Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , |
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 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 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 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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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 |
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info:eu-repo/semantics/article |
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article |
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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 |
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2045-2322 |
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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 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 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 |
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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 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 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 |
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Universidade Federal de Minas Gerais |
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