Higher levels of ACE2 association in certain comorbidities explain its association with the severity of COVID-19. It has been demonstrated that ACE2 is highly expressed in the esophagus of patients with Barrett’s esophagus (BE) and that the acidic pH associated with this condition is a key inducer of ACE2 expression. In-vitro analyses have depicted that in primary monocyte culture, ACE2 expression was significantly high at pH 6 and 6.5 when compared to pH 7.
The reduction of pH alone also significantly increased SARS-CoV-2 infection of human monocytes. Furthermore, when human coronary artery endothelial cells were treated with proton pump inhibitors like omeprazole or lansoprazole in-vitro, the expression of ACE2 decreased in comparison to untreated cells.
Additionally, in two independent cohorts of 551 and 806 RT-qPCR confirmed COVID-19 patients the effects of gastrointestinal discomfort and COVID-19 severity were analyzed. Patients taking proton pump inhibitors (PPI) prior to the COVID-19 infection had a 2- to 3-fold increased risk of death compared to those not using the drug. These clinical findings indicate that the reduction of physiological pH caused by stomach acid may play a significant role in SARS-CoV-2 infection and COVID-19 severity.
In conclusion, acidic pH increases SARS-CoV-2 infection by up-regulating the ACE2 receptor. This implies that patients with gastroesophageal reflux disease (GERD) or Barrett’s esophagus (BE) are at a higher risk of contracting the SARS-CoV-2 infection.
A clear mechanism on how acidic pH elevates ACE2 expression is not yet established. But, the patients, families, and healthcare professionals must be aware that acidosis can lead to severe COVID-19 and increase the mortality rate and thus take necessary precautions and plan treatment regimes accordingly.
Source: Frontiers in Medicine
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