença , Caracteres Sexuais , Fatores Sexuais
12.
Sci Immunol ; 5(50)2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826343

RESUMO

Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients. This pattern was mirrored in scRNA-seq signatures of NK cells in bronchoalveolar lavage from COVID-19 patients. Unsupervised high-dimensional analysis of peripheral blood NK cells furthermore identified distinct NK cell immunotypes that were linked to disease severity. Hallmarks of these immunotypes were high expression of perforin, NKG2C, and Ksp37, reflecting increased presence of adaptive NK cells in circulation of patients with severe disease. Finally, arming of CD56bright NK cells was observed across COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This study provides a detailed map of the NK cell activation landscape in COVID-19 disease.


Assuntos
Betacoronavirus/genética , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Células Matadoras Naturais/imunologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Índice de Gravidade de Doença , Imunidade Adaptativa , Antígeno CD56/metabolismo , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Feminino , Citometria de Fluxo/métodos , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Pandemias , Fenótipo , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Reação em Cadeia da Polimerase , Estudos Prospectivos , Mapas de Interação de Proteínas/imunologia , Receptores KIR/metabolismo , Testes Sorológicos , Suécia/epidemiologia
13.
Environ Res ; 188: 109858, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32846644

RESUMO

According to numerous recent publications, the COVID-19 patients have lymphopenia, higher infection-related biomarkers and several elevated inflammatory cytokines (i.e. tumor necrosis factor (TNF)-α, interleukin IL-2R and IL-6). The total number of B cells, T cells and NK cells are significantly decreased. RNA viruses, SARS-CoV-2 included, hit the innate immune system in order to cause infection, through TLRs 3, 7 and 8. Imiquimod is an immune-stimulator that activates TLR 7 and can be used to enhance the innate and adaptive immunity. Preclinical and clinical trials are proposed.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Imiquimode/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Receptor 7 Toll-Like/agonistas , Imunidade Adaptativa , Betacoronavirus , Citocinas , Humanos , Imunidade Inata , Pandemias
14.
Physiol Genomics ; 52(9): 401-407, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32809918

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic, infecting over 16 million people worldwide with a significant mortality rate. However, there is no current Food and Drug Administration-approved drug that treats coronavirus disease 2019 (COVID-19). Damage to T lymphocytes along with the cytokine storm are important factors that lead to exacerbation of clinical cases. Here, we are proposing intravenous oxytocin (OXT) as a candidate for adjunctive therapy for COVID-19. OXT has anti-inflammatory and proimmune adaptive functions. Using the Library of Integrated Network-Based Cellular Signatures (LINCS), we used the transcriptomic signature for carbetocin, an OXT agonist, and compared it to gene knockdown signatures of inflammatory (such as interleukin IL-1ß and IL-6) and proimmune markers (including T cell and macrophage cell markers like CD40 and ARG1). We found that carbetocin's transcriptomic signature has a pattern of concordance with inflammation and immune marker knockdown signatures that are consistent with reduction of inflammation and promotion and sustaining of immune response. This suggests that carbetocin may have potent effects in modulating inflammation, attenuating T cell inhibition, and enhancing T cell activation. Our results also suggest that carbetocin is more effective at inducing immune cell responses than either lopinavir or hydroxychloroquine, both of which have been explored for the treatment of COVID-19.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Perfilação da Expressão Gênica , Ocitocina/análogos & derivados , Pneumonia Viral/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Imunidade Adaptativa/genética , Betacoronavirus/imunologia , Linhagem Celular , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Bases de Dados Genéticas , Interações Hospedeiro-Patógeno , Humanos , Ocitocina/farmacologia , Pandemias , Pneumonia Viral/genética , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Linfócitos T/imunologia , Linfócitos T/virologia , Transcriptoma
15.
J Infect Dis ; 222(9): 1452-1461, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32766833

RESUMO

BACKGROUND: The COVID-19 pandemic necessitates better understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high-throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population. METHODS: Spike protein subunits S1 and receptor binding domain, and nucleoprotein were coupled to microspheres. Sera collected before emergence of SARS-CoV-2 (n = 224) and of non-SARS-CoV-2 influenza-like illness (n = 184), and laboratory-confirmed cases of SARS-CoV-2 infection (n = 115) with various severities of COVID-19 were tested for SARS-CoV-2-specific IgG concentrations. RESULTS: Our assay discriminated SARS-CoV-2-induced antibodies and those induced by other viruses. The assay specificity was 95.1%-99.0% with sensitivity 83.6%-95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to nonhospitalized cases. CONCLUSIONS: The bead-based serological assay for quantitation of SARS-CoV-2-specific antibodies proved to be robust and can be conducted in many laboratories. We demonstrated that testing of antibodies against multiple antigens increases sensitivity and specificity compared to single-antigen-specific IgG determination.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Imunoglobulina G/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Imunidade Adaptativa , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Estudos de Casos e Controles , Feminino , Humanos , Imunoensaio , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Proteínas Nucleares/imunologia , Gravidade do Paciente , Curva ROC , Soroconversão , Estudos Soroepidemiológicos , Glicoproteína da Espícula de Coronavírus/imunologia
16.
J Cancer Res Clin Oncol ; 146(11): 2721-2730, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32772231

RESUMO

Activation Induced cytidine Deaminase (AID) is an essential enzyme of the adaptive immune system. Its canonical activity is restricted to B lymphocytes, playing an essential role in the diversification of antibodies by enhancing specificity and changing affinity. This is possible through its DNA deaminase function, leading to mutations in DNA. In the last decade, AID has been assigned an additional function: that of a powerful DNA demethylator. Adverse cellular conditions such as chronic inflammation can lead to its deregulation and overexpression. It is an important driver of B-cell lymphoma due to its natural ability to modify DNA through deamination, leading to mutations and epigenetic changes. However, the deregulation of AID is not restricted to lymphoid cells. Recent findings have provided new insights into the role that this protein plays in the development of non-lymphoid cancers, with some research shedding light on novel AID-driven mechanisms of cellular transformation. In this review, we provide an updated narrative of the normal physiological functions of AID. Additionally, we review and discuss the recent research studies that have implicated AID in carcinogenesis in varying tissue types including lymphoid and non-lymphoid cancers. We review the mechanisms, whereby AID promotes carcinogenesis and highlight important areas of future research.


Assuntos
Imunidade Adaptativa/fisiologia , Citidina Desaminase/fisiologia , Neoplasias/enzimologia , Animais , Transformação Celular Neoplásica/imunologia , Humanos , Neoplasias/imunologia
17.
Chem Biol Interact ; 329: 109209, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32750325

RESUMO

Kinetic modeling of the behavior of complex chemical and biochemical systems is an effective approach to study of the mechanisms of the process. A kinetic model of coronaviral infection development with a description of the dynamic behavior of the main variables, including the concentration of viral particles, affected cells, and pathogenic microflora, is proposed. Changes in the concentration of hydrogen ions in the lungs and the pH -dependence of carbonic anhydrase activity (a key breathing enzyme) are critical. A significant result is the demonstration of an acute bifurcation transition that determines life or system collapse. This transition is connected with exponential growth of concentrations of the process participants and with functioning of the key enzyme carbonic anhydrase in development of toxic effects. Physical and chemical interpretations of the therapeutic effects of the body temperature rise and the potential therapeutic effect of "thermoheliox" (respiration with a thermolized mixture of helium and oxygen) are given. The phenomenon of "thermovaccination" is predicted, which involves stimulation of the immune response by "thermoheliox".


Assuntos
Infecções por Coronaviridae/metabolismo , Hélio/química , Oxigênio/química , Imunidade Adaptativa , Temperatura Corporal , Anidrases Carbônicas/metabolismo , Infecções por Coronaviridae/patologia , Infecções por Coronaviridae/terapia , Hélio/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Cinética , Pulmão/metabolismo , Modelos Teóricos , Oxigênio/uso terapêutico
18.
JCI Insight ; 5(18)2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32796155

RESUMO

Evaluation of potential immunity against the novel severe acute respiratory syndrome (SARS) coronavirus that emerged in 2019 (SARS-CoV-2) is essential for health, as well as social and economic recovery. Generation of antibody response to SARS-CoV-2 (seroconversion) may inform on acquired immunity from prior exposure, and antibodies against the SARS-CoV-2 spike protein receptor binding domain (S-RBD) are speculated to neutralize virus infection. Some serology assays rely solely on SARS-CoV-2 nucleocapsid protein (N-protein) as the antibody detection antigen; however, whether such immune responses correlate with S-RBD response and COVID-19 immunity remains unknown. Here, we generated a quantitative serological ELISA using recombinant S-RBD and N-protein for the detection of circulating antibodies in 138 serial serum samples from 30 reverse transcription PCR-confirmed, SARS-CoV-2-hospitalized patients, as well as 464 healthy and non-COVID-19 serum samples that were collected between June 2017 and June 2020. Quantitative detection of IgG antibodies against the 2 different viral proteins showed a moderate correlation. Antibodies against N-protein were detected at a rate of 3.6% in healthy and non-COVID-19 sera collected during the pandemic in 2020, whereas 1.9% of these sera were positive for S-RBD. Approximately 86% of individuals positive for S-RBD-binding antibodies exhibited neutralizing capacity, but only 74% of N-protein-positive individuals exhibited neutralizing capacity. Collectively, our studies show that detection of N-protein-binding antibodies does not always correlate with presence of S-RBD-neutralizing antibodies and caution against the extensive use of N-protein-based serology testing for determination of potential COVID-19 immunity.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Betacoronavirus/fisiologia , Infecções por Coronavirus , Nucleocapsídeo/imunologia , Pandemias , Pneumonia Viral , Glicoproteína da Espícula de Coronavírus/imunologia , Imunidade Adaptativa/imunologia , Anticorpos Neutralizantes/análise , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Ligação Proteica , Sensibilidade e Especificidade , Soroconversão , Testes Sorológicos/métodos
19.
Front Immunol ; 11: 1748, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849623

RESUMO

Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in lethality of COVID-19. In this review, we will discuss the phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging. Furthermore, we will discuss inflamm-aging, a low-grade inflammatory state triggered by continuous antigenic stimulation, which may ultimately increase all-cause mortality. In general, the elderly are less capable of responding to neo-antigens, because of lower naïve T cell frequency. Furthermore, they have an expansion of memory T cells with a shrinkage of the T cell diversity repertoire. When infected by SARS-CoV-2, young people present with a milder disease as they frequently clear the virus through an efficient adaptive immune response. Indeed, antibody-secreting cells and follicular helper T cells are thought to be effectively activated in young patients that present a favorable prognosis. In contrast, the elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage. The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19.


Assuntos
Imunidade Adaptativa , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Imunidade Inata , Imunossenescência , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Fatores Etários , Animais , Anticorpos Antivirais/sangue , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/virologia , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Inflamação/imunologia , Pandemias , Plasmócitos/imunologia , Pneumonia Viral/virologia , Linfócitos T Auxiliares-Indutores/imunologia
20.
Front Immunol ; 11: 1962, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849656

RESUMO

Platelets, small anucleate cells circulating in the blood, are critical mediators in haemostasis and thrombosis. Interestingly, recent studies demonstrated that platelets contain both pro-inflammatory and anti-inflammatory molecules, equipping platelets with immunoregulatory function in both innate and adaptive immunity. In the context of infectious diseases, platelets are involved in early detection of invading microorganisms and are actively recruited to sites of infection. Platelets exert their effects on microbial pathogens either by direct binding to eliminate or restrict dissemination, or by shaping the subsequent host immune response. Reciprocally, many invading microbial pathogens can directly or indirectly target host platelets, altering platelet count or/and function. In addition, microbial pathogens can impact the host auto- and alloimmune responses to platelet antigens in several immune-mediated diseases, such as immune thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. In this review, we discuss the mechanisms that contribute to the bidirectional interactions between platelets and various microbial pathogens, and how these interactions hold relevant implications in the pathogenesis of many infectious diseases. The knowledge obtained from "well-studied" microbes may also help us understand the pathogenesis of emerging microbes, such as SARS-CoV-2 coronavirus.


Assuntos
Betacoronavirus , Plaquetas/imunologia , Plaquetas/metabolismo , Infecções por Coronavirus/imunologia , Interações Hospedeiro-Patógeno/imunologia , Pneumonia Viral/imunologia , Imunidade Adaptativa , Infecções por Coronavirus/virologia , Hemostasia , Humanos , Imunidade Inata , Inflamação/imunologia , Pandemias , Pneumonia Viral/virologia , Trombose/metabolismo
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