Genomic and Ancestral Variation Underlies the Severity of COVID-19 Clinical Manifestation in Individuals of European Descent.

Priyanka Upadhyai,Gokul Suresh,Rahul Parit,Ranajit Das

doi:10.3390/life11090921

Abstract

The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by a wide spectrum of clinical phenotypes ranging from asymptomatic to symptomatic with mild or moderate presentation and severe disease. COVID-19 susceptibility, severity and recovery have demonstrated high variability worldwide. Variances in the host genetic architecture may underlie the inter-individual and population-scale differences in COVID-19 presentation. We performed a genome-wide association analysis employing the genotyping data from AncestryDNA for COVID-19 patients of European descent and used asymptomatic subjects as the control group. We identified 621 genetic variants that were significantly distinct between asymptomatic and acutely symptomatic COVID-19 patients (multiple-testing corrected p-value < 0.001). These variants were found to be associated with pathways governing host immunity, such as interferon, interleukin and cytokine signalling, and known COVID-19 comorbidities, such as obesity and cholesterol metabolism. Further, our ancestry analysis revealed that the asymptomatic COVID-19 patients possess discernibly higher proportions of the Ancestral North Eurasian (ANE) and Eastern Hunter-Gatherer (EHG) ancestry, which was introduced to Europe through Bell Beaker culture (Yamnaya related) and lower fractions of Western Hunter-Gatherer (WHG) ancestry, while severely symptomatic patients have higher fractions of WHG and lower ANE/EHG ancestral components, thereby delineating the likely ancestral differences between the two groups.

Highlights

We further developed several multiple linear regression models with different combinations of various European ancestry fractions obtained from ADMIXTURE, alongside demographic and healthcare information pertaining to age, gender, body mass index (BMI) and comorbidities based on the self-reported phenotype questionnaire
We compared the genomes of asymptomatic COVID-19 patients (N = 197) with that those characterized by severe disease (N = 1492)
We would like to emphasize here that while our findings indicate that there is a conserved set of single nucleotide variant (SNV) which are independently predictive of both severe COVID-19 symptoms and risk factors, such as obesity, higher cholesterol level and habits such as smoking, these SNVs themselves might not be causative of severe COVID-19 symptoms

Summary

Introduction

Since its outbreak in December 2019 in Wuhan, China, the coronavirus disease (COVID19) has ravaged the world, causing 217,901,675 infections and 4,523,766 deaths worldwide (https://covid19.who.int, assessed on 31 August 2021). It is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1,2] and has a broad spectrum of clinical manifestations among patients ranging from asymptomatic, symptomatic with mild or moderate respiratory disease, severe alveolar damage, pneumonia and respiratory failure [3,4,5]. More than 35% of infected individuals display neurological symptoms ranging from headache, loss of smell (anosmia), loss of taste (ageusia), dizziness and cerebrovascular disease [6].

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