CIRCULATING ACE2 ACTIVITY IS INCREASED IN DIAGNOSED COVID-19 PATIENTS

7 Feb 2025 12 a.m. 12 a.m.
WCN25-AB-1523, Poster Board= FRI-199

Introduction:

The angiotensin converting enzyme 2 (ACE2) is the cell entry receptor for SARS-CoV-2. SARS-CoV2 participates in ACE2 shedding from cell membrane, increasing soluble ACE2. ACE2 has been shown to cooperate with the receptor AXL, internalizing SARS-CoV-2. The present study aims to evaluate if the initial serum levels of circulating ACE2 activity, sAXL and its ligand, the vitamin-K dependent protein Gas6, are related with the disease prognosis. 

Methods:

Serum samples were collected from 2043 COVID-19 diagnosed patients, at two referent centers from Spain, on their first emergency attendance between 2020 and 2021. Age, sex, previous comorbidities, and clinical and analytical variables were recorded. Patients were categorized depending on their disease progression during hospitalization, considering severe disease when needed admission to intensive care unit (ICU), required mechanical ventilation or died due to COVID-19. Serum Gas6 and sAXL levels were measured by ELISA. Serum ACE2 activity was measured by a fluorescence enzymatic activity assay. 

Results:

Patients with severe COVID-19 were older, the majority men (60%) and presented more comorbidities such as hypertension or chronic kidney disease (see baseline characteristics according the severity of the disease in Table 1). A total of 1953 patients were followed up during the first 30 days of hospitalization with a median follow-up of 7 days (IQR 5-14). From them, 310 patients presented a severe outcome. Elevated circulating ACE2 activity and higher levels of Gas6 were related with worse survival (Log-rank<0.001 and Log-rank<0.001, respectively) (Figure 1). Using a multivariate cox regression model adjusted by age, gender, comorbidities, treatment and analytical values, we also found that increased circulating ACE2 activity and higher levels of GAS6 were associated with worse outcomes while high sAXL levels were associated with better outcomes (Table 2). Table 1. Patients characteristics at baseline by the severity of COVID-19.Figure 1. Patients follow-up during the first 30 days of hospitalization.Table 2. Cox by intrahospital severity.

Conclusions:

Elevated circulating ACE2 activity and higher levels of Gas6 at admission to the Emergency Department is a risk factor for severe COVID-19 disease. On the other hand, higher levels of sAXL at admission could be used as biomarker of good prognosis of COVID-19 disease.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.