Genomic variation underlies the severity of COVID19 clinical manifestation in individuals of European descent

ABSTRACT

Background: The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterised by a wide spectrum of clinical phenotypes ranging in acuteness from asymptomatic, symptomatic with mild or moderate manifestation and severe involving pneumonia and respiratory distress. COVID-19 susceptibility, severity and recovery have demonstrated high variability worldwide. Variances in the host genetic architecture may potentially control the inter-individual and population scale differences in COVID-19 presentation. Methods: We performed a genome-wide association study (GWAS) employing the genotyping data from Ancestry DNA COVID-19 host genetic study that included COVID-19 positive patients and healthy individuals who had tested negative for SARS-CoV-2 infection at the time of recruitment. We restricted our analysis only to the individuals of European descents to avoid genetic structure in the dataset, arising due to the presence of people from different ancestries. Further, we uniquely employed the asymptomatic individuals as controls instead of healthy individuals. Results and Discussion: Our data revealed striking genomic differences between COVID-19 asymptomatic and severely symptomatic individuals. We identified 621 genetic variants that were significantly distinct (Multiple-testing corrected P<0.001) between asymptomatic and acutely symptomatic COVID-19 patients. These variants were found to be associated with pathways governing host immunity, such as innate and adaptive immune system, interferon signaling, interleukin signaling, antigen processing by MHC, cytokine signaling and known COVID-19 comorbidities, such as obesity, cholesterol metabolism and smoking. Variants modulating drug responses including to anti-retroviral agents were also found to vary significantly between asymptomatic and severe patient groups.