TY - JOUR
T1 - Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19)
AU - Bourgonje, Arno R.
AU - Abdulle, Amaal E.
AU - Timens, Wim
AU - Hillebrands, Jan-Luuk
AU - Navis, Gerjan J.
AU - Gordijn, Sanne J.
AU - Bolling, Marieke C.
AU - Dijkstra, Gerard
AU - Voors, Adriaan A.
AU - Osterhaus, Albert D. M. E.
AU - van der Voort, Peter H. J.
AU - Mulder, Douwe J.
AU - van Goor, Harry
N1 - © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
PY - 2020/6/10
Y1 - 2020/6/10
N2 - 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.
AB - 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.
KW - angiotensin-converting enzyme 2 (ACE2)
KW - coronavirus disease 2019 (COVID-19)
KW - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
KW - renin-angiotensin-aldosterone system (RAAS)
KW - pathophysiology
KW - pathology
KW - organ involvement
KW - risk factors
KW - treatment
KW - ACUTE-RESPIRATORY-SYNDROME
KW - RENAL ACE2 EXPRESSION
KW - MYOCARDIAL-INFARCTION
KW - SARS CORONAVIRUS
KW - SEX-DIFFERENCES
KW - LUNG INJURY
KW - CLINICAL CHARACTERISTICS
KW - FUNCTIONAL RECEPTOR
KW - BLOOD-PRESSURE
KW - UP-REGULATION
U2 - 10.1002/path.5471
DO - 10.1002/path.5471
M3 - Review article
C2 - 32418199
SN - 0022-3417
VL - 251
SP - 228
EP - 248
JO - The Journal of Pathology
JF - The Journal of Pathology
IS - 3
ER -