Frontiers in Medicine (Aug 2021)

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

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

DOI
https://doi.org/10.3389/fmed.2021.637885
Journal volume & issue
Vol. 8

Abstract

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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 ACE2 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 ACE2. Here, we showed that patients with Barrett's esophagus (BE) have a higher expression of ACE2 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 ACE2 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.

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