Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01–3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01–3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10–2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.
Highlights
The ongoing coronavirus disease 2019 (COVID-19) pandemic has affected around 336 million individuals, causing the death of nearly 5,560,718 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected subjects around the world [1]
An altered ACE/angiotensin-converting enzyme 2 (ACE2) expression ratio could contribute to severe outcomes in COVID-19 patients [8], as it does for cardiovascular diseases [9]
A total of 481 individuals with COVID-19 were included in this study, 22% of them were in a severe stage and 86 subjects died with a median age of 64.5 years
Summary
The ongoing coronavirus disease 2019 (COVID-19) pandemic has affected around 336 million individuals, causing the death of nearly 5,560,718 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected subjects around the world [1]. The severity of COVID-19 and its clinical manifestations and outcomes are related to the internalization mechanism of the virus into the host cell, host genetics variants, advanced age, gender, and comorbidities [5]. In this sense, the homeostasis of the renin–angiotensin system is another risk factor underlying the pathogenesis of COVID-19 because angiotensin-converting enzyme 2 (ACE2) is the predominant receptor by which the SARS-CoV-2 virus enters and infects cells [6, 7]. The insertion/deletion (I/D) polymorphisms play a pivotal role in cardiovascular and respiratory diseases; for instance, the D/D genotype has been associated with SARS progression [10, 11] It has been associated with poor clinical outcomes of acute respiratory distress syndrome (ARDS), where individuals with the D/D genotype had significantly higher mortality than those who carry the I/I genotype [12]. Different reports have proposed that ACE2 polymorphisms rs2285666 (G870A) could modulate the susceptibility to SARS-CoV-2 infection by contributing to higher expression of ACE2 receptor [13, 14]
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