An analysis of comorbidities in three series of COVID-19 cases from Wuhan in China supports an association between increased expression of angiotensin-converting enzyme 2 (ACE2) and more severe and fatal disease.
The correspondence, published in Lancet Respiratory Medicine, said the most frequent comorbidities reported in patients with COVID-19 were often treated with ACE inhibitors.
The studies – here, here and here – identified cerebrovascular disease, diabetes and hypertension as the major comorbidities in severe and fatal COVID-19 cases.
Professor Michael Roth, from the Department of Biomedicine and Internal Medicine at the Basel University Hospital in Switzerland, and colleagues said coronaviruses including SARS-CoV and SARSCoV-2 bind to their target cells through ACE2 which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels.
“The expression of ACE2 is substantially increased in patients with type 1 or type 2 diabetes, who are treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs),” they wrote.
“Hypertension is also treated with ACE inhibitors and ARBs, which results in an upregulation of ACE2. ACE2 can also be increased by thiazolidinediones and ibuprofen.”
“These data suggest that ACE2 expression is increased in diabetes and treatment with ACE inhibitors and ARBs increases ACE2 expression. Consequently, the increased expression of ACE2 would facilitate infection with COVID-19.”
They said their hypothesis, that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19, was conflicting because ACE2 also reduces inflammation and has been suggested as a potential new therapy for inflammatory lung diseases, cancer, diabetes and hypertension.
“A further aspect that should be investigated is the genetic predisposition for an increased risk of SARS-CoV-2 infection, which might be due to ACE2 polymorphisms that have been linked to diabetes mellitus, cerebral stroke, and hypertension, specifically in Asian populations.”
“Summarising this information, the sensitivity of an individual might result from a combination of both therapy and ACE2 polymorphism.”
They suggested ACE inhibitors and ARBs should be monitored in patients with cardiac diseases, hypertension, or diabetes who were at higher risk of severe COVID-19. There was no evidence that calcium channel blockers increased ACE2 expression.
However cardiologists have said there is currently “no clinical evidence to show that ACE inhibitors or ARBs either worsen susceptibility to COVID-19 infection or affect the outcomes of those infected.”
A statement from the High Blood Pressure Research Council of Australia said its views were shared by the International Society of Hypertension, the European Society of Hypertension, and the European Society of Cardiology Council on Hypertension.
“In the absence of data and in view of the documented beneficial health effects of these medicines in patients with elevated blood pressure and other cardiac conditions the HBPRCA recommends that the routine use of ACE-Inhibitors or ARBs should continue and patients should not cease blood pressure lowering medications unless advised to do so by their physician.”
Associate Professor Nigel Jepson
Clinical director of the Eastern Heart Clinic and senior staff specialist at the Prince of Wales Hospital Associate Professor Nigel Jepson told the limbic the evidence presented was observational and with small numbers.
“It’s really speculative at best that treatment with these drugs in the context of COVID-19 is related to infectivity or increases the consequence of infection. We strongly recommend doctors and their patients continue their treatments.”
The ESC has also put out an advisory statement warning against discontinuation of antihypertensive therapy.
Professor Jepson said cardiologists were concerned that their older patients with CVD and other risk factors were more likely to develop complications if they contracted COVID-19.
“We’re encouraging the cancellation of routine, non-urgent follow up in our clinics and our rooms and we are warning our patients to expect a call. Obviously we are seeing urgent patients with new or changing symptoms,” he said.
“From a cath lab point of view we are in active discussion about the timing of cutting back on electives. We haven’t the formal word from our area but it has been implied and we are just working out how to do it with public and private patients.”
He said the threat of a diminished workforce, PPE shortages and reduced ICU availability meant a lot of possibilities were being considered.
“The message we are getting from Europe is we can’t be too prepared.”