ACE2 Serum Levels as Predictor of Infectability and Outcome in COVID-19

Abstract

BackgroundCOVID‐19 can generate a broad spectrum of severity and symptoms. Many studies analysed the determinants of severity but not among some types of symptoms. More importantly, very few studies analysed patients highly exposed to the virus that nonetheless remain uninfected.MethodsWe analysed serum levels of ACE2, Angiotensin II and anti-Spike antibodies in 2 different cohorts at high risk of viral exposure, highly exposed but uninfected subjects, either high risk health care workers or persons cohabiting with infected close relatives and seropositive patients with symptoms. We tested the ability of the sera of these subjects to neutralize lentivirus pseudotyped with the Spike-protein.ResultsWe found that the serum levels of ACE2 are significantly higher in highly exposed but uninfected subjects. Moreover, sera from this seronegative persons can neutralize SARS-CoV-2 infection in cellular assays more strongly that sera from non-exposed negative controls eventhough they do not have anti-CoV-2 IgG antibodies suggesting that high levels of ACE2 in serum may somewhat protect against an active infection without generating a conventional antibody response. Finally, we show that among patients with symptoms, ACE2 levels were significantly higher in infected patients who developed cutaneous as compared with respiratory symptoms and ACE2 was also higher in those with milder symptoms.ConclusionsThese findings suggest that soluble ACE2 could be used as a potential biomarker to predict SARS-CoV-2 infection risk and to discriminate COVID-19 disease subtypes.

Circulating angiotensin converting enzyme 2 and COVID-19

“…Despite these findings, current research on cACE2 levels and activity in several cohorts of COVID-19 patients has generated controversy. These studies range from very high or high[ 49 , 50 , 52 , 54 , 55 , 57 , 62 ] to unaltered or even decreased cACE2 levels[ 51 , 58 , 60 ] compared to controls. The effect of age and gender on cACE2 was explored, and there was a trend for cACE2 levels to rise with age.…”

Counter-regulatory renin-angiotensin system in hypertension: Review and update in the era of COVID-19 pandemic

“…By contrast, a few trials did not find evidence for altered ACE2 as well as other RAS components [224] . However, more recent studies demonstrate that sACE2 level or activity is significantly positively associated with the severity of COVID-19, indicating that sACE2 could be a useful biomarker for predicting the risk of severe disease [225] , [226] , [227] , [228] , [229] , [230] . The infection of lung epithelial cells by various SARS-CoV-2 variants can be neutralized by soluble rhACE2 [231] .…”

Biological effects of COVID-19 on lung cancer: Can we drive our decisions

“…Interestingly, the maintenance of the ACE2 serum levels improves the survival of patients with lung cancer, increasing the immune system’s capacity to induct an inflammatory storm that can eliminate SARS-CoV-2 from the lungs ( 115 ). Finally, ACE2 may be considered a biomarker and future therapeutic target against COVID-19 infection, although several studies need to be conducted to confirm this aspect ( 116 ).…”