| Title: | Interplay between demographic, clinical and polygenic risk factors for severe COVID-19 |
| Journal: | International Journal of Epidemiology |
| Published: | 30 Jun 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35770811/ |
| DOI: | https://doi.org/10.1093/ije/dyac137 |
| URL: | https://academic.oup.com/ije/advance-article-pdf/doi/10.1093/ije/dyac137/44318908/dyac137.pdf |
Publication 7575
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Abstract
BACKGROUND: We aimed to identify clinical, socio-demographic and genetic risk factors for severe COVID-19 (hospitalization, critical care admission or death) in the general population. METHODS: In this observational study, we identified 9560 UK Biobank participants diagnosed with COVID-19 during 2020. A polygenic risk score (PRS) for severe COVID-19 was derived and optimized using publicly available European and trans-ethnic COVID-19 genome-wide summary statistics. We estimated the risk of hospital or critical care admission within 28 days or death within 100 days following COVID-19 diagnosis, and assessed associations with socio-demographic factors, immunosuppressant use and morbidities reported at UK Biobank enrolment (2006-2010) and the PRS. To improve biological understanding, pathway analysis was performed using genetic variants comprising the PRS. RESULTS: We included 9560 patients followed for a median of 61 (interquartile range = 34-88) days since COVID-19 diagnosis. The risk of severe COVID-19 increased with age and obesity, and was higher in men, current smokers, those living in socio-economically deprived areas, those with historic immunosuppressant use and individuals with morbidities and higher co-morbidity count. An optimized PRS, enriched for single-nucleotide polymorphisms in multiple immune-related pathways, including the 'oligoadenylate synthetase antiviral response' and 'interleukin-10 signalling' pathways, was associated with severe COVID-19 (adjusted odds ratio 1.32, 95% CI 1.11-1.58 for the highest compared with the lowest PRS quintile). CONCLUSION: This study conducted in the pre-SARS-CoV-2-vaccination era, emphasizes the novel insights to be gained from using genetic data alongside commonly considered clinical and socio-demographic factors to develop greater biological understanding of severe COVID-19 outcomes.5 Authors
- Samantha S R Crossfield
- Natalie J M Chaddock
- Mark M Iles
- Mar Pujades-Rodriguez
- Ann W Morgan
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