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2.
Nat Commun ; 12(1): 3463, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103497

RESUMO

Numerous reports document the spread of SARS-CoV-2, but there is limited information on its introduction before the identification of a local case. This may lead to incorrect assumptions when modeling viral origins and transmission. Here, we utilize a sample pooling strategy to screen for previously undetected SARS-CoV-2 in de-identified, respiratory pathogen-negative nasopharyngeal specimens from 3,040 patients across the Mount Sinai Health System in New York. The patients had been previously evaluated for respiratory symptoms or influenza-like illness during the first 10 weeks of 2020. We identify SARS-CoV-2 RNA from specimens collected as early as 25 January 2020, and complete SARS-CoV-2 genome sequences from multiple pools of samples collected between late February and early March, documenting an increase prior to the later surge. Our results provide evidence of sporadic SARS-CoV-2 infections a full month before both the first officially documented case and emergence of New York as a COVID-19 epicenter in March 2020.


Assuntos
COVID-19/epidemiologia , Pandemias , SARS-CoV-2/fisiologia , Humanos , Nasofaringe/virologia , New York/epidemiologia , Filogenia , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação
3.
Nat Commun ; 12(1): 3431, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103499

RESUMO

The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that despite the large size of the viral RNA genome (~30 kb), infectious full-length cDNA is readily assembled in vitro by a circular polymerase extension reaction (CPER) methodology without the need for technically demanding intermediate steps. Overlapping cDNA fragments are generated from viral RNA and assembled together with a linker fragment containing CMV promoter into a circular full-length viral cDNA in a single reaction. Transfection of the circular cDNA into mammalian cells results in the recovery of infectious SARS-CoV-2 virus that exhibits properties comparable to the parental virus in vitro and in vivo. CPER is also used to generate insect-specific Casuarina virus with ~20 kb genome and the human pathogens Ross River virus (Alphavirus) and Norovirus (Calicivirus), with the latter from a clinical sample. Additionally, reporter and mutant viruses are generated and employed to study virus replication and virus-receptor interactions.


Assuntos
Genética Reversa , SARS-CoV-2/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Chlorocebus aethiops , Culicidae/virologia , Furina/metabolismo , Genoma Viral , Células HEK293 , Humanos , Camundongos , Mutação/genética , Células NIH 3T3 , Reação em Cadeia da Polimerase , Células RAW 264.7 , Receptores Virais/metabolismo , Células Vero , Proteínas Virais/química , Replicação Viral
4.
Nat Commun ; 12(1): 3449, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103510

RESUMO

Most COVID-19 vaccines require two doses, however with limited vaccine supply, policymakers are considering single-dose vaccination as an alternative strategy. Using a mathematical model combined with optimization algorithms, we determined optimal allocation strategies with one and two doses of vaccine under various degrees of viral transmission. Under low transmission, we show that the optimal allocation of vaccine vitally depends on the single-dose efficacy. With high single-dose efficacy, single-dose vaccination is optimal, preventing up to 22% more deaths than a strategy prioritizing two-dose vaccination for older adults. With low or moderate single-dose efficacy, mixed vaccination campaigns with complete coverage of older adults are optimal. However, with modest or high transmission, vaccinating older adults first with two doses is best, preventing up to 41% more deaths than a single-dose vaccination given across all adult populations. Our work suggests that it is imperative to determine the efficacy and durability of single-dose vaccines, as mixed or single-dose vaccination campaigns may have the potential to contain the pandemic much more quickly.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Vacinação , Número Básico de Reprodução , COVID-19/transmissão , COVID-19/virologia , Relação Dose-Resposta Imunológica , Hospitalização , Humanos , Imunidade , Unidades de Terapia Intensiva , SARS-CoV-2/imunologia
5.
Pan Afr Med J ; 38: 248, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34104296

RESUMO

Yellow fever (YF) is a viral haemorrhagic fever caused by yellow fever virus transmitted by Aedes mosquitoes. Since 2013, in Chad, four cases of yellow fever have been detected and confirmed as part of the national fever surveillance program. We here report the last clinical case confirmed in the health district of Lai. The patient was a 57-year-old man with no significant medical and surgical history and unknown immunisation status. He consulted on April 21st, 2020 for fever, moderate to low abundance jaundice and epistaxis (nosebleed) and painful hepatomegaly. Paraclinical examinations, such as RT-PCR, objectified yellow fever virus in post-mortem tissue sample. Thus, confirmed yellow fever cases in this district, the low level of vaccination coverage, the circulation of the virus and the presence of vector in the country should warn of a real threat of reemergence of yellow fever in Chad.


Assuntos
Febre Amarela/diagnóstico , Vírus da Febre Amarela/isolamento & purificação , Aedes/virologia , Animais , Chade , Humanos , Masculino , Pessoa de Meia-Idade , Mosquitos Vetores/virologia , Recidiva , Febre Amarela/transmissão , Febre Amarela/virologia , Vacina contra Febre Amarela/administração & dosagem
6.
Adv Sci (Weinh) ; 8(11): e2003503, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34105286

RESUMO

While the ongoing COVID-19 pandemic affirms an urgent global need for effective vaccines as second and third infection waves are spreading worldwide and generating new mutant virus strains, it has also revealed the importance of mitigating the transmission of SARS-CoV-2 through the introduction of restrictive social practices. Here, it is demonstrated that an architecturally- and chemically-diverse family of nanostructured anionic polymers yield a rapid and continuous disinfecting alternative to inactivate coronaviruses and prevent their transmission from contact with contaminated surfaces. Operating on a dramatic pH-drop mechanism along the polymer/pathogen interface, polymers of this archetype inactivate the SARS-CoV-2 virus, as well as a human coronavirus surrogate (HCoV-229E), to the minimum detection limit within minutes. Application of these anionic polymers to frequently touched surfaces in medical, educational, and public-transportation facilities, or personal protection equipment, can provide rapid and repetitive protection without detrimental health or environmental complications.


Assuntos
COVID-19/transmissão , Desinfetantes/uso terapêutico , Polímeros/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , COVID-19/prevenção & controle , COVID-19/virologia , Humanos , Pandemias , Polímeros/química , SARS-CoV-2/patogenicidade
7.
PLoS One ; 16(6): e0252507, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34061896

RESUMO

We recently developed 'cellular' reagents-lyophilized bacteria overexpressing proteins of interest-that can replace commercial pure enzymes in typical diagnostic and molecular biology reactions. To make cellular reagent technology widely accessible and amenable to local production with minimal instrumentation, we now report a significantly simplified method for preparing cellular reagents that requires only a common bacterial incubator to grow and subsequently dry enzyme-expressing bacteria at 37°C with the aid of inexpensive chemical desiccants. We demonstrate application of such dried cellular reagents in common molecular and synthetic biology processes, such as PCR, qPCR, reverse transcription, isothermal amplification, and Golden Gate DNA assembly, in building easy-to-use testing kits, and in rapid reagent production for meeting extraordinary diagnostic demands such as those being faced in the ongoing SARS-CoV-2 pandemic. Furthermore, we demonstrate feasibility of local production by successfully implementing this minimized procedure and preparing cellular reagents in several countries, including the United Kingdom, Cameroon, and Ghana. Our results demonstrate possibilities for readily scalable local and distributed reagent production, and further instantiate the opportunities available via synthetic biology in general.


Assuntos
Teste para COVID-19/normas , COVID-19/diagnóstico , COVID-19/epidemiologia , Testes Diagnósticos de Rotina/normas , Indicadores e Reagentes/normas , Reação em Cadeia da Polimerase em Tempo Real/normas , SARS-CoV-2/genética , COVID-19/virologia , Teste para COVID-19/métodos , Camarões/epidemiologia , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Geobacillus stearothermophilus/genética , Geobacillus stearothermophilus/metabolismo , Gana/epidemiologia , Humanos , Indicadores e Reagentes/química , Indicadores e Reagentes/metabolismo , Indicadores e Reagentes/provisão & distribuição , Técnicas de Diagnóstico Molecular , Plasmídeos/química , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Biologia Sintética/métodos , Transformação Bacteriana , Reino Unido/epidemiologia
8.
MAbs ; 13(1): 1919285, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34074219

RESUMO

The newly emerging variants of SARS-CoV-2 from South Africa (B.1.351/501Y.V2) and Brazil (P.1/501Y.V3) have led to a higher infection rate and reinfection of COVID-19 patients. We found that the mutations K417N, E484K, and N501Y within the receptor-binding domains (RBDs) of the virus could confer ~2-fold higher binding affinity to the human receptor, angiotensin converting enzyme 2 (ACE2), compared to the wildtype RBD. The mutated version of RBD also completely abolishes the binding of bamlanivimab, a therapeutic antibody, in vitro. Detailed analysis shows that the ~10-fold gain of binding affinity between ACE2 and Y501-RBD, which also exits in the high contagious variant B.1.1.7/501Y.V1 from the United Kingdom, is compromised by additional introduction of the K417/N/T mutation. Mutation of E484K leads to the loss of bamlanivimab binding to RBD, although this mutation does not affect the binding between RBD and ACE2.


Assuntos
Anticorpos Monoclonais Humanizados/metabolismo , Antivirais/metabolismo , COVID-19/virologia , Mutação , SARS-CoV-2/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Sítios de Ligação , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , Interações Hospedeiro-Patógeno , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Receptores Virais/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética
10.
J Korean Med Sci ; 36(22): e161, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34100564

RESUMO

BACKGROUND: The aim of this study was to evaluate the subjective and objective olfactory function in coronavirus disease 2019 (COVID-19) patients and the effect of olfactory training. METHODS: A prospective cohort study was performed in 53 patients who recovered from COVID-19 and visited our tertiary hospital. Subjective olfactory function was evaluated using the 11-point Likert scale (0-10) and the Korean version of the Questionnaire of Olfactory Disorders (QOD). Objective olfactory function was evaluated using Cross-Cultural Smell Identification Test (CC-SIT). Confirmed patients were followed up after 2 months of olfactory training. RESULTS: The median, interquartile range (Q1-Q3) score of subjective olfactory function significantly deteriorated in patients with olfactory dysfunction (OD) than in those without OD, even after 3 months of onset (11-point Likert scale, 8, 6-9 vs. 10, 10-10; short version of QOD-negative statements, 19, 16-21 vs. 21, 21-21; QOD-visual analogue scale, 7, 1-13 vs. 0, 0-0; all P < 0.001). However, the objective olfactory function was not significantly different between the two groups (median, interquartile range; 11, 9-11 vs. 11, 9-11, P = 0.887). The percentage of patients with objective hyposmia (CC-SIT ≤ 10) was also not significantly different (47.4% vs. 40%, P = 0.762). OD in COVID-19 was normalized after 2 months of olfactory training in 70% of patients even after 3 months of olfactory impairment. CONCLUSION: Although subjective olfactory function is significantly decreased in the OD group, the objective olfactory function was not significantly different. Moreover, olfactory training is effective in COVID-19 patients with OD.


Assuntos
COVID-19/diagnóstico , Transtornos do Olfato/patologia , Adulto , COVID-19/complicações , COVID-19/virologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/etiologia , Estudos Prospectivos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Inquéritos e Questionários , Centros de Atenção Terciária
11.
FASEB J ; 35(7): e21713, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34105201

RESUMO

Syrian golden hamsters (Mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) manifests lung pathology. In this study, efforts were made to check the infectivity of a local SARS-CoV-2 isolate in a self-limiting and non-lethal hamster model and evaluate the differential expression of lung proteins during acute infection and convalescence. The findings of this study confirm the infectivity of this isolate in vivo. Analysis of clinical parameters and tissue samples show the pathophysiological manifestation of SARS-CoV-2 infection similar to that reported earlier in COVID-19 patients and hamsters infected with other isolates. However, diffuse alveolar damage (DAD), a common histopathological feature of human COVID-19 was only occasionally noticed. The lung-associated pathological changes were very prominent on the 4th day post-infection (dpi), mostly resolved by 14 dpi. Here, we carried out the quantitative proteomic analysis of the lung tissues from SARS-CoV-2-infected hamsters on day 4 and day 14 post-infection. This resulted in the identification of 1585 proteins of which 68 proteins were significantly altered between both the infected groups. Pathway analysis revealed complement and coagulation cascade, platelet activation, ferroptosis, and focal adhesion as the top enriched pathways. In addition, we also identified altered expression of two pulmonary surfactant-associated proteins (Sftpd and Sftpb), known for their protective role in lung function. Together, these findings will aid in understanding the mechanism(s) involved in SARS-CoV-2 pathogenesis and progression of the disease.


Assuntos
COVID-19/metabolismo , COVID-19/patologia , Interações Hospedeiro-Patógeno , Pulmão/metabolismo , Pulmão/virologia , Proteômica , SARS-CoV-2/patogenicidade , Animais , COVID-19/virologia , Cricetinae , Modelos Animais de Doenças , Feminino , Pulmão/patologia , Masculino , Proteoma/análise , Proteoma/biossíntese , Reprodutibilidade dos Testes , Carga Viral
12.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072468

RESUMO

Senescence, sterile inflammation, and infection cause dysfunction of corneal endothelial cells, leading to visual morbidity that may require corneal transplantation. With increasing age, the extracellular matrix is modified by non-enzymatic glycation forming advanced glycation end products (AGEs). The modifications are primarily sensed by the receptors for the AGEs (RAGE) and are manifested as a type I interferon response. Interestingly, in our study, human corneal endothelial cells (HCEn) cells did not respond to the typical RAGE ligands, including the AGEs, high mobility group box 1 (HMGB1), and serum amyloid-A (SAA). Instead, HCEn cells responded exclusively to the CpG DNA, which is possessed by typical corneal pathogen, herpes simplex virus-1 (HSV-1). Upon HSV-1 infection, the surface expression of RAGE was increased, and endocytosed HSV-1 was associated with RAGE and CpG DNA receptor, TLR9. RAGE DNA transfection markedly increased interferon-ß secretion by CpG DNA or HSV-1 infection. HSV-1 infection-induced interferon-ß secretion was abolished by TLR9 inhibition and partially by RAGE inhibition. Global transcriptional response analysis confirmed that RAGE and TLR9 were both significantly involved in type I interferon responses. We conclude that RAGE is a sensor of HSV-1 infection and provokes a type I interferon response.


Assuntos
Epitélio Posterior/metabolismo , Epitélio Posterior/virologia , Herpesvirus Humano 1 , Ceratite Herpética/metabolismo , Ceratite Herpética/virologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Biomarcadores , Células Cultivadas , Biologia Computacional/métodos , Ilhas de CpG , Metilação de DNA , Suscetibilidade a Doenças , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Epitélio Posterior/patologia , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Receptor para Produtos Finais de Glicação Avançada/genética , Transcriptoma
13.
Cells ; 10(5)2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064516

RESUMO

Sphingolipids are important structural membrane components and, together with cholesterol, are often organized in lipid rafts, where they act as signaling molecules in many cellular functions. They play crucial roles in regulating pathobiological processes, such as cancer, inflammation, and infectious diseases. The bioactive metabolites ceramide, sphingosine-1-phosphate, and sphingosine have been shown to be involved in the pathogenesis of several microbes. In contrast to ceramide, which often promotes bacterial and viral infections (for instance, by mediating adhesion and internalization), sphingosine, which is released from ceramide by the activity of ceramidases, kills many bacterial, viral, and fungal pathogens. In particular, sphingosine is an important natural component of the defense against bacterial pathogens in the respiratory tract. Pathologically reduced sphingosine levels in cystic fibrosis airway epithelial cells are normalized by inhalation of sphingosine, and coating plastic implants with sphingosine prevents bacterial infections. Pretreatment of cells with exogenous sphingosine also prevents the viral spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from interacting with host cell receptors and inhibits the propagation of herpes simplex virus type 1 (HSV-1) in macrophages. Recent examinations reveal that the bactericidal effect of sphingosine might be due to bacterial membrane permeabilization and the subsequent death of the bacteria.


Assuntos
Infecções Bacterianas/imunologia , Micoses/imunologia , Transdução de Sinais/imunologia , Esfingosina/metabolismo , Viroses/imunologia , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/metabolismo , Infecções Bacterianas/microbiologia , Parede Celular/efeitos dos fármacos , Ceramidas/metabolismo , Modelos Animais de Doenças , Herpesvirus Humano 1/imunologia , Humanos , Lisofosfolipídeos/metabolismo , Microdomínios da Membrana/imunologia , Microdomínios da Membrana/metabolismo , Micoses/tratamento farmacológico , Micoses/metabolismo , Micoses/microbiologia , SARS-CoV-2/imunologia , Esfingolipídeos/metabolismo , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Esfingosina/uso terapêutico , Viroses/tratamento farmacológico , Viroses/metabolismo , Viroses/virologia
14.
Viruses ; 13(5)2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064525

RESUMO

Mucins and mucin-like molecules are highly glycosylated, high-molecular-weight cell surface proteins that possess a semi-rigid and highly extended extracellular domain. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein, has recently been found to restrict HIV-1 infectivity through virion incorporation that sterically hinders virus particle attachment to target cells. Here, we report the identification of a family of antiviral cellular proteins, named the Surface-Hinged, Rigidly-Extended Killer (SHREK) family of virion inactivators (PSGL-1, CD43, TIM-1, CD34, PODXL1, PODXL2, CD164, MUC1, MUC4, and TMEM123) that share similar structural characteristics with PSGL-1. We demonstrate that SHREK proteins block HIV-1 infectivity by inhibiting virus particle attachment to target cells. In addition, we demonstrate that SHREK proteins are broad-spectrum host antiviral factors that block the infection of diverse viruses such as influenza A. Furthermore, we demonstrate that a subset of SHREKs also blocks the infectivity of a hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) pseudovirus. These results suggest that SHREK proteins may be a part of host innate immunity against enveloped viruses.


Assuntos
COVID-19/imunologia , Infecções por HIV/imunologia , Glicoproteínas de Membrana/metabolismo , Ligação Viral , Animais , COVID-19/virologia , Cães , Células HEK293 , HIV-1/imunologia , Células HeLa , Interações entre Hospedeiro e Microrganismos , Humanos , Imunidade Inata , Células Madin Darby de Rim Canino , Mucinas/farmacologia , SARS-CoV-2/imunologia
15.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065210

RESUMO

Previous studies have shown that COVID-19 leads to thrombotic complications, which have been associated with high morbidity and mortality rates. Neutrophils are the largest population of white blood cells and play a pivotal role in innate immunity. During an infection, neutrophils migrate from circulation to the infection site, contributing to killing pathogens. This mechanism is regulated by chemokines such as IL-8. Moreover, it was shown that neutrophils play an important role in thromboinflammation. Through a diverse repertoire of mechanisms, neutrophils, apart from directly killing pathogens, are able to activate the formation of thrombi. In COVID-19 patients, neutrophil activation promotes neutrophil extracellular trap (NET) formation, platelet aggregation, and cell damage. Furthermore, neutrophils participate in the pathogenesis of endothelitis. Overall, this review summarizes recent progress in research on the pathogenesis of COVID-19, highlighting the role of the prothrombotic action of neutrophils in NET formation.


Assuntos
COVID-19/imunologia , Armadilhas Extracelulares/imunologia , Imunidade Inata , Pulmão/imunologia , Neutrófilos/imunologia , Trombose/imunologia , COVID-19/complicações , COVID-19/patologia , COVID-19/terapia , Síndrome da Liberação de Citocina/metabolismo , Síndrome da Liberação de Citocina/virologia , Armadilhas Extracelulares/virologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Rim/citologia , Rim/imunologia , Rim/patologia , Rim/virologia , Pulmão/citologia , Pulmão/patologia , Pulmão/virologia , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/virologia , SARS-CoV-2 , Trombose/complicações , Trombose/patologia , Trombose/virologia
16.
Int J Mol Sci ; 22(10)2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34065289

RESUMO

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10-5) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.


Assuntos
COVID-19/genética , COVID-19/metabolismo , Predisposição Genética para Doença , Receptores CCR5/genética , Receptores CCR5/metabolismo , Alelos , Brônquios/metabolismo , Brônquios/patologia , Brônquios/virologia , COVID-19/fisiopatologia , Cromossomos Humanos/genética , Estudos de Coortes , Biologia Computacional , Bases de Dados Genéticas , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Polimorfismo de Nucleotídeo Único , Sequenciamento Completo do Exoma
17.
Biosensors (Basel) ; 11(5)2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34065688

RESUMO

Zika virus (ZIKV) is a mosquito-borne infection, predominant in tropical and subtropical regions causing international concern due to the ZIKV disease having been associated with congenital disabilities, especially microcephaly and other congenital abnormalities in the fetus and newborns. Development of strategies that minimize the devastating impact by monitoring and preventing ZIKV transmission through sexual intercourse, especially in pregnant women, since no vaccine is yet available for the prevention or treatment, is critically important. ZIKV infection is generally asymptomatic and cross-reactivity with dengue virus (DENV) is a global concern. An innovative screen-printed electrode (SPE) was developed for amperometric detection of the non-structural protein (NS2B) of ZIKV by exploring the intrinsic redox catalytic activity of Prussian blue (PB), incorporated into a carbon nanotube-polypyrrole composite. Thus, this immunosensor has the advantage of electrochemical detection without adding any redox-probe solution (probe-less detection), allowing a point-of-care diagnosis. It was responsive to serum samples of only ZIKV positive patients and non-responsive to negative ZIKV patients, even if the sample was DENV positive, indicating a possible differential diagnosis between them by NS2B. All samples used here were confirmed by CDC protocols, and immunosensor responses were also checked in the supernatant of C6/36 and in Vero cell cultures infected with ZIKV.


Assuntos
Técnicas Biossensoriais , Imunoensaio , Zika virus/isolamento & purificação , Ferrocianetos , Humanos , Nanotubos de Carbono , Polímeros , Pirróis , Zika virus/imunologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia
18.
Int J Mol Sci ; 22(10)2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34065735

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still an ongoing global health crisis. Immediately after the inhalation of SARS-CoV-2 viral particles, alveolar type II epithelial cells harbor and initiate local innate immunity. These particles can infect circulating macrophages, which then present the coronavirus antigens to T cells. Subsequently, the activation and differentiation of various types of T cells, as well as uncontrollable cytokine release (also known as cytokine storms), result in tissue destruction and amplification of the immune response. Vitamin D enhances the innate immunity required for combating COVID-19 by activating toll-like receptor 2. It also enhances antimicrobial peptide synthesis, such as through the promotion of the expression and secretion of cathelicidin and ß-defensin; promotes autophagy through autophagosome formation; and increases the synthesis of lysosomal degradation enzymes within macrophages. Regarding adaptive immunity, vitamin D enhances CD4+ T cells, suppresses T helper 17 cells, and promotes the production of virus-specific antibodies by activating T cell-dependent B cells. Moreover, vitamin D attenuates the release of pro-inflammatory cytokines by CD4+ T cells through nuclear factor κB signaling, thereby inhibiting the development of a cytokine storm. SARS-CoV-2 enters cells after its spike proteins are bound to angiotensin-converting enzyme 2 (ACE2) receptors. Vitamin D increases the bioavailability and expression of ACE2, which may be responsible for trapping and inactivating the virus. Activation of the renin-angiotensin-aldosterone system (RAS) is responsible for tissue destruction, inflammation, and organ failure related to SARS-CoV-2. Vitamin D inhibits renin expression and serves as a negative RAS regulator. In conclusion, vitamin D defends the body against SARS-CoV-2 through a novel complex mechanism that operates through interactions between the activation of both innate and adaptive immunity, ACE2 expression, and inhibition of the RAS system. Multiple observation studies have shown that serum concentrations of 25 hydroxyvitamin D are inversely correlated with the incidence or severity of COVID-19. The evidence gathered thus far, generally meets Hill's causality criteria in a biological system, although experimental verification is not sufficient. We speculated that adequate vitamin D supplementation may be essential for mitigating the progression and severity of COVID-19. Future studies are warranted to determine the dosage and effectiveness of vitamin D supplementation among different populations of individuals with COVID-19.


Assuntos
Imunidade Adaptativa , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/imunologia , Imunidade Inata , SARS-CoV-2/imunologia , Vitamina D/metabolismo , Vitamina D/farmacologia , COVID-19/mortalidade , COVID-19/fisiopatologia , COVID-19/virologia , Síndrome da Liberação de Citocina/complicações , Citocinas/metabolismo , Humanos , Receptores Virais/metabolismo , Sistema Renina-Angiotensina/fisiologia
19.
Viruses ; 13(5)2021 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066046

RESUMO

The aim of this study was to determine whether self-collected pure saliva (SCPS) is comparable to nasopharyngeal (NP) swabs in the quantitative detection of SARS-CoV-2 by RT-PCR in asymptomatic, mild patients with confirmed COVID-19. Thirty-one patients aged from 18 to 85 years were included between 9 June and 11 December 2020. A SCPS sample and a NP sample were taken for each patient. Quantitative PCR was performed to detect SARS-CoV-2 viral load. Results of SCPS vs. NP samples testing were compared. Statistical analyses were performed. Viral load was significantly correlated (r = 0.72). The concordance probability was estimated at 73.3%. In symptomatic adults, SCPS performance was similar to that of NP swabs (Percent Agreement = 74.1%; p = 0.11). Thus, the salivary test based on pure oral saliva samples easily obtained by noninvasive techniques has a fair agreement with the nasopharyngeal one in asymptomatic, mild patients with a confirmed diagnosis of COVID-19.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Nasofaringe/virologia , SARS-CoV-2/isolamento & purificação , Saliva/virologia , Adulto , Idoso , Doenças Assintomáticas , Testes Diagnósticos de Rotina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral , Reação em Cadeia da Polimerase em Tempo Real , Manejo de Espécimes/métodos , Carga Viral/métodos , Adulto Jovem
20.
Int J Mol Sci ; 22(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34066226

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) caused by the betacoronavirus SARS-CoV-2 is now a worldwide challenge for healthcare systems. Although the leading cause of mortality in patients with COVID-19 is hypoxic respiratory failure due to viral pneumonia and acute respiratory distress syndrome, accumulating evidence has shown that the risk of thromboembolism is substantially high in patients with severe COVID-19 and that a thromboembolic event is another major complication contributing to the high morbidity and mortality in patients with COVID-19. Endothelial dysfunction is emerging as one of the main contributors to the pathogenesis of thromboembolic events in COVID-19. Endothelial dysfunction is usually referred to as reduced nitric oxide bioavailability. However, failures of the endothelium to control coagulation, inflammation, or permeability are also instances of endothelial dysfunction. Recent studies have indicated the possibility that SARS-CoV-2 can directly infect endothelial cells via the angiotensin-converting enzyme 2 pathway and that endothelial dysfunction caused by direct virus infection of endothelial cells may contribute to thrombotic complications and severe disease outcomes in patients with COVID-19. In this review, we summarize the current understanding of relationships between SARS-CoV-2 infection, endothelial dysfunction, and pulmonary and extrapulmonary complications in patients with COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/mortalidade , COVID-19/fisiopatologia , Citocinas/metabolismo , Células Endoteliais/virologia , Endotélio Vascular/virologia , Tromboembolia/virologia , COVID-19/complicações , COVID-19/virologia , Células Endoteliais/patologia , Endotélio Vascular/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Pulmão/patologia , Pulmão/virologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/virologia , SARS-CoV-2/patogenicidade , Tromboembolia/complicações
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