#2395 Elevated circulating ACE2 activity is related with a major COVID-19 severity

Abstract Background and Aims The angiotensin 2 converser enzyme (ACE2) is the cell entry receptor for SARS-CoV-2. SARS-CoV2 participates in ACE2 shedding from cell membrane, increasing soluble ACE2. The present study aims to evaluate if ACE2 serum levels are to COVID-19 prognosis. Method During the first wave of COVID-19 pandemic and during March and April 2020, 2118 first emergency attendance serum samples from diagnosed COVID-19 patients from Barcelona Vall d'Hebron Hospital were obtained. Age, sex, previous comorbidities, clinical and analytical variables were collected from the patient clinical records. Patients that were admitted to ICU, required mechanical ventilation or died due to COVID-19 were considered severe patients. Serum ACE2 activity was measured by enzymatic activity assay. Results Patients with severe COVID-19 were older and with a major number of comorbidities (Table 1). Circulating ACE2 activity at admission was increased in 0.34 relative fluorescence units (RFUs)/ng/μL (CI 95%: 0.24-0.43, p < 0.001) in patients that developed severe COVID-19. A logistic regression model adjusted by age, sex, diabetes, hypertension, obesity, cardiovascular disease, chronic kidney disease and renin angiotensin blockers, showed that high circulating ACE2 activity was still related to a worse prognosis (OR: 2.0, 95% CI: 1.7–2.4, p < 0.001). High serum ACE2 activity ≥0.56 RFU/ng/μL provided the best sensitivity (62%) and specificity (61%) relation, whereas values ≥1.3 RFU/ng/μL were significantly related to a worse prognosis of the disease with a 95% specificity. Conclusion High levels of circulating ACE2 activity when patients with COVID-19 are admitted to the Emergency Department are independently related with a subsequent severe disease. Additionally, although most of the comorbidities analyzed are significantly increased in severe COVID-19 patients as compared to mild COVID-19 patients, the results of the logistic regression model point out that they seem not to be a risk factor in the overall model, except for obesity, age and sex.