Angiotensin‐converting enzyme 2 (ACE2), SARS‐CoV‐2 and the pathophysiology of coronavirus disease 2019 (COVID‐19)

Abstract

Angiotensin‐converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID‐19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter‐regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin–angiotensin–aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID‐19 severity and progression, including age, sex, ethnicity, medication, and several co‐morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2‐expressing organs do not equally participate in COVID‐19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID‐19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS‐CoV‐2 infection is crucially important as it has major implications for understanding COVID‐19 pathophysiology and the development of evidence‐based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers, and RAAS inhibitors. Ultimately, prevention is key to combat COVID‐19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID‐19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID‐19 severity. In addition, we discuss the relevant pathological changes resulting from SARS‐CoV‐2 infection. Finally, we highlight a selection of potential treatment modalities for COVID‐19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Stem cell therapy in coronavirus disease 2019: current evidence and future potential

“…[34] The S protein on the virus recognizes the spike protein present on angiotensin-converting enzyme-2 (ACE-2) making it the port-of entry into the host cells. [35] The ACE-2 receptor is present ubiquitously and predominantly in the alveolar cells, making the lungs most vulnerable for the infection. [36] ACE-2 receptors have not been detected in the bone marrow, lymph nodes, thymus, spleen, lymphocytes and macrophages.…”

Comparison of renin–angiotensin–aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes

“…Hence, RAAS inhibitors may decrease poor clinical outcomes by limiting the deleterious effects of angiotensin-II in multisystem in ammation, as well as by preventing the occurrence of hypokalaemia [25,26]. Further, these drugs could also circumvent SARS-CoV-2 induced ACE2 downregulation in host cells, so that the preventive effects of ACE2 against severe disease are not lost [27].…”

Genotypic and antigenic study of SARS-CoV-2 from an Indian isolate

“…Angiotensin-converting enzyme 2 (ACE2) acts as a cell receptor that facilitates viral entry to the host cell(Bourgonje et al 2020). The recent tissue-specific expressional analysis revealed that ACE2 expression levels were the highest in the intestine, kidneys, heart, and adipose tissue, and moderate for lungs, liver, bladder, and adrenal gland(Zou et.al.2020;Qi F et.…”