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Decrease in Angiotensin-Converting Enzyme activity but not concentration in plasma/lungs in COVID-19 patients offers

Henry Daniell1, Smruti K Nair1, Yao Shi1

  • 1W. D. Miller Professor & Director of Translational Research, Vice Chair, Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, 547 Levy Building, Philadelphia, PA 19104-6030, USA.

Molecular Therapy. Methods & Clinical Development
|July 12, 2022
PubMed

Insights

Reduced soluble ACE2 activity in COVID-19 patients indicates a potential biomarker for disease severity and recovery. This finding could lead to new diagnostic tools and therapeutic targets for coronavirus disease 2019.

Area of Science:

  • Biochemistry
  • Immunology
  • Virology

Background:

  • Current COVID-19 treatments lack definitive metabolic markers for assessing disease progression and recovery.
  • Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) utilizes the angiotensin-converting-enzyme 2 (ACE2) receptor for cellular entry.
  • COVID-19 is linked to dysregulation of the renin-angiotensin system.

Purpose of the Study:

  • To evaluate soluble ACE2 (sACE2) activity in plasma and saliva of COVID-19 patients.
  • To investigate the correlation between sACE2 activity, Ang (1-7) levels, and disease severity.
  • To explore ACE2 levels in lung autopsy samples.

Main Methods:

  • Assessed sACE2 activity in plasma and saliva from 80 hospitalized COVID-19 patients and 27 controls.
  • Measured ACE2 and Ang (1-7) levels in plasma and membrane ACE2 (mACE2) in lung autopsy samples.
  • Compared sACE2 activity and ACE2 levels between COVID-19 patients and non-COVID-19 volunteers/controls.

Main Results:

  • sACE2 activity was significantly reduced in the plasma of COVID-19 patients compared to controls.
  • Reduced sACE2 activity in early hospitalization correlated with disease severity and was restored during recovery.
  • sACE2 activity was also substantially lower in the saliva of COVID-19 patients.
  • A strong inverse correlation was observed between sACE2 concentration, sACE2 activity, and Ang (1-7) levels.
  • No significant difference in membrane ACE2 levels was found in lung autopsy tissues between COVID-19 and other conditions.

Conclusions:

  • Soluble ACE2 activity may serve as a potential biomarker for evaluating COVID-19 severity and recovery.
  • Targeting sACE2 activity presents a potential therapeutic strategy for managing COVID-19.
  • Further research is warranted to validate sACE2 as a clinical tool for disease management and quarantine termination.
Keywords:
COVID-19SARS-CoV-2 diagnosis/treatment, soluble Angiotensin-Converting Enzyme 2, biomarker in plasma/saliva, Corona virus, COVID-19 disease, ACE2 activity/concentration, RAS pathwayangiotensin-converting-enzymebiomarkercoronavirus diseaseplasma markersaliva marker

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