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1.
Front Immunol ; 12: 666983, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854516

RESUMO

The emergence of viruses with pandemic potential such as the SARS-CoV-2 coronavirus causing COVID-19 poses a global health challenge. There is remarkable progress in vaccine technology in response to this threat, but their design often overlooks the innate arm of immunity. Gamma Delta (γδ) T cells are a subset of T cells with unique features that gives them a key role in the innate immune response to a variety of homeostatic alterations, from cancer to microbial infections. In the context of viral infection, a growing body of evidence shows that γδ T cells are particularly equipped for early virus detection, which triggers their subsequent activation, expansion and the fast deployment of antiviral functions such as direct cytotoxic pathways, secretion of cytokines, recruitment and activation of other immune cells and mobilization of a trained immunity memory program. As such, γδ T cells represent an attractive target to stimulate for a rapid and effective resolution of viral infections. Here, we review the known aspects of γδ T cells that make them crucial component of the immune response to viruses, and the ways that their antiviral potential can be harnessed to prevent or treat viral infection.


Assuntos
/imunologia , Interações Hospedeiro-Patógeno , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Imunidade Adaptativa , Animais , Terapia Combinada , Citotoxicidade Imunológica , Gerenciamento Clínico , Suscetibilidade a Doenças/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Receptores Imunológicos/metabolismo
2.
Int J Mol Sci ; 22(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807915

RESUMO

Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under investigation. Several pieces of experimental evidence suggest that genetic variants influencing the onset, maintenance and resolution of the immune response may be fundamental in predicting the evolution of the disease. The identification of genetic variants behind immune system reactivity and function in COVID-19 may help in the elaboration of personalized therapeutic strategies. In the frenetic look for universally shared treatment plans, those genetic variants that are common to other diseases/models may also help in addressing future research in terms of drug repurposing. In this paper, we discuss the most recent updates about the role of immunogenetics in determining the susceptibility to and the history of SARS-CoV-2 infection. We propose a narrative review of available data, speculating about lessons that we have learnt from other viral infections and immunosenescence, and discussing what kind of aspects of research should be deepened in order to improve our knowledge of how host genetic variability impacts the outcome for COVID-19 patients.


Assuntos
/imunologia , Imunogenética , Sistema ABO de Grupos Sanguíneos/imunologia , /epidemiologia , Suscetibilidade a Doenças/imunologia , Predisposição Genética para Doença , Antígenos HLA/sangue , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Imunidade/genética , Índice de Gravidade de Doença
3.
Emerg Microbes Infect ; 10(1): 638-650, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33704016

RESUMO

SARS-CoV-2 is the causative agent of COVID-19 and responsible for the current global pandemic. We and others have previously demonstrated that cats are susceptible to SARS-CoV-2 infection and can efficiently transmit the virus to naïve cats. Here, we address whether cats previously exposed to SARS-CoV-2 can be re-infected with SARS-CoV-2. In two independent studies, SARS-CoV-2-infected cats were re-challenged with SARS-CoV-2 at 21 days post primary challenge (DPC) and necropsies performed at 4, 7 and 14 days post-secondary challenge (DP2C). Sentinels were co-mingled with the re-challenged cats at 1 DP2C. Clinical signs were recorded, and nasal, oropharyngeal, and rectal swabs, blood, and serum were collected and tissues examined for histologic lesions. Viral RNA was transiently shed via the nasal, oropharyngeal and rectal cavities of the re-challenged cats. Viral RNA was detected in various tissues of re-challenged cats euthanized at 4 DP2C, mainly in the upper respiratory tract and lymphoid tissues, but less frequently and at lower levels in the lower respiratory tract when compared to primary SARS-CoV-2 challenged cats at 4 DPC. Viral RNA and antigen detected in the respiratory tract of the primary SARS-CoV-2 infected cats at early DPCs were absent in the re-challenged cats. Naïve sentinels co-housed with the re-challenged cats did not shed virus or seroconvert. Together, our results indicate that cats previously infected with SARS-CoV-2 can be experimentally re-infected with SARS-CoV-2; however, the levels of virus shed was insufficient for transmission to co-housed naïve sentinels. We conclude that SARS-CoV-2 infection in cats induces immune responses that provide partial, non-sterilizing immune protection against re-infection.


Assuntos
Anticorpos Antivirais/sangue , Suscetibilidade a Doenças/imunologia , Eliminação de Partículas Virais , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Gatos , Linhagem Celular , Chlorocebus aethiops , RNA Viral/isolamento & purificação , /virologia , Células Vero , Carga Viral
4.
Environ Health ; 20(1): 34, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771185

RESUMO

BACKGROUND: An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution. OBJECTIVES: To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps. METHODS: An international group of researchers interested in children's environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps. DISCUSSION: Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a "dirty" environment in conveying protection - an example of the "hygiene hypothesis"; and what are the long term health effects of SARS-Cov-2 infection in early life. CONCLUSION: A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.


Assuntos
/epidemiologia , Saúde da Criança , Exposição Ambiental/efeitos adversos , Saúde Ambiental , Adulto , Fatores Etários , Poluição do Ar/efeitos adversos , Poluição do Ar/prevenção & controle , /patologia , Criança , Suscetibilidade a Doenças/epidemiologia , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/patologia , Exposição Ambiental/prevenção & controle , Desenvolvimento Fetal , Humanos , Hipótese da Higiene , Imunidade Inata , Sistema Respiratório/patologia , Sistema Respiratório/virologia
6.
Int J Mol Sci ; 22(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440862

RESUMO

Sjogren's syndrome (SS) is a chronic autoimmune disease characterized by the infiltration of exocrine glands including salivary and lachrymal glands responsible for the classical dry eyes and mouth symptoms (sicca syndrome). The spectrum of disease manifestations stretches beyond the classical sicca syndrome with systemic manifestations including arthritis, interstitial lung involvement, and neurological involvement. The pathophysiology underlying SS is not well deciphered, but several converging lines of evidence have supported the conjuncture of different factors interplaying together to foster the initiation and perpetuation of the disease. The innate and adaptive immune system play a cardinal role in this process. In this review, we discuss the inherent parts played by both the innate and adaptive immune system in the pathogenesis of SS.


Assuntos
Imunidade Adaptativa , Suscetibilidade a Doenças/imunologia , Imunidade Inata , Síndrome de Sjogren/imunologia , Animais , Comunicação Celular/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Especificidade de Órgãos/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
7.
Viruses ; 13(1)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445593

RESUMO

Although mobile genetic elements, or transposons, have played an important role in genome evolution, excess activity of mobile elements can have detrimental consequences. Already, the enhanced expression of transposons-derived nucleic acids can trigger autoimmune reactions that may result in severe autoinflammatory disorders. Thus, cells contain several layers of protective measures to restrict transposons and to sense the enhanced activity of these "intragenomic pathogens". This review focuses on our current understanding of immunogenic patterns derived from the most active elements in humans, the retrotransposons long interspersed element (LINE)-1 and Alu. We describe the role of known pattern recognition receptors in nucleic acid sensing of LINE-1 and Alu and the possible consequences for autoimmune diseases.


Assuntos
Retroelementos , Elementos Alu , Animais , Suscetibilidade a Doenças/imunologia , Predisposição Genética para Doença , Interações Hospedeiro-Patógeno , Humanos , Elementos Nucleotídeos Longos e Dispersos
8.
Sci Rep ; 10(1): 22218, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33335252

RESUMO

Cytomegalovirus (CMV) infection is a major complication during allogeneic stem cell transplantation (allo-SCT). However, mechanisms of adaptive immunity that drive this remain unclear. To define early immunological responses to CMV after transplantation, we using next-generation sequencing to examine the repertoire of T-cell receptors in CD8+/CMV pp65 tetramer+ cells (CMV-CTLs) in peripheral blood samples obtained from 16 allo-SCT recipients with HLA-A*24:02 at the time of CMV reactivation. In most patients, TCR beta repertoire of CMV-CTLs was highly skewed (median Inverse Simpson's index: 1.595) and, 15 of 16 patients shared at least one TCR-beta clonotype with ≥ 2 patients. The shared TCRs were dominant in 12 patients and, two clonotypes were shared by about half of the patients. Similarity analysis showed that CDR3 sequences of shared TCRs were more similar than unshared TCRs. TCR beta repertoires of CMV-CTLs in 12 patients were also analyzed after 2-4 weeks to characterize the short-term dynamics of TCR repertoires. In ten patients, we observed persistence of prevailing clones. In the other two patients, TCR repertoires became more diverse, major clones declined, and new private clones subsequently emerged. These results provided the substantive clue to understand the immunological behavior against CMV reactivation after allo-SCT.


Assuntos
Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/metabolismo , Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Receptores de Antígenos de Linfócitos T/metabolismo , Especificidade do Receptor de Antígeno de Linfócitos T , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Adulto , Idoso , Biomarcadores , Evolução Clonal , Suscetibilidade a Doenças/imunologia , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/genética , Imunologia de Transplantes , Transplante Homólogo , Adulto Jovem
9.
Eur Rev Med Pharmacol Sci ; 24(21): 11409-11420, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33215463

RESUMO

OBJECTIVE: Diabetes is a lifestyle disease and it has become an epidemic worldwide in recent decades. In the ongoing COVID-19 pandemic situation, diabetes has become a serious health concern since large numbers of patients are vulnerable to die from the virus. Thus, diabetic patients affected by COVID-19 cause a major health crisis now. Reports show that large occurrence of diabetes makes it a serious comorbidity in COVID-19 patients. MATERIALS AND METHODS: It is crucial to understand how COVID-19 affects diabetes patients. This paper has reviewed published literature extensively to understand the pattern, importance, care, and medication. RESULTS: This review summarizes the association between COVID-19 and diabetes in terms of susceptibility for pneumonia and other diseases. It also discusses the harshness of COVID-19 with diabetes populations and immunological impacts. It further adds the ACE2 receptor role in diabetes with COVID-19 patients. CONCLUSIONS: Finally, this paper illustrates different types of diabetes management techniques, such as blood glucose management, self-management, mental health management, and therapeutic management. It also summarizes the current knowledge about diabetic patients with COVID-19 to fight this pandemic.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Suscetibilidade a Doenças/imunologia , Pneumonia Viral/imunologia , Betacoronavirus/metabolismo , Betacoronavirus/patogenicidade , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/imunologia , Humanos , Hipoglicemiantes/administração & dosagem , Pâncreas/patologia , Pandemias/prevenção & controle , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/metabolismo , Replicação Viral/imunologia
10.
Int J Mol Sci ; 21(17)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32883007

RESUMO

When facing an acute viral infection, our immune systems need to function with finite precision to enable the elimination of the pathogen, whilst protecting our bodies from immune-related damage. In many instances however this "perfect balance" is not achieved, factors such as ageing, cancer, autoimmunity and cardiovascular disease all skew the immune response which is then further distorted by viral infection. In SARS-CoV-2, although the vast majority of COVID-19 cases are mild, as of 24 August 2020, over 800,000 people have died, many from the severe inflammatory cytokine release resulting in extreme clinical manifestations such as acute respiratory distress syndrome (ARDS) and hemophagocytic lymphohistiocytosis (HLH). Severe complications are more common in elderly patients and patients with cardiovascular diseases. Natural killer (NK) cells play a critical role in modulating the immune response and in both of these patient groups, NK cell effector functions are blunted. Preliminary studies in COVID-19 patients with severe disease suggests a reduction in NK cell number and function, resulting in decreased clearance of infected and activated cells, and unchecked elevation of tissue-damaging inflammation markers. SARS-CoV-2 infection skews the immune response towards an overwhelmingly inflammatory phenotype. Restoration of NK cell effector functions has the potential to correct the delicate immune balance required to effectively overcome SARS-CoV-2 infection.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Suscetibilidade a Doenças/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , Células Matadoras Naturais/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Autoimunidade , Infecções por Coronavirus/metabolismo , Humanos , Imunomodulação , Células Matadoras Naturais/metabolismo , Pandemias , Pneumonia Viral/metabolismo
11.
Proc Natl Acad Sci U S A ; 117(41): 25897-25903, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-32963094

RESUMO

The rapid growth rate of COVID-19 continues to threaten to overwhelm healthcare systems in multiple countries. In response, severely affected countries have had to impose a range of public health strategies achieved via nonpharmaceutical interventions. Broadly, these strategies have fallen into two categories: 1) "mitigation," which aims to achieve herd immunity by allowing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to spread through the population while mitigating disease burden, and 2) "suppression," aiming to drastically reduce SARS-CoV-2 transmission rates and halt endogenous transmission in the target population. Using an age-structured transmission model, parameterized to simulate SARS-CoV-2 transmission in the United Kingdom, we assessed the long-term prospects of success using both of these approaches. We simulated a range of different nonpharmaceutical intervention scenarios incorporating social distancing applied to differing age groups. Our modeling confirmed that suppression of SARS-CoV-2 transmission is possible with plausible levels of social distancing over a period of months, consistent with observed trends. Notably, our modeling did not support achieving herd immunity as a practical objective, requiring an unlikely balancing of multiple poorly defined forces. Specifically, we found that 1) social distancing must initially reduce the transmission rate to within a narrow range, 2) to compensate for susceptible depletion, the extent of social distancing must be adaptive over time in a precise yet unfeasible way, and 3) social distancing must be maintained for an extended period to ensure the healthcare system is not overwhelmed.


Assuntos
Infecções por Coronavirus/transmissão , Imunidade Coletiva , Modelos Teóricos , Pneumonia Viral/transmissão , Fatores Etários , Betacoronavirus/fisiologia , Controle de Doenças Transmissíveis/métodos , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Suscetibilidade a Doenças/epidemiologia , Suscetibilidade a Doenças/imunologia , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Reino Unido/epidemiologia
12.
PLoS Negl Trop Dis ; 14(9): e0008608, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32925918

RESUMO

The receptor Signaling Lymphocyte-Activation Molecule Family 1 (SLAMF1) controls susceptibility to Infection by the lethal Trypanosoma cruzi Y strain. To elucidate whether genetic diversity of the parasite was related with disease susceptibility, we further analyzed the role of SLAMF1 using 6 different Trypanosoma cruzi strains including Y. The interaction of SLAMF1 receptor with T. cruzi was evidenced by fluorescence microscopy, flow cytometry and quantitative PCR. All the strains, except VFRA, showed a decrease in parasite load in infected macrophages in Slamf1-/- compared to BALB/c. In macrophages gene expression NADPH oxidase (NOX2), and reactive oxygen species (ROS) production increased in Slamf1-/- compared to BALB/c in 5 out of 6 strains. However, Slamf1-/-macrophages infected with VFRA strain exhibited a divergent behavior, with higher parasite load, lower NOX2 expression and ROS production compared to BALB/c. Parasitological and immunological studies in vivo with Y strain showed that in the absence of SLAMF1 the immune response protected mice from the otherwise lethal Y infection favoring a proinflammatory response likely involving CD4, CD8, dendritic cells and classically activated macrophages. In the case of VFRA, no major changes were observed in the absence of SLAMF1. Thus, the results suggest that the T. cruzi affects SLAMF1-dependent ROS production, controlling parasite replication in macrophages and affecting survival in mice in a strain-dependent manner. Further studies will focus in the identification of parasite molecules involved in SLAMF1 interaction to explain the immunopathogenesis of the disease.


Assuntos
Macrófagos/parasitologia , Espécies Reativas de Oxigênio/metabolismo , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Trypanosoma cruzi/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Doença de Chagas/imunologia , Chlorocebus aethiops , Células Dendríticas/imunologia , Suscetibilidade a Doenças/imunologia , Células HEK293 , Coração/parasitologia , Humanos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Miocárdio/patologia , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Carga Parasitária , Células Vero
13.
Front Immunol ; 11: 1582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793223

RESUMO

Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Hiperglicemia/imunologia , Síndrome Metabólica/imunologia , Obesidade/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal , Humanos , Sistema Imunitário/metabolismo , Inflamação/imunologia , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral/imunologia
14.
Rev Endocr Metab Disord ; 21(4): 451-463, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32743793

RESUMO

In light of the most challenging public health crisis of modern history, COVID-19 mortality continues to rise at an alarming rate. Patients with co-morbidities such as hypertension, cardiovascular disease, and diabetes mellitus (DM) seem to be more prone to severe symptoms and appear to have a higher mortality rate. In this review, we elucidate suggested mechanisms underlying the increased susceptibility of patients with diabetes to infection with SARS-CoV-2 with a more severe COVID-19 disease. The worsened prognosis of COVID-19 patients with DM can be attributed to a facilitated viral uptake assisted by the host's receptor angiotensin-converting enzyme 2 (ACE2). It can also be associated with a higher basal level of pro-inflammatory cytokines present in patients with diabetes, which enables a hyperinflammatory "cytokine storm" in response to the virus. This review also suggests a link between elevated levels of IL-6 and AMPK/mTOR signaling pathway and their role in exacerbating diabetes-induced complications and insulin resistance. If further studied, these findings could help identify novel therapeutic intervention strategies for patients with diabetes comorbid with COVID-19.


Assuntos
Comorbidade , Infecções por Coronavirus/imunologia , Diabetes Mellitus/imunologia , Suscetibilidade a Doenças/imunologia , Pandemias , Pneumonia Viral/imunologia , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus/epidemiologia , Suscetibilidade a Doenças/epidemiologia , Humanos , Pneumonia Viral/epidemiologia
15.
Environ Health Prev Med ; 25(1): 43, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32838734

RESUMO

BACKGROUND: World Health Organization (WHO) recommends that viral load ([VL) is a primary tool that clinicians and researchers have used to monitor patients on antiretroviral therapy (ART), an antiviral drug against retroviruses. Whereas, CD4 cell counts can only be used to monitor clinical response to ART in the absence of VL testing service. Therefore, this study is aimed to assess the level of immunological status and virological suppression, and identify associated factors among human immunodeficiency virus ([HIV)-infected adults who were taking antiretroviral drugs of combination regimen know as highly active antiretroviral therapy (HAART). METHODS: A hospital-based cross-sectional study was conducted at the University of Gondar comprehensive specialized referral hospital from February to April 2018. A total of 323 adult participants on HAART were selected using a systematic random sampling technique and enrolled into the study. Blood samples for viral load determination and CD4 cell count were collected. Binary logistic regression analysis was used to determine factors associated with immunologic status and virological suppression in HIV patients on HAART. Odds ratio with 95% CI was used to measure the strength of association. RESULTS: Virological suppression (VL level < 1000 copies/ml) was found in 82% (95% CI 77.7, 86.1) of study participants, and it has been associated with CD4 cell count between 350 and 499 cells/mm3 (adjusted odds ratio (AOR) = 2.56; 95% CI 1.14, 5.75) and > 499 cells/mm3 (AOR = 7.71; 95% CI 3.48, 17.09) at VL testing and current age > 45 years old (AOR = 5.99; 95% CI 2.12, 16.91). Similarly, favorable immunological status (≥ 400 cells/mm3 for male and ≥ 466 cells/mm3 for female) was observed in 52.9% (95% CI 47.4, 58.8) of the study participants. Baseline CD4 cell count of > 200 cells/mm3, age at enrollment of 26 through 40 years old, and urban residence were significantly associated with favorable immunological status. CONCLUSION: Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.


Assuntos
Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Contagem de Linfócito CD4 , Suscetibilidade a Doenças/imunologia , Carga Viral , Adulto , Idoso , Estudos Transversais , Etiópia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Int J Immunogenet ; 47(4): 319-323, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32654378

RESUMO

Susceptibility to viral infection, development of immunity, response to treatment and patient clinical outcomes are all under the control of heritable factors in the host. In the context of the current SARS-Cov-2 pandemic, this review considers existing immunogenetic knowledge of virus-immune system interactions. A major focus is to highlight areas in which work is required in order to improve understanding of antiviral immune responses and to move towards improved patient management.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/imunologia , Imunidade Inata/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/patologia , Suscetibilidade a Doenças/imunologia , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pandemias , Pneumonia Viral/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo
17.
Immunol Lett ; 226: 38-45, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659267

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of deadly Coronavirus disease-19 (COVID-19) pandemic, which emerged as a major threat to public health across the world. Although there is no clear gender or socioeconomic discrimination in the incidence of COVID-19, individuals who are older adults and/or with comorbidities and compromised immunity have a relatively higher risk of contracting this disease. Since no specific drug has yet been discovered, strengthening immunity along with maintaining a healthy living is the best way to survive this disease. As a healthy practice, calorie restriction in the form of intermittent fasting (IF) in several clinical settings has been reported to promote several health benefits, including priming of the immune response. This dietary restriction also activates autophagy, a cell surveillance system that boosts up immunity. With these prevailing significance in priming host defense, IF could be a potential strategy amid this outbreak to fighting off SARS-CoV-2 infection. Currently, no review so far available proposing IF as an encouraging strategy in the prevention of COVID-19. A comprehensive review has therefore been planned to highlight the beneficial role of fasting in immunity and autophagy, that underlie the possible defense against SARS-CoV-2 infection. The COVID-19 pathogenesis and its impact on host immune response have also been briefly outlined. This review aimed at revisiting the immunomodulatory potential of IF that may constitute a promising preventive approach against COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/metabolismo , Suscetibilidade a Doenças , Jejum , Interações Hospedeiro-Patógeno , Pneumonia Viral/etiologia , Pneumonia Viral/metabolismo , Autofagia , Restrição Calórica , Resistência à Doença/imunologia , Suscetibilidade a Doenças/imunologia , Jejum/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Evasão da Resposta Imune , Imunidade , Pandemias
18.
Vaccine ; 38(35): 5564-5568, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32654907

RESUMO

COVID-19 is affecting different countries all over the world with great variation in infection rate and death ratio. Some reports suggested a relation between the Bacillus Calmette-Guérin (BCG) vaccine and the malaria treatment to the prevention of SARS-CoV-2 infection. Some reports related infant's lower susceptibility to the COVID-19. Some other reports a higher risk in males compared to females in such COVID-19 pandemic. Also, some other reports claimed the possible use of chloroquine and hydroxychloroquine as prophylactic in such a pandemic. The present commentary is to discuss the possible relation between those factors and SARS-CoV-2 infection.


Assuntos
Envelhecimento , Vacina BCG/imunologia , Quimioprevenção , Cloroquina/farmacologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/prevenção & controle , Hidroxicloroquina/farmacologia , Pandemias/prevenção & controle , Pneumonia Viral/mortalidade , Pneumonia Viral/prevenção & controle , Caracteres Sexuais , Antivirais/farmacologia , Antivirais/uso terapêutico , Cloroquina/uso terapêutico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Suscetibilidade a Doenças/imunologia , Feminino , Mapeamento Geográfico , Humanos , Hidroxicloroquina/uso terapêutico , Lactente , Internacionalidade , Masculino , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão
19.
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
20.
Int J Dermatol ; 59(9): 1043-1056, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32621284

RESUMO

Recommendations were made recently to limit or stop the use of oral and systemic immunotherapies for skin diseases due to potential risks to the patients during the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic. Herein, we attempt to identify potentially safe immunotherapies that may be used in the treatment of cutaneous diseases during the current COVID-19 pandemic. We performed a literature review to approximate the risk of SARS-CoV-2 infection, including available data on the roles of relevant cytokines, cell subsets, and their mediators in eliciting an optimal immune response against respiratory viruses in murine gene deletion models and humans with congenital deficiencies were reviewed for viral infections risk and if possible coronaviruses specifically. Furthermore, reported risk of infections of biologic and non-biologic therapeutics for skin diseases from clinical trials and drug data registries were evaluated. Many of the immunotherapies used in dermatology have data to support their safe use during the COVID-19 pandemic including the biologics that target IgE, IL-4/13, TNF-α, IL-17, IL-12, and IL-23. Furthermore, we provide evidence to show that oral immunosuppressive medications such as methotrexate and cyclosporine do not significantly increase the risk to patients. Most biologic and conventional immunotherapies, based on doses and indications in dermatology, do not appear to increase risk of viral susceptibility and are most likely safe for use during the COVID-19 pandemic. The limitation of this study is availability of data on COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/imunologia , Fármacos Dermatológicos/efeitos adversos , Suscetibilidade a Doenças/induzido quimicamente , Pneumonia Viral/epidemiologia , Dermatopatias/tratamento farmacológico , Animais , Betacoronavirus/imunologia , Produtos Biológicos/efeitos adversos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/virologia , Dermatologia/métodos , Dermatologia/estatística & dados numéricos , Modelos Animais de Doenças , Suscetibilidade a Doenças/imunologia , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/estatística & dados numéricos , Humanos , Fatores Imunológicos/efeitos adversos , Camundongos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Índice de Gravidade de Doença , Dermatopatias/imunologia
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