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
Affiliations
- Leandro Jimenez
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Leandro Jimenez
- Scientific Platform Pasteur-University of São Paulo, São Paulo, Brazil
- Ana Campos Codo
- Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, São Paulo, Brazil
- Vanderson de Souza Sampaio
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
- Vanderson de Souza Sampaio
- Universidade do Estado do Amazonas, Manaus, Brazil
- Vanderson de Souza Sampaio
- Fundação de Vigilância em Saúde do Amazonas, Manaus, Brazil
- Vanderson de Souza Sampaio
- Faculdade de Medicina da Universidade Federal do Amazonas, Manaus, Brazil
- Antonio E. R. Oliveira
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Lucas Kaoru Kobo Ferreira
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Gustavo Gastão Davanzo
- Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, São Paulo, Brazil
- Lauar de Brito Monteiro
- Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, São Paulo, Brazil
- João Victor Virgilio-da-Silva
- Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, São Paulo, Brazil
- Mayla Gabriela Silva Borba
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
- Gabriela Fabiano de Souza
- Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, São Paulo, Brazil
- Nathalia Zini
- Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil
- Flora de Andrade Gandolfi
- Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil
- Stéfanie Primon Muraro
- Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, São Paulo, Brazil
- José Luiz Proença-Modena
- Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, São Paulo, Brazil
- Fernando Almeida Val
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
- Fernando Almeida Val
- Universidade do Estado do Amazonas, Manaus, Brazil
- Fernando Almeida Val
- Faculdade de Medicina da Universidade Federal do Amazonas, Manaus, Brazil
- Gisely Cardoso Melo
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
- Gisely Cardoso Melo
- Universidade do Estado do Amazonas, Manaus, Brazil
- Wuelton Marcelo Monteiro
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
- Wuelton Marcelo Monteiro
- Universidade do Estado do Amazonas, Manaus, Brazil
- Maurício Lacerda Nogueira
- Faculdade de Medicina de São José do Rio Preto, São Paulo, Brazil
- Marcus Vinícius Guimarães Lacerda
- Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
- Marcus Vinícius Guimarães Lacerda
- Universidade do Estado do Amazonas, Manaus, Brazil
- Marcus Vinícius Guimarães Lacerda
- Faculdade de Medicina da Universidade Federal do Amazonas, Manaus, Brazil
- Pedro M. Moraes-Vieira
- Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, São Paulo, Brazil
- Pedro M. Moraes-Vieira
- 0Obesity and Comorbidities Research Center, University of Campinas, São Paulo, Brazil
- Pedro M. Moraes-Vieira
- 1Experimental Medicine Research Cluster, University of Campinas, São Paulo, Brazil
- Helder I. Nakaya
- Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil
- Helder I. Nakaya
- Scientific Platform Pasteur-University of São Paulo, São Paulo, Brazil
- Helder I. Nakaya
- 2Hospital Israelita Albert Einstein, São Paulo, Brazil
- DOI
- https://doi.org/10.3389/fmed.2021.637885
- Journal volume & issue
-
Vol. 8
Abstract
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.
Keywords
