Abstract
Coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to scale and threaten human health and public safety. It is essential to identify those risk factors that lead to a poor prognosis of the disease. A predisposing host genetic background could be one of these factors that explain the interindividual variability to COVID-19 severity. Thus, we have studied whether the rs4341 and rs4343 polymorphisms of the angiotensin converting enzyme (ACE) gene, key regulator of the renin-aldosterone-angiotensin system (RAAS), could explain the different outcomes of 128 COVID-19 patients with diverse degree of severity (33 asymptomatic or mildly symptomatic, 66 hospitalized in the general ward, and 29 admitted to the ICU). We found that G allele of rs4341 and rs4343 was associated with severe COVID-19 in hypertensive patients, independently of gender (p<0.05). G-carrier genotypes of both polymorphisms were also associated with higher mortality (p< 0.05) and higher severity of COVID-19 in dyslipidemic (p<0.05) and type 2 diabetic patients (p< 0.01). The association of G alleles with disease severity was adjusted for age, sex, BMI and number of comorbidities, suggesting that both the metabolic comorbidities and the G allele act synergistically on COVID-19 outcome. Although we did not find a direct association between serum ACE levels and COVID-19 severity, we found higher levels of ACE in the serum of patients with the GG genotype of rs4341 and rs4343 (p<0.05), what could explain the higher susceptibility to develop severe forms of the disease in patients with the GG genotype, in addition to hypertension and dyslipidemia. In conclusion, our preliminary study suggests that the G-containing genotypes of rs4341 and rs4343 confer an additional risk of adverse COVID-19 prognosis. Thus, rs4341 and rs4343 polymorphisms of ACE could be predictive markers of severity of COVID-19 in those patients with hypertension, dyslipidemia or diabetes. The knowledge of these genetic data could contribute to precision management of SARS-CoV-2 infected patients when admitted to hospital.
Highlights
At the time of writing this paper, the COVID-19 has resulted in a pandemic with more than 187 million of confirmed cases around the world that has caused more than 4 million deaths [1] (July 2021)
A higher frequency of males was found in both groups of hospitalized patients when compared to asymptomatic/mildly symptomatic patients (p
A higher frequency of hypertension (p < 0.001) and dyslipidemia (p < 0.001) was found in both groups of hospitalized patients when compared to asymptomatic/mildly symptomatic patients, and a similar tendency was observed when examining the frequency of type 2 diabetes mellitus (p
Summary
At the time of writing this paper, the COVID-19 has resulted in a pandemic with more than 187 million of confirmed cases around the world that has caused more than 4 million deaths [1] (July 2021). In our midst, approximately 10% of patients require hospital admission [2] and 20% of hospitalized patients develop severe respiratory diseases which may quickly progress to respiratory failure, shock and multiorgan dysfunction [3]. In hospitalized COVID-19 patients, more than 30% may require intensive care treatment and around 39% of ICU admitted patients die [4]. It is essential to identify those individuals more likely to develop severe forms of the disease for an early precision management. Many individuals with these features do not develop severe symptoms, and the causes are not fully understood [3, 5]
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