Why do we die? Uncovering the genetic connections causing COVID-19 disease severity 

Abstract

SARS-CoV-2 attacks randomly causing deaths among certain populations. Additionally, this disease seems to kill males preferentially. This study investigates why by examining single nucleotide polymorphisms (SNPs) correlated with increased protein expression associated with viral infection of cells leading to disease proliferation. ACE2, the assumed host cell receptor for the virus is believed to be assisted by co-receptors ENPEP and ANPEP. TMPRSS2 cleaves the S viral protein into two sub-units allowing viral binding to the ACE2 receptor. ACE2 found on the X-chromosome has SNPs increasing ACE2 expression found at frequencies greater than 50% in all male populations analyzed which could account for the increase in male deaths. Females would undergo X-inactivation for the SNPs and have protection from the increased ACE2 expression in all their cells. ACE2, ENPEP, and TMPRSS2 were also found to have population specific SNP patterns which could account for the increased prevalence of disease among certain populations.