Research detects a more dangerous SARS-CoV-2 mutation
The study included an index cohort made up of 1,485 men (average age 69 years) and 537 women (75 years), which aimed to test the team's hypotheses, and a validation group made up of 1,123 men (74 years) and 575 women (76 years).
The team assessed various factors that can influence ACE2 levels, including the use of ACE inhibitors, ARBs, and mineralocorticoid receptor antagonists (MRAs), the presence of chronic obstructive pulmonary disorder, and any history of a coronary artery by-pass graft or atrial fibrillation. What did the study find?
Among the index participants, there was no association between ACE2 plasma levels and the use of any of the three drugs. Among those in the validation group, the use of ACE inhibitors and ARBS was in fact, associated with decreased ACE2 levels. However, the use of MRAs was weakly associated with higher ACE2 levels.
The researchers say that, to the best of their knowledge, theirs is the first comprehensive study investigating the link between drugs targeting the RAAS and plasma ACE2 levels among cardiovascular patients.
"We found no evidence that ACE inhibitors and ARBs were linked to increased ACE2 concentrations in plasma. In fact, they predicted lower concentrations of ACE2 in the validation cohort, although we did not see this in the index cohort," says Voors.
He adds that it is not clear what the effects of using MRAs are on ACE2 levels since the weak association observed in the validation group was not observed in the index group:
"Our findings do not suggest that MRAs should be discontinued in heart failure patients who develop COVID-19. They are a very effective treatment for heart failure, and the hypothetical effects on viral infection should be weighed carefully against their proven benefits." Men had higher levels of ACE2 than women
The study found that being male was the factor most strongly associated with a raised ACE2 level.
Since the concentration of ACE2 is particularly high in the testes, the team thinks this may explain why levels are higher among men and why susceptibility to COVID-19 is greater among men.
"These data might explain the higher incidence and fatality rate of COVID-19 in men, but do not support previous reports suggesting that ACE inhibitors or ARBs increase the vulnerability for COVID-19 through increased plasma ACE2 concentrations," concludes the team.
In an associated editorial, Gavin Oudit (University of Alberta, Canada) and Marc Pfeffer (Harvard Medical School, USA) say: "When faced with the rapidly expanding COVID-19 pandemic and in the absence of definitive data, the results of Sama et al obtained in heart failure patients in the pre-COVID-19 period offer supporting evidence to continue ACE inhibitors or ARBs in patients at risk for SARS-CoV-2 infection." Source: Men’s blood contains greater concentrations of enzyme that helps COVID-19 infect cells - https://www.escardio.org/The-ESC/Press-Office/Press-releases/Men-s-blood-contains-greater-concentrations-of-enzyme-that-helps-COVID-19-infect-cells Journal reference: Circulating plasma concentrations of angiotensin-converting enzyme 2 in men and women with heart failure and effects of renin-angiotensin-aldosterone inhibitors”, by Iziah E. Sama et al. European Heart Journal. doi:10.1093/eurheartj/ehaa373, https://academic.oup.com/eurheartj/article-lookup/doi/10.1093/eurheartj/ehaa373
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