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1.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502134

RESUMO

The current spreading coronavirus SARS-CoV-2 is highly infectious and pathogenic. In this study, we screened the gene expression of three host receptors (ACE2, DC-SIGN and L-SIGN) of SARS coronaviruses and dendritic cells (DCs) status in bulk and single cell transcriptomic datasets of upper airway, lung or blood of COVID-19 patients and healthy controls. In COVID-19 patients, DC-SIGN gene expression was interestingly decreased in lung DCs but increased in blood DCs. Within DCs, conventional DCs (cDCs) were depleted while plasmacytoid DCs (pDCs) were augmented in the lungs of mild COVID-19. In severe cases, we identified augmented types of immature DCs (CD22+ or ANXA1+ DCs) with MHCII downregulation. In this study, our observation indicates that DCs in severe cases stimulate innate immune responses but fail to specifically present SARS-CoV-2. It provides insights into the profound modulation of DC function in severe COVID-19.


Assuntos
COVID-19/imunologia , Moléculas de Adesão Celular/genética , Células Dendríticas/imunologia , Regulação da Expressão Gênica/imunologia , Lectinas Tipo C/genética , Receptores de Superfície Celular/genética , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/diagnóstico , COVID-19/patologia , COVID-19/virologia , Moléculas de Adesão Celular/metabolismo , Conjuntos de Dados como Assunto , Células Dendríticas/metabolismo , Estudo de Associação Genômica Ampla , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Lectinas Tipo C/metabolismo , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Análise da Randomização Mendeliana , Nasofaringe/imunologia , Nasofaringe/patologia , Nasofaringe/virologia , RNA-Seq , Receptores de Superfície Celular/metabolismo , Índice de Gravidade de Doença , Análise de Célula Única
2.
Biosensors (Basel) ; 11(7)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34356695

RESUMO

The availability of antigen tests for SARS-CoV-2 represents a major step for the mass surveillance of the incidence of infection, especially regarding COVID-19 asymptomatic and/or early-stage patients. Recently, we reported the development of a Bioelectric Recognition Assay-based biosensor able to detect the SARS-CoV-2 S1 spike protein expressed on the surface of the virus in just three minutes, with high sensitivity and selectivity. The working principle was established by measuring the change of the electric potential of membrane-engineered mammalian cells bearing the human chimeric spike S1 antibody after attachment of the respective viral protein. In the present study, we applied the novel biosensor to patient-derived nasopharyngeal samples in a clinical set-up, with absolutely no sample pretreatment. More importantly, membrane-engineered cells were pre-immobilized in a proprietary biomatrix, thus enabling their long-term preservation prior to use as well as significantly increasing their ease-of-handle as test consumables. The plug-and-apply novel biosensor was able to detect the virus in positive samples with a 92.8% success rate compared to RT-PCR. No false negative results were recorded. These findings demonstrate the potential applicability of the biosensor for the early, routine mass screening of SARS-CoV-2 on a scale not yet realized.


Assuntos
Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/análise , COVID-19/imunologia , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Linhagem Celular , Diagnóstico Precoce , Humanos , Limite de Detecção , Nasofaringe/imunologia , Nasofaringe/virologia , Vigilância da População , SARS-CoV-2/imunologia
3.
Int J Mol Sci ; 22(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34360686

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as with the influenza virus, has been shown to spread more rapidly during winter. Severe coronavirus disease 2019 (COVID-19), which can follow SARS-CoV-2 infection, disproportionately affects older persons and males as well as people living in temperate zone countries with a tropical ancestry. Recent evidence on the importance of adequately warming and humidifying (conditioning) inhaled air in the nasal cavity for reducing SARS-CoV-2 infectivity in the upper respiratory tract (URT) is discussed, with particular reference to: (i) the relevance of air-borne SARS-CoV-2 transmission, (ii) the nasal epithelium as the initial site of SARS-CoV-2 infection, (iii) the roles of type 1 and 3 interferons for preventing viral infection of URT epithelial cells, (iv) weaker innate immune responses to respiratory viral infections in URT epithelial cells at suboptimal temperature and humidity, and (v) early innate immune responses in the URT for limiting and eliminating SARS-CoV-2 infections. The available data are consistent with optimal nasal air conditioning reducing SARS-CoV-2 infectivity of the URT and, as a consequence, severe COVID-19. Further studies on SARS-CoV-2 infection rates and viral loads in the nasal cavity and nasopharynx in relation to inhaled air temperature, humidity, age, gender, and genetic background are needed in this context. Face masks used for reducing air-borne virus transmission can also promote better nasal air conditioning in cold weather. Masks can, thereby, minimise SARS-CoV-2 infectivity and are particularly relevant for protecting more vulnerable persons from severe COVID-19.


Assuntos
Ar , COVID-19/imunologia , COVID-19/virologia , Nasofaringe/imunologia , Nasofaringe/virologia , SARS-CoV-2/patogenicidade , Fatores Etários , COVID-19/genética , Humanos , Umidade , Inalação , Fatores Sexuais , Temperatura
4.
Nat Commun ; 12(1): 4193, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234122

RESUMO

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.


Assuntos
Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/imunologia , Neoplasias Nasofaríngeas/imunologia , Evasão Tumoral/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/imunologia , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/terapia , Infecções por Vírus Epstein-Barr/virologia , Feminino , Regulação Viral da Expressão Gênica/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Metionina Adenosiltransferase/antagonistas & inibidores , Metionina Adenosiltransferase/metabolismo , Camundongos , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/virologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/virologia , Nasofaringe/imunologia , Nasofaringe/patologia , Nasofaringe/cirurgia , Nasofaringe/virologia , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Deleção de Sequência , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Evasão Tumoral/efeitos dos fármacos , Sequenciamento Completo do Genoma , Ensaios Antitumorais Modelo de Xenoenxerto
5.
PLoS One ; 16(6): e0253321, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34166410

RESUMO

BACKGROUND: Antigen-detecting rapid diagnostic tests (Ag-RDTs) for the detection of SARS-CoV-2 offer new opportunities for testing in the context of the COVID-19 pandemic. Nasopharyngeal swabs (NPS) are the reference sample type, but oropharyngeal swabs (OPS) may be a more acceptable sample type in some patients. METHODS: We conducted a prospective study in a single screening center to assess the diagnostic performance of the Panbio™ COVID-19 Ag Rapid Test (Abbott) on OPS compared with reverse-transcription quantitative PCR (RT-qPCR) using NPS during the second pandemic wave in Switzerland. RESULTS: 402 outpatients were enrolled in a COVID-19 screening center, of whom 168 (41.8%) had a positive RT-qPCR test. The oropharyngeal Ag-RDT clinical sensitivity compared to nasopharyngeal RT-qPCR was 81% (95%CI: 74.2-86.6). Two false positives were noted out of the 234 RT-qPCR negative individuals, which resulted in a clinical specificity of 99.1% (95%CI: 96.9-99.9) for the Ag-RDT. For cycle threshold values ≤ 26.7 (≥ 1E6 SARS-CoV-2 genomes copies/mL, a presumed cut-off for infectious virus), 96.3% sensitivity (95%CI: 90.7-99.0%) was obtained with the Ag-RDT using OPS. INTERPRETATION: Based on our findings, the diagnostic performance of the Panbio™ Covid-19 RDT with OPS samples, if taken by a trained person and high requirements regarding quality of the specimen, meet the criteria required by the WHO for Ag-RDTs (sensitivity ≥80% and specificity ≥97%) in a high incidence setting in symptomatic individuals.


Assuntos
Antígenos Virais/imunologia , Teste Sorológico para COVID-19 , COVID-19 , Nasofaringe , SARS-CoV-2 , Antígenos Virais/genética , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/genética , COVID-19/imunologia , Teste de Ácido Nucleico para COVID-19 , Humanos , Nasofaringe/imunologia , Nasofaringe/virologia , Estudos Prospectivos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Suíça/epidemiologia
6.
Biomed Res Int ; 2021: 4923852, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816612

RESUMO

Background: Haemophilus influenzae (H. influenzae) strains, which commonly reside as commensals within the human pharynx and can remain as an asymptomatic carrier, but become invasive leading to pneumonia, septic arthritis, or meningitis. The Pentavac (pentavalent vaccine, manufactured by India, SII (DTwP-HepB-Hib)) was introduced to the Iranian National Immunization Plan in November 2014. The aim of this study is to investigate H. influenzae type b (Hib) carrier rate among children under 6 years old in Tehran. Methods: This cross-sectional study was performed on 902 children including vaccinated/unvaccinated in the age of 6 months to 6 years, in Tehran. Sampling was performed from July 2019 to September 2019. Nasopharyngeal samples were taken from children by sterile swab. The PCR method was used to extract DNA. Then, all H. influenzae isolates were initially confirmed by molecular tests. BexA was used to distinguish typeable H. influenzae strains from nontypeable Haemophilus influenzae (NTHi). Results: A total of 902 children were enrolled in the study: 452 were female (51%). H. influenzae carriage rate was 267 (29%), of that 150 samples (16.6%) were typeable. The nasopharyngeal Hib carrier rate in the children was 2.6% (24/902). 262 cases did not receive Hib vaccine. Analysis in nonnursery's children aged 4 to 6 (unvaccinated) years showed that the lower educational level of father, mother, and family number correlated with increased odds of colonization of children with Hib. Conclusion: Our findings showed a significant decrease (60%) in the overall Hib nasopharyngeal carriage in healthy children under six years after 5 years after the start of Hib vaccination.


Assuntos
Portador Sadio , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Infecções por Haemophilus , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae tipo b/imunologia , Nasofaringe , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacinação , Portador Sadio/imunologia , Portador Sadio/microbiologia , Portador Sadio/patologia , Portador Sadio/prevenção & controle , Criança , Pré-Escolar , Estudos Transversais , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/patologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/imunologia , Humanos , Lactente , Irã (Geográfico) , Masculino , Nasofaringe/imunologia , Nasofaringe/microbiologia , Vacina Antipólio de Vírus Inativado/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
7.
Nephron ; 145(4): 363-370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33902031

RESUMO

BACKGROUND/AIMS: The coronavirus disease 2019 (CO-VID-19) pandemic is the major current health emergency worldwide, adding a significant burden also to the community of nephrologists for the management of their patients. Here, we analyzed the impact of COVID-19 infection in renal patients to assess the time to viral clearance, together with the production and persistence of IgG and IgM antibody response, in consideration of the altered immune capacity of this fragile population. METHODS: Viral clearance and antibody kinetics were investigated in 49 renal patients recovered from COVID-19 infection: 7 of them with chronic decompensated renal failure, 31 under dialysis treatment, and 11 kidney transplant recipients. RESULTS: The time span between the diagnosis of infection and recovery based on laboratory testing (2 negative nasopharyngeal swabs in consecutive days) was 31.7 ± 13.3 days. Three new positive cases were detected from 8 to 13 days following recovery. At the first serological determination after swab negativization, all the patients developed IgG and IgM antibodies. The semiquantitative analysis showed a progressive increase in IgG and a slow reduction in IgM. DISCUSSION/CONCLUSION: In subjects with decompensated chronic kidney disease, under dialysis and in transplant recipients, viral clearance is lengthened compared to the general population. However, in spite of their common status of immunodepression, all of them were able to produce specific antibodies. These data might provide useful insights for monitoring and planning health-care activities in the weak category of patients with compromised renal function recovered from COVID-19.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Transplante de Rim , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/análise , COVID-19/epidemiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Falência Renal Crônica/complicações , Falência Renal Crônica/imunologia , Falência Renal Crônica/terapia , Cinética , Masculino , Pessoa de Meia-Idade , Nasofaringe/imunologia , Nasofaringe/virologia , Estudos Retrospectivos , Transplantados , Resultado do Tratamento
8.
PLoS One ; 16(4): e0249972, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33831118

RESUMO

We evaluated the diagnostic accuracy of two newly developed, point-of-care, rapid antigen tests (RATs) for detecting SARS-CoV-2, the AFIAS COVID-19 Ag and the ichromaTM COVID-19 Ag, and investigated antigen kinetics. A total of 200 serially collected nasopharyngeal (NP) specimens from 38 COVID-19 patients and 122 specimens from negative controls were analyzed. Diagnostic sensitivity and specificity were assessed in comparison to molecular test results and subdivided according to targeted genes (E, RdRP, and N) and days post-symptom onset (PSO). For the kinetics evaluation, cut-off-indices from serial NP specimens were used according to the number of days PSO. Both RATs showed sensitivity of 91.3‒100% for specimens with cycle threshold (Ct) < 25. The specificity of AFIAS was 98.7‒98.9% and that of ichromaTM was 100.0%. The kappa values of AFIAS and ichromaTM for the molecular testing of specimens with Ct < 25 (RdRP) were 0.97 and 1.00, respectively. The sensitivity of AFIAS and ichromaTM for all genes was lower for specimens collected at 8‒14 PSO than for those collected before 7-days PSO. The kinetics profiles showed that antigen levels gradually decreased from ≤ 7-days PSO to > 22-days PSO. Both RATs showed excellent specificity and acceptable sensitivity for NP specimens with higher viral loads and for specimens collected within 7-days PSO. Hence, they have the potential to become useful tools for the early detection of SARS-CoV-2. However, because of concerns about false negativity, RATs should be used in conjunction with molecular tests.


Assuntos
Antígenos Virais/imunologia , Teste Sorológico para COVID-19 , COVID-19 , Nasofaringe , SARS-CoV-2/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/imunologia , Nasofaringe/virologia , Sensibilidade e Especificidade
9.
Biosci Trends ; 15(2): 93-99, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33776018

RESUMO

As the COVID-19 epidemic is still ongoing, a more rapid detection of SARS-CoV-2 infection such as viral antigen-detection needs to be evaluated for early diagnosis of COVID-19 disease. Here, we report the dynamic changes of SARS-CoV-2 viral antigens in nasopharyngeal swabs of COVID-19 patients and its association with the viral nucleic acid clearance and clinical outcomes. Eighty-five COVID-19 patients were enrolled for detection of SARS-CoV-2 viral antigens, including 57 anti-SARS-CoV-2 antibody negative cases and 28 antibody positive cases. The viral antigen could be detected in 52.63% (30/57) patients with SARS-CoV-2 antibody negative at the early stage of SARS-CoV-2 infection, especially in the first 5 days after disease onset (p = 0.0018) and disappeared in about 8 days after disease onset. Viral antigens were highly detectable in patients with low Ct value (less than 30) of SARS-CoV-2 nucleic acid RT-PCT assay, suggesting the expression of viral antigen was associated with high viral load. Furthermore, positive antigen detection indicated disease progression, nine cases with positive antigen (9/30, 30.0%), in contrast to two cases (2/27, 7.40%) (p = 0.0444) with negative antigen, which progressed into severe disease. Thus, the viral antigens were persistent in early stages of infection when virus was in highly replicating status, and viral antigen detection promises to rapidly screen positive patients in the early stage of SARS-CoV-2 infection.


Assuntos
Antígenos Virais/análise , Teste para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/imunologia , Adolescente , Adulto , Idoso , Antígenos Virais/sangue , COVID-19/imunologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Teste para COVID-19/tendências , China/epidemiologia , Progressão da Doença , Diagnóstico Precoce , Reações Falso-Negativas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/imunologia , Nasofaringe/virologia , Pandemias , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Fatores de Tempo , Carga Viral , Adulto Jovem
10.
Diagnosis (Berl) ; 8(3): 322-326, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-33554511

RESUMO

OBJECTIVES: Novel point-of-care antigen assays present a promising opportunity for rapid screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The purpose of this study was the clinical assessment of the new Roche SARS-CoV-2 Rapid Antigen Test. METHODS: The clinical performance of Roche SARS-CoV-2 Rapid Antigen Test was evaluated vs. a reverse transcription polymerase chain reaction (RT-PCR) laboratory-based assay (Seegene AllplexTM2019-nCoV) in nasopharyngeal swabs collected from a series of consecutive patients referred for SARS-CoV-2 diagnostics to the Pederzoli Hospital (Peschiera del Garda, Verona, Italy) over a 2-week period. RESULTS: The final study population consisted of 321 consecutive patients (mean age, 46 years and IQR, 32-56 years; 181 women, 56.4%), with 149/321 (46.4%) positive for SARS-CoV-2 RNA via the Seegene AllplexTM2019-nCoV Assay, and 109/321 (34.0%) positive with Roche SARS-CoV-2 Rapid Antigen Test, respectively. The overall accuracy of Roche SARS-CoV-2 Rapid Antigen Test compared to molecular testing was 86.9%, with 72.5% sensitivity and 99.4% specificity. Progressive decline in performance was observed as cycle threshold (Ct) values of different SARS-CoV-2 gene targets increased. The sensitivity was found to range between 97-100% in clinical samples with Ct values <25, between 50-81% in those with Ct values between 25 and <30, but low as 12-18% in samples with Ct values between 30 and <37. CONCLUSIONS: The clinical performance of Roche SARS-CoV-2 Rapid Antigen Test is excellent in nasopharyngeal swabs with Ct values <25, which makes it a reliable screening test in patients with high viral load. However, mass community screening would require the use of more sensitive techniques.


Assuntos
Antígenos Virais/análise , Teste Sorológico para COVID-19/normas , COVID-19/diagnóstico , COVID-19/virologia , Técnicas de Diagnóstico Molecular/normas , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Adulto , Antígenos Virais/imunologia , COVID-19/imunologia , Teste de Ácido Nucleico para COVID-19/normas , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Nasofaringe/imunologia , Nasofaringe/virologia , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Carga Viral
11.
PLoS One ; 16(2): e0247606, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33617597

RESUMO

BACKGROUND: Since COVID-19 pandemic is a global crisis, tests with high sensitivity and specificity are crucial for the identification and management of COVID-19 patients. There is an urgent need for low-cost rapid antigen COVID-19 test with a good diagnostic performance. Although various antigen rapid detection tests are widely available, strong evidence of their usefulness in clinical practice are still limited. Therefore, our aim was to evaluate clinical performance of STANDARD Q COVID-19 Ag Test (SD Biosensor, Gyeonggi-do, South Korea). METHODS: The performance of the STANDARD Q COVID-19 Ag Test for the detection of SARS-CoV-2 antigen was evaluated in comparison to RT-qPCR results in 120 symptomatic patients (median age 49, IQR 36-70) who presented to health care facility in Novi Sad, Vojvodina, Serbia. RESULTS: Twenty five out of 120 samples have been tested positive using STANDARD Q COVID-19 Ag Test, and all of them were also positive on RT-qPCR. Overall, the STANDARD Q COVID-19 Ag Test showed sensitivity of 58.1% (95% CI 42.1-73.0) but it was higher in the early days of disease, when the highest viral loads were detected. During the first five days after the symptom onset, the sensitivity ranged from 66.7% to 100% and the pooled accuracy and Kappa values were high (0.92 and 0.852). CONCLUSIONS: A strong agreement between performance of STANDARD Q COVID-19 Ag Test and RT-qPCR was observed during the first five days of illness, suggesting that this rapid antigenic test can be very useful for COVID-19 diagnosis in the early phase of disease.


Assuntos
Antígenos Virais/análise , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Nasofaringe , SARS-CoV-2/isolamento & purificação , Diagnóstico Precoce , Humanos , Pessoa de Meia-Idade , Nasofaringe/imunologia , Nasofaringe/virologia , Sensibilidade e Especificidade , Sérvia/epidemiologia
12.
Immunogenetics ; 73(1): 53-63, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33426583

RESUMO

The function of a tissue is determined by its construction and cellular composition. The action of different genes can thus only be understood properly when seen in the context of the environment in which they are expressed and function. We now experience a renaissance in morphological research in fish, not only because, surprisingly enough, large structures have remained un-described until recently, but also because improved methods for studying morphological characteristics in combination with expression analysis are at hand. In this review, we address anatomical features of teleost immune tissues. There are approximately 30,000 known teleost fish species and only a minor portion of them have been studied. We aim our review at the Atlantic salmon (Salmo salar) and other salmonids, but when applicable, we also present information from other species. Our focus is the anatomy of the kidney, thymus, spleen, the interbranchial lymphoid tissue (ILT), the newly discovered salmonid cloacal bursa and the naso-pharynx associated lymphoid tissue (NALT).


Assuntos
Peixes/imunologia , Tecido Linfoide/anatomia & histologia , Animais , Peixes/anatomia & histologia , Peixes/crescimento & desenvolvimento , Brânquias/anatomia & histologia , Brânquias/crescimento & desenvolvimento , Brânquias/imunologia , Rim/anatomia & histologia , Rim/crescimento & desenvolvimento , Rim/imunologia , Tecido Linfoide/crescimento & desenvolvimento , Tecido Linfoide/imunologia , Nasofaringe/anatomia & histologia , Nasofaringe/crescimento & desenvolvimento , Nasofaringe/imunologia , Salmo salar/anatomia & histologia , Salmo salar/crescimento & desenvolvimento , Salmo salar/imunologia , Baço/anatomia & histologia , Baço/crescimento & desenvolvimento , Baço/imunologia , Timo/anatomia & histologia , Timo/crescimento & desenvolvimento , Timo/imunologia
13.
J Transl Med ; 19(1): 32, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413422

RESUMO

BACKGROUND: Although it is becoming evident that individual's immune system has a decisive influence on SARS-CoV-2 disease progression, pathogenesis is largely unknown. In this study, we aimed to profile the host transcriptome of COVID-19 patients from nasopharyngeal samples along with virus genomic features isolated from respective host, and a comparative analyses of differential host responses in various SARS-CoV-2 infection systems. RESULTS: Unique and rare missense mutations in 3C-like protease observed in all of our reported isolates. Functional enrichment analyses exhibited that the host induced responses are mediated by innate immunity, interferon, and cytokine stimulation. Surprisingly, induction of apoptosis, phagosome, antigen presentation, hypoxia response was lacking within these patients. Upregulation of immune and cytokine signaling genes such as CCL4, TNFA, IL6, IL1A, CCL2, CXCL2, IFN, and CCR1 were observed in lungs. Lungs lacked the overexpression of ACE2 as suspected, however, high ACE2 but low DPP4 expression was observed in nasopharyngeal cells. Interestingly, directly or indirectly, viral proteins specially non-structural protein mediated overexpression of integrins such as ITGAV, ITGA6, ITGB7, ITGB3, ITGA2B, ITGA5, ITGA6, ITGA9, ITGA4, ITGAE, and ITGA8 in lungs compared to nasopharyngeal samples suggesting the possible way of enhanced invasion. Furthermore, we found comparatively highly expressed transcription factors such as CBP, CEBP, NFAT, ATF3, GATA6, HDAC2, TCF12 which have pivotal roles in lung injury. CONCLUSIONS: Even though this study incorporates a limited number of cases, our data will provide valuable insights in developing potential studies to elucidate the differential host responses on the viral pathogenesis in COVID-19, and incorporation of further data will enrich the search of an effective therapeutics.


Assuntos
COVID-19/genética , COVID-19/imunologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Adulto , Idoso de 80 Anos ou mais , COVID-19/virologia , Proteases 3C de Coronavírus/genética , Proteases 3C de Coronavírus/imunologia , Citocinas/genética , Feminino , Variação Genética , Humanos , Imunidade Inata/genética , Integrinas/genética , Pulmão/imunologia , Masculino , Pessoa de Meia-Idade , Modelos Imunológicos , Mutação de Sentido Incorreto , Nasofaringe/imunologia , Nasofaringe/virologia , Pandemias , RNA-Seq , SARS-CoV-2/isolamento & purificação , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Transcriptoma , Pesquisa Médica Translacional
14.
Mucosal Immunol ; 14(2): 305-316, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33244161

RESUMO

The novel coronavirus SARS-CoV-2 enters into the human body mainly through the ACE2 + TMPRSS2+ nasal epithelial cells. The initial host response to this pathogen occurs in a peculiar immune microenvironment that, starting from the Nasopharynx-Associated Lymphoid Tissue (NALT) system, is the product of a long evolutionary process that is aimed to first recognize exogenous airborne agents. In the present work, we want to critically review the latest molecular and cellular findings on the mucosal response to SARS-CoV-2 in the nasal cavity and in NALT, and to analyze its impact in the subsequent course of COVID-19. Finally, we want to explore the possibility that the regulation of the systemic inflammatory network against the virus can be modulated starting from the initial phases of the nasal and nasopharyngeal response and this may have several clinical and epidemiological implications starting from a mucosal vaccine development.


Assuntos
COVID-19/imunologia , Nasofaringe/virologia , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/patologia , COVID-19/transmissão , Vacinas contra COVID-19/imunologia , Humanos , Evasão da Resposta Imune , Tecido Linfoide/imunologia , Nasofaringe/imunologia , Serina Endopeptidases/metabolismo , Internalização do Vírus
15.
Enferm Clin ; 31 Suppl 1: S40-S48, 2021 Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33168452

RESUMO

In the current crisis caused by SARS-CoV-2, there is a global need to know and combat the virus. One of the strategies is to track and diagnose cases in order to isolate and interrupt the epidemiological chain. Therefore, the aim of this article is to describe the different most used diagnostic tests and analyze their validity and indications for use according to scientific evidence and the main recommendations of scientific societies and reference organizations at national and international level. Since the beginning of the pandemic, the availability of tests has been subject to the conditions of the manufacturing market itself and to the guidelines set in each country. Among the most used types of tests, it is worth highlighting PCR, antibody detection tests (IgG and IGM) and total antibodies (Ab), also known as rapid tests, and tests for the detection of antigens in nasopharyngeal exudate or other upper/lower respiratory samples. For each of these tests, it is necessary to know their recommendations for use and the procedure for taking samples, which is essential to minimize alterations in the results due to poor handling. Likewise, it is necessary to determine the most appropriate moment for taking samples and their adequate interpretation of the results obtained, which must always be considered together with the patient's symptoms for clinical decision-making.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Guias de Prática Clínica como Assunto , SARS-CoV-2 , Anticorpos Antivirais/análise , Teste de Ácido Nucleico para COVID-19/métodos , Teste Sorológico para COVID-19/métodos , Teste para COVID-19/estatística & dados numéricos , Erros de Diagnóstico , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Nasofaringe/imunologia , Reprodutibilidade dos Testes , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Manejo de Espécimes/métodos
16.
Nat Commun ; 11(1): 5854, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203890

RESUMO

SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectively. Classifier performance is stable across a wide range of viral load, suggesting utility in mitigating false positive or false negative results of direct SARS-CoV-2 tests.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Imunidade Inata/genética , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Diagnóstico Diferencial , Expressão Gênica , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/imunologia , Nasofaringe/imunologia , Nasofaringe/virologia , Pandemias , Pneumonia Viral/diagnóstico , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologia , SARS-CoV-2 , Sensibilidade e Especificidade , Carga Viral
17.
Expert Rev Vaccines ; 19(10): 959-972, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33107359

RESUMO

Introduction: Nasopharyngeal colonization is a precondition for mucosal and invasive pneumococcal disease. Prevention of colonization may reduce pneumococcal transmission and disease incidence. Therefore, several protein-based pneumococcal vaccines are currently under investigation. Areas covered: We aimed to better understand the host immune responses to pneumococcal proteins in the upper respiratory tract (URT) that could facilitate the development of serotype-independent pneumococcal vaccines. English peer-reviewed papers reporting immunological mechanisms involved in host immune response to pneumococcal proteins in the URT were retrieved through a PubMed search using the terms 'pneumococcal proteins,' 'nasopharyngeal colonization' and/or 'cellular/humoral host immune response.' Expert opinion: Although pneumococcal protein antigens induce humoral immune responses, as well as IL-17A-mediated immunity, none of them, when used as single antigen, is sufficient to control and broadly protect against pneumococcal colonization. Novel vaccines should contain multiple conserved protein antigens to activate both arms of the immune system and evoke protection against the whole spectrum of pneumococcal variants by reducing, rather than eradicating, pneumococcal carriage. The highest efficacy would likely be achieved when the vaccine is intranasally applied, inducing mucosal immunity and enhancing the first line of defense by restricting pneumococcal density in the URT, which in turn will lead to reduced transmission and protection against disease.


Assuntos
Nasofaringe/microbiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Administração Intranasal , Animais , Proteínas de Bactérias/imunologia , Humanos , Imunidade nas Mucosas , Nasofaringe/imunologia , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/imunologia , Sistema Respiratório/imunologia , Sistema Respiratório/microbiologia , Sorogrupo , Streptococcus pneumoniae/imunologia
18.
Clin Immunol ; 220: 108576, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32866645

RESUMO

Upper respiratory tract is the primary site of SARS-CoV-2 replication. Releasing of pro and anti-inflammatory mediators plays an important role in the immunopathogenesis of Coronavirus Disease 2019 (COVID-19). The aim of this study was to evaluate the early inflammatory response in upper airway by measuring of IFN-γ, TGF-ß1 and RANTES at mRNA level. Forty five SARS-CoV-2 infected patients were enrolled, whose were divided in two groups: asymptomatic and symptomatic. Twenty healthy persons, SARS-CoV-2 negative were included as controls. Higher IFN-γ expression was detected in SARS-CoV-2 infected patients in comparison with controls (p = 0.0393). IFN-γ expression was increased in symptomatic patients (p = 0.0405). TGF-ß1 and RANTES expressions were lower in SARS-CoV-2 infected patients than controls (p < 0.0001; p = 0.0011, respectively). A significant correlation between IFN-γ and TGF-ß1 was observed in SARS-CoV-2 asymptomatic patients (r = +0.61, p = 0.0014). The findings suggest that imbalance between IFN-γ and TGF-ß1 expression could be an impact in clinical expression of SARS-CoV-2 infection.


Assuntos
Betacoronavirus/patogenicidade , Quimiocina CCL5/genética , Infecções por Coronavirus/imunologia , Interferon gama/genética , Pneumonia Viral/imunologia , RNA Mensageiro/genética , Fator de Crescimento Transformador beta1/genética , Adulto , Doenças Assintomáticas , Betacoronavirus/imunologia , COVID-19 , Estudos de Casos e Controles , Quimiocina CCL5/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interferon gama/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Nasofaringe/imunologia , Nasofaringe/patologia , Nasofaringe/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Pneumonia Viral/virologia , RNA Mensageiro/imunologia , SARS-CoV-2 , Índice de Gravidade de Doença , Fator de Crescimento Transformador beta1/imunologia
19.
PLoS Biol ; 18(9): e3000849, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32898168

RESUMO

Despite limited genomic diversity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown a wide range of clinical manifestations in different patient populations. The mechanisms behind these host differences are still unclear. Here, we examined host response gene expression across infection status, viral load, age, and sex among shotgun RNA sequencing profiles of nasopharyngeal (NP) swabs from 430 individuals with PCR-confirmed SARS-CoV-2 and 54 negative controls. SARS-CoV-2 induced a strong antiviral response with up-regulation of antiviral factors such as OAS1-3 and IFIT1-3 and T helper type 1 (Th1) chemokines CXCL9/10/11, as well as a reduction in transcription of ribosomal proteins. SARS-CoV-2 culture in human airway epithelial (HAE) cultures replicated the in vivo antiviral host response 7 days post infection, with no induction of interferon-stimulated genes after 3 days. Patient-matched longitudinal specimens (mean elapsed time = 6.3 days) demonstrated reduction in interferon-induced transcription, recovery of transcription of ribosomal proteins, and initiation of wound healing and humoral immune responses. Expression of interferon-responsive genes, including ACE2, increased as a function of viral load, while transcripts for B cell-specific proteins and neutrophil chemokines were elevated in patients with lower viral load. Older individuals had reduced expression of the Th1 chemokines CXCL9/10/11 and their cognate receptor CXCR3, as well as CD8A and granzyme B, suggesting deficiencies in trafficking and/or function of cytotoxic T cells and natural killer (NK) cells. Relative to females, males had reduced B cell-specific and NK cell-specific transcripts and an increase in inhibitors of nuclear factor kappa-B (NF-κB) signaling, possibly inappropriately throttling antiviral responses. Collectively, our data demonstrate that host responses to SARS-CoV-2 are dependent on viral load and infection time course, with observed differences due to age and sex that may contribute to disease severity.


Assuntos
Antivirais/imunologia , Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Regulação da Expressão Gênica , Humanos , Imunidade/genética , Cinética , Masculino , Pessoa de Meia-Idade , Nasofaringe/imunologia , Nasofaringe/virologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Proteínas Ribossômicas/genética , SARS-CoV-2 , Fatores Sexuais , Transdução de Sinais/genética , Carga Viral , Cicatrização/genética , Adulto Jovem
20.
Infect Immun ; 88(10)2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32719155

RESUMO

Group A Streptococcus (GAS) is the etiologic agent of numerous high-morbidity and high-mortality diseases. Infections are typically highly proinflammatory. During the invasive infection necrotizing fasciitis, this is in part due to the GAS protease SpeB directly activating interleukin-1ß (IL-1ß) independent of the canonical inflammasome pathway. The upper respiratory tract is the primary site for GAS colonization, infection, and transmission, but the host-pathogen interactions at this site are still largely unknown. We found that in the murine nasopharynx, SpeB enhanced IL-1ß-mediated inflammation and the chemotaxis of neutrophils. However, neutrophilic inflammation did not restrict infection and instead promoted GAS replication and disease. Inhibiting IL-1ß or depleting neutrophils, which both promote invasive infection, prevented GAS infection of the nasopharynx. Mice pretreated with penicillin became more susceptible to GAS challenge, and this reversed the attenuation from neutralization or depletion of IL-1ß, neutrophils, or SpeB. Collectively, our results suggest that SpeB is essential to activate an IL-1ß-driven neutrophil response. Unlike during invasive tissue infections, this is beneficial in the upper respiratory tract because it disrupts colonization resistance mediated by the microbiota. This provides experimental evidence that the notable inflammation of strep throat, which presents with significant swelling, pain, and neutrophil influx, is not an ineffectual immune response but rather is a GAS-directed remodeling of this niche for its pathogenic benefit.


Assuntos
Nasofaringe/imunologia , Receptores Tipo I de Interleucina-1/imunologia , Transdução de Sinais/imunologia , Infecções Estreptocócicas/imunologia , Streptococcus pyogenes/patogenicidade , Animais , Antibacterianos/efeitos adversos , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Caspase 1/genética , Caspase 1/imunologia , Quimiotaxia de Leucócito , Exotoxinas/genética , Exotoxinas/imunologia , Inflamação , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Interleucina-1beta/imunologia , Camundongos , Nasofaringe/microbiologia , Neutrófilos/imunologia , Faringite/genética , Faringite/imunologia , Faringite/microbiologia , Receptores Tipo I de Interleucina-1/genética , Transdução de Sinais/efeitos dos fármacos , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/genética , Streptococcus pyogenes/crescimento & desenvolvimento , Virulência/efeitos dos fármacos , Virulência/genética
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