Circulating ACE2 activity predicts mortality and disease severity in hospitalized COVID-19 patients

Fagyas, Miklós and Fejes, Zsolt and Sütő, Renáta and Nagy, Zsuzsanna and Székely, Borbála and Pócsi, Marianna and Ivády, Gergely and Bíró, Edina and Bekő, Gabriella and Nagy, Attila and Kerekes, György and Szentkereszty, Zoltán and Papp, Zoltán and Tóth, Attila and Kappelmayer, János and Nagy, Béla Jr. (2022) Circulating ACE2 activity predicts mortality and disease severity in hospitalized COVID-19 patients. International Journal of Infectious Diseases, 115. pp. 8-16. ISSN 1201-9712

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Abstract

Objectives Angiotensin-converting enzyme 2 (ACE2) represents the primary receptor for SARS-CoV-2 to enter endothelial cells. Here we investigated circulating ACE2 activity to predict the severity and mortality of COVID-19. Methods Serum ACE2 activity was measured in COVID-19 (110 critically ill and 66 severely ill subjects at hospital admission and 106 follow-up samples) and in 32 non-COVID-19 severe sepsis patients. Associations between ACE2, inflammation-dependent biomarkers, pre-existing comorbidities, and clinical outcomes were studied. Results Initial ACE2 activity was significantly higher in critically ill COVID-19 patients (54.4 [36.7-90.8] mU/L) than in severe COVID-19 (34.5 [25.2-48.7] mU/L; P<0.0001) and non-COVID-19 sepsis patients (40.9 [21.4-65.7] mU/L; P=0.0260) regardless of comorbidities. Circulating ACE2 activity correlated with inflammatory biomarkers and was further elevated during the hospital stay in critically ill patients. Based on ROC-curve analysis and logistic regression test, baseline ACE2 independently indicated the severity of COVID-19 with an AUC value of 0.701 (95% CI [0.621-0.781], P<0.0001). Furthermore, non-survivors showed higher serum ACE2 activity vs. survivors at hospital admission (P<0.0001). Finally, high ACE2 activity (≥45.4 mU/L) predicted a higher risk (65 vs. 37%) for 30-day mortality (Log-Rank P<0.0001). Conclusions Serum ACE2 activity correlates with COVID-19 severity and predicts mortality.

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