BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2

Detalhes bibliográficos
Autor(a) principal: Fabiani de Morais Batista
Data de Publicação: 2023
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFMS
Texto Completo: https://repositorio.ufms.br/handle/123456789/6264
Resumo: Coronavirus disease 2019 (COVID-19) is highly infectious. Studies have documented the relationship between COVID-19 severity and circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer. In patients with severe COVID-19, elevated levels of IL-6 and interleukin 2 (IL-2) and tumor necrosis factor-Alpha (TNF-α) have been found. Other markers are similarly identified when critically ill COVID-19 patients had higher circulating levels of IL-2, IL-7, IL-10, and TNF-α. A better understanding of immune responses to SARS-CoV-2 infection that differentiate cases from levels of severity is critical for an accurate assessment of prognosis and identification of future biomarkers. The aim of the study was to identify differences in serological biomarker levels between individuals with mild and severe COVID-19. Methods: Participants from four Brazilian cities, aged over 18 years, were included from October 2020 to June 2021. Participants were tested for the presence of SARS-CoV-2 through Polymerase Chain Reaction with Quantitative Reverse Editing (RT-qPCR) and additionally had a blood sample collected for further analysis of biomarkers. Participants were divided into index cases (participants with clinical suspicion of flu, with up to 11 days of symptoms, with a positive test for SARS-CoV-2, hospitalized or not) and household contacts of non-hospitalized index cases (regardless of whether or not they had symptoms), which made it possible to analyze the selection of asymptomatic positive participants and a negative control group. Analysis of serological biomarkers was performed using MAGPIX Luminex® xMAP® technology, using three different MILLIPLEX® Map panels. Seventy-one biomarkers were quantified from participants with SARS-CoV-2 infection and control group. We correlated the levels of biological markers with negative control (C), asymptomatic (A), non-hospitalized (mild-M) and hospitalized (severe-S) groups. Results: 48 participants were included, most of them female (67%), with a median age of 47 years. Among angiogenesis biomarkers, we identified 6/17 (EGF, IL-8, HGF, HB-EGF, VEGF-C, VEGF-A) that showed significantly elevated levels in severe cases. Among cardiovascular disease biomarkers, 7/10 showed significant differences between groups (D-dimer, GDF-15, myoglobin, sICAM-1, MPO, P-selectin and Lipocalinlipocalin-2/NGAL). The D-dimer biomarkers, GDF-15 and sICAM-1 had the highest levels in severe cases when compared to the other groups. Of the cytokine/chemokine evaluations, 9/44 showed a statistically significant difference between groups (IL-6, IL-7, IL-18, IP-10, M-CSF, MDC, MIP-1 beta, PDGF-AA and TNF alpha). IL-6, IP-10, M-CSF, MDC and MIP-1 beta were higher in severe cases than in group C. Conclusion: This is the first compressive study in Brazil that identified and described levels of biological markers related to levels of cytokines, cardiac and endothelial system. It can be seen that most of the changes in biomarkers, when compared between the groups, showed a statistically significant difference. Although it was possible to find changes in most biomarkers in hospitalized participants, additional studies are motivated to improve the association with clinical evolution, monitoring and risk factors of individuals with COVID-19.
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spelling 2023-07-07T16:05:04Z2023-07-07T16:05:04Z2023https://repositorio.ufms.br/handle/123456789/6264Coronavirus disease 2019 (COVID-19) is highly infectious. Studies have documented the relationship between COVID-19 severity and circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer. In patients with severe COVID-19, elevated levels of IL-6 and interleukin 2 (IL-2) and tumor necrosis factor-Alpha (TNF-α) have been found. Other markers are similarly identified when critically ill COVID-19 patients had higher circulating levels of IL-2, IL-7, IL-10, and TNF-α. A better understanding of immune responses to SARS-CoV-2 infection that differentiate cases from levels of severity is critical for an accurate assessment of prognosis and identification of future biomarkers. The aim of the study was to identify differences in serological biomarker levels between individuals with mild and severe COVID-19. Methods: Participants from four Brazilian cities, aged over 18 years, were included from October 2020 to June 2021. Participants were tested for the presence of SARS-CoV-2 through Polymerase Chain Reaction with Quantitative Reverse Editing (RT-qPCR) and additionally had a blood sample collected for further analysis of biomarkers. Participants were divided into index cases (participants with clinical suspicion of flu, with up to 11 days of symptoms, with a positive test for SARS-CoV-2, hospitalized or not) and household contacts of non-hospitalized index cases (regardless of whether or not they had symptoms), which made it possible to analyze the selection of asymptomatic positive participants and a negative control group. Analysis of serological biomarkers was performed using MAGPIX Luminex® xMAP® technology, using three different MILLIPLEX® Map panels. Seventy-one biomarkers were quantified from participants with SARS-CoV-2 infection and control group. We correlated the levels of biological markers with negative control (C), asymptomatic (A), non-hospitalized (mild-M) and hospitalized (severe-S) groups. Results: 48 participants were included, most of them female (67%), with a median age of 47 years. Among angiogenesis biomarkers, we identified 6/17 (EGF, IL-8, HGF, HB-EGF, VEGF-C, VEGF-A) that showed significantly elevated levels in severe cases. Among cardiovascular disease biomarkers, 7/10 showed significant differences between groups (D-dimer, GDF-15, myoglobin, sICAM-1, MPO, P-selectin and Lipocalinlipocalin-2/NGAL). The D-dimer biomarkers, GDF-15 and sICAM-1 had the highest levels in severe cases when compared to the other groups. Of the cytokine/chemokine evaluations, 9/44 showed a statistically significant difference between groups (IL-6, IL-7, IL-18, IP-10, M-CSF, MDC, MIP-1 beta, PDGF-AA and TNF alpha). IL-6, IP-10, M-CSF, MDC and MIP-1 beta were higher in severe cases than in group C. Conclusion: This is the first compressive study in Brazil that identified and described levels of biological markers related to levels of cytokines, cardiac and endothelial system. It can be seen that most of the changes in biomarkers, when compared between the groups, showed a statistically significant difference. Although it was possible to find changes in most biomarkers in hospitalized participants, additional studies are motivated to improve the association with clinical evolution, monitoring and risk factors of individuals with COVID-19.A doença por Coronavírus 2019 (COVID-19) é altamente infecciosa. Estudos documentaram a relação entre a gravidade da COVID-19 e os níveis circulantes de proteína C reativa (PCR), interleucina-6 (IL-6) e D-dímero. Em pacientes com a COVID-19 grave, foram encontrados níveis elevados de IL-6 e interleucina 2 (IL-2) e fator de necrose tumoral-Alfa (TNF-α). Outros marcadores são identificados de forma semelhante quando pacientes com COVID-19 em estado crítico apresentaram maiores níveis circulantes de IL-2, IL-7, IL-10 e TNF-α. Uma melhor compreensão das respostas imunes à infecção por SARS-CoV-2 que diferencie casos leves de graves é fundamental para uma avaliação acurada do prognóstico e identificação de futuros biomarcadores. O objetivo do estudo foi identificar diferenças nos níveis de biomarcadores sorológicos entre indivíduos com COVID-19 leve e grave. Métodos: Foram incluídos participantes de quatro cidades brasileiras, maiores de 18 anos, no período de outubro de 2020 a junho de 2021. Os participantes foram testados para presença de SARS-CoV-2 através da Reação em Cadeia da Polimerase com Transcrição Reversa Quantitativa (RT-qPCR) e, adicionalmente, tiveram uma amostra de sangue coletada para posterior análise dos biomarcadores. Os participantes foram divididos em casos índices (participantes com suspeita clínica de gripe, com até 11 dias de sintomas, com teste positivo para SARS-CoV-2, hospitalizados ou não) e contatos domiciliares de casos índices não hospitalizados (independentemente de apresentarem ou não sintomas), o que possibilitou a análise de amostras de participantes positivos assintomáticos e grupo controle negativo. A análise dos biomarcadores sorológicos foi realizada utilizando a tecnologia MAGPIX Luminex® xMAP®, usando três painéis MILLIPLEX® Map diferentes. Setenta e um biomarcadores foram quantificados de participantes com infecção por SARS-CoV-2 e grupo controle. Correlacionamos os níveis dos marcadores biológicos com os grupos controle Negativo (C), assintomático (A), não hospitalizado (leve-M) e hospitalizado (grave-S). Resultados: Foram incluídos 48 participantes, sendo a maioria do sexo feminino (67%), com mediana de idade de 47 anos. Dentre os biomarcadores de angiogênese, identificamos 6/17 (EGF, IL-8, HGF, HB-EGF, VEGF-C, VEGF-A) que apresentaram níveis significativamente elevados nos casos graves. Entre os biomarcadores de doenças cardiovasculares, 7/10 apresentaram diferenças significativas entre os grupos (D-dímero, GDF-15, mioglobina, sICAM-1, MPO, P-selectina e Lipocalinlipocalin-2/NGAL). Os biomarcadores D-dímero, GDF-15 e sICAM-1 estavam com os níveis mais elevados nos casos graves quando comparados com os demais grupos. Das citocinas/quimiocinas avaliadas, 9/44 apresentaram diferença estatisticamente significativa entre os grupos (IL-6, IL-7, IL-18, IP-10, M-CSF, MDC, MIP-1 beta, PDGF-AA e TNF alfa). IL-6, IP-10, M-CSF, MDC e MIP-1 beta foram maiores nos casos graves do que no grupo C. Conclusão: Este é o primeiro estudo compressivo no Brasil que identificou e descreveu níveis de marcadores biológicos relacionados aos níveis de citocinas, sistema cardíaco e endotelial. Pode-se observar que a maioria das alterações dos biomarcadores, quando comparados entre os grupos, apresentaram diferença estatisticamente significativa. Embora tenha sido possível encontrar alterações da maioria dos biomarcadores em participantes hospitalizados, estudos adicionais são necessários visando melhorar a associação com a evolução clínica, monitoramento e os fatores de riscos dos indivíduos com a COVID-19.Fundação Universidade Federal de Mato Grosso do SulUFMSBrasilCOVID-19. SARS-CoV-2. Gravidade. Biomarcadores. Imunidade.BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisJulio Henrique Rosa CrodaFabiani de Morais Batistainfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da UFMSinstname:Universidade Federal de Mato Grosso do Sul (UFMS)instacron:UFMSORIGINALDissertação_Fabiani de Morais Batista_PPG-DIP_UFMS_Versão final_05072023_Publicada.pdfDissertação_Fabiani de Morais Batista_PPG-DIP_UFMS_Versão final_05072023_Publicada.pdfapplication/pdf2060925https://repositorio.ufms.br/bitstream/123456789/6264/-1/Disserta%c3%a7%c3%a3o_Fabiani%20de%20Morais%20Batista_PPG-DIP_UFMS_Vers%c3%a3o%20final_05072023_Publicada.pdfd6c533147599c3430474be0e4ab80a5cMD5-1123456789/62642023-07-07 12:05:07.14oai:repositorio.ufms.br:123456789/6264Repositório InstitucionalPUBhttps://repositorio.ufms.br/oai/requestri.prograd@ufms.bropendoar:21242023-07-07T16:05:07Repositório Institucional da UFMS - Universidade Federal de Mato Grosso do Sul (UFMS)false
dc.title.pt_BR.fl_str_mv BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2
title BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2
spellingShingle BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2
Fabiani de Morais Batista
COVID-19. SARS-CoV-2. Gravidade. Biomarcadores. Imunidade.
title_short BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2
title_full BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2
title_fullStr BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2
title_full_unstemmed BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2
title_sort BIOMARCADORES ASSOCIADOS A GRAVIDADE NA INFECÇÃO POR SARS-CoV-2
author Fabiani de Morais Batista
author_facet Fabiani de Morais Batista
author_role author
dc.contributor.advisor1.fl_str_mv Julio Henrique Rosa Croda
dc.contributor.author.fl_str_mv Fabiani de Morais Batista
contributor_str_mv Julio Henrique Rosa Croda
dc.subject.por.fl_str_mv COVID-19. SARS-CoV-2. Gravidade. Biomarcadores. Imunidade.
topic COVID-19. SARS-CoV-2. Gravidade. Biomarcadores. Imunidade.
description Coronavirus disease 2019 (COVID-19) is highly infectious. Studies have documented the relationship between COVID-19 severity and circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer. In patients with severe COVID-19, elevated levels of IL-6 and interleukin 2 (IL-2) and tumor necrosis factor-Alpha (TNF-α) have been found. Other markers are similarly identified when critically ill COVID-19 patients had higher circulating levels of IL-2, IL-7, IL-10, and TNF-α. A better understanding of immune responses to SARS-CoV-2 infection that differentiate cases from levels of severity is critical for an accurate assessment of prognosis and identification of future biomarkers. The aim of the study was to identify differences in serological biomarker levels between individuals with mild and severe COVID-19. Methods: Participants from four Brazilian cities, aged over 18 years, were included from October 2020 to June 2021. Participants were tested for the presence of SARS-CoV-2 through Polymerase Chain Reaction with Quantitative Reverse Editing (RT-qPCR) and additionally had a blood sample collected for further analysis of biomarkers. Participants were divided into index cases (participants with clinical suspicion of flu, with up to 11 days of symptoms, with a positive test for SARS-CoV-2, hospitalized or not) and household contacts of non-hospitalized index cases (regardless of whether or not they had symptoms), which made it possible to analyze the selection of asymptomatic positive participants and a negative control group. Analysis of serological biomarkers was performed using MAGPIX Luminex® xMAP® technology, using three different MILLIPLEX® Map panels. Seventy-one biomarkers were quantified from participants with SARS-CoV-2 infection and control group. We correlated the levels of biological markers with negative control (C), asymptomatic (A), non-hospitalized (mild-M) and hospitalized (severe-S) groups. Results: 48 participants were included, most of them female (67%), with a median age of 47 years. Among angiogenesis biomarkers, we identified 6/17 (EGF, IL-8, HGF, HB-EGF, VEGF-C, VEGF-A) that showed significantly elevated levels in severe cases. Among cardiovascular disease biomarkers, 7/10 showed significant differences between groups (D-dimer, GDF-15, myoglobin, sICAM-1, MPO, P-selectin and Lipocalinlipocalin-2/NGAL). The D-dimer biomarkers, GDF-15 and sICAM-1 had the highest levels in severe cases when compared to the other groups. Of the cytokine/chemokine evaluations, 9/44 showed a statistically significant difference between groups (IL-6, IL-7, IL-18, IP-10, M-CSF, MDC, MIP-1 beta, PDGF-AA and TNF alpha). IL-6, IP-10, M-CSF, MDC and MIP-1 beta were higher in severe cases than in group C. Conclusion: This is the first compressive study in Brazil that identified and described levels of biological markers related to levels of cytokines, cardiac and endothelial system. It can be seen that most of the changes in biomarkers, when compared between the groups, showed a statistically significant difference. Although it was possible to find changes in most biomarkers in hospitalized participants, additional studies are motivated to improve the association with clinical evolution, monitoring and risk factors of individuals with COVID-19.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-07-07T16:05:04Z
dc.date.available.fl_str_mv 2023-07-07T16:05:04Z
dc.date.issued.fl_str_mv 2023
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dc.publisher.country.fl_str_mv Brasil
publisher.none.fl_str_mv Fundação Universidade Federal de Mato Grosso do Sul
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