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We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models. None examined ACE2 in human lungs.
Previous studies suggest that dysregulation of ACE2 activity in the lungs could promote early neutrophil infiltration and subsequent uncontrolled activation of the RAS.8 In mice models, acute lung injury was observed in response to SARS-CoV-1 spike protein, so it is plausible that similar responses will be observed with SARS-CoV-2.9 This is particularly problematic in organs containing high ACE2 such as the lungs as it may contribute to cytokine release syndrome (cytokine storm) and the subsequent respiratory failure that has been observed in those who have died from the disease.7 Many prescribed drugs in common use are known to mediate effects through the RAS pathway. Over 45 million of these prescriptions were issued in the UK last year alone, and of these, 15 million were for ACE inhibitors (ACE-I) and angiotensin receptor blockers (ARBs). Acting through the RAS pathway, these drugs may impact ACE2 regulation but their role in the COVID-19 pandemic is not clear. Given the number of people that are potentially on these drugs, it has caused substantial public concern and clinical uncertainty about continuation or cessation of prescribed medications during the pandemic.
If this hypothesis were to be confirmed, it could lead to a conflict regarding treatment because ACE2 reduces inflammation and has been suggested as a potential new therapy for inflammatory lung diseases, cancer, diabetes, and hypertension
We suggest that patients with cardiac diseases, hypertension, or diabetes, who are treated with ACE2-increasing drugs, are at higher risk for severe COVID-19 infection and, therefore, should be monitored for ACE2-modulating medications, such as ACE inhibitors or ARBs
archived sick care jobs saved or created!, commonly prescribed immune-suppressing mRNA medications not limited to ACE-inhibitors or ARBs
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