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1.
Urol Clin North Am ; 47(4): 433-442, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008494

RESUMO

Natural killer (NK) cells are potently cytolytic innate lymphocytes involved in the immune surveillance of tumors and virally infected cells. Although much progress has been made in manipulating the ability of T cells to recognize and eliminate tumors, a comprehensive understanding of NK-cell infiltration into solid tumors, and their amenability to immunomodulation, remains incomplete. This article discusses recent studies showing that urologic tumors are infiltrated by NK cells and that these NK cells are often dysfunctional, but that strategies interfering with inhibitory axes have significant potential to alleviate this dysfunction.


Assuntos
Imunoterapia/métodos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Terapia de Alvo Molecular/métodos , Neoplasias Urogenitais/terapia , Terapia Biológica/métodos , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Masculino , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Medição de Risco , Resultado do Tratamento , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias Urogenitais/imunologia
2.
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
3.
Nat Rev Immunol ; 20(10): 615-632, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32887954

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most formidable challenge to humanity in a century. It is widely believed that prepandemic normalcy will never return until a safe and effective vaccine strategy becomes available and a global vaccination programme is implemented successfully. Here, we discuss the immunological principles that need to be taken into consideration in the development of COVID-19 vaccine strategies. On the basis of these principles, we examine the current COVID-19 vaccine candidates, their strengths and potential shortfalls, and make inferences about their chances of success. Finally, we discuss the scientific and practical challenges that will be faced in the process of developing a successful vaccine and the ways in which COVID-19 vaccine strategies may evolve over the next few years.


Assuntos
Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/prevenção & controle , Vacinas Virais/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Vetores Genéticos/química , Vetores Genéticos/imunologia , Humanos , Imunidade Coletiva/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Esquemas de Imunização , Imunogenicidade da Vacina , Segurança do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Vacinas Atenuadas , Vacinas de DNA , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
4.
Front Immunol ; 11: 1782, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760409

RESUMO

As the SARS-CoV-2 virus wreaks havoc on the populations, health care infrastructures and economies of nations around the world, finding ways to protect health care workers and bolster immune responses in the general population while we await an effective vaccine will be the difference between life and death for many people. Recent studies show that innate immune populations may possess a form of memory, termed Trained Immunity (TRIM), where innate immune cells undergo metabolic, mitochondrial, and epigenetic reprogramming following exposure to an initial stimulus that results in a memory phenotype of enhanced immune responses when exposed to a secondary, heterologous, stimulus. Throughout the literature, it has been shown that the induction of TRIM using such inducers as the BCG vaccine and ß-glucan can provide protection through altered immune responses against a range of viral infections. Here we hypothesize a potential role for ß-glucan in decreasing worldwide morbidity and mortality due to COVID-19, and posit several ideas as to how TRIM may actually shape the observed epidemiological phenomena related to COVID-19. We also evaluate the potential effects of ß-glucan in relation to the immune dysregulation and cytokine storm observed in COVID-19. Ultimately, we hypothesize that the use of oral ß-glucan in a prophylactic setting could be an effective way to boost immune responses and abrogate symptoms in COVID-19, though clinical trials are necessary to confirm the efficacy of this treatment and to further examine differential effects of ß-glucan's from various sources.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/dietoterapia , Infecções por Coronavirus/imunologia , Fibras na Dieta/uso terapêutico , Memória Imunológica/efeitos dos fármacos , Pneumonia Viral/dietoterapia , Pneumonia Viral/imunologia , beta-Glucanas/uso terapêutico , Administração Oral , Adulto , Fatores Etários , Animais , Antivirais/administração & dosagem , Antivirais/imunologia , Antivirais/farmacologia , Vacina BCG/imunologia , Criança , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Citocinas/sangue , Fibras na Dieta/administração & dosagem , Epigênese Genética/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Profilaxia Pré-Exposição , beta-Glucanas/administração & dosagem , beta-Glucanas/imunologia , beta-Glucanas/farmacologia
5.
Adv Biol Regul ; 77: 100741, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32773102

RESUMO

Pandemic coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and poses an unprecedented challenge to healthcare systems due to the lack of a vaccine and specific treatment options. Accordingly, there is an urgent need to understand precisely the pathogenic mechanisms underlying this multifaceted disease. There is increasing evidence that the immune system reacts insufficiently to SARS-CoV-2 and thus contributes to organ damage and to lethality. In this review, we suggest that the overwhelming production of reactive oxygen species (ROS) resulting in oxidative stress is a major cause of local or systemic tissue damage that leads to severe COVID-19. It increases the formation of neutrophil extracellular traps (NETs) and suppresses the adaptive arm of the immune system, i.e. T cells that are necessary to kill virus-infected cells. This creates a vicious cycle that prevents a specific immune response against SARS-CoV-2. The key role of oxidative stress in the pathogenesis of severe COVID-19 implies that therapeutic counterbalancing of ROS by antioxidants such as vitamin C or NAC and/or by antagonizing ROS production by cells of the mononuclear phagocyte system (MPS) and neutrophil granulocytes and/or by blocking of TNF-α can prevent COVID-19 from becoming severe. Controlled clinical trials and preclinical models of COVID-19 are needed to evaluate this hypothesis.


Assuntos
Antioxidantes/uso terapêutico , Infecções por Coronavirus/epidemiologia , Armadilhas Extracelulares/imunologia , Linfopenia/epidemiologia , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Acetilcisteína/uso terapêutico , Ácido Ascórbico/uso terapêutico , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/genética , Citocinas/imunologia , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/metabolismo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Linfopenia/tratamento farmacológico , Linfopenia/imunologia , Linfopenia/virologia , NF-kappa B/genética , NF-kappa B/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/virologia , Estresse Oxidativo/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/virologia
6.
Nat Commun ; 11(1): 3858, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737343

RESUMO

Checkpoint blockade therapy has provided noteworthy benefits in multiple cancers in recent years; however, its clinical benefits remain confined to 10-40% of patients with extremely high costs. Here, we design an ultrafast, low-temperature, and universal self-assembly route to integrate immunology-associated large molecules into metal-organic-framework (MOF)-gated mesoporous silica (MS) as cancer vaccines. Core MS nanoparticles, acting as an intrinsic immunopotentiator, provide the niche, void, and space to accommodate antigens, soluble immunopotentiators, and so on, whereas the MOF gatekeeper protects the interiors from robust and off-target release. A combination of MOF-gated MS cancer vaccines with systemic programmed cell death 1 (PD-1) blockade therapy generates synergistic effects that potentiate antitumour immunity and reduce the effective dose of an anti-PD-1 antibody to as low as 1/10 of that for PD-1 blockade monotherapy in E.G7-OVA tumour-bearing mice, with eliciting the robust adaptive OVA-specific CD8+ T-cell responses, reversing the immunosuppressive pathway and inducing durable tumour suppression.


Assuntos
Anticorpos Neutralizantes/farmacologia , Vacinas Anticâncer/farmacologia , Linfoma/terapia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/administração & dosagem , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antígenos de Neoplasias/administração & dosagem , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/química , Citotoxicidade Imunológica , Composição de Medicamentos , Feminino , Humanos , Imunidade Inata/efeitos dos fármacos , Imunoterapia/métodos , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Linfoma/imunologia , Linfoma/mortalidade , Linfoma/patologia , Estruturas Metalorgânicas/síntese química , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Receptor de Morte Celular Programada 1/imunologia , Dióxido de Silício/química , Análise de Sobrevida , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Appl Microbiol Biotechnol ; 104(18): 7777-7785, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32780290

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19. KEY POINTS: • Microbial coinfection is a nonnegligible factor in COVID-19. • Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment. • Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/epidemiologia , Linfopenia/epidemiologia , Micoses/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Viroses/epidemiologia , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/microbiologia , Síndrome da Liberação de Citocina/virologia , Citocinas/biossíntese , Progressão da Doença , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Linfócitos/microbiologia , Linfócitos/virologia , Linfopenia/tratamento farmacológico , Linfopenia/microbiologia , Linfopenia/virologia , Micoses/tratamento farmacológico , Micoses/microbiologia , Micoses/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/microbiologia , Pneumonia Viral/virologia , Viroses/tratamento farmacológico , Viroses/microbiologia , Viroses/virologia
9.
Virus Res ; 288: 198114, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32800805

RESUMO

The current COVID-19 pandemic has urged the scientific community internationally to find answers in terms of therapeutics and vaccines to control SARS-CoV-2. Published investigations mostly on SARS-CoV and to some extent on MERS has taught lessons on vaccination strategies to this novel coronavirus. This is attributed to the fact that SARS-CoV-2 uses the same receptor as SARS-CoV on the host cell i.e. human Angiotensin Converting Enzyme 2 (hACE2) and is approximately 79% similar genetically to SARS-CoV. Though the efforts on COVID-19 vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19 vaccine before September, 2020 as per very optimistic estimates. This is because a successful COVID-19 vaccine will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline healthcare workers and those involved in essentials industries. Various platforms for vaccine development are available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this novel coronavirus which has crippled the world in terms of economy, human health and life.


Assuntos
Anticorpos Antivirais/biossíntese , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais/imunologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Vetores Genéticos/química , Vetores Genéticos/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Imunização Passiva/métodos , Imunogenicidade da Vacina , Segurança do Paciente , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Receptores Virais/genética , Receptores Virais/imunologia , Receptores Virais/metabolismo , Vacinas Atenuadas , Vacinas de DNA , Vacinas de Subunidades , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/biossíntese , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/biossíntese
10.
Aquat Toxicol ; 227: 105596, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32827874

RESUMO

In aquatic animals, hypoxia is associated with growth retardation, impaired immunity, susceptibility to pathogens, oxidative stress, and mortality. However, the relative long-term effects of hypoxia on bivalves, including abalone, are not well understood. In this study, we examined the effects of exposure to hypoxic (2.5 and 4 mg O2 L-1) and normoxic (8 mg O2 L-1) conditions on the growth, survival, and immune and antioxidant responses of the economically important Pacific abalone Haliotis discus hannai over a 4 month period. We observed that exposure to 2.5 mg O2 L-1 resulted in marked reductions in assessed shell parameters, average meat weight, and survival compared with exposure to 4 and 8 mg O2 L-1. There were also significant reductions in oxygen consumption and ammonia-N excretion in abalone exposed to 2.5 mg O2 L-1. We also detected initial immunosuppression in the 2.5 mg O2 L-1-treated abalone, as evidenced by a significant reduction in total hemocytes and inhibition of antibacterial and lysozyme activities. Furthermore, intracellular malondialdehyde concentrations were significantly elevated at 1 month in the 2.5 mg O2 L-1 treatment group, whereas there were reductions in the levels of glutathione and enzymatic activities of catalase and superoxide dismutase, thereby indicating potential hypoxia-induced oxidative stress and a depression of antioxidant capacity. After 4 months of treatment, severe hypoxia (2.5 mg O2 L-1) had significantly modulated all measured parameters, whereas exposure to 4 and 8 mg O2 L-1 had induced no significant effects. Collectively, our observations indicate that under long-term exposure to hypoxia, Pacific abalone failed to maintain an effective antioxidant defense system and adequate immunity, with the observed biochemical disruptions leading to a reduction in growth and survival.


Assuntos
Eutrofização , Gastrópodes/imunologia , Imunidade Inata/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Catalase/farmacologia , Gastrópodes/efeitos dos fármacos , Hipóxia , Estresse Oxidativo , Estresse Fisiológico , Superóxido Dismutase , Poluentes Químicos da Água/toxicidade
12.
Nature ; 584(7820): 286-290, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32760002

RESUMO

The histone deacetylases (HDACs) are a superfamily of chromatin-modifying enzymes that silence transcription through the modification of histones. Among them, HDAC3 is unique in that interaction with nuclear receptor corepressors 1 and 2 (NCoR1/2) is required to engage its catalytic activity1-3. However, global loss of HDAC3 also results in the repression of transcription, the mechanism of which is currently unclear4-8. Here we report that, during the activation of macrophages by lipopolysaccharides, HDAC3 is recruited to activating transcription factor 2 (ATF2)-bound sites without NCoR1/2 and activates the expression of inflammatory genes through a non-canonical mechanism. By contrast, the deacetylase activity of HDAC3 is selectively engaged at ATF3-bound sites that suppress Toll-like receptor signalling. Loss of HDAC3 in macrophages safeguards mice from lethal exposure to lipopolysaccharides, but this protection is not conferred upon genetic or pharmacological abolition of the catalytic activity of HDAC3. Our findings show that HDAC3 is a dichotomous transcriptional activator and repressor, with a non-canonical deacetylase-independent function that is vital for the innate immune system.


Assuntos
Histona Desacetilases/metabolismo , Inflamação/genética , Inflamação/metabolismo , Fator 2 Ativador da Transcrição/metabolismo , Fator 3 Ativador da Transcrição/metabolismo , Animais , Biocatálise , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/genética , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Masculino , Camundongos , Correpressor 1 de Receptor Nuclear , Correpressor 2 de Receptor Nuclear , Proteínas Repressoras/metabolismo , Transcrição Genética/efeitos dos fármacos
13.
Molecules ; 25(12)2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604797

RESUMO

Viruses can be spread from one person to another; therefore, they may cause disorders in many people, sometimes leading to epidemics and even pandemics. New, previously unstudied viruses and some specific mutant or recombinant variants of known viruses constantly appear. An example is a variant of coronaviruses (CoV) causing severe acute respiratory syndrome (SARS), named SARS-CoV-2. Some antiviral drugs, such as remdesivir as well as antiretroviral drugs including darunavir, lopinavir, and ritonavir are suggested to be effective in treating disorders caused by SARS-CoV-2. There are data on the utilization of antiretroviral drugs against SARS-CoV-2. Since there are many studies aimed at the identification of the molecular mechanisms of human immunodeficiency virus type 1 (HIV-1) infection and the development of novel therapeutic approaches against HIV-1, we used HIV-1 for our case study to identify possible molecular pathways shared by SARS-CoV-2 and HIV-1. We applied a text and data mining workflow and identified a list of 46 targets, which can be essential for the development of infections caused by SARS-CoV-2 and HIV-1. We show that SARS-CoV-2 and HIV-1 share some molecular pathways involved in inflammation, immune response, cell cycle regulation.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Mineração de Dados/métodos , Infecções por HIV/epidemiologia , Infecções por HIV/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Anti-Inflamatórios/uso terapêutico , Antígenos de Diferenciação/genética , Antígenos de Diferenciação/imunologia , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Proteínas do Sistema Complemento/genética , Proteínas do Sistema Complemento/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Bases de Dados Genéticas , Regulação da Expressão Gênica , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/efeitos dos fármacos , HIV-1/imunologia , HIV-1/patogenicidade , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Inflamação , Interferons/genética , Interferons/imunologia , Interleucinas/genética , Interleucinas/imunologia , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Redes e Vias Metabólicas/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Proteínas Repressoras/genética , Proteínas Repressoras/imunologia , Transdução de Sinais , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/imunologia
14.
PLoS Pathog ; 16(7): e1008737, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32726355

RESUMO

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. An unbalanced immune response, characterized by a weak production of type I interferons (IFN-Is) and an exacerbated release of proinflammatory cytokines, contributes to the severe forms of the disease. SARS-CoV-2 is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2003 and 2013, respectively. Although IFN treatment gave some encouraging results against SARS-CoV and MERS-CoV in animal models, its potential as a therapeutic against COVID-19 awaits validation. Here, we describe our current knowledge of the complex interplay between SARS-CoV-2 infection and the IFN system, highlighting some of the gaps that need to be filled for a better understanding of the underlying molecular mechanisms. In addition to the conserved IFN evasion strategies that are likely shared with SARS-CoV and MERS-CoV, novel counteraction mechanisms are being discovered in SARS-CoV-2-infected cells. Since the last coronavirus epidemic, we have made considerable progress in understanding the IFN-I response, including its spatiotemporal regulation and the prominent role of plasmacytoid dendritic cells (pDCs), which are the main IFN-I-producing cells. While awaiting the results of the many clinical trials that are evaluating the efficacy of IFN-I alone or in combination with antiviral molecules, we discuss the potential benefits of a well-timed IFN-I treatment and propose strategies to boost pDC-mediated IFN responses during the early stages of viral infection.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Células Dendríticas/imunologia , Imunidade Inata/imunologia , Interferon Tipo I/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Células Dendríticas/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Prognóstico
16.
Front Immunol ; 11: 1439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655577

RESUMO

In December 2019, following a cluster of pneumonia cases in China caused by a novel coronavirus (CoV), named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infection disseminated worldwide and, on March 11th, 2020, the World Health Organization officially declared the pandemic of the relevant disease named coronavirus disease 2019 (COVID-19). In Europe, Italy was the first country facing a true health policy emergency, and, as at 6.00 p.m. on May 2nd, 2020, there have been more than 209,300 confirmed cases of COVID-19. Due to the increasing number of patients experiencing a severe outcome, global scientific efforts are ongoing to find the most appropriate treatment. The usefulness of specific anti-rheumatic drugs came out as a promising treatment option together with antiviral drugs, anticoagulants, and symptomatic and respiratory support. For this reason, we feel a duty to share our experience and our knowledge on the use of these drugs in the immune-rheumatologic field, providing in this review the rationale for their use in the COVID-19 pandemic.


Assuntos
Betacoronavirus/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Imunidade Adaptativa/efeitos dos fármacos , Adulto , Anticoagulantes/uso terapêutico , Antirreumáticos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Hidroxicloroquina/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Interleucina-1/antagonistas & inibidores , Interleucina-6/antagonistas & inibidores , Inibidores de Janus Quinases/uso terapêutico , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/etiologia
17.
Front Immunol ; 11: 1512, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655581

RESUMO

Natural Killer (NK) cells are innate immune responders critical for viral clearance and immunomodulation. Despite their vital role in viral infection, the contribution of NK cells in fighting SARS-CoV-2 has not yet been directly investigated. Insights into pathophysiology and therapeutic opportunities can therefore be inferred from studies assessing NK cell phenotype and function during SARS, MERS, and COVID-19. These studies suggest a reduction in circulating NK cell numbers and/or an exhausted phenotype following infection and hint toward the dampening of NK cell responses by coronaviruses. Reduced circulating NK cell levels and exhaustion may be directly responsible for the progression and severity of COVID-19. Conversely, in light of data linking inflammation with coronavirus disease severity, it is necessary to examine NK cell potential in mediating immunopathology. A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. In this review, we summarize the current understanding of how NK cells respond in both early and late coronavirus infections, and the implication for ongoing COVID-19 clinical trials. Using this immunological lens, we outline recommendations for therapeutic strategies against COVID-19 in clearing the virus while preventing the harm of immunopathological responses.


Assuntos
Transferência Adotiva/métodos , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Células Matadoras Naturais/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Corticosteroides/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Ácido Ascórbico/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Suscetibilidade a Doenças/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Memória Imunológica , Interferon Tipo I/metabolismo , Interferon Tipo I/uso terapêutico , Células Matadoras Naturais/efeitos dos fármacos , Camundongos , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia
18.
Eur J Pharmacol ; 882: 173328, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32603692

RESUMO

The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. Nevertheless, at the same time, the high quantity of clinical data, generated by a large number of rapidly infected people, require accurate tests regarding effective medical treatments. Several in vitro and in vivo studies were rapidly initiated after the outbreak of the pandemic COVID-19. Initial clinical studies revealed the promising potential of remdesivir that demonstrated a powerful and specific in vitro antiviral activity for COVID-19. Promising effects appear to be attributable to hydroxychloroquine. Remdesivir and hydroxychloroquine are being tested in ongoing randomized trials. In contrast, oseltamivir was not effective and corticosteroids are not currently recommended. However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment.


Assuntos
Adjuvantes Imunológicos/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Mediadores da Inflamação/farmacologia , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Monofosfato de Adenosina/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Alanina/análogos & derivados , Alanina/farmacologia , Alanina/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Ensaios Clínicos como Assunto , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Glucocorticoides/farmacologia , Glucocorticoides/uso terapêutico , Heparina de Baixo Peso Molecular/farmacologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Mediadores da Inflamação/uso terapêutico , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Resultado do Tratamento
19.
Am J Med Sci ; 360(3): 216-221, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32622469

RESUMO

The potentially lethal infection caused by the novel Severe Acute Respiratory Disease Coronavirus-2 (SARS-CoV-2) has evolved into a global crisis. Following the initial viral infection is the host inflammatory response that frequently results in excessive secretion of inflammatory cytokines (e.g., IL-6 and TNFα), developing into a self-targeting, toxic "cytokine storm" causing critical pulmonary tissue damage. The need for a therapeutic that is available immediately is growing daily but the de novo development of a vaccine may take years. Therefore, repurposing of approved drugs offers a promising approach to address this urgent need. Inhaled furosemide, a small molecule capable of inhibiting IL-6 and TNFα, may be an agent capable of treating the Coronavirus Disease 2019 cytokine storm in both resource-rich and developing countries. Furosemide is a "repurpose-able" small molecule therapeutics, that is safe, easily synthesized, handled, and stored, and is available in reasonable quantities worldwide.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Furosemida/administração & dosagem , Imunidade Inata/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Administração por Inalação , Antivirais/administração & dosagem , Antivirais/farmacocinética , Betacoronavirus/imunologia , Betacoronavirus/metabolismo , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Furosemida/farmacocinética , Humanos , Imunidade Inata/fisiologia , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Inibidores de Simportadores de Cloreto de Sódio e Potássio/farmacocinética
20.
Eur J Clin Invest ; 50(9): e13342, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32645207

RESUMO

COVID-19 pandemia is a major concern for patients and healthcare systems. The fear of infection by patients with concomitant rheumatic diseases (either adult or children) and connective tissue diseases is arising worldwide, because of their immunological background and immunological therapies. Analysing the basic biology of single diseases, the data suggest that there is an "immunological umbrella" that seems to protect against the infection, through IFN type 1 and NK cell function. To date, reports from China, United States and Europe did not reveal an higher risk of infection, either for rheumatoid arthritis, juvenile idiopathic arthritis nor for lupus erythematosus. Antimalarials, anti-IL6-Anti-IL6 receptor, anti-IL1, anti-GM-CSF receptor and JAK1/2/3 inhibitors, are under investigation in COVID-dedicated clinical trials to control the inflammation raised by SARS-CoV-2 infection. Initial reports on the occurrence of autoimmune phenomena in the convalescence phase of SARS-CoV-2 infection suggests that the immunological consequences of the infection need to be strictly understood. Reporting of the study conforms to broad EQUATOR guidelines (Simera et al January 2010 issue of EJCI).


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Imunossupressores/administração & dosagem , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Doenças Reumáticas/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Imunidade Adaptativa/efeitos dos fármacos , Imunidade Adaptativa/imunologia , Idoso , Antirreumáticos/administração & dosagem , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Surtos de Doenças/estatística & dados numéricos , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Fatores Imunológicos/administração & dosagem , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologia , Medição de Risco , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/imunologia
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