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1.
Cell Rep Methods ; 1(2): 100011, 2021 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-34235498

RESUMEN

We have developed a rapid, accurate, and cost-effective serologic test for SARS-CoV-2 virus, which caused the COVID-19 pandemic, on the basis of antibody-dependent agglutination of antigen-coated latex particles. When validated using plasma samples that are positive or negative for SARS-CoV-2, the agglutination assay detected antibodies against the receptor-binding domain of the spike (S-RBD) or the nucleocapsid protein of SARS-CoV-2 with 100% specificity and ∼98% sensitivity. Furthermore, we found that the strength of the S-RBD antibody response measured by the agglutination assay correlated with the efficiency of the plasma in blocking RBD binding to the angiotensin-converting enzyme 2 in a surrogate neutralization assay, suggesting that the agglutination assay might be used to identify individuals with virus-neutralizing antibodies. Intriguingly, we found that >92% of patients had detectable antibodies on the day of a positive viral RNA test, suggesting that the agglutination antibody test might complement RNA testing for the diagnosis of SARS-CoV-2 infection.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Pandemias , COVID-19/diagnóstico , Anticuerpos Antivirales , Aglutinación
2.
JCI Insight ; 6(13)2021 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-34081630

RESUMEN

BACKGROUNDThe role of humoral immunity in COVID-19 is not fully understood, owing, in large part, to the complexity of antibodies produced in response to the SARS-CoV-2 infection. There is a pressing need for serology tests to assess patient-specific antibody response and predict clinical outcome.METHODSUsing SARS-CoV-2 proteome and peptide microarrays, we screened 146 COVID-19 patients' plasma samples to identify antigens and epitopes. This enabled us to develop a master epitope array and an epitope-specific agglutination assay to gauge antibody responses systematically and with high resolution.RESULTSWe identified linear epitopes from the spike (S) and nucleocapsid (N) proteins and showed that the epitopes enabled higher resolution antibody profiling than the S or N protein antigen. Specifically, we found that antibody responses to the S-811-825, S-881-895, and N-156-170 epitopes negatively or positively correlated with clinical severity or patient survival. Moreover, we found that the P681H and S235F mutations associated with the coronavirus variant of concern B.1.1.7 altered the specificity of the corresponding epitopes.CONCLUSIONEpitope-resolved antibody testing not only affords a high-resolution alternative to conventional immunoassays to delineate the complex humoral immunity to SARS-CoV-2 and differentiate between neutralizing and non-neutralizing antibodies, but it also may potentially be used to predict clinical outcome. The epitope peptides can be readily modified to detect antibodies against variants of concern in both the peptide array and latex agglutination formats.FUNDINGOntario Research Fund (ORF) COVID-19 Rapid Research Fund, Toronto COVID-19 Action Fund, Western University, Lawson Health Research Institute, London Health Sciences Foundation, and Academic Medical Organization of Southwestern Ontario (AMOSO) Innovation Fund.


Asunto(s)
Pruebas de Aglutinación/métodos , Formación de Anticuerpos/inmunología , Prueba Serológica para COVID-19/métodos , COVID-19/inmunología , Epítopos de Linfocito B/inmunología , SARS-CoV-2/inmunología , Secuencia de Aminoácidos , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Especificidad de Anticuerpos/inmunología , COVID-19/sangre , COVID-19/mortalidad , Epítopos/inmunología , Epítopos de Linfocito B/química , Epítopos de Linfocito B/genética , Humanos , Inmunidad Humoral , Análisis por Micromatrices/métodos , Nucleocápside/química , Nucleocápside/genética , Nucleocápside/inmunología , Péptidos/inmunología , SARS-CoV-2/genética , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología
3.
Infect Dis Model ; 6: 112-122, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33385101

RESUMEN

The modelling is widely used in determining the best strategies for the mitigation of the impact of infectious diseases. Currently, the modelling of a complex system such as the spread of COVID-19 infection is among the topical issues. The aim of this article is graph-based modelling of the COVID-19 infection spread. The article investigates the studies related to the modelling of COVID-19 pandemic and analyses the factors affecting the spread of the disease and its main characteristics. We propose a conceptual model of COVID-19 epidemic by considering the social distance, the duration of contact with an infected person and their location-based demographic characteristics. Based on the hypothetical scenario of the spread of the virus, a graph model of the process are developed starting from the first confirmed infection case to human-to-human transmission of the virus and visualized by considering the epidemiological characteristics of COVID-19. The application of graph for the pandemic modelling allows for considering multiple factors affecting the epidemiological process and conducting numerical experiments. The advantage of this approach is justified with the fact that it enables the reverse analysis the spread as a result of the dynamic record of detected cases of the infection in the model. This approach allows for to determining undetected cases of infection based on the social distance and duration of contact and eliminating the uncertainty significantly. Note that social, economic, demographic factors, the population density, mental values and etc. affect the increase in number of cases of infection and hence, the research was not able to consider all factors. In future research will analyze multiple factors impacting the number of infections and their use in the models will be considered.

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