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1.
J Clin Invest ; 131(21)2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34499051

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2-specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing "original antigenic sin."


Asunto(s)
Linfocitos B/inmunología , Linfocitos B/virología , COVID-19/inmunología , COVID-19/virología , Coronavirus/inmunología , SARS-CoV-2/inmunología , Adulto , Anciano , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Especificidad de Anticuerpos , Estudios de Casos y Controles , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Proteínas de la Nucleocápside de Coronavirus/inmunología , Reacciones Cruzadas , Femenino , Interacciones Microbiota-Huesped/inmunología , Humanos , Inmunoglobulina G/sangre , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pandemias , Fosfoproteínas/inmunología , Estaciones del Año , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/inmunología
2.
Emerg Infect Dis ; 26(7): 1478-1488, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32267220

RESUMEN

A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein-specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.


Asunto(s)
Anticuerpos Antivirales/sangre , Betacoronavirus/inmunología , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/diagnóstico , COVID-19 , Prueba de COVID-19 , Ensayo de Inmunoadsorción Enzimática , Humanos , Pruebas de Neutralización , Pandemias , SARS-CoV-2 , Sensibilidad y Especificidad , Pruebas Serológicas
3.
Emerg Infect Dis ; 25(10): 1868-1877, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31423970

RESUMEN

Middle East respiratory syndrome coronavirus (MERS-CoV) infections in humans can cause asymptomatic to fatal lower respiratory lung disease. Despite posing a probable risk for virus transmission, asymptomatic to mild infections can go unnoticed; a lack of seroconversion among some PCR-confirmed cases has been reported. We found that a MERS-CoV spike S1 protein-based ELISA, routinely used in surveillance studies, showed low sensitivity in detecting infections among PCR-confirmed patients with mild clinical symptoms and cross-reactivity of human coronavirus OC43-positive serum samples. Using in-house S1 ELISA and protein microarray, we demonstrate that most PCR-confirmed MERS-CoV case-patients with mild infections seroconverted; nonetheless, some of these samples did not have detectable levels of virus-neutralizing antibodies. The use of a sensitive and specific serologic S1-based assay can be instrumental in the accurate estimation of MERS-CoV prevalence.


Asunto(s)
Anticuerpos Antivirales/inmunología , Infecciones por Coronavirus/inmunología , Inmunidad Humoral/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Infecciones por Coronavirus/virología , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Factores de Tiempo
4.
J Clin Virol ; 92: 25-31, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28505571

RESUMEN

BACKGROUND: Diagnostic requests for both Zika virus (ZIKV) and dengue virus (DENV) infections in returning travelers have significantly increased during the recent ZIKV outbreak in the Americás. These flaviviruses have overlapping clinical syndromes and geographical distribution, but diagnostic differentiation is important because of different clinical consequences. As flaviviruses are known to have a short viremic period, diagnostics often rely on serological methods, which are challenging due to extensive cross-reactive antibodies. OBJECTIVE: To re-evaluate the performance of DENV serological assays in laboratory confirmed ZIKV-infected travelers. STUDY DESIGN: The extent of cross-reactivity of the DENV NS1 antigen, IgM and IgG ELISA was analyzed in 152 clinical blood samples collected from 69 qRT-PCR and 24 virus neutralization titer (VNT) confirmed ZIKV-infected travelers. RESULTS: The majority of travelers in the presented cohort returned to the Netherlands from Suriname and presented with symptoms of fever and rash. Twenty-three percent of the female travelers were pregnant. None of the 39 ZIKV RNA positive blood samples were cross-reactive in the DENV NS1 antigen ELISA. The rates of cross-reactivity of the DENV IgM and IgG ELISÁs were 31% and 54%, respectively, after excluding travelers with (potential) previous DENV exposure. CONCLUSIONS: Although the DENV NS1 antigen assay was highly specific in this cohort of laboratory confirmed ZIKV-infected travelers, we demonstrate high percentages of cross-reactivity of DENV IgM and IgG ELISÁs of which diagnostic laboratories should be aware. In addition, the high rate of DENV IgG background of >25% complicates a proper serological diagnosis in this group.


Asunto(s)
Anticuerpos Antivirales/sangre , Virus del Dengue/inmunología , Virus del Dengue/aislamiento & purificación , Dengue/diagnóstico , Enfermedad Relacionada con los Viajes , Infección por el Virus Zika/diagnóstico , Virus Zika/inmunología , Adulto , Estudios de Cohortes , Reacciones Cruzadas , Dengue/virología , Virus del Dengue/genética , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Persona de Mediana Edad , Países Bajos , ARN Viral/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Pruebas Serológicas , Suriname , Proteínas no Estructurales Virales/sangre , Proteínas no Estructurales Virales/inmunología , Virus Zika/genética , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/virología
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