Loading...
Publication
Harmonização dos valores de anticorpos IgG contra a proteína Spike do vírus SARS-CoV-2
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 4.29 MB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
O surgimento da COVID-19 conduziu ao rápido desenvolvimento de vacinas e testes de diagnóstico. Para avaliar a resposta de anticorpos IgG contra a proteína Spike do vírus SARS-CoV-2 (IgG anti-S SARS-CoV-2) em profissionais de saúde do meio hospitalar, foi realizado um estudo de coorte entre 2020 e 2022 em três centros hospitalares portugueses: Centro Hospitalar de Lisboa Ocidental (CHLO), Centro Hospitalar Tondela-Viseu (CHTV) e Centro Hospitalar e Universitário de Coimbra (CHUC). Os níveis de anticorpos foram medidos em seis momentos: antes da vacinação, após vacinação completa, aos 3, 6 e 12 meses após a segunda dose, e após a dose de reforço. Cada hospital utilizou um método analítico distinto: CMIA da Abbott, ECLIA Elecsys® da Roche e ADVIA Centaur® da Siemens, o que gerou desafios na comparabilidade dos dados. O presente estudo teve como objetivo harmonizar os anticorpos IgG anti-S SARS-CoV-2 entre os hospitais para permitir uma análise conjunta e uma melhor compreensão da dinâmica da imunidade nos profissionais de saúde em Portugal. Para assegurar uma conversão adequada dos títulos de anticorpos obtidos por métodos laboratoriais diferentes, foram aplicadas e comparadas várias estratégias de harmonização, nomeadamente a conversão internacional proposta pela Organização Mundial da Saúde (WHO) e a interpolação de quantis, seguida da aplicação de regressão de Deming. A interpolação de quantis seguida de regressão revelou-se mais eficaz do que a conversão recomendada pela OMS, ao preservar as características individuais de distribuição dos dados de cada hospital e ao permitir que os valores harmonizados refletissem a escala e a magnitude do método usado como referência (CMIA da Abbott).
Após a harmonização, observou-se o padrão esperado de tendência temporal do título de anticorpos, com um aumento acentuado após a vacinação, seguido de um declínio ao longo dos meses e, por fim, um novo aumento mais pronunciado após a dose de reforço. Embora não tenha sido realizada uma validação laboratorial através da análise cruzada das amostras, uma limitação importante para a confirmação definitiva da abordagem, a metodologia demonstrou ser prática, reprodutível e com elevado potencial de aplicação em estudos multicêntricos e multinacionais que requerem a integração de dados serológicos obtidos por diferentes plataformas, nomeadamente no âmbito de colaborações europeias e internacionais. Após a harmonização, a análise estatística recorreu a modelos mistos para avaliar a evolução do título de anticorpos ao longo do tempo e a regressões lineares para analisar separadamente cada fase. Os modelos mistos evidenciaram aumentos significativos após a vacinação e o reforço, destacando diferenças entre os centros hospitalares. Nas análises por fase, além das variações entre os centros hospitalares no período pós-reforço, observou-se que indivíduos acima dos 50 anos apresentaram uma resposta imunitária superior. Estes resultados sugerem que tanto as características individuais como as diferenças institucionais influenciaram a resposta imunitária dos profissionais de saúde.
The emergence of COVID-19 led to the rapid development of vaccines and diagnostic tests. To assess the IgG antibody response against the Spike protein of the SARS-CoV-2 virus (IgG anti-S SARS-CoV-2) in healthcare workers within hospital settings, a cohort study was conducted between 2020 and 2022 across three Portuguese hospital centers: Centro Hospitalar de Lisboa Ocidental (CHLO), Centro Hospitalar Tondela-Viseu (CHTV) and Centro Hospitalar e Universitário de Coimbra (CHUC). Antibody levels were measured at six-time points: before vaccination, after complete vaccination, at 3, 6, and 12 months following the second dose, and after the booster dose. Each hospital used a distinct analytical method: Abbott’s CMIA, Roche’s Elecsys® ECLIA, and Siemens’ ADVIA Centaur®, which created challenges in data comparability. The present study aimed to harmonize IgG anti-S SARS-CoV-2 antibody measurements across the hospitals to enable joint analysis and a better understanding of the dynamics of immunity among healthcare workers in Portugal. To ensure the appropriate conversion of antibody titers obtained through different laboratory methods, several har monization strategies were applied and compared, namely the international conversion proposed by the World Health Organization (WHO) and quantile interpolation followed by Deming regression. Quantile interpolation com bined with regression proved more effective than the WHO-recommended conversion, as it preserved the individual distribution characteristics of each hospital’s data and allowed the harmonized values to reflect the scale and magnitude of the reference method (Abbott’s CMIA). After harmonization, the expected temporal pattern of antibody titers was observed, with a sharp increase after vaccination, followed by a gradual decline over the months and a more pronounced rise after the booster dose. Although no labora tory validation through cross-analysis of samples was performed, which is an important limitation for the definitive confirmation of the approach, the methodology proved practical, reproducible, and highly promising for appli cation in multicenter and multinational studies that require the integration of serological data obtained through different platforms, particularly within the scope of European and international collaborations. Following harmoni zation, statistical analysis relied on mixed models to assess the evolution of antibody titers over time and on linear regressions to analyze each phase se parately. The mixed models revealed significant increases after vaccination and booster administration, highlighting differences between the hospital centers. In the phase-specific analyses, in addition to variations between hospital centers in the post-booster period, it was observed that individuals over 50 years of age exhibited a superior immune response. These findings suggest that both individual characteristics and institutional differences in fluence the immune response of healthcare workers.
The emergence of COVID-19 led to the rapid development of vaccines and diagnostic tests. To assess the IgG antibody response against the Spike protein of the SARS-CoV-2 virus (IgG anti-S SARS-CoV-2) in healthcare workers within hospital settings, a cohort study was conducted between 2020 and 2022 across three Portuguese hospital centers: Centro Hospitalar de Lisboa Ocidental (CHLO), Centro Hospitalar Tondela-Viseu (CHTV) and Centro Hospitalar e Universitário de Coimbra (CHUC). Antibody levels were measured at six-time points: before vaccination, after complete vaccination, at 3, 6, and 12 months following the second dose, and after the booster dose. Each hospital used a distinct analytical method: Abbott’s CMIA, Roche’s Elecsys® ECLIA, and Siemens’ ADVIA Centaur®, which created challenges in data comparability. The present study aimed to harmonize IgG anti-S SARS-CoV-2 antibody measurements across the hospitals to enable joint analysis and a better understanding of the dynamics of immunity among healthcare workers in Portugal. To ensure the appropriate conversion of antibody titers obtained through different laboratory methods, several har monization strategies were applied and compared, namely the international conversion proposed by the World Health Organization (WHO) and quantile interpolation followed by Deming regression. Quantile interpolation com bined with regression proved more effective than the WHO-recommended conversion, as it preserved the individual distribution characteristics of each hospital’s data and allowed the harmonized values to reflect the scale and magnitude of the reference method (Abbott’s CMIA). After harmonization, the expected temporal pattern of antibody titers was observed, with a sharp increase after vaccination, followed by a gradual decline over the months and a more pronounced rise after the booster dose. Although no labora tory validation through cross-analysis of samples was performed, which is an important limitation for the definitive confirmation of the approach, the methodology proved practical, reproducible, and highly promising for appli cation in multicenter and multinational studies that require the integration of serological data obtained through different platforms, particularly within the scope of European and international collaborations. Following harmoni zation, statistical analysis relied on mixed models to assess the evolution of antibody titers over time and on linear regressions to analyze each phase se parately. The mixed models revealed significant increases after vaccination and booster administration, highlighting differences between the hospital centers. In the phase-specific analyses, in addition to variations between hospital centers in the post-booster period, it was observed that individuals over 50 years of age exhibited a superior immune response. These findings suggest that both individual characteristics and institutional differences in fluence the immune response of healthcare workers.
Description
Dissertação de mestrado em Estatística Médica, apresentada à Universidade de Aveiro, 2025
Orientadora Vânia Gaio (Departamento de Epidemiologia, INSA)
Orientadora Vânia Gaio (Departamento de Epidemiologia, INSA)
Keywords
Anticorpos IgG Harmonização Profissionais de Saúde SARS-CoV-2 Estados de Saúde e de Doença Observação em Saúde e Vigilância Harmonization Healthcare Workers IgG Antibody