Abstract: BRIEF RESEARCH REPORT published: 20 August 2021 doi: 10.3389/fmed.2021.637885 Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19 Leandro Jimenez 1,2 , Ana Campos Codo 3 , Vanderson de Souza Sampaio 4,5,6,7 , Antonio E. R. Oliveira 1 , Lucas Kaoru Kobo Ferreira 1 , Gustavo Gastão Davanzo 3 , Lauar de Brito Monteiro 3 , João Victor Virgilio-da-Silva 3 , Mayla Gabriela Silva Borba 4 , Gabriela Fabiano de Souza 3 , Nathalia Zini 8 , Flora de Andrade Gandolfi 8 , Stéfanie Primon Muraro 3 , José Luiz Proença-Modena 3 , Fernando Almeida Val 4,5,7 , Gisely Cardoso Melo 4,5 , Wuelton Marcelo Monteiro 4,5 , Maurício Lacerda Nogueira 8 , Marcus Vinícius Guimarães Lacerda 4,5,9 , Pedro M. Moraes-Vieira 3,10,11 and Helder I. Nakaya 1,2,12* Edited by: Hu Zhang, Sichuan University, China Reviewed by: Y. F. Gu, Zhejiang University, China Chenyu Sun, AMITA Health St Joseph Hospital, United States *Correspondence: Helder I. Nakaya hnakaya@usp.br Specialty section: This article was submitted to Gastroenterology, a section of the journal Frontiers in Medicine Received: 04 December 2020 Accepted: 26 July 2021 Published: 20 August 2021 Citation: Jimenez L, Campos Codo A, Sampaio VdS, Oliveira AER, Ferreira LKK, Davanzo GG, Brito Monteiro Ld, Victor Virgilio-da-Silva J, Borba MGS, Fabiano de Souza G, Zini N, Andrade Gandolfi Fd, Muraro SP, Luiz Proença-Modena J, Val FA, Cardoso Melo G, Monteiro WM, Nogueira ML, Lacerda MVG, Moraes-Vieira PM and Nakaya HI (2021) Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19. Front. Med. 8:637885. doi: 10.3389/fmed.2021.637885 Frontiers in Medicine | www.frontiersin.org 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 Faculdade de Medicina da Universidade Federal do Amazonas, Manaus, Brazil, 10 Obesity and Comorbidities Research Center, University of Campinas, São Paulo, Brazil, 11 Experimental Medicine Research Cluster, University of Campinas, São Paulo, Brazil, 12 Hospital Israelita Albert Einstein, São Paulo, Brazil 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..