Angiotensin converting enzyme 2 level and its significance in COVID-19 and other diseases patients

Abstract

Background: Angiotensin-converting enzyme 2 (ACE2) expressions and its modulation are of great interest as being a key receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) and the protective arm of the rennin-angiotensin axis, maintaining cardiovascular homeostasis. However, ACE2 expressions and their modulation in the healthy and disease background are yet to be explored.

Method: We performed a meta-analysis, extracting the data for ACE2 expression in human subjects with various diseases, including SARS-CoV2 infection without or with co-morbidity. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Out of 203 studies, 39 met the inclusion criteria with SARS-CoV2 patients without co-morbidity, SARS-CoV2 patients with co-morbidity, cardiovascular (CVD) patients, diabetes patients, kidney disorders patients, pulmonary disease patients, and other viral infections patients.

Results: Angiotensin-converting enzyme 2 expression was significantly increased in all diseases. There was an elevated level of ACE2, especially membrane-bound ACE2, in COVID-19 patients compared to healthy controls. A statistically significant increase in ACE2 expression was observed in CVD patients and patients with other viral diseases compared to healthy subjects. Moreover, subgroup analysis of ACE2 expression as soluble and membrane-bound ACE2 revealed a remarkable increase in membrane-bound ACE2 in CVD patients, patients with viral infection compared to soluble ACE2 and pooled standard mean difference (SMD) with the random-effects model was 0.37 and 2.23 respectively.

Conclusion: It was observed that utilizing the ACE2 by SARS-CoV2 for its entry and its consequence leads to several complications. So there is a need to investigate the underlying mechanism along with novel therapeutic strategies.

Keywords: RAS; SARS-CoV2; cardiovascular diseases; membrane-bound ACE2; soluble ACE2.

FIGURE 1

Studies included in the review and meta‐analysis is depicted using a PRISMA flow chart.

FIGURE 2

Forest plot of studies, which measured (A) Total angiotensin‐converting enzyme 2 (ACE2) (B) soluble and membrane bound ACE2 in diseases compared to healthy subjects. The overall effect size was presented as the standard mean difference with 95% CI and inverse variance (IV) method. The square (blue colour) represents the sample size and corresponding weightage.

FIGURE 3

Forest plot of studies, which measured soluble and membrane‐bound angiotensin‐converting enzyme 2 in (A) COVID19 patients, (B) COVID19 patients with comorbidities, (C) cardiovascular (CVD) patients, (D) diabetes patients, (E) kidney disorders patients, (F) pulmonary disease patients and (G) patients with other viral infection compared to healthy subjects. The overall effect size was presented as the standard mean difference with 95% CI and inverse variance (IV) method. The square (blue colour) represents the sample size and corresponding weightage.

FIGURE 4

The violin rank plot of angiotensin‐converting enzyme 2 (ACE2) expression (fold change) showed an elevated levels in all diseases except kidney disorders. The numbers in parenthesis indicate the total subjects. The solid (−) and dashed (‐‐) lines indicate the median value and interquartile range, respectively. *p < .05 indicates statistical significance vs healthy subjects and # p > .05 statistically nonsignificant vs healthy subjects. (B, C) The heat map of ACE2 expression in various diseases and their correlation were analysed with the Spearman correlation coefficient method.