Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be harmful in patients with diabetes during COVID-19 pandemic

Diabetes Metab Syndr. 2020 Jul-Aug;14(4):349-350. doi: 10.1016/j.dsx.2020.04.019. Epub 2020 Apr 15.


The novel coronavirus disease 2019 (COVID-19) outbreak once again demonstrated the importance of the renin-angiotensin system (RAS) in patients with diabetes. Activation of the RAS increases in patients with diabetes. The virus attaches to the ACE2 enzyme at low cytosolic pH values and enters into the cell and causes infection. Especially in the presence of diabetes mellitus and accompanying comorbid conditions such as hypertension, obesity, old age, and smoking, cytosolic pH is low, thus the virus easily may enter the cell by attaching to ACE2. ACEIs and ARBs lead to a reduction in angiotensin II level by increasing the ACE2 level, thus they cause a low cytosolic pH. Increased cardiac ACE2 levels due to ACEIs and ARBs can trigger cardiac arrhythmias and myocarditis by causing the virus to easily enter the heart tissue. There is ACE2 activity in the rostral ventrolateral medulla in the brain stem. The release of angiotensin 1-7 in the brain stem leads to the activation of the sympathetic nervous system. This activation causes systemic vasoconstriction and the patient's blood pressure increases. The most important event is the increased sympathetic activity via the central stimulation, this activity increases pulmonary capillary leaking, causing the ARDS. As the cytosolic pH, which is already low in patients with diabetes will decrease further with the mechanisms mentioned above, the viral load will increase and the infection will be exacerbated. As a result, the use of ACEIs and ARBs in patients with diabetes can lead to increased morbidity and mortality of COVID-19.

Keywords: Angiotensin converting enzyme inhibitors; Angiotensin receptor antagonists; Diabetes mellitus; Novel coronavirus disease 2019 (COVID-19); Renin-angiotensin system.

Publication types

  • Letter

MeSH terms

  • Angiotensin I
  • Angiotensin II / metabolism
  • Angiotensin Receptor Antagonists / adverse effects*
  • Angiotensin-Converting Enzyme 2
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Betacoronavirus* / metabolism
  • COVID-19
  • Coronavirus Infections / epidemiology*
  • Coronavirus Infections / mortality
  • Diabetes Mellitus / drug therapy*
  • Heart / virology
  • Humans
  • Hydrogen-Ion Concentration
  • Pandemics
  • Peptide Fragments
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / epidemiology*
  • Pneumonia, Viral / mortality
  • SARS-CoV-2


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Peptide Fragments
  • Angiotensin II
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)