Why do my patients keep asking me about ACE inhibitors and COVID-19?
Hypertension is a common problem affecting 3.5% of children and adolescents and correlating with increased cardiovascular risk in young adults. Common first-line therapies include angiotensin converting enzyme inhibitors (ACEi), such as ramipril, lisinopril and enalapril.
Over the last few weeks, a storm has erupted over the use of ACEi with the suggestion that they could be associated with severe COVID-19. A statement by the European Society of Cardiology, was quickly followed by most national hypertension societies, including the American Society of Pediatric Nephrology and the High Blood Pressure Research Council of Australia, recommending the continuation of ACEi in patients with COVID-19.
How are ACEi linked with COVID-19?
The COVID-19 literature to date has suggested increased mortality for adults with hypertension and for those with diabetes, a patient cohort frequently treated with ACEi. Although medication use has not been reported in patients with COVID-19, a letter to the Lancet postulated that the use of ACEi could be implicated in the increased mortality rate described in patients with hypertension.
Human coronoviruses, such as SARS-CoV-2, gain entry to the cell through ACE2 which is expressed by epithelial cells of the lung and kidney. Thus a treatment that increases the expression of ACE2 at the cell surface could increase the severity of COVID-19 infection. There is animal evidence that circulating ACE2 levels are increased by treatment with ACEi. But also conflicting evidence in humans showing no association between circulating ACE2 levels and the use of ACEi.
Interestingly, there is clinical data to suggest that ACE inhibition may actually be a potential therapy for viral pneumonia. Though it should be noted that this is confined to retrospective, observational data, clinical trials are underway to examine the use of recombinant ACE2 and losartan in adults with COVID-19, highlighting that the use of ACEi in patients with COVID-19 is not clearcut.
How does this impact our patients?
A growing body of evidence, summarised by the DFTB team here, shows that children are at much less risk of severe disease than adults. Indeed, only 1 of 731 patients with confirmed COVID-19 infection in the largest study to date, had clinically critical disease. The data on ACEi in COVID-19 is inconclusive and pending further data there is no evidence to change anti-hypertensive management in children at this point in time.
The Bottom Line
There is currently no evidence, in children or adults, to support changing blood pressure medication due to the COVID-19 pandemic.
I want to know more!
If you want to read more about HTN then please review the 2017 Hypertension guidelines from the American Academy of Paediatrics.
If you’d like to know more about ACE2, hypertension, and COVID-19 then check out the dedicated ACE2 NephJC page.
For up to date reviews of the COVID-19 literature as it pertains to the kidney along with management guidelines check out the COVID-19 NephJC page.
If you are aware of resources that you think would be useful to the nephrology community then please tag it with #CoronaKidney and they will be added to the page after they are reviewed.