title: Evolution of COVID-19 susceptibility and severity: did our evolutionary past drive genetic vulnerability to the pandemic?
title: The evolution of COVID-19 susceptibility and severity: did our evolutionary past drive genetic vulnerability to the pandemic?
titleType: AlternativeTitle
Creators: name: Le Vot, Louise
Publisher: name: The University of Edinburgh
Year: 2023
Subjects: subject: epidemiology
subject: infectious disease
subject: Genomics
subject: susceptibility evolution

description: The sanitary crisis that is COVID-19 (COrona Virus Disease - 2019) is still impacting us to this day. Despite humans having been exposed to various kinds of coronaviruses in the past, this particular strain (thought to have originated in bats and later been transmitted to humans via zoonotic spillage) was the first identified and recorded coronavirus epidemic to have taken off in humans and going global in such a ubiquitous manner. Although the reasons for this development remain quite unclear, the human genome (i.e. the collection of all of the genetic material of an individual) has been under scrutiny for COVID-19-associated Single Nucleotide Polymorphisms (SNPs) to better understand the drivers of the pandemic. When it comes to scanning the genome for such SNPs, one of the most valuable tools is Genome-Wide Association Studies (GWAS). Using this technique, many SNPs were found to be COVID-19-associated, (i.e. linked to variations in response to exposure/infection by the disease when genetically mutated), several of which were inherited from Neanderthals (Homo neanderthalensis), giving the pandemic somewhat of archaic origins. A previous project1 took this a step further, investigating the evolutionary history of COVID-19-associated SNPs in humans since our Last Common Ancestors (LCAs) with 15 other mammalian species. Considering the non-human allele to be the ancestral allele (from the LCA), the aim was to determine the trajectory of susceptibility and sensitivity to COVID-19 infections according to the evolution of the direction of effect of given SNPs in the human lineage since aforementioned LCA. The results of this project denoted a potential SNP driven evolution towards more frequent hospitalisation of patients infected with COVID-19, as well as reduced susceptibility to severe symptoms and infection by the disease. Building upon that, this current project aims to tailor and extend the existing coding scripts to two other datasets describing human genetic susceptibility to various diseases: cancer as well as a consortium of infectious diseases and other conditions (i.e. Consortium) obtained respectively from the available databases: GWAS catalogue and IEU open GWAS project. We further split the consortium into three categories: cancer, infection-related conditions (IRC) and non-infection-related conditions (NIRC). The goal being to build profiles of evolution of direction of effect since the considered LCA specific to those datasets for side-by-side comparison with COVID-19’s. This investigation gave quite an interesting yield, with the IRC and NIRC groups showing no significance in the direction of effect of the GWAS variants between the humans and any of the other 15 species (with non-significant trends towards susceptibility and resistance respectively). Thus, suggesting that this grouping of other diseases and conditions seems to remain more stable overtime in terms of overall sensitivity to their associated diseases than COVID-19-associated SNPs have. This hints at a non-proven difference in profile between those non-pandemic infectious diseases and our current plight. Cancer was used as a form of control as it is not an infectious disease and can thus clue us on whether the host/pathogen relationship might influence the genomic evolutionary profile investigated here. The cancer cohorts from both the GWAS catalogue and the IEU open GWAS project did show significance. Both groups showed an increase in resistance to cancer since our LCAs with the other mammalian species. Another interesting approach to consider is gene ontology, which could help determine whether it is protein-coding or non-protein-coding SNPs that tend to be of bigger effect in terms of both susceptibility and protection for COVID-19. It also highlights the fact that most COVID-19-associated SNPs of susceptible effect seem to largely affect elements of inflammation or cell growth regulation, in other words, they seem to be related to immunity, which is the body’s line of defence against infection. Finally, we hope to observe whether the human genome is passively degenerating (i.e. accumulating deleterious SNPs) due to its small effective population or if there is more at play when comparing infectious and non-infectious conditions. We also hope to investigate whether the human sensitivity and response to COVID-19 infection might differ from that of other infectious diseases and if an increase in susceptibility to some Emerging Infectious Disease (EID) might potentially set the scene for the next pandemic. In a way, being able to quicken targeting of potentially successful EID, hopefully assisting in the prevention or mitigation of upcoming pandemics through appropriate control measures.