Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress

Detalhes bibliográficos
Autor(a) principal: Átila Duque Rossi
Data de Publicação: 2021
Outros Autores: Hugo José Alves, Helena Toledo Scheid, Débora Souza Faffe, Rafael Mello Galliez, Renata Eliane de Ávila, Gustavo Gomes Resende, Mauro Martins Teixeira, Orlando da Costa Ferreira Júnior, Terezinha Marta Castineiras, Renan Pedra Souza, João Locke Ferreira de Araújo, Amilcar Tanuri, Renato Santana de Aguiar, Shana Priscila Coutinho Barroso, Cynthia Chester Cardoso, Tailah Bernardo de Almeida, Marcelo Ribeiro-alves, Camila de Almeida Velozo, Jéssica Maciel de Almeida, Isabela de Carvalho Leitão, Sâmila Natiane Ferreira, Jéssica da Silva Oliveira
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da UFMG
Texto Completo: https://doi.org/10.1038/s41598-021-88944-8
http://hdl.handle.net/1843/56358
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https://orcid.org/0000-0003-0105-1312
https://orcid.org/0000-0002-0752-120X
https://orcid.org/0000-0001-7919-612X
https://orcid.org/0000-0002-2591-1818
Resumo: ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. However, it is still unclear whether expression levels of these factors could reflect disease severity. Here, a case–control study was conducted with 213 SARS-CoV-2 positive individuals where cases were defined as COVID-19 patients with respiratory distress requiring oxygen support (N = 38) and controls were those with mild to moderate symptoms of the disease who did not need oxygen therapy along the entire clinical course (N = 175). ACE2 and TMPRSS2 mRNA levels were evaluated in nasopharyngeal swab samples by RT-qPCR and logistic regression analyzes were applied to estimate associations with respiratory outcomes. ACE2 and TMPRSS2 levels positively correlated with age, which was also strongly associated with respiratory distress. Increased nasopharyngeal ACE2 levels showed a protective effect against this outcome (adjOR = 0.30; 95% CI 0.09–0.91), while TMPRSS2/ACE2 ratio was associated with risk (adjOR = 4.28; 95% CI 1.36–13.48). On stepwise regression, TMPRSS2/ACE2 ratio outperformed ACE2 to model COVID-19 severity. When nasopharyngeal swabs were compared to bronchoalveolar lavages in an independent cohort of COVID-19 patients under mechanical ventilation, similar expression levels of these genes were observed. These data suggest nasopharyngeal TMPRSS2/ACE2 as a promising candidate for further prediction models on COVID-19.
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spelling 2023-07-15T00:20:58Z2023-07-15T00:20:58Z2021119658https://doi.org/10.1038/s41598-021-88944-82045-2322http://hdl.handle.net/1843/56358https://orcid.org/0000-0001-6235-8807https://orcid.org/0000-0003-1450-0148https://orcid.org/0000-0002-5795-429Xhttps://orcid.org/0000-0001-5255-5938https://orcid.org/0000-0003-0348-8374https://orcid.org/0000-0001-6566-9280https://orcid.org/0000-0002-6944-3008https://orcid.org/0000-0002-1970-8936https://orcid.org/0000-0002-4746-6049https://orcid.org/0000-0002-9479-4432https://orcid.org/0000-0001-8338-8351https://orcid.org/0000-0001-7890-9255https://orcid.org/0000-0002-3695-4434https://orcid.org/0000-0002-8663-3364https://orcid.org/0000-0003-0105-1312https://orcid.org/0000-0002-0752-120Xhttps://orcid.org/0000-0001-7919-612Xhttps://orcid.org/0000-0002-2591-1818ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. However, it is still unclear whether expression levels of these factors could reflect disease severity. Here, a case–control study was conducted with 213 SARS-CoV-2 positive individuals where cases were defined as COVID-19 patients with respiratory distress requiring oxygen support (N = 38) and controls were those with mild to moderate symptoms of the disease who did not need oxygen therapy along the entire clinical course (N = 175). ACE2 and TMPRSS2 mRNA levels were evaluated in nasopharyngeal swab samples by RT-qPCR and logistic regression analyzes were applied to estimate associations with respiratory outcomes. ACE2 and TMPRSS2 levels positively correlated with age, which was also strongly associated with respiratory distress. Increased nasopharyngeal ACE2 levels showed a protective effect against this outcome (adjOR = 0.30; 95% CI 0.09–0.91), while TMPRSS2/ACE2 ratio was associated with risk (adjOR = 4.28; 95% CI 1.36–13.48). On stepwise regression, TMPRSS2/ACE2 ratio outperformed ACE2 to model COVID-19 severity. When nasopharyngeal swabs were compared to bronchoalveolar lavages in an independent cohort of COVID-19 patients under mechanical ventilation, similar expression levels of these genes were observed. These data suggest nasopharyngeal TMPRSS2/ACE2 as a promising candidate for further prediction models on COVID-19.porUniversidade Federal de Minas GeraisUFMGBrasilICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIAICB - DEPARTAMENTO DE FARMACOLOGIAScientific ReportsCOVID-19Desconforto respiratorioCOVID-19SARS-CoV-2Respiratory distressAssociation between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distressinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.nature.com/articles/s41598-021-88944-8Átila Duque RossiHugo José AlvesHelena Toledo ScheidDébora Souza FaffeRafael Mello GalliezRenata Eliane de ÁvilaGustavo Gomes ResendeMauro Martins TeixeiraOrlando da Costa Ferreira JúniorTerezinha Marta CastineirasRenan Pedra SouzaJoão Locke Ferreira de AraújoAmilcar TanuriRenato Santana de AguiarShana Priscila Coutinho BarrosoCynthia Chester CardosoTailah Bernardo de AlmeidaMarcelo Ribeiro-alvesCamila de Almeida VelozoJéssica Maciel de AlmeidaIsabela de Carvalho LeitãoSâmila Natiane FerreiraJéssica da Silva Oliveirainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/56358/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALAssociation between ACE2 and TMPRSS2 nasopharyngeal expression and COVID‑19 respiratory distress.pdfAssociation between ACE2 and TMPRSS2 nasopharyngeal expression and COVID‑19 respiratory distress.pdfapplication/pdf620579https://repositorio.ufmg.br/bitstream/1843/56358/2/Association%20between%20ACE2%20and%20TMPRSS2%20nasopharyngeal%20expression%20and%20COVID%e2%80%9119%20respiratory%20distress.pdf9077d42c2bea0b6d1bb76ef6c1f6a1faMD521843/563582023-07-14 21:20:58.408oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-15T00:20:58Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.pt_BR.fl_str_mv Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
title Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
spellingShingle Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
Átila Duque Rossi
COVID-19
SARS-CoV-2
Respiratory distress
COVID-19
Desconforto respiratorio
title_short Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
title_full Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
title_fullStr Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
title_full_unstemmed Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
title_sort Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
author Átila Duque Rossi
author_facet Átila Duque Rossi
Hugo José Alves
Helena Toledo Scheid
Débora Souza Faffe
Rafael Mello Galliez
Renata Eliane de Ávila
Gustavo Gomes Resende
Mauro Martins Teixeira
Orlando da Costa Ferreira Júnior
Terezinha Marta Castineiras
Renan Pedra Souza
João Locke Ferreira de Araújo
Amilcar Tanuri
Renato Santana de Aguiar
Shana Priscila Coutinho Barroso
Cynthia Chester Cardoso
Tailah Bernardo de Almeida
Marcelo Ribeiro-alves
Camila de Almeida Velozo
Jéssica Maciel de Almeida
Isabela de Carvalho Leitão
Sâmila Natiane Ferreira
Jéssica da Silva Oliveira
author_role author
author2 Hugo José Alves
Helena Toledo Scheid
Débora Souza Faffe
Rafael Mello Galliez
Renata Eliane de Ávila
Gustavo Gomes Resende
Mauro Martins Teixeira
Orlando da Costa Ferreira Júnior
Terezinha Marta Castineiras
Renan Pedra Souza
João Locke Ferreira de Araújo
Amilcar Tanuri
Renato Santana de Aguiar
Shana Priscila Coutinho Barroso
Cynthia Chester Cardoso
Tailah Bernardo de Almeida
Marcelo Ribeiro-alves
Camila de Almeida Velozo
Jéssica Maciel de Almeida
Isabela de Carvalho Leitão
Sâmila Natiane Ferreira
Jéssica da Silva Oliveira
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Átila Duque Rossi
Hugo José Alves
Helena Toledo Scheid
Débora Souza Faffe
Rafael Mello Galliez
Renata Eliane de Ávila
Gustavo Gomes Resende
Mauro Martins Teixeira
Orlando da Costa Ferreira Júnior
Terezinha Marta Castineiras
Renan Pedra Souza
João Locke Ferreira de Araújo
Amilcar Tanuri
Renato Santana de Aguiar
Shana Priscila Coutinho Barroso
Cynthia Chester Cardoso
Tailah Bernardo de Almeida
Marcelo Ribeiro-alves
Camila de Almeida Velozo
Jéssica Maciel de Almeida
Isabela de Carvalho Leitão
Sâmila Natiane Ferreira
Jéssica da Silva Oliveira
dc.subject.por.fl_str_mv COVID-19
SARS-CoV-2
Respiratory distress
topic COVID-19
SARS-CoV-2
Respiratory distress
COVID-19
Desconforto respiratorio
dc.subject.other.pt_BR.fl_str_mv COVID-19
Desconforto respiratorio
description ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. However, it is still unclear whether expression levels of these factors could reflect disease severity. Here, a case–control study was conducted with 213 SARS-CoV-2 positive individuals where cases were defined as COVID-19 patients with respiratory distress requiring oxygen support (N = 38) and controls were those with mild to moderate symptoms of the disease who did not need oxygen therapy along the entire clinical course (N = 175). ACE2 and TMPRSS2 mRNA levels were evaluated in nasopharyngeal swab samples by RT-qPCR and logistic regression analyzes were applied to estimate associations with respiratory outcomes. ACE2 and TMPRSS2 levels positively correlated with age, which was also strongly associated with respiratory distress. Increased nasopharyngeal ACE2 levels showed a protective effect against this outcome (adjOR = 0.30; 95% CI 0.09–0.91), while TMPRSS2/ACE2 ratio was associated with risk (adjOR = 4.28; 95% CI 1.36–13.48). On stepwise regression, TMPRSS2/ACE2 ratio outperformed ACE2 to model COVID-19 severity. When nasopharyngeal swabs were compared to bronchoalveolar lavages in an independent cohort of COVID-19 patients under mechanical ventilation, similar expression levels of these genes were observed. These data suggest nasopharyngeal TMPRSS2/ACE2 as a promising candidate for further prediction models on COVID-19.
publishDate 2021
dc.date.issued.fl_str_mv 2021
dc.date.accessioned.fl_str_mv 2023-07-15T00:20:58Z
dc.date.available.fl_str_mv 2023-07-15T00:20:58Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/56358
dc.identifier.doi.pt_BR.fl_str_mv https://doi.org/10.1038/s41598-021-88944-8
dc.identifier.issn.pt_BR.fl_str_mv 2045-2322
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https://orcid.org/0000-0003-1450-0148
https://orcid.org/0000-0002-5795-429X
https://orcid.org/0000-0001-5255-5938
https://orcid.org/0000-0003-0348-8374
https://orcid.org/0000-0001-6566-9280
https://orcid.org/0000-0002-6944-3008
https://orcid.org/0000-0002-1970-8936
https://orcid.org/0000-0002-4746-6049
https://orcid.org/0000-0002-9479-4432
https://orcid.org/0000-0001-8338-8351
https://orcid.org/0000-0001-7890-9255
https://orcid.org/0000-0002-3695-4434
https://orcid.org/0000-0002-8663-3364
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url https://doi.org/10.1038/s41598-021-88944-8
http://hdl.handle.net/1843/56358
https://orcid.org/0000-0001-6235-8807
https://orcid.org/0000-0003-1450-0148
https://orcid.org/0000-0002-5795-429X
https://orcid.org/0000-0001-5255-5938
https://orcid.org/0000-0003-0348-8374
https://orcid.org/0000-0001-6566-9280
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https://orcid.org/0000-0002-1970-8936
https://orcid.org/0000-0002-4746-6049
https://orcid.org/0000-0002-9479-4432
https://orcid.org/0000-0001-8338-8351
https://orcid.org/0000-0001-7890-9255
https://orcid.org/0000-0002-3695-4434
https://orcid.org/0000-0002-8663-3364
https://orcid.org/0000-0003-0105-1312
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ICB - DEPARTAMENTO DE FARMACOLOGIA
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
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