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1.
Nat Immunol ; 22(11): 1452-1464, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34611361

RESUMO

There is limited understanding of the viral antibody fingerprint following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children. Herein, SARS-CoV-2 proteome-wide immunoprofiling of children with mild/moderate or severe coronavirus disease 2019 (COVID-19) versus multisystem inflammatory syndrome in children versus hospitalized control patients revealed differential cytokine responses, IgM/IgG/IgA epitope diversity, antibody binding and avidity. Apart from spike and nucleocapsid, IgG/IgA recognized epitopes in nonstructural protein (NSP) 2, NSP3, NSP12-NSP14 and open reading frame (ORF) 3a-ORF9. Peptides representing epitopes in NSP12, ORF3a and ORF8 demonstrated SARS-CoV-2 serodiagnosis. Antibody-binding kinetics with 24 SARS-CoV-2 proteins revealed antibody parameters that distinguish children with mild/moderate versus severe COVID-19 or multisystem inflammatory syndrome in children. Antibody avidity to prefusion spike correlated with decreased illness severity and served as a clinical disease indicator. The fusion peptide and heptad repeat 2 region induced SARS-CoV-2-neutralizing antibodies in rabbits. Thus, we identified SARS-CoV-2 antibody signatures in children associated with disease severity and delineate promising serodiagnostic and virus neutralization targets. These findings might guide the design of serodiagnostic assays, prognostic algorithms, therapeutics and vaccines in this important but understudied population.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/complicações , COVID-19/imunologia , SARS-CoV-2/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Adolescente , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/metabolismo , COVID-19/diagnóstico , Criança , Pré-Escolar , Progressão da Doença , Epitopos/metabolismo , Feminino , Hospitalização , Humanos , Imunidade Humoral , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Masculino , Prognóstico , Proteoma , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
2.
Nat Commun ; 13(1): 2979, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35624101

RESUMO

Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5-11, 12-21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron. Children <5 years of age hospitalized with severe acute COVID-19 have lower neutralizing antibodies to SARS-CoV-2 variants compared with patients >5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children.


Assuntos
COVID-19 , SARS-CoV-2 , Adolescente , Anticorpos Antivirais , COVID-19/complicações , Criança , Pré-Escolar , Humanos , Glicoproteínas de Membrana , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus , Síndrome de Resposta Inflamatória Sistêmica , Proteínas do Envelope Viral
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