Association between ACE2 and TMPRSS2 nasopharyngeal expression and COVID-19 respiratory distress
Authors: Rossi Átila Duque , de Araújo João Locke Ferreira , de Almeida Tailah Bernardo , Ribeiro-Alves Marcelo , de Almeida Velozo Camila , Almeida Jéssica Maciel de , de Carvalho Leitão Isabela , Ferreira Sâmila Natiane , da Silva Oliveira Jéssica , Alves Hugo José , Scheid Helena Toledo , Faffe Débora Souza , Galliez Rafael Mello , de Ávila Renata Eliane , Resende Gustavo Gomes , Teixeira Mauro Martins ,   COVID-19 UFRJ Workgroup, Herlinger Alice Laschuk , dos Santos Carvalho Aliny , dos Santos André Felipe Andrade , Castiñeiras Anna Carla Pinto , Teixeira Bianca Isabelle Barreto , da Silva Bianca Ortiz , Clarkson Bruno , Dematté Bruno Eduardo , Nacif Camila , de Silva Camille Victória Leal Correia , Voloch Carolina Moreira , Nascimento Caroline Macedo , da Graça Carolyne Lalucha Alves L. , Gonçalves Cassia Cristina Alves , Policarpo Cíntia , Mariani Diana , Goudouri Ekaterini Simões , da Costa Elaine Sobral , da Silva Elisangela Costa , Riscarolli Enrico Bruno , dos Santos Nascimento Érica Ramos , Medeiros Fabio Hecht Castro , Monteiro Fábio Luís Lima , dos Santos Fernanda Leitão , de Castro Fernando Luz , Moreira Filipe Romero Rebello , Schiffler Francine Bittencourt , Kraychete Gabriela Bergiante , da Cunha Gabriele Silveira , da Cunha Gisely Novaes Borges , de Lira Guilherme Sant’Anna , da Silva Gustavo Peixoto Duarte , Westgarth Harrison James , de Oliveira Helena D.’Anunciação , Toma Helena Keito , Fang Huang Ling , Gonçalves Inês Corrêa , da Silva Ingrid Camelo , de Almeida Isabela Labarba Carvalho , de Oliveira Joissy Aprigio , de Menezes Juliana Cazarin , Fortuna Juliana Tiemi Sato , Monteiro Karyne Ferreira , França Kissyla Harley Della Pascoa , Renault Laura Zalcberg , da Costa Lendel Correia , Correa Leticia Averbug , de Jesus Ribeiro Liane , Boullosa Lídia Theodoro , de Faria Cavalcante Liliane Tavares , dos Santos Costa Luana , Millioni Lucas Matos , da Costa Luciana Jesus , Higa Luiza Mendonça , dos Santos Durães Marcela , de Souza Marcelo Amaral , de Paula Tôrres Marcelo Calado , Campos Mariana Freire , Quinto Mariana , de Menezes Mariane Talon , Correia Marisa Souza , de Queiroz Mateus Rodrigues , Cosentino Matheus Augusto Calvano , de Melo Mayla Gabryele Miranda , da Costa Mirela D’arc Ferreira , da Paz Pedro Henrique Costa , dos Santos Cunha da Costa Raissa Mirella , Coelho Raquel Fernandes , Maia Richard Araujo , de Moraes Brindeiro Rodrigo , Ferreira Romina Carvalho , Lisboa Sérgio Machado , dos Santos Miranda Thamiris , Ota Victor Akira , Bastos Victoria Cortes , Gomes Viviane Guimarães , da Costa Ferreira Júnior Orlando , Castiñeiras Terezinha Marta P. P. , Souza Renan Pedra , Tanuri Amilcar , Aguiar Renato Santana de , Barroso Shana Priscila Coutinho , Cardoso Cynthia Chester 
Published: May 2021

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.