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

Átila Duque Rossi,Orlando Da Costa Ferreira Júnior,Gabriela Bergiante Kraychete,Ekaterini Simões Goudouri,Francine Bittencourt Schiffler,Rodrigo De Moraes Brindeiro,Isabela Labarba Carvalho De Almeida,Raquel Fernandes Coelho,Marcela Dos Santos Durães,Camila Nacif,Lucas Matos Millioni,Romina Carvalho Ferreira,Bianca Ortiz Da Silva,Liliane Tavares De Faria Cavalcante,Karyne Ferreira Monteiro,Isabela De Carvalho Leitão,Luciana Jesus Da Costa,Sérgio Machado Lisboa,Bruno Clarkson,Carolyne Lalucha Alves L Da Graça,Matheus Augusto Calvano Cosentino,Helena D.’Anunciação De Oliveira,Harrison James Westgarth,Jéssica Maciel De Almeida,Aliny Dos Santos Carvalho,Marcelo Amaral De Souza,Gabriele Silveira Da Cunha,Victoria Cortes Bastos,Enrico Bruno Riscarolli,Mateus Rodrigues De Queiroz,Elaine Sobral Da Costa,Lídia Theodoro Boullosa,João Locke Ferreira De Araújo,Mariana Quinto,Bianca Isabelle Barreto Teixeira,Leticia Averbug Correa,Richard Araujo Maia,Marisa Souza Correia,Joissy Aprigio De Oliveira,Helena Keito Toma,Hugo José Alves,Fabio Hecht Castro Medeiros,Marcelo Calado De Paula Tôrres,Mariane Talon De Menezes,Diana Mariani,Gisely Novaes Borges Da Cunha,Camille Victória Leal Correia De Silva,Gustavo Peixoto Duarte Da Silva,Sâmila Natiane Ferreira,Mayla Gabryele Miranda De Melo,Inês Corrêa Gonçalves,Laura Zalcberg Renault,Jéssica Da Silva Oliveira,Caroline Macedo Nascimento,Thamiris Dos Santos Miranda,Victor Akira Ota,Mirela D’Arc Ferreira Da Costa,Viviane Guimarães Gomes,Elisangela Costa Da Silva,Liane De Jesus Ribeiro,Bruno Eduardo Dematté,Érica Ramos Dos Santos Nascimento,Juliana Cazarin De Menezes,Luana Dos Santos Costa,Filipe Romero Rebello Moreira,Ingrid Camelo Da Silva,Mauro Martins Teixeira,Lendel Correia Da Costa,Fernando Luz De Castro,Guilherme Sant’Anna De Lira,Alice Laschuk Herlinger,Anna Carla Pinto Castiñeiras,Renata Eliane De Ávila,Mariana Freire Campos,Cíntia Policarpo,Carolina M Voloch ,Shana Priscila Coutinho Barroso,Juliana T.s Fortuna ,Fernanda Nunes Santos ,Gustavo Gomes Resende,Amílcar Tanuri ,Kíssyla Harley Della Pascôa França ,Renan Pedra De Souza ,Marcelo Ribeiro-Alves,Raíssa Mirella Dos Santos Cunha Da Costa ,Helena Toledo Scheid,André F Santos ,Débora S Faffe ,Tailah Bernardo De Almeida,Renato Santana Aguiar ,Cássia Cristina Alves Gonçalves ,Rafael Mello Galliez,Terezinha Marta Pereira Pinto Castiñeiras ,Luiza M Higa ,Huang Fang ,Pedro Paz ,Camila De Almeida Velozo,Fábio L Monteiro ,Cynthia Chester Cardoso

doi: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.

Highlights

angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 are key players on SARS-CoV-2 entry into host cells
ACE2 and TMPRSS2 are associated with respiratory distress susceptibility on COVID-19 patients, 213 SARSCoV-2 RT-quantitative PCR (qPCR) positive individuals were enrolled in this case–control study
Cases were defined as COVID-19 patients who required oxygen support over the course of SARS-CoV-2 infection while controls were COVID19 patients that presented only mild symptoms of the disease

Summary

Introduction

ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. it is still unclear whether expression levels of these factors could reflect disease 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. Some infected individuals may develop intense respiratory distress, pulmonary infiltrates, and secondary bacterial pneumonia[2] This scenario can evolve to an even more critical condition of respiratory failure, septic shock and multi-organ disfunction[2]. ACE2 deficiency has been linked to exacerbation of adipose tissue inflammation upon high calorie diet induced obesity in mice, reinforcing its potential anti-inflammatory e ffects[13]

Methods

Results

Conclusion