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1.
J Diabetes Res ; 2020: 8205261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134395

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues to cause havoc to many countries of the globe, with no end in sight, due to nonavailability of a given vaccine or treatment regimen. The pandemic has so far had a relatively limited impact on the African continent, which contributes more than 93% of global malaria burden. However, the limited burden of COVID-19 pandemic on the African region could have long-term implications on the health and wellbeing of affected inhabitants due to its malaria-endemic status. Malaria causes recurrent insulin resistance with episodes of infection at relatively low parasitaemia. Angiotensin-converting enzyme 2 (ACE2) which is widely distributed in the human body is implicated in the pathogenesis of malaria, type 2 diabetes mellitus (T2DM), and COVID-19. Use of ACE2 by the COVID-19 virus induces inflammation and oxidative stress, which can lead to insulin resistance. Although COVID-19 patients in malaria-endemic African region may not exhibit severe signs and symptoms of the disease, their risk of exhibiting heightened insulin resistance and possible future development of T2DM is high due to their prior exposure to malaria. African governments must double efforts at containing the continued spread of the virus without neglecting existing malarial control measures if the region is to avert the plausible long-term impact of the pandemic in terms of future development of T2DM.


Assuntos
Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Doenças Endêmicas , Malária/epidemiologia , Pneumonia Viral/epidemiologia , África/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Humanos , Resistência à Insulina/fisiologia , Malária/complicações , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/patologia , Estado Pré-Diabético/virologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
2.
Biomed Pharmacother ; 131: 110748, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152916

RESUMO

The severe form of COVID-19 has significant sex disparities, with high fatalities commonly reported among males than females. The incidence of COVID-19 has also been higher in males compared with their female counterparts. This trend could be attributed to a better responsive and robust immune system in females. Cytokine storm is one of the pathophysiological features of severe COVID-19, and it occurs as a result of over-activation of immune cells leading to severe inflammation and tissue damage. Nevertheless, it is well modulated in females compared to their male counterparts. Severe inflammation in males is reported to facilitate progression of mild to severe COVID-19. The sex hormones, estrogens and androgens which exist in varying functional levels respectively in females and males are cited as the underlying cause for the differential immune response to COVID-19. Evidence abounds that estrogen modulate the immune system to protect females from severe inflammation and for that matter severe COVID-19. On the contrary, androgen has been implicated in over-activation of immune cells, cytokine storm and the attendant severe inflammation, which perhaps predispose males to severe COVID-19. In this review efforts are made to expand understanding and explain the possible roles of the immune system, the sex hormones and the angiotensin-converting enzyme (ACE) systems in male bias to severe COVID-19. Also, this review explores possible therapeutic avenues including androgen deprivation therapy (ADT), estrogen-based therapy, and ACE inhibitors for consideration in the fight against COVID-19.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Criança , Pré-Escolar , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Suscetibilidade a Doenças , Feminino , Hormônios Esteroides Gonadais/fisiologia , Humanos , Imunidade Inata , Lactente , Recém-Nascido , Inflamação , Masculino , Camundongos , Pessoa de Meia-Idade , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Isomerases de Dissulfetos de Proteínas/fisiologia , Receptores de Superfície Celular/fisiologia , Receptores Virais/fisiologia , Distribuição por Sexo , Fumar/efeitos adversos , Adulto Jovem
4.
Radiographics ; 40(6): 1574-1599, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33001783

RESUMO

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in coronavirus disease 2019 (COVID-19), which was declared an official pandemic by the World Health Organization on March 11, 2020. The infection has been reported in most countries around the world. As of August 2020, there have been over 21 million cases of COVID-19 reported worldwide, with over 800 000 COVID-19-associated deaths. It has become apparent that although COVID-19 predominantly affects the respiratory system, many other organ systems can also be involved. Imaging plays an essential role in the diagnosis of all manifestations of the disease, as well as its related complications, and proper utilization and interpretation of imaging examinations is crucial. With the growing global COVID-19 outbreak, a comprehensive understanding of the diagnostic imaging hallmarks, imaging features, multisystemic involvement, and evolution of imaging findings is essential for effective patient management and treatment. To date, only a few articles have been published that comprehensively describe the multisystemic imaging manifestations of COVID-19. The authors provide an inclusive system-by-system image-based review of this life-threatening and rapidly spreading infection. In part 1 of this article, the authors discuss general aspects of the disease, with an emphasis on virology, the pathophysiology of the virus, and clinical presentation of the disease. The key imaging features of the varied pathologic manifestations of this infection that involve the pulmonary and peripheral and central vascular systems are also described. Part 2 will focus on key imaging features of COVID-19 that involve the cardiac, neurologic, abdominal, dermatologic and ocular, and musculoskeletal systems, as well as pediatric and pregnancy-related manifestations of the virus. Vascular complications pertinent to each system will be also be discussed in part 2. Online supplemental material is available for this article. ©RSNA, 2020.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pandemias , Pneumonia Viral/diagnóstico por imagem , Tromboembolia/diagnóstico por imagem , Trombose/diagnóstico por imagem , Angiografia/métodos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Progressão da Doença , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Inflamação , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Artéria Pulmonar/diagnóstico por imagem , Receptores Virais/fisiologia , Síndrome do Desconforto Respiratório do Adulto/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Adulto/etiologia , Avaliação de Sintomas , Tromboembolia/sangue , Tromboembolia/etiologia , Trombose/sangue , Trombose/etiologia , Microangiopatias Trombóticas/diagnóstico por imagem , Microangiopatias Trombóticas/etiologia , Tomografia Computadorizada por Raios X/métodos , Ultrassonografia/métodos
5.
J Chin Med Assoc ; 83(10): 895-897, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33009240

RESUMO

An outbreak of pneumonia associated with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, China, in December 2019, and has been spread worldwide rapidly now. Over 5.3-million confirmed cases and 340,000 disease-associated deaths have been found till May 25, 2020. The potential pathophysiology for SARS-CoV-2 to affect the target is via the receptor, angiotensin-converting enzyme 2 (ACE2). ACE2 can be found in the respiratory, cardiovascular, gastrointestinal tract, urinary tract, and reproductive organs such as human ovaries and Leydig cells in the testis. This receptor plays a dominant role in the fertility function. Considering the crucial roles of testicular cells of the male reproductive system, increasing numbers of studies focus on the effects of SARS-CoV-2 on the testis. In this literature, we reviewed several studies to evaluate the relevance between SARS-CoV-2, ACE receptor, and female and male reproductive system and found that the risk of being attacked by SARS-CoV-2 is higher in males than in females. Since men infected with SARS-CoV-2 virus may have the risk of impaired reproductive performance, such as the orchitis and an elevated of luteinizing hormone (LH), and additionally, SARS-CoV-2 virus may be found in semen, although the latter is still debated, all suggest that we should pay much attention to sexual transmitted disease and male fertility after recovering from COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Genitália/virologia , Pneumonia Viral/complicações , Feminino , Fertilidade , Humanos , Masculino , Pandemias , Peptidil Dipeptidase A/fisiologia , Caracteres Sexuais
6.
PLoS One ; 15(10): e0240647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112891

RESUMO

The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 mRNA than any other organ. By immunohistochemistry, duodenum, kidney and testis showed strong signals, whereas the signal was weak in the respiratory tract. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2-expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2. These include several interferon-stimulated response elements sites for STAT1, IRF8, and IRF9. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.


Assuntos
Betacoronavirus/fisiologia , Biologia Computacional , Infecções por Coronavirus/virologia , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/virologia , Receptores Virais/fisiologia , Envelhecimento/metabolismo , Sítios de Ligação , Proteínas de Transporte/biossíntese , Proteínas de Transporte/genética , Feminino , Regulação Enzimológica da Expressão Gênica , Ontologia Genética , Humanos , Interferons/fisiologia , Pulmão/metabolismo , Masculino , Metaloproteases/biossíntese , Metaloproteases/genética , Neovascularização Fisiológica/fisiologia , Especificidade de Órgãos , Peptidil Dipeptidase A/biossíntese , Peptidil Dipeptidase A/genética , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , Receptores Virais/biossíntese , Receptores Virais/genética , Sistema Renina-Angiotensina/fisiologia , Caracteres Sexuais , Análise de Célula Única , Fatores de Transcrição/metabolismo , Sítio de Iniciação de Transcrição , Ligação Viral
7.
J Chin Med Assoc ; 83(9): 812-816, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32902940

RESUMO

The 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) is a pandemic disease worldwide. The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is continuing at a rapid speed. Till May 4, 2020, there have been 3,407,747 confirmed cases and 238,198 deaths globally. The common symptoms in pregnant women are fever, cough, and dyspnea. Angiotensin-converting enzyme 2 (ACE2) has transient overexpression and increased activity during pregnancy, which is now confirmed as the receptor of SARS-CoV-2 and plays essential roles in human infection and transmission. There is no evidence that pregnant women are more susceptible to SARS-CoV-2. To date, there is no valid medication or vaccination. The immune suppression or modulation during pregnancy increases the risk of severe pneumonia. Remdesivir is an antiviral medication targeting ribonucleic acid (RNA) synthesis that has clinical improvement in the treatment of SARS-CoV-2. Chloroquine is controversial in its effectiveness and safety to treat SARS-CoV-2. Remdesivir is safe in pregnancy. Chloroquine has not been formally assigned to a pregnancy category by the Food and Drug Administration (FDA). The management strategy includes monitoring fetal heart rate and uterine contractions; early oxygenation if O2 saturation is less than 95%; empiric antibiotics for prevention of secondary infection; corticosteroid to treat maternal SARS-CoV-2 disease routinely is not suggested, only for fetal lung maturation in selected cases; and consideration of delivery is according to the obstetric indication, gestational age, and severity of the disease. During epidemics, delivery at 32-34 weeks is considered. The indication for the Cesarean section should be flexible to minimize the risk of infection during the delivery. The newborn should be in isolation ward immediately after birth; breastfeeding is not contraindicated but should avoid direct transmission infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Recém-Nascido , Pandemias , Pneumonia Viral/epidemiologia , Gravidez , Sistema Renina-Angiotensina/fisiologia
8.
Comput Math Methods Med ; 2020: 1352982, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32908574

RESUMO

The current emergence of coronavirus (SARS-CoV-2) puts the world in threat. The structural research on the receptor recognition by SARS-CoV-2 has identified the key interactions between SARS-CoV-2 spike protein and its host (epithelial cell) receptor, also known as angiotensin-converting enzyme 2 (ACE2). It controls both the cross-species and human-to-human transmissions of SARS-CoV-2. In view of this, we propose and analyze a mathematical model for investigating the effect of CTL responses over the viral mutation to control the viral infection when a postinfection immunostimulant drug (pidotimod) is administered at regular intervals. Dynamics of the system with and without impulses have been analyzed using the basic reproduction number. This study shows that the proper dosing interval and drug dose both are important to eradicate the viral infection.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Modelos Biológicos , Pneumonia Viral/tratamento farmacológico , Ácido Pirrolidonocarboxílico/análogos & derivados , Tiazolidinas/administração & dosagem , Número Básico de Reprodução , Betacoronavirus/genética , Betacoronavirus/imunologia , Simulação por Computador , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Relação Dose-Resposta a Droga , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Conceitos Matemáticos , Mutação , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Ácido Pirrolidonocarboxílico/administração & dosagem , Receptores Virais/fisiologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Linfócitos T Citotóxicos/imunologia
10.
Biomolecules ; 10(9)2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32933047

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face a microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (severe acute respiratory syndrome (SARS-CoV) and middle east respiratory syndrome (MERS-CoV)) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summarize the possible and logical answers to these questions.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/transmissão , Coronavirus/patogenicidade , Pandemias , Pneumonia Viral/transmissão , Fatores Etários , Animais , Betacoronavirus/genética , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Surtos de Doenças , Reservatórios de Doenças/virologia , Feminino , Saúde Global , Especificidade de Hospedeiro , Interações Hospedeiro-Patógeno , Humanos , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Especificidade de Órgãos , Peptídeo Hidrolases/fisiologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Receptores Virais/fisiologia , Fatores de Risco , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/epidemiologia , Proteínas Virais/fisiologia , Tropismo Viral , Virulência , Internalização do Vírus
11.
Mol Neurobiol ; 57(12): 5263-5275, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32869183

RESUMO

Similar to its predecessors, coronavirus disease 2019 (COVID-19) exhibits neurotrophic properties, which lead to progression of neurologic sequelae. Besides direct viral invasion to the central nervous system (CNS), indirect CNS involvement through viral-mediated immune response is plausible. Aberrant immune pathways such as extreme release of cytokines (cytokine storm), autoimmunity mediated by cross-reactivity between CNS components and viral particles, and microglial activation propagate CNS damage in these patients. Here, we review the currently available evidence to discuss the plausible immunologic pathways that may contribute to the development of COVID-19 neurological complications, namely Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, Guillain-Barre syndrome, seizure, and brainstem involvement.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Doenças do Sistema Nervoso/etiologia , Pandemias , Pneumonia Viral/complicações , Animais , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Tronco Encefálico/fisiopatologia , Tronco Encefálico/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Efeito Citopatogênico Viral , Surtos de Doenças , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/imunologia , Humanos , Camundongos , Esclerose Múltipla/etiologia , Esclerose Múltipla/imunologia , Proteínas do Tecido Nervoso/fisiologia , Doenças do Sistema Nervoso/imunologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/imunologia , Neuroglia/patologia , Neuroglia/virologia , Neurônios/patologia , Neurônios/virologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/imunologia , Receptores Virais/fisiologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , Convulsões/etiologia , Convulsões/imunologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/imunologia
12.
Viruses ; 12(9)2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32911874

RESUMO

Since the global outbreak of SARS-CoV-2 (COVID-19), infections of diverse human organs along with multiple symptoms continue to be reported. However, the susceptibility of the brain to SARS-CoV-2, and the mechanisms underlying neurological infection are still elusive. Here, we utilized human embryonic stem cell-derived brain organoids and monolayer cortical neurons to investigate infection of brain with pseudotyped SARS-CoV-2 viral particles. Spike-containing SARS-CoV-2 pseudovirus infected neural layers within brain organoids. The expression of ACE2, a host cell receptor for SARS-CoV-2, was sustained during the development of brain organoids, especially in the somas of mature neurons, while remaining rare in neural stem cells. However, pseudotyped SARS-CoV-2 was observed in the axon of neurons, which lack ACE2. Neural infectivity of SARS-CoV-2 pseudovirus did not increase in proportion to viral load, but only 10% of neurons were infected. Our findings demonstrate that brain organoids provide a useful model for investigating SARS-CoV-2 entry into the human brain and elucidating the susceptibility of the brain to SARS-CoV-2.


Assuntos
Betacoronavirus/fisiologia , Neurônios/virologia , Organoides/virologia , Prosencéfalo/virologia , Glicoproteína da Espícula de Coronavírus/fisiologia , Axônios/enzimologia , Diferenciação Celular , Células Cultivadas , Córtex Cerebral/citologia , Células-Tronco Embrionárias/virologia , Células HEK293 , Humanos , Proteínas do Tecido Nervoso/fisiologia , Células-Tronco Neurais/enzimologia , Células-Tronco Neurais/virologia , Neurônios/enzimologia , Peptidil Dipeptidase A/fisiologia , Prosencéfalo/citologia , Receptores Virais/fisiologia , Carga Viral , Tropismo Viral , Internalização do Vírus
13.
Adv Rheumatol ; 60(1): 50, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962761

RESUMO

The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself.Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena.Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Pneumonia Viral/imunologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Fatores Etários , Animais , Formação de Anticorpos , Betacoronavirus/patogenicidade , Transtornos da Coagulação Sanguínea/etiologia , Comorbidade , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Humanos , Imunidade Inata , Inflamação/imunologia , Pulmão/patologia , Linfopenia/imunologia , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Fatores de Risco , Síndrome Respiratória Aguda Grave/imunologia , Índice de Gravidade de Doença , Fatores Sexuais , Internalização do Vírus
14.
Curr Hypertens Rep ; 22(9): 62, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32852624

RESUMO

PURPOSE OF REVIEW: Angiotensin-converting enzyme 2 (ACE2), a specific high-affinity angiotensin II-hydrolytic enzyme, is the vector that facilitates cellular entry of SARS-CoV-1 and the novel SARS-CoV-2 coronavirus. SARS-CoV-2, which crossed species barriers to infect humans, is highly contagious and associated with high lethality due to multi-organ failure, mostly in older patients with other co-morbidities. RECENT FINDINGS: Accumulating clinical evidence demonstrates that the intensity of the infection and its complications are more prominent in men. It has been postulated that potential functional modulation of ACE2 by estrogen may explain the sex difference in morbidity and mortality. We review here the evidence regarding the role of estrogenic hormones in ACE2 expression and regulation, with the intent of bringing to the forefront potential mechanisms that may explain sex differences in SARS-CoV-2 infection and COVID-19 outcomes, assist in management of COVID-19, and uncover new therapeutic strategies.


Assuntos
Infecções por Coronavirus/etiologia , Estrogênios/fisiologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/etiologia , Fatores Sexuais , Betacoronavirus , Feminino , Humanos , Masculino , Pandemias
16.
Artigo em Inglês | MEDLINE | ID: mdl-32738193

RESUMO

There is an urgent need for vaccines and therapeutics to prevent and treat COVID-19. Rapid SARS-CoV-2 countermeasure development is contingent on the availability of robust, scalable, and readily deployable surrogate viral assays to screen antiviral humoral responses, define correlates of immune protection, and down-select candidate antivirals. Here, we generate a highly infectious recombinant vesicular stomatitis virus (VSV) bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein and show that this recombinant virus, rVSV-SARS-CoV-2 S, closely resembles SARS-CoV-2 in its entry-related properties. The neutralizing activities of a large panel of COVID-19 convalescent sera can be assessed in a high-throughput fluorescent reporter assay with rVSV-SARS-CoV-2 S, and neutralization of rVSV-SARS-CoV-2 S and authentic SARS-CoV-2 by spike-specific antibodies in these antisera is highly correlated. Our findings underscore the utility of rVSV-SARS-CoV-2 S for the development of spike-specific therapeutics and for mechanistic studies of viral entry and its inhibition.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Glicoproteína da Espícula de Coronavírus/fisiologia , Vírus da Estomatite Vesicular Indiana/fisiologia , Animais , Antivirais/farmacologia , Betacoronavirus/genética , Betacoronavirus/fisiologia , Linhagem Celular , Chlorocebus aethiops , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Avaliação Pré-Clínica de Medicamentos , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Mutação , Testes de Neutralização , Pandemias/prevenção & controle , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Receptores Virais/genética , Receptores Virais/fisiologia , Recombinação Genética , Serina Endopeptidases/fisiologia , Glicoproteína da Espícula de Coronavírus/genética , Células Vero , Vírus da Estomatite Vesicular Indiana/genética , Vacinas Virais/genética , Vacinas Virais/imunologia , Internalização do Vírus , Replicação Viral/genética
17.
Hypertension ; 76(3): 651-661, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32783758

RESUMO

Discovery of ACE2 (angiotensin-converting enzyme 2) revealed that the renin-angiotensin system has 2 counterbalancing arms. ACE2 is a major player in the protective arm, highly expressed in lungs and gut with the ability to mitigate cardiopulmonary diseases such as inflammatory lung disease. ACE2 also exhibits activities involving gut microbiome, nutrition, and as a chaperone stabilizing the neutral amino acid transporter, B0AT1, in gut. But the current interest in ACE2 arises because it is the cell surface receptor for the novel coronavirus, severe acute respiratory syndrome coronavirus-2, to infect host cells, similar to severe acute respiratory syndrome coronavirus-2. This suggests that ACE2 be considered harmful, however, because of its important other roles, it is paradoxically a potential therapeutic target for cardiopulmonary diseases, including coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2. This review describes the discovery of ACE2, its physiological functions, and its place in the renin-angiotensin system. It illustrates new analyses of the structure of ACE2 that provides better understanding of its actions particularly in lung and gut, shedding of ACE2 by ADAM17 (a disintegrin and metallopeptidase domain 17 protein), and role of TMPRSS2 (transmembrane serine proteases 2) in severe acute respiratory syndrome coronavirus-2 entry into host cells. Cardiopulmonary diseases are associated with decreased ACE2 activity and the mitigation by increasing ACE2 activity along with its therapeutic relevance are addressed. Finally, the potential use of ACE2 as a treatment target in COVID-19, despite its role to allow viral entry into host cells, is suggested.


Assuntos
Infecções por Coronavirus , Hipertensão Pulmonar , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral , Betacoronavirus/fisiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Gerenciamento Clínico , Humanos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/virologia , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Sistema Renina-Angiotensina/fisiologia
18.
Mol Neurobiol ; 57(12): 4921-4928, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32813238

RESUMO

The global pandemic of novel coronavirus disease 2019 (COVID-19) has taken the entire human race by surprise and led to an unprecedented number of mortalities worldwide so far. Current clinical studies have interpreted that angiotensin-converting enzyme 2 (ACE2) is the host receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). In addition, ACE2 is the major component of the renin-angiotensin system. ACE2 deteriorates angiotensin II, a peptide that is responsible for the promotion of stroke. The downregulation of ACE2 further activates an immunological cascade. Thus, researchers need to explore and examine the possible links between COVID-19 and ischemic stroke (IS). Human ACE2 expression level and pattern in various tissues might be decisive for the vulnerability, symptoms, and treatment outcomes of the SARS-CoV-2 infection. The swift increase in the knowledge of SARS-CoV-2 has given creditable evidence that SARS-CoV-2 infected patients also encounter neurological deficits. As the SARS-CoV-2 binds to ACE2, it will hamper the activity of ACE2 in providing neuroprotection, especially in the case of stroke patients. Due to the downregulation of ACE2, the inflammatory response is activated in the ischemic penumbra. The COVID-19 pandemic has affected people with various pre-existing diseases, including IS, in such a way that these patients need special care and attention for their survival. Several clinical trials are currently ongoing worldwide as well as many other projects are in different stages of conceptualization and planning to facilitate the effective management of stroke patients with COVID-19 infection.


Assuntos
Betacoronavirus , Isquemia Encefálica/etiologia , Infecções por Coronavirus/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Acidente Vascular Cerebral/etiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Barreira Hematoencefálica , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/imunologia , Isquemia Encefálica/fisiopatologia , Quimiotaxia de Leucócito , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Citocinas/fisiologia , Encefalite Viral/complicações , Encefalite Viral/fisiopatologia , Hemodinâmica , Humanos , Inflamação , Modelos Imunológicos , Modelos Neurológicos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/etiologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Receptores Virais/fisiologia , Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/fisiopatologia
19.
Gastroenterol Hepatol ; 43(8): 464-471, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32859408

RESUMO

The SARS-CoV-2 pandemic is leading to high mortality and a global health crisis. The primary involvement is respiratory; however, the virus can also affect other organs, such as the gastrointestinal tract and liver. The most common symptoms are anorexia and diarrhea. In about half of the cases, viral RNA could be detected in the stool, which is another line of transmission and diagnosis. covid19 has a worse prognosis in patients with comorbidities, although there is not enough evidence in case of previous digestive diseases. Digestive endoscopies may give rise to aerosols, which make them techniques with a high risk of infection. Experts and scientific organizations worldwide have developed guidelines for preventive measures. The available evidence on gastrointestinal and hepatic involvement, the impact on patients with previous digestive diseases and operating guidelines for Endoscopy Units during the pandemic are reviewed.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Doenças do Sistema Digestório/etiologia , Sistema Digestório/virologia , Pandemias , Pneumonia Viral/complicações , Aerossóis , Anorexia/etiologia , Antivirais/efeitos adversos , Betacoronavirus/isolamento & purificação , Betacoronavirus/fisiologia , Estudos de Coortes , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Diarreia/etiologia , Doenças do Sistema Digestório/virologia , Endoscopia do Sistema Digestório/efeitos adversos , Fezes/virologia , Humanos , Imunossupressores/efeitos adversos , Intestinos/química , Intestinos/virologia , Hepatopatias/etiologia , Estudos Multicêntricos como Assunto , Pandemias/prevenção & controle , Peptidil Dipeptidase A/análise , Peptidil Dipeptidase A/fisiologia , Equipamento de Proteção Individual , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Receptores Virais/análise , Receptores Virais/fisiologia , Risco , Precauções Universais
20.
ACS Nano ; 14(9): 12234-12247, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32845122

RESUMO

The first step of SARS-CoV-2 infection is binding of the spike protein's receptor binding domain to the host cell's ACE2 receptor on the plasma membrane. Here, we have generated a versatile imaging probe using recombinant Spike receptor binding domain conjugated to fluorescent quantum dots (QDs). This probe is capable of engaging in energy transfer quenching with ACE2-conjugated gold nanoparticles to enable monitoring of the binding event in solution. Neutralizing antibodies and recombinant human ACE2 blocked quenching, demonstrating a specific binding interaction. In cells transfected with ACE2-GFP, we observed immediate binding of the probe on the cell surface followed by endocytosis. Neutralizing antibodies and ACE2-Fc fully prevented binding and endocytosis with low nanomolar potency. Importantly, we will be able to use this QD nanoparticle probe to identify and validate inhibitors of the SARS-CoV-2 Spike and ACE2 receptor binding in human cells. This work enables facile, rapid, and high-throughput cell-based screening of inhibitors for coronavirus Spike-mediated cell recognition and entry.


Assuntos
Endocitose , Nanopartículas Metálicas/química , Peptidil Dipeptidase A/metabolismo , Pontos Quânticos/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Betacoronavirus/metabolismo , Infecções por Coronavirus/metabolismo , Ouro , Humanos , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/metabolismo , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/química , Vírion
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