Abstract
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.
Highlights
The current COVID-19 pandemic remains a global menace
We found that plasma concentrations of angiotensin-converting enzyme 2 (ACE2) were significantly lower in diabetics patients (2973.83 ± 2196.79 pg/mL) than in the non-diabetes mellitus (DM) group (4308.21 ± 2352.42 pg/mL) (Figure 1A), which indicated that downregulated ACE2 levels were correlated with impaired glucose homeostasis in patients with diabetes
To investigate the causes of lower plasma concentrations of ACE2 in diabetics with chronic disease, we evaluated the influence of medications on ACE2
Summary
The current COVID-19 pandemic remains a global menace. According to the data on 19 March 2021, it has infected more than 1.23 billion people globally with over 2.7 million deaths [1]. Recent data suggest that patients with comorbid conditions such as cardiac diseases, hypertension, and diabetes mellitus (DM), are at increased risk of contracting severe SARS-CoV-2 infection [3, 4]. The underlying causes of high morbidity and mortality of these patients are unrevealed. ACE2 deficiency disrupts glucose homeostasis and worsens inflammation in diabetic animal models [7, 8], whether or not the changes of ACE2 levels contribute to the susceptibility and high mortality of COVID-19 patients with chronic diseases to remains obscure
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