771 THE SERUM ACE2 MOLECULE IN SARS-COV2 / COVID-19 INFECTION AND ITS POTENTIAL PROGNOSTIC AND THERAPEUTIC ROLE (ACCEPT STUDY)
Authors: Fioretti Francesco , Praderio Angelica , De Angelis Maria Grazia , Inciardi Riccardo Maria , Sammartino Antonio , Ravasio Francesco , Nodari Savina 
Published: December 2022

Abstract

Background
It is well known that the entry of the SARS- CoV-2 virus into cells is mediated by the binding between the virus Spike-glycoprotein (S) and the membrane ACE2-receptor (ACE2R). When SARS-CoV-2 binds to ACE2R, with subsequent membrane fusion and virus entry into the cell, a down-regulation of these receptors occurs. ACE2R downregulation plays a crucial role in the pulmonary and systemic inflammatory response. Also ACE2 deficiency is thought to play an important role in the pathogenesis of SARS-CoV-2 infection. The down-regulation of ACE2 induced by viral infection could be particularly harmful in subjects with pre-existing ACE2 deficiency, for example due to advanced age, the presence of DM, arterial hypertension or pre-existing heart disease, including HF. Literature data suggest an association between the patient's age and comorbidities and a greater risk of severe clinical course and with a worse prognosis. However, serious clinical pictures requiring hospitalization or leading to death have also been observed in young subjects or subjects without comorbidities.

Aim of the Study
we aimed to identify predicting factors of a higher risk in terms of severity of the clinical course and worse prognosis in the population of the Brescia area, affected by a large number of cases in the first period of COVID-19 outbreak. In particular, we aimed to verify whether there is correlation between levels of serum ACE2 (sACE2) and the risk of SARS-CoV-2 infection, as well as between sACE2 and the different severity of the clinical manifestations of COVID-19 in patients with and without CV diseases.

Methods
we consecutively enrolled subjects with previous documented SARS-CoV-2 infection and divided our sample into three groups: pts with asymptomatic course; pts with symptomatic course but without the need for hospitalization for COVID-19; pts with severe symptomatic course requiring hospitalization in intensive care unit. Blood samples were taken for sACE2 dosage. We compared the concentrations of sACE2 in these groups in relation to the age, clinical course, comorbidities, and ongoing therapies.

Results
at March 2022, we enrolled 178 pts, 51 (28%) were hospitalized for COVID-19, whereas 78 (44%) had symptomatic course without hospitalization and 49 (28%) were completely pauci-asymptomatic. Only 6 pts (4%) had myocarditis or pericarditis SARS-CoV-2-related. Between hospitalized pts, male sex (67%), older age and higher BMI were most frequent. Moreover, chronic heart failure (20%), a diagnosis of cardiopathy (29%) and AF or atrial flutter (22%) were most frequent (Table 1). Plasma concentrations of sACE2 will be dosed and analyzed in relation to the clinical characteristics of each patient.

Perspectives
ACCEPT study will help to clarify the relationship between ACE2 molecule, the risk of SARS-CoV2 infection and the severity of clinical presentation of COVID-19 in pts with or without CV diseases.