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

• Main Authors: Átila Duque Rossi, João Locke Ferreira de Araújo, 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, Hugo José Alves, Helena Toledo Scheid, Débora Souza Faffe, Rafael Mello Galliez, Renata Eliane de Ávila, Gustavo Gomes Resende, Mauro Martins Teixeira, COVID-19 UFRJ Workgroup, Orlando da Costa Ferreira Júnior, Terezinha Marta P. P. Castiñeiras, Renan Pedra Souza, Amilcar Tanuri, Renato Santana de Aguiar, Shana Priscila Coutinho Barroso, Cynthia Chester Cardoso
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-05-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-021-88944-8

Abstract 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.