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

Wooster, L.; Nicholson, C. J.; Sigurslid, H. H.; Lino Cardenas, C. L.; Malhotra, R.

The mechanisms underlying risk of developing severe outcomes due to COVID-19 have not yet been fully elucidated. The SARS-CoV-2 virus has a marked affinity to the human angiotensin-converting enzyme 2 (ACE2) receptor. The ACE2 locus is highly polymorphic, and this genetic variability may affect COVID-19 disease severity. Here, we analyzed associations 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 sex identified six of these ten SNPs to be significantly associated with hospitalization. These results provide preliminary evidence of a 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.