Host genetic susceptibility to COVID-19 and pandemic -associated stressors

ABSTRACT

Background: Single nucleotide polymorphisms (SNPs) in IL-6, IL-1β, and IL-10 genes have been reported to impact infectious disease outcomes and are associated with altered emotional states. High levels of these cytokines, which have a role in regulating inflammation, have been detected among individuals with severe COVID-19 disease. The objective of this study was to examine if proinflammatory SNPs in the promoter region of IL-6, IL-1β, and IL-10 genes are associated with more severe COVID-19 disease and/or increased anxiety/stress levels in response to pandemicassociated stressors in a vulnerable Hispanic population that is part of the Puerto Rico Colorectal Cancer Registry. Methods: TaqMan® SNP Genotyping Assays (ThermoFisher Scientific) for IL-1β (rs1143627), IL-6 (rs1800795), and IL-10 (rs1800871) were performed according to the manufacturer's recommendations in individuals between the ages of 21 to 75 (n=136). We assessed their anxiety and stress levels using the Generalized Anxiety Disorder Questionnaire (GAD-7) and the Perceived Stress Scale (PSS). Of these individuals, we evaluated those that had been previously infected with COVID-19 (n=38) for their symptom severity through a questionnaire. Chi-Square tests and Multivariate Logistic Regressions were used to calculate associations and ORs. Results: Preliminary analysis showed an association between having the homozygous IL-1β proinflammatory SNP and reporting fever as a symptom (OR=2.50, p-value=0.05). Individuals with the homozygous IL-10 pro-inflammatory SNP had higher odds of reporting difficulty breathing (OR= 4.51, p-value = 0.02), shortness of breath (OR=7.82, p-value=0.006), and fatigue as symptoms (OR=4.43, p-value=0.020. Further analysis also showed an association between having the homozygous IL-10 pro-inflammatory SNP and reporting at least 1 severe COVID-19 symptom (OR=3.38, p-value=0.046). Those with the homozygous or heterozygous IL-6 pro-inflammatory allele were less likely to report higher anxiety levels than those with the wild-type allele (OR=0.1447, p-value=0.04). We also observed that individuals between the ages of 21 to 49 were more likely to report changes in diet (OR=1.65, p-value=0.059) and constantly disinfecting as a pandemic-related stressor (OR=1.87, p-value=0.04) compared to individuals between the ages of 50 to 79. Conclusions: Pro-inflammatory IL-1β and IL-10 SNPs were associated with reporting fever and more severe symptoms of COVID-19, respectively. Data analysis using a larger sample size is warranted and is currently underway. Studies focused on examining that factors that contribute to more severe COVID-19 symptoms and how pandemic-associated stressors promote higher inflammation levels as a result of increased stress/anxiety are needed to fully understand the longterm effects the pandemic on public health, including possible increases in cancer incidence due to chronic inflammation.