AUTHOR=Jimenez Leandro , Campos Codo Ana , Sampaio Vanderson de Souza , Oliveira Antonio E. R. , Ferreira Lucas Kaoru Kobo , Davanzo Gustavo Gastão , Brito Monteiro Lauar de , Victor Virgilio-da-Silva João , Borba Mayla Gabriela Silva , Fabiano de Souza Gabriela , Zini Nathalia , Andrade Gandolfi Flora de , Muraro Stéfanie Primon , Luiz Proença-Modena José , Val Fernando Almeida , Cardoso Melo Gisely , Monteiro Wuelton Marcelo , Nogueira Maurício Lacerda , Lacerda Marcus Vinícius Guimarães , Moraes-Vieira Pedro M. , Nakaya Helder I. 

TITLE=Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.637885

DOI=10.3389/fmed.2021.637885

ISSN=2296-858X

ABSTRACT=<p>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect a broad range of human tissues by using the host receptor angiotensin-converting enzyme 2 (ACE2). Individuals with comorbidities associated with severe COVID-19 display higher levels of <italic>ACE2</italic> in the lungs compared to those without comorbidities, and conditions such as cell stress, elevated glucose levels and hypoxia may also increase the expression of <italic>ACE2</italic>. Here, we showed that patients with Barrett's esophagus (BE) have a higher expression of <italic>ACE2</italic> in BE tissues compared to normal squamous esophagus, and that the lower pH associated with BE may drive this increase in expression. Human primary monocytes cultured in reduced pH displayed increased <italic>ACE2</italic> expression and higher viral load upon SARS-CoV-2 infection. We also showed in two independent cohorts of 1,357 COVID-19 patients that previous use of proton pump inhibitors is associated with 2- to 3-fold higher risk of death compared to those not using the drugs. Our work suggests that pH has a great influence on SARS-CoV-2 Infection and COVID-19 severity.</p>