Polymorphisms in the ACE2 Locus Associate with Severity of COVID-19 Infection

Data from clinical studies suggests a strong association between underlying cardiometabolic disease and worse outcomes in COVID-19. Given that the SARS-CoV-2 virus has a unique marked affinity to the human angiotensin-converting enzyme 2 (ACE2) receptor, one potential explanation behind this phenomenon may involve the higher expression of ACE2 receptor in these patients. Here, we analyzed association between polymorphisms in the ACE2 locus and COVID-19 severity in 62 patients found to be COVID-19 positive by polymerase chain reaction. Of these patients, 23 required hospitalization due to COVID-19 infection. Of 61 ACE2 single nucleotide polymorphisms (SNPs) genotyped in this patient cohort, 10 were significantly associated with tissue expression of ACE2. Logistic regression adjusted for age and for sex identified six of these ten SNPs to be significantly associated with hospitalization. These results provide preliminary evidence of a genetic link between the ACE2 genotype and COVID-19 disease severity and suggest that the ACE2 genotype may inform COVID-19 risk stratification and need for more intense therapy.