Predictors of COVID-19 severity among a cohort of Egyptian patients

Abstract Background As the outbreak of COVID-19 progresses, prognostic markers for the identification of high-risk individuals are urgently needed. The angiotensin system is implicated in the pathogenesis of COVID-19 as ACE2 is the cellular receptor for SARS-COV-2 virus, and expression of the ACE2 gene could regulate an individual’s susceptibility to infection. In addition, the balance between ACE and ACE2 activity may play a role in the severity of COVID-19. Aim of work The aim of the work is to explore the role of ACE 1 I/D and ACE2 G8790A gene variants and serum ACE l/ACE2 ratio as risk factors for severity of COVID-19 infection. Methods One hundred and eighty COVID-19 patients were divided into three groups: mild (60 patients), moderate (60 patients), and severe (60 patients). The enzyme levels of ACE and ACE2 were measured by ELISA. ACE I/D (rs4646994) was assayed using PCR and ACE2 (rs2285666) gene variant was determined using real-time PCR. Results ACE/ACE2 ratio was significantly lower in the mild group than in the moderate-to-severe group ( P < 0.001). GG (reference) genotype and G allele of ACE2 were more frequent in mild group, AA (variant) genotype, and A allele were more frequent in severe group ( P value < 0.001). In the multiple logistic regression, COVID-19 severity was associated with older age (> 50y) (OR 10.4, 95% CI 3.8–28.4, P < 0.001), comorbidities (OR 8.2, 95% CI 1.6–42.1, P 0.012), and higher ACE/ACE2 ratio (OR 8.3, 95% CI 3.7–18.6 P < 0.001) were independent significant predictors of severity. Haplotype analysis revealed that patients with D allele of the ACE gene combined with the A allele of the ACE2 gene had nearly double the risk of having severe COVID infection (OR = 1.9, 95% CI 1.1–3.5, P = 0.024). Conclusion Old age (> 50 years), presence of comorbidities, and a high ACE/ACE2 ratio are recognized as pivotal predictors of COVID-19 severity.