The Role of Angiotensin Converting Enzyme Insertion/Deletion Genetic Polymorphism in The Risk, Severity and Prognosis of COVID-19 Infection

Abstract

Background: COVID-19 pandemic got the world’s attention since the beginning of 2020. It has been observed that infected individuals present with different symptoms of varying severity; in addition, not all individuals get infected despite exposure. Risk factors such as age, sex and comorbidities play a major role in this variability; however, genetics may also be important in driving the differences in the incidence and severity of the disease. An Insertion/Deletion (I/D) polymorphism in the ACE-I gene may explain these genetic differences. The aim of this study is to determine whether the ACE I/D genetic polymorphism can be used as a marker of risk, severity and prognosis of COVID-19 infections.

Methods: More than 350 Lebanese subjects presented to AUBMC for COVID-19 PCR testing were recruited, and results are reported in this thesis on 266 subjects (142 cases and 124 controls), for whom clinical data and genotyping are complete. Clinical data were collected via filling a questionnaire and accessing the medical records. Peripheral blood was withdrawn for DNA isolation and ACE genotyping by standard PCR followed by band visualization on an agarose gel.

Results: The frequency of the D allele was most common (69%), which is congruent with previously reported literature in Middle Easterners. We showed that almost all previously reported factors and comorbidities also predict disease susceptibility and severity in the Lebanese. We also found a positive correlation between the ACE1 I-allele and the risk of contracting the COVID-19 disease. More specifically, the frequency of II genotype was significantly highest in cases compared to controls with individuals with the II genotype having a higher risk (OR=2.373) for contracting the COVID-19 disease. These results confirm Delanghe et al.’s simulations, and to our knowledge, we are the first to evaluate such an association in patients. As for disease severity, our results are in agreement with the literature whereby DD vs. II+DI was significantly higher in cases with the severe disease when compared to mild and moderate disease (P=0.003), hospitalized compared to non-hospitalized cases (P=0.027), and hypoxic compared to non-hypoxic cases (P=0.088). These results translate into the fact that subjects with DD genotype have a higher probability of experiencing severe COVID-19 symptoms (OR=7.173), to be hospitalized (OR=3.398), and/or to be hypoxic (OR=4.735).

Conclusion: These preliminary results show a positive correlation between the ACE1 I-allele and the risk of contracting the COVID-19 disease, and between ACE1 D-allele and worse outcome of the COVID-19 infection. As such, genotyping for ACE1 I/D in parallel to COVID-19 testing could be used to elicit the disease risk and severity for better prognosis and management.