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1.
Front Immunol ; 11: 565278, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013929

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an outbreak of a pandemic worldwide. For better understanding the viral spike (S) protein variations and its potential effects on the interaction with the host immune system and also in vaccine development, the cell epitopes, glycosylation profile and their changes during the global transmission course were characterized and compared with SARS-CoV for their glycosylation profile. We analyzed totally 7,813 sequences screened from 8,897 whole genome sequences on GISAID database up to April 26, and 18 S protein amino acid variations with relatively high frequency (≥10-3) were identified. A total of 228 sequences of variants had multiple variations, of note, most of them harboring the D614G mutation. Among the predicted 69 linear B cell epitopes, 175 discontinuous B cell epitopes and 41 cytotoxic T lymphocyte epitopes in the viral S protein, we found that the protein structure and its potential function of some sites changed, such as the linear epitope length shortened and discontinuous epitope disappeared of G476S. In addition, we detected 9 predicted N-glycosylation sites and 3 O-glycosylation sites unique to SARS-CoV-2, but no evidently observed variation of the glycan sites so far. Our findings provided an important snapshot of temporal and geographical distributions on SARS-CoV-2 S protein cell epitopes and glycosylation sites, which would be an essential basis for the selection of vaccine candidates.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Sequência de Aminoácidos , Infecções por Coronavirus/virologia , Genoma Viral/genética , Glicosilação , Interações Hospedeiro-Patógeno/imunologia , Humanos , Glicoproteínas de Membrana/imunologia , Pandemias , Pneumonia Viral/virologia , Conformação Proteica , Glicoproteína da Espícula de Coronavírus/química , Sequenciamento Completo do Genoma
2.
Signal Transduct Target Ther ; 5(1): 221, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024073
3.
Front Immunol ; 11: 565278, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-796802

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an outbreak of a pandemic worldwide. For better understanding the viral spike (S) protein variations and its potential effects on the interaction with the host immune system and also in vaccine development, the cell epitopes, glycosylation profile and their changes during the global transmission course were characterized and compared with SARS-CoV for their glycosylation profile. We analyzed totally 7,813 sequences screened from 8,897 whole genome sequences on GISAID database up to April 26, and 18 S protein amino acid variations with relatively high frequency (≥10-3) were identified. A total of 228 sequences of variants had multiple variations, of note, most of them harboring the D614G mutation. Among the predicted 69 linear B cell epitopes, 175 discontinuous B cell epitopes and 41 cytotoxic T lymphocyte epitopes in the viral S protein, we found that the protein structure and its potential function of some sites changed, such as the linear epitope length shortened and discontinuous epitope disappeared of G476S. In addition, we detected 9 predicted N-glycosylation sites and 3 O-glycosylation sites unique to SARS-CoV-2, but no evidently observed variation of the glycan sites so far. Our findings provided an important snapshot of temporal and geographical distributions on SARS-CoV-2 S protein cell epitopes and glycosylation sites, which would be an essential basis for the selection of vaccine candidates.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Sequência de Aminoácidos , Infecções por Coronavirus/virologia , Genoma Viral/genética , Glicosilação , Interações Hospedeiro-Patógeno/imunologia , Humanos , Glicoproteínas de Membrana/imunologia , Pandemias , Pneumonia Viral/virologia , Conformação Proteica , Glicoproteína da Espícula de Coronavírus/química , Sequenciamento Completo do Genoma
4.
Signal Transduct Target Ther ; 5(1): 221, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: covidwho-834864
5.
Signal Transduct Target Ther ; 5(1): 186, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883951

RESUMO

Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus or bacteria, but its association with diminished cholesterol levels in COVID-19 patients is unknown. Here, we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19. Intriguingly, we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients' blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity. We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression, while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients. Using an infectious disease mouse model, inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages. These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.


Assuntos
Betacoronavirus/patogenicidade , Colesterol/biossíntese , Infecções por Coronavirus/genética , Síndrome da Liberação de Citocina/genética , Interações Hospedeiro-Patógeno/genética , Leucócitos Mononucleares/imunologia , Pneumonia Viral/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Betacoronavirus/imunologia , Estudos de Casos e Controles , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Regulação da Expressão Gênica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Unidades de Terapia Intensiva , Interleucina-1beta/genética , Interleucina-1beta/imunologia , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/imunologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/virologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/virologia , NF-kappa B/genética , NF-kappa B/imunologia , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Cultura Primária de Células , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/imunologia , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 2/imunologia , Análise de Sobrevida , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
6.
Nat Commun ; 11(1): 4382, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873802

RESUMO

Fusarium graminearum is a causal agent of Fusarium head blight (FHB) and a deoxynivalenol (DON) producer. In this study, OSP24 is identified as an important virulence factor in systematic characterization of the 50 orphan secreted protein (OSP) genes of F. graminearum. Although dispensable for growth and initial penetration, OSP24 is important for infectious growth in wheat rachis tissues. OSP24 is specifically expressed during pathogenesis and its transient expression suppresses BAX- or INF1-induced cell death. Osp24 is translocated into plant cells and two of its 8 cysteine-residues are required for its function. Wheat SNF1-related kinase TaSnRK1α is identified as an Osp24-interacting protein and shows to be important for FHB resistance in TaSnRK1α-overexpressing or silencing transgenic plants. Osp24 accelerates the degradation of TaSnRK1α by facilitating its association with the ubiquitin-26S proteasome. Interestingly, TaSnRK1α also interacts with TaFROG, an orphan wheat protein induced by DON. TaFROG competes against Osp24 for binding with the same region of TaSnRKα and protects it from degradation. Overexpression of TaFROG stabilizes TaSnRK1α and increases FHB resistance. Taken together, Osp24 functions as a cytoplasmic effector by competing against TaFROG for binding with TaSnRK1α, demonstrating the counteracting roles of orphan proteins of both host and fungal pathogens during their interactions.


Assuntos
Proteínas Fúngicas/metabolismo , Fusarium/patogenicidade , Doenças das Plantas/imunologia , Proteínas de Plantas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Triticum/microbiologia , Fatores de Virulência/metabolismo , Resistência à Doença , Fusarium/imunologia , Fusarium/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Plantas Geneticamente Modificadas , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/imunologia , Proteólise , Tricotecenos/metabolismo , Triticum/imunologia
7.
Front Immunol ; 11: 2069, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32973815

RESUMO

COVID-19 disease have become so far the most important sanitary crisis in the XXI century. In light of the events, any clinical resource should be considered to alleviate this crisis. Severe COVID-19 cases present a so-called cytokine storm as the most life-threatening symptom accompanied by lung fibrosis. Galectin-3 has been widely described as regulator of both processes. Hereby, we present compelling evidences on the potential role of galectin-3 in COVID-19 in the regulation of the inflammatory response, fibrosis and infection progression. Moreover, we provide a strong rationale of the utility of measuring plasma galectin-3 as a prognosis biomarker for COVID-19 patients and propose that inhibition of galectin-3 represents a feasible and promising new therapeutical approach.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Galectina 3/antagonistas & inibidores , Galectina 3/sangue , Terapia de Alvo Molecular/métodos , Pneumonia Viral/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , Índice de Gravidade de Doença , Animais , Betacoronavirus/química , Biomarcadores/sangue , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Progressão da Doença , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Prognóstico , Fibrose Pulmonar/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
8.
Front Immunol ; 11: 2037, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983152

RESUMO

Coronaviruses were first discovered in the 1960s and are named due to their crown-like shape. Sometimes, but not often, a coronavirus can infect both animals and humans. An acute respiratory disease, caused by a novel coronavirus (severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2 previously known as 2019-nCoV) was identified as the cause of coronavirus disease 2019 (COVID-19) as it spread throughout China and subsequently across the globe. As of 14th July 2020, a total of 13.1 million confirmed cases globally and 572,426 deaths had been reported by the World Health Organization (WHO). SARS-CoV-2 belongs to the ß-coronavirus family and shares extensive genomic identity with bat coronavirus suggesting that bats are the natural host. SARS-CoV-2 uses the same receptor, angiotensin-converting enzyme 2 (ACE2), as that for SARS-CoV, the coronavirus associated with the SARS outbreak in 2003. It mainly spreads through the respiratory tract with lymphopenia and cytokine storms occuring in the blood of subjects with severe disease. This suggests the existence of immunological dysregulation as an accompanying event during severe illness caused by this virus. The early recognition of this immunological phenotype could assist prompt recognition of patients who will progress to severe disease. Here we review the data of the immune response during COVID-19 infection. The current review summarizes our understanding of how immune dysregulation and altered cytokine networks contribute to the pathophysiology of COVID-19 patients.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Animais , Quirópteros/virologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interleucina-6/sangue , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/metabolismo
9.
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
11.
Cell Mol Immunol ; 17(10): 1095-1097, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32895485
12.
Proc Natl Acad Sci U S A ; 117(40): 24620-24626, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32883878

RESUMO

The reduced development of COVID-19 for children compared to adults provides some tantalizing clues on the pathogenesis and transmissibility of this pandemic virus. First, ACE2, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor, is reduced in the respiratory tract in children. Second, coronavirus associated with common colds in children may offer some protection, due to cross-reactive humoral immunity and T cell immunity between common coronaviruses and SARS-CoV-2. Third, T helper 2 immune responses are protective in children. Fourth, surprisingly, eosinophilia, associated with T helper 2, may be protective. Fifth, children generally produce lower levels of inflammatory cytokines. Finally, the influence of the downturn in the global economy, the impact of living in quarters among families who are the most at risk, and factors including the openings of some schools, are considered. Those most disadvantaged socioeconomically may suffer disproportionately with COVID-19.


Assuntos
Betacoronavirus/metabolismo , Infecções por Coronavirus/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Mucosa Respiratória/metabolismo , Infecções Respiratórias/imunologia , Criança , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Infecções Respiratórias/virologia , Células Th2/fisiologia
13.
Int J Mol Sci ; 21(18)2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32933166

RESUMO

The glycans on enveloped viruses are synthesized by host-cell machinery. Some of these glycans on zoonotic viruses of mammalian reservoirs are recognized by human natural antibodies that may protect against such viruses. These antibodies are produced mostly against carbohydrate antigens on gastrointestinal bacteria and fortuitously, they bind to carbohydrate antigens synthesized in other mammals, neutralize and destroy viruses presenting these antigens. Two such antibodies are: anti-Gal binding to α-gal epitopes synthesized in non-primate mammals, lemurs, and New World monkeys, and anti-N-glycolyl neuraminic acid (anti-Neu5Gc) binding to N-glycolyl-neuraminic acid (Neu5Gc) synthesized in apes, Old World monkeys, and many non-primate mammals. Anti-Gal appeared in Old World primates following accidental inactivation of the α1,3galactosyltransferase gene 20-30 million years ago. Anti-Neu5Gc appeared in hominins following the inactivation of the cytidine-monophosphate-N-acetyl-neuraminic acid hydroxylase gene, which led to the loss of Neu5Gc <6 million-years-ago. It is suggested that an epidemic of a lethal virus eliminated ancestral Old World-primates synthesizing α-gal epitopes, whereas few mutated offspring lacking α-gal epitopes and producing anti-Gal survived because anti-Gal destroyed viruses presenting α-gal epitopes, following replication in parental populations. Similarly, anti-Neu5Gc protected few mutated hominins lacking Neu5Gc in lethal virus epidemics that eliminated parental hominins synthesizing Neu5Gc. Since α-gal epitopes are presented on many zoonotic viruses it is suggested that vaccines elevating anti-Gal titers may be of protective significance in areas endemic for such zoonotic viruses. This protection would be during the non-primate mammal to human virus transmission, but not in subsequent human to human transmission where the virus presents human glycans. In addition, production of viral vaccines presenting multiple α-gal epitopes increases their immunogenicity because of effective anti-Gal-mediated targeting of vaccines to antigen presenting cells for extensive uptake of the vaccine by these cells.


Assuntos
Antígenos Virais/imunologia , Glicoproteínas/imunologia , Viroses/imunologia , Animais , Reações Antígeno-Anticorpo , Evolução Molecular , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Primatas
14.
Emerg Microbes Infect ; 9(1): 2190-2199, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32940572

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Avaliação de Resultados da Assistência ao Paciente , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Especificidade de Órgãos , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Fatores de Tempo
15.
Proc Natl Acad Sci U S A ; 117(40): 25018-25025, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32943538

RESUMO

Respiratory failure in the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is hypothesized to be driven by an overreacting innate immune response, where the complement system is a key player. In this prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, we describe systemic complement activation and its association with development of respiratory failure. Clinical data and biological samples were obtained at admission, days 3 to 5, and days 7 to 10. Respiratory failure was defined as PO2/FiO2 ratio of ≤40 kPa. Complement activation products covering the classical/lectin (C4d), alternative (C3bBbP) and common pathway (C3bc, C5a, and sC5b-9), the lectin pathway recognition molecule MBL, and antibody serology were analyzed by enzyme-immunoassays; viral load by PCR. Controls comprised healthy blood donors. Consistently increased systemic complement activation was observed in the majority of COVID-19 patients during hospital stay. At admission, sC5b-9 and C4d were significantly higher in patients with than without respiratory failure (P = 0.008 and P = 0.034). Logistic regression showed increasing odds of respiratory failure with sC5b-9 (odds ratio 31.9, 95% CI 1.4 to 746, P = 0.03) and need for oxygen therapy with C4d (11.7, 1.1 to 130, P = 0.045). Admission sC5b-9 and C4d correlated significantly to ferritin (r = 0.64, P < 0.001; r = 0.69, P < 0.001). C4d, sC5b-9, and C5a correlated with antiviral antibodies, but not with viral load. Systemic complement activation is associated with respiratory failure in COVID-19 patients and provides a rationale for investigating complement inhibitors in future clinical trials.


Assuntos
Betacoronavirus/imunologia , Ativação do Complemento , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Insuficiência Respiratória/imunologia , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Feminino , Interações Hospedeiro-Patógeno/imunologia , Humanos , Masculino , Lectina de Ligação a Manose/sangue , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Insuficiência Respiratória/virologia , Carga Viral
16.
J Neurovirol ; 26(5): 631-641, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32876900

RESUMO

A subset of patients with coronavirus 2 disease (COVID-19) experience neurological complications. These complications include loss of sense of taste and smell, stroke, delirium, and neuromuscular signs and symptoms. The etiological agent of COVID-19 is SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), an RNA virus with a glycoprotein-studded viral envelope that uses ACE2 (angiotensin-converting enzyme 2) as a functional receptor for infecting the host cells. Thus, the interaction of the envelope spike proteins with ACE2 on host cells determines the tropism and virulence of SARS-CoV-2. Loss of sense of taste and smell is an initial symptom of COVID-19 because the virus enters the nasal and oral cavities first and the epithelial cells are the receptors for these senses. Stroke in COVID-19 patients is likely a consequence of coagulopathy and injury to cerebral vascular endothelial cells that cause thrombo-embolism and stroke. Delirium and encephalopathy in acute and post COVID-19 patients are likely multifactorial and secondary to hypoxia, metabolic abnormalities, and immunological abnormalities. Thus far, there is no clear evidence that coronaviruses cause inflammatory neuromuscular diseases via direct invasion of peripheral nerves or muscles or via molecular mimicry. It appears that most of neurologic complications in COVID-19 patients are indirect and as a result of a bystander injury to neurons.


Assuntos
Betacoronavirus/patogenicidade , Encefalopatias/complicações , Infecções por Coronavirus/complicações , Transtornos do Olfato/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Acidente Vascular Cerebral/complicações , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/virologia , Encefalopatias/imunologia , Encefalopatias/patologia , Encefalopatias/virologia , Efeito Espectador , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/virologia , Neurônios/patologia , Neurônios/virologia , Transtornos do Olfato/imunologia , Transtornos do Olfato/patologia , Transtornos do Olfato/virologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Embolia Pulmonar/imunologia , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/virologia
17.
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
18.
J Neurovirol ; 26(5): 631-641, 2020 10.
Artigo em Inglês | MEDLINE | ID: covidwho-739689

RESUMO

A subset of patients with coronavirus 2 disease (COVID-19) experience neurological complications. These complications include loss of sense of taste and smell, stroke, delirium, and neuromuscular signs and symptoms. The etiological agent of COVID-19 is SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), an RNA virus with a glycoprotein-studded viral envelope that uses ACE2 (angiotensin-converting enzyme 2) as a functional receptor for infecting the host cells. Thus, the interaction of the envelope spike proteins with ACE2 on host cells determines the tropism and virulence of SARS-CoV-2. Loss of sense of taste and smell is an initial symptom of COVID-19 because the virus enters the nasal and oral cavities first and the epithelial cells are the receptors for these senses. Stroke in COVID-19 patients is likely a consequence of coagulopathy and injury to cerebral vascular endothelial cells that cause thrombo-embolism and stroke. Delirium and encephalopathy in acute and post COVID-19 patients are likely multifactorial and secondary to hypoxia, metabolic abnormalities, and immunological abnormalities. Thus far, there is no clear evidence that coronaviruses cause inflammatory neuromuscular diseases via direct invasion of peripheral nerves or muscles or via molecular mimicry. It appears that most of neurologic complications in COVID-19 patients are indirect and as a result of a bystander injury to neurons.


Assuntos
Betacoronavirus/patogenicidade , Encefalopatias/complicações , Infecções por Coronavirus/complicações , Transtornos do Olfato/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Acidente Vascular Cerebral/complicações , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/virologia , Encefalopatias/imunologia , Encefalopatias/patologia , Encefalopatias/virologia , Efeito Espectador , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/virologia , Neurônios/patologia , Neurônios/virologia , Transtornos do Olfato/imunologia , Transtornos do Olfato/patologia , Transtornos do Olfato/virologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Embolia Pulmonar/imunologia , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/virologia
19.
Front Immunol ; 11: 2147, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-776207

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
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