COVID-19 Research Paper Volume 13, Issue 9 pp 12301—12307

Low plasma angiotensin-converting enzyme 2 level in diabetics increases the risk of severe COVID-19 infection

Yanliang Zhang1, *, , Yangyang Sun2, *, , Kang Liu3, *, , Raphael N Alolga2, , Xueqiang Xu3, , Ganzhu Feng4, , Pingxi Xiao5, ,

  • 1 Department of Infectious Diseases, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
  • 2 State Key Laboratory of Natural Medicines, Clinical Metabolomics Center, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China
  • 3 Department of Nephrology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
  • 4 Department of Respiratory Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
  • 5 Department of Cardiology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, China
* Equal contribution

Received: December 5, 2020       Accepted: April 2, 2021       Published: May 6, 2021
How to Cite

Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Patients with pre-existing chronic diseases are more susceptible to coronavirus disease 2019 (COVID-19), yet the underlying causes of increased risk are of infection remain unclear. Angiotensin-converting- enzyme 2 (ACE2), the cell surface receptor that recognizes the coronavirus spike protein has protective effects against inflammation and chronic hyperglycemia in animal models. The roles of ACE2 in severe SARS-CoV-2 infections remains ambiguous due to contradictory findings. In this study, we aimed to investigate the relationship between human plasma ACE2 levels in diabetics and the high risk of severe SARS-CoV-2 infection. First, the medical records of 245 patients with SARS-CoV-2-positive who have chronic diseases were analyzed. We also recruited 404 elderly subjects with comorbid chronic diseases such as diabetes mellitus, coronary heart disease, cerebrovascular disease, hypertension and obesity, and investigated the ACE2 plasma levels. Plasma concentrations of ACE2 were much lower (2973.83±2196.79 pg/mL) in diabetics with chronic disease than in healthy controls (4308.21±2352.42 pg/ml), and the use of hypoglycemia drugs was associated with lower circulating concentrations of ACE2 (P=1.49E-08). Diabetics with lower plasma levels of ACE2 may be susceptible to severe COVID-19. Our findings suggest that the poor prognosis in patients with diabetes infected with SARS-CoV-2 may be due to low circulating ACE2 levels.


DM: Diabetes mellitus; HTTP: Hypertension; CVD: Cardiovascular diseases; WBC: White blood cell; NEU: Neutrophil; LYM: Lymphocyte; Hb: Hemoglobin; PLT: Platelet count; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALB: Albumin; CRP: C-reactive protein; PCT: Procalcitonin; BNP: B-natriuretic peptide; Cr: Creatinine; BMI: Body mass index; HbA1c: Hemoglobin A1C; TG: Triglyceride; TC: Triglyceride cholesterol; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; BUN: Blood urea nitrogen; ACEI/ABR: Angiotensin-converting enzyme inhibitor/ Angiotensin receptor blocker.