Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19

Detalhes bibliográficos
Autor(a) principal: Beltrão, Fabyan Esberard de Lima
Data de Publicação: 2021
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFPB
Texto Completo: https://repositorio.ufpb.br/jspui/handle/123456789/22991
Resumo: The new coronavirus (SARS-CoV-2) can cause pulmonary and systemic inflammation and multiple organ dysfunction. Findings suggest that dysfunctions in in-hospital thyroid hormones and the Non-Thyroid Disease Syndrome (NTIS) are associated with poor clinical outcomes during COVID-19 hospitalization. Moreover, researchers found correlations between type 2 deiodinase (especially his Thr92Ala-DIO2 polymorphism) and acute lung injury and pulmonary fibrosis. However, studies that assess thyroid function and THR92ALA-D2 polymorphism in patients with COVID-19 are still insufficient and inconclusive. This study aimed to evaluate the association of thyroid function biomarkers, NTIS prevalence, and Thr92Ala polymorphism-DIO2 with COVID-19 mortality and COVID-19 severity biomarkers in the hospital setting. This study is a cohort, observational, longitudinal and prospective study that evaluate COVID-19 hospitalized patients. Our study includes a total of 274 patients with COVID-19 admitted to the Metropolitan Hospital of the João Pessoa-PB city (Northeast of Brazil) between June and August 2020. We assess the patient's thyroid hormones (TSH, free T3, free T4, and reverse T3), COVID-19 biomarkers, and Thr92Ala-DIO2 polymorphism genotype. Results: The cut-off level of free T3 (≤2.6 pg/mL) and reverse T3 (≤0.38 ng/mL) were associated with 3.46 and 5.94 OR of mortality, respectively. NTIS (fT3 ≤ 2.0 pg/mL) was correlated with 7.05 OR of mortality ([CI 1.78– 28.3], p = 0.005). The cut-off product level of rT3xfT3 (≤ 1.29) was associated with 8.08 OR mortality ([CI 3.14–24.2], p = 0.0001). We assessed 220 patients (we lack data of 54 patients) Thr92Ala-DIO2 polymorphism genotype and found the following result: Thr/Thr (n=79), Ala/Thr (n=119) and Ala/Ala (n=23). The overall mortality was 17.3% (n=220), lethality was lower in Ala/Thr patients (12.6%) when compared to Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The Kaplan-Meier curve showed a significantly higher chance of survival in patients with the heterozygous allele (Ala/Thr) than patients with homozygous alleles (HR 0.53, p = 0.048). Univariate and multivariate logistic regression adjusted for multiple covariates showed a mortality Ala/Thr reduction that ranged from 51-66%. To assure our results, we did a meta-analysis of 5 studies (including this one) about Thr92Ala-DIO2 polymorphism that confirmed the association of the Ala/Thr genotype with better clinical outcomes.
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spelling Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19COVID-19TireoidePolimorfismo THR92ALA-D2ThyroidTHR92ALA-D2 polymorphismCNPQ::CIENCIAS DA SAUDE::NUTRICAOThe new coronavirus (SARS-CoV-2) can cause pulmonary and systemic inflammation and multiple organ dysfunction. Findings suggest that dysfunctions in in-hospital thyroid hormones and the Non-Thyroid Disease Syndrome (NTIS) are associated with poor clinical outcomes during COVID-19 hospitalization. Moreover, researchers found correlations between type 2 deiodinase (especially his Thr92Ala-DIO2 polymorphism) and acute lung injury and pulmonary fibrosis. However, studies that assess thyroid function and THR92ALA-D2 polymorphism in patients with COVID-19 are still insufficient and inconclusive. This study aimed to evaluate the association of thyroid function biomarkers, NTIS prevalence, and Thr92Ala polymorphism-DIO2 with COVID-19 mortality and COVID-19 severity biomarkers in the hospital setting. This study is a cohort, observational, longitudinal and prospective study that evaluate COVID-19 hospitalized patients. Our study includes a total of 274 patients with COVID-19 admitted to the Metropolitan Hospital of the João Pessoa-PB city (Northeast of Brazil) between June and August 2020. We assess the patient's thyroid hormones (TSH, free T3, free T4, and reverse T3), COVID-19 biomarkers, and Thr92Ala-DIO2 polymorphism genotype. Results: The cut-off level of free T3 (≤2.6 pg/mL) and reverse T3 (≤0.38 ng/mL) were associated with 3.46 and 5.94 OR of mortality, respectively. NTIS (fT3 ≤ 2.0 pg/mL) was correlated with 7.05 OR of mortality ([CI 1.78– 28.3], p = 0.005). The cut-off product level of rT3xfT3 (≤ 1.29) was associated with 8.08 OR mortality ([CI 3.14–24.2], p = 0.0001). We assessed 220 patients (we lack data of 54 patients) Thr92Ala-DIO2 polymorphism genotype and found the following result: Thr/Thr (n=79), Ala/Thr (n=119) and Ala/Ala (n=23). The overall mortality was 17.3% (n=220), lethality was lower in Ala/Thr patients (12.6%) when compared to Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The Kaplan-Meier curve showed a significantly higher chance of survival in patients with the heterozygous allele (Ala/Thr) than patients with homozygous alleles (HR 0.53, p = 0.048). Univariate and multivariate logistic regression adjusted for multiple covariates showed a mortality Ala/Thr reduction that ranged from 51-66%. To assure our results, we did a meta-analysis of 5 studies (including this one) about Thr92Ala-DIO2 polymorphism that confirmed the association of the Ala/Thr genotype with better clinical outcomes.NenhumaO novo Coronavírus (SARS-CoV-2) pode causar inflamação pulmonar e sistêmica, levando a disfunção múltipla de órgãos. Alterações nos hormônios tireoidianos intra-hospitalar e a Síndrome da Doença Não Tireoidiana (NTIS) estão associados a desfechos clínicos desfavoráveis durante a internação e a desiodase tipo 2 e seu polimorfismo Thr92Ala-DIO2 têm sido associados a lesão pulmonar aguda e fibrose pulmonar. Estudos avaliando a função tireoidiana e o polimorfismo THR92ALA-D2, em pacientes com COVID-19 ainda são escassos e inconclusivos, baseados nestes fatos o trabalho teve como objetivo avaliar a associação entre os testes da função tireoidiana, a prevalência da NTIS e o polimorfismo Thr92Ala-DIO2 do gene da desiodase tipo 2, com mortalidade e biomarcadores de gravidade em pacientes admitidos em um hospital terciário especializado em COVID-19. Trata-se de um estudo do tipo coorte, observacional, longitudinal e prospectivo. A amostra foi constituída por 274 pacientes confirmados para COVID-19, admitidos no Hospital Metropolitano do Município de João Pessoa-PB, Nordeste do Brasil entre junho e agosto de 2020. Os pacientes foram submetidos a dosagem da função tireoidiana (TSH, T3 livre, T4 livre, T3 reverso), biomarcadores hormonais e imunológicos e genotipagem para o polimorfismo Thr92Ala-DIO2. Resultados: Um nível de corte de T3 livre (≤2,6 pg/mL) e T3 reverso (≤0,38 ng/mL) foi associado a 3,46 e 5,94 OR de mortalidade, respectivamente. NTIS (fT3≤ 2,0 pg/mL) foi associada a 7,05 OR de mortalidade ([IC 1,78–28,3], p =0,005) e o produto rT3xfT3 ≤ 1,29 com um OR de 8,08 de mortalidade ([CI 3,14–24,2], p = 0,0001). Com relação ao polimorfismo Thr92Ala-DIO2, 220 pacientes consecutivos foram genotipados e estratificados em três subgrupos: Thr/Thr (n=79), Thr/Ala (n=119) e Ala/Ala (n=23). Enquanto a mortalidade geral foi de 17,3%, a letalidade foi menor nos pacientes Ala/Thr (12,6%) quando comparados aos pacientes Thr/Thr (21,7%) ou pacientes Ala/Ala (23%). Na curva Kaplan-Meier mostrou sobrevida significativamente melhor em pacientes com o alelo heterozigoto (Thr/Ala) quando comparada com pacientes com alelos homozigotos (HR 0,53, p = 0,048). Na regressão logística univariada e multivariada ajustada para múltiplas covariáveis revelou uma redução que variou de 51-66%. A associação do genótipo Thr/Ala com melhores resultados clínicos foi confirmada em uma metanálise de 5 estudos, incluindo o presente.Universidade Federal da ParaíbaBrasilCiências da NutriçãoPrograma de Pós-Graduação em Ciências da NutriçãoUFPBGonçalves, Maria da Conceição Rodrigueshttp://lattes.cnpq.br/0107894093263204Ramos, Helton Estrelahttp://lattes.cnpq.br/5624505454133902Beltrão, Fabyan Esberard de Lima2022-06-06T18:53:58Z2022-01-192022-06-06T18:53:58Z2021-12-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/22991porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2022-08-09T14:24:03Zoai:repositorio.ufpb.br:123456789/22991Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2022-08-09T14:24:03Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19
title Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19
spellingShingle Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19
Beltrão, Fabyan Esberard de Lima
COVID-19
Tireoide
Polimorfismo THR92ALA-D2
Thyroid
THR92ALA-D2 polymorphism
CNPQ::CIENCIAS DA SAUDE::NUTRICAO
title_short Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19
title_full Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19
title_fullStr Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19
title_full_unstemmed Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19
title_sort Avaliação da função tireoidiana e polimorfismo THR92ALA-D2 do gene da desiodase tipo 2 como biomarcadores de mortalidade na Covid-19
author Beltrão, Fabyan Esberard de Lima
author_facet Beltrão, Fabyan Esberard de Lima
author_role author
dc.contributor.none.fl_str_mv Gonçalves, Maria da Conceição Rodrigues
http://lattes.cnpq.br/0107894093263204
Ramos, Helton Estrela
http://lattes.cnpq.br/5624505454133902
dc.contributor.author.fl_str_mv Beltrão, Fabyan Esberard de Lima
dc.subject.por.fl_str_mv COVID-19
Tireoide
Polimorfismo THR92ALA-D2
Thyroid
THR92ALA-D2 polymorphism
CNPQ::CIENCIAS DA SAUDE::NUTRICAO
topic COVID-19
Tireoide
Polimorfismo THR92ALA-D2
Thyroid
THR92ALA-D2 polymorphism
CNPQ::CIENCIAS DA SAUDE::NUTRICAO
description The new coronavirus (SARS-CoV-2) can cause pulmonary and systemic inflammation and multiple organ dysfunction. Findings suggest that dysfunctions in in-hospital thyroid hormones and the Non-Thyroid Disease Syndrome (NTIS) are associated with poor clinical outcomes during COVID-19 hospitalization. Moreover, researchers found correlations between type 2 deiodinase (especially his Thr92Ala-DIO2 polymorphism) and acute lung injury and pulmonary fibrosis. However, studies that assess thyroid function and THR92ALA-D2 polymorphism in patients with COVID-19 are still insufficient and inconclusive. This study aimed to evaluate the association of thyroid function biomarkers, NTIS prevalence, and Thr92Ala polymorphism-DIO2 with COVID-19 mortality and COVID-19 severity biomarkers in the hospital setting. This study is a cohort, observational, longitudinal and prospective study that evaluate COVID-19 hospitalized patients. Our study includes a total of 274 patients with COVID-19 admitted to the Metropolitan Hospital of the João Pessoa-PB city (Northeast of Brazil) between June and August 2020. We assess the patient's thyroid hormones (TSH, free T3, free T4, and reverse T3), COVID-19 biomarkers, and Thr92Ala-DIO2 polymorphism genotype. Results: The cut-off level of free T3 (≤2.6 pg/mL) and reverse T3 (≤0.38 ng/mL) were associated with 3.46 and 5.94 OR of mortality, respectively. NTIS (fT3 ≤ 2.0 pg/mL) was correlated with 7.05 OR of mortality ([CI 1.78– 28.3], p = 0.005). The cut-off product level of rT3xfT3 (≤ 1.29) was associated with 8.08 OR mortality ([CI 3.14–24.2], p = 0.0001). We assessed 220 patients (we lack data of 54 patients) Thr92Ala-DIO2 polymorphism genotype and found the following result: Thr/Thr (n=79), Ala/Thr (n=119) and Ala/Ala (n=23). The overall mortality was 17.3% (n=220), lethality was lower in Ala/Thr patients (12.6%) when compared to Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The Kaplan-Meier curve showed a significantly higher chance of survival in patients with the heterozygous allele (Ala/Thr) than patients with homozygous alleles (HR 0.53, p = 0.048). Univariate and multivariate logistic regression adjusted for multiple covariates showed a mortality Ala/Thr reduction that ranged from 51-66%. To assure our results, we did a meta-analysis of 5 studies (including this one) about Thr92Ala-DIO2 polymorphism that confirmed the association of the Ala/Thr genotype with better clinical outcomes.
publishDate 2021
dc.date.none.fl_str_mv 2021-12-15
2022-06-06T18:53:58Z
2022-01-19
2022-06-06T18:53:58Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/123456789/22991
url https://repositorio.ufpb.br/jspui/handle/123456789/22991
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Ciências da Nutrição
Programa de Pós-Graduação em Ciências da Nutrição
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Ciências da Nutrição
Programa de Pós-Graduação em Ciências da Nutrição
UFPB
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFPB
instname:Universidade Federal da Paraíba (UFPB)
instacron:UFPB
instname_str Universidade Federal da Paraíba (UFPB)
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reponame_str Biblioteca Digital de Teses e Dissertações da UFPB
collection Biblioteca Digital de Teses e Dissertações da UFPB
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)
repository.mail.fl_str_mv diretoria@ufpb.br|| diretoria@ufpb.br
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