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.
Highlights
Coronavirus disease 2019 (COVID-19) is caused by the recently emerged coronavirus, SARS-CoV-2, which was first reported in December 2019 in the city of Wuhan, Hubei province, PR China [1]
Angiotensin-converting enzyme 2 (ACE2) is widely distributed throughout human tissues and a myriad of factors have been implicated in influencing its expression and functional activity
Demographic characteristics, lifestyle, varying comorbidities, and medication usage are all considered to have an impact on ACE2 expression and activity
Summary
Coronavirus disease 2019 (COVID-19) is caused by the recently emerged coronavirus, SARS-CoV-2, which was first reported in December 2019 in the city of Wuhan, Hubei province, PR China [1]. To SARS-CoV-1, which was responsible for the SARS outbreak in 2002–2004, the main target of SARS-CoV-2 is the respiratory tract, leading to typical clinical signs including fever, dry cough, fatigue, and dyspnoea [4]. The disease progresses to a severe form in 10–20% of patients, requiring hospital admission or even intensive care unit (ICU) treatment [5]. Current clinical management strategies include prevention of further dissemination of the virus, control of inflammation, and supportive care, the latter intended to maintain efficient respiratory gas exchange through oxygen supplementation, positive airway pressure, and mechanical ventilation. Effective and safe disease-modifying or preventive treatments, such as targeted antiviral drugs, biological response modifiers or vaccines, are not yet available
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