SARS-CoV-2, primarily considered a respiratory virus, is increasingly recognized as having gastrointestinal aspects based on its presence in the gastrointestinal (GI) tract and feces. SARS-CoV-2 uses as a receptor angiotensin-converting enzyme 2 (ACE-2), a critical member of the renin-angiotensin-aldosterone system (RAAS) involved in the regulation of blood pressure and fluid system. In addition to the systemic endocrine functions, RAAS components are also involved in intracrine and organ-specific local functions. The angiotensin-converting enzyme 2 (ACE-2) is a key component of RAAS and a receptor for SARS-CoV-2. It is expressed in many tissues with gastrointestinal (GI) tract ACE-2 levels far exceeding those in the respiratory tract. SARS-CoV-2 binding to its receptor results in a deficiency of ACE-2 activity in endocrine, intracrine, and local lung and GI tract ACE-2. The local ACE-2 has different organ-specific functions, including hypertension-independent activities; dysregulations of these functions may contribute to multiorgan COVID-19 pathology, its severity, long-term effects, and mortality. We review supporting evidence from this standpoint. Notably, COVID-19 comorbidities involving hypertension, obesity, heart disease, kidney disease, and diabetes are associated with gastrointestinal problems and display ACE-2 deficits. While RAAS inhibitors target both endocrine and intracrine ACE-2 activity, the deficit of the local ACE-2 activity in the lungs and more so in the gut have not been targeted. Consequently, the therapeutic approach to COVID-19 should be carefully reconsidered. Ongoing clinical trials testing oral probiotic bound ACE-2 delivery are promising.
【저자키워드】 COVID-19, ACE-2 receptor, microbiota, RAAS inhibitors, Gastrointestinal infection, 【초록키워드】 SARS-CoV-2, clinical trial, Mortality, obesity, severity, lung, Comorbidity, Local, hypertension, angiotensin-converting enzyme 2, ACE-2, respiratory virus, Kidney disease, RAAS, respiratory tract, receptor, inhibitor, disease, Critical, function, binding, Multiorgan, GI Tract, Evidence, Therapeutic approach, blood pressure, Endocrine, Gut, dysregulation, deficiency, Regulation, tissue, functions, component, COVID-19 pathology, while, Effects, involved, addition, contribute, expressed, increasingly, diabete, gastrointestinal problem, organ-specific, 【제목키워드】 SARS-CoV-2, ACE-2, Effect,