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 ofACE2in the lungs compared to those without comorbidities, and conditions such as cell stress, elevated glucose levels and hypoxia may also increase the expression ofACE2. Here we showed that patients with Barrett’s esophagus (BE) have a higher expression ofACE2in 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 increasedACE2expression 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.