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

  • Jimenez, Leandro1, 2
  • Campos Codo, Ana3
  • Sampaio, Vanderson de Souza4, 5, 6, 7
  • Oliveira, Antonio E. R.1
  • Ferreira, Lucas Kaoru Kobo1
  • Davanzo, Gustavo Gastão3
  • Brito Monteiro, Lauar de3
  • Victor Virgilio-da-Silva, João3
  • Borba, Mayla Gabriela Silva4
  • Fabiano de Souza, Gabriela3
  • Zini, Nathalia8
  • Andrade Gandolfi, Flora de8
  • Muraro, Stéfanie Primon3
  • Luiz Proença-Modena, José3
  • Val, Fernando Almeida4, 5, 7
  • Cardoso Melo, Gisely4, 5
  • Monteiro, Wuelton Marcelo4, 5
  • Nogueira, Maurício Lacerda8
  • Lacerda, Marcus Vinícius Guimarães4, 5, 7
  • Moraes-Vieira, Pedro M.3, 9, 10
  • And 1 more
  • 1 Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo , (Brazil)
  • 2 Scientific Platform Pasteur-University of São Paulo, São Paulo , (Brazil)
  • 3 Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, São Paulo , (Brazil)
  • 4 Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus , (Brazil)
  • 5 Universidade do Estado do Amazonas, Manaus , (Brazil)
  • 6 Fundação de Vigilância em Saúde do Amazonas, Manaus , (Brazil)
  • 7 Faculdade de Medicina da Universidade Federal do Amazonas, Manaus , (Brazil)
  • 8 Faculdade de Medicina de São José do Rio Preto, São Paulo , (Brazil)
  • 9 Obesity and Comorbidities Research Center, University of Campinas, São Paulo , (Brazil)
  • 10 Experimental Medicine Research Cluster, University of Campinas, São Paulo , (Brazil)
  • 11 Hospital Israelita Albert Einstein, São Paulo , (Brazil)
Published Article
Frontiers in Medicine
Frontiers Media SA
Publication Date
Aug 20, 2021
DOI: 10.3389/fmed.2021.637885
  • Medicine
  • Brief Research Report


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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