The influence of pH on SARS CoV 2 infection and COVID 19 severity

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 viral load upon SARS-CoV-2 infection. We also showed in two independent cohorts of 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by Brazilian National Council for Scientific and Technological Development (grant number 313662/2017-7); the Sao Paulo Research Foundation (grant numbers 2018/14933-2; 2018/21934-5; 2017/27131-9; 2013/08216-2; 2020/04836-0); and CAPES. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The protocol was approved by the Brazilian Committee of Ethics in Human Research (CAAE: 30152620.1.0000.0005 and 30615920.2.0000.0005). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Publicly available transcriptomic data were obtained from the Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/)