Genetic risk factors for death with SARS-CoV-2 from the UK Biobank

Abstract

<jats:p>We present here genetic risk factors for survivability from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 19 (COVID-19). At the time of writing it is too early to determine comprehensively and without doubt all risk factors, but there is an urgency due to the global pandemic crisis that merits this early analysis. We have nonetheless discovered 5 novel risk variants in 4 genes, discovered by examining 193 deaths from 1,412 confirmed infections in a group of 5,871 UK Biobank participants tested for the virus. We also examine the distribution of these genetic variants across broad ethnic groups and compare it to data from the UK Office of National Statistics for increased risk of death from SARS-CoV-2. We confidently identify the gene ERAP2 with a high-risk variant, as well as three other genes of potential interest. Although mostly rare, a common theme of genetic risk factors affecting survival might be the inability to launch or modulate an effective immune and stress response to infection from the SARS-CoV-2 virus.</jats:p>

The role of host genetics in susceptibility to severe viral infections in humans and insights into host genetics of severe COVID-19: A systematic review

“…As of August 21, 2020, we found 5 studies (one of them is a preprint) associating COVID-19 severity with different genes as in Table 2 ( Ellinghaus et al, 2020 ; Kuo et al, 2020 ; Lu et al, 2020 ; Wu et al, 2020 ; Zhao et al, 2020 ).…”

ERAP1 and ERAP2 Enzymes: A Protective Shield for RAS against COVID-19?

“…In this context, given the role of ERAP enzymes in the regulation of RAS, hypertension, antigen processing, inflammatory disorders, and cytokines and NO release, we hypothesize that knowledge of ERAP1 and ERAP2 genotypes may be useful in identifying the appropriate therapy for each COVID-19 patient. In line with this hypothesis, a missense variant in the ERAP2 gene has been linked to an increased risk of death in a small cohort of COVID-19 patients from the U.K. Biobank [ 55 ]. Furthermore, ERAP1 has been involved in the generation of peptides from the SARS-CoV2-S1 spike protein with the optimal length to bind MHC class I molecules, including the possible SARS-CoV2-protective HLA-B*15:03 allele [ 56 , 57 ].…”

Immunogenetic Predictors of Severe COVID-19

“…When studying the genotype of 193 infected patients, scientists identified four genes with missense variants—the rs150892504 allele of the ERAP2 gene, the s138763430 allele of the BRF2 gene, the rs117665206 allele of the TMEM181 gene, the rs147149459 allele of the ALOXE3 gene. Among the described mutations, it is possible to distinguish alterations in the ERAP2 gene encoding metalloaminopeptidase involved in the final modification of antigens for presentation by MHC-I molecules [ 9 ].…”