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.
Keywords: COVID-19; epidemiology; polygenic risk score; risk prediction.
【저자키워드】 COVID-19, Epidemiology, polygenic risk score, risk prediction., 【초록키워드】 Critical care, severe COVID-19, Hospitalization, UK biobank, obesity, hospital, polymorphism, risk, Pathway analysis, outcomes, morbidity, Patient, COVID-19 diagnosis, Factors, death, co-morbidity, age, Genetic variant, General population, Admission, Smokers, association, genetic data, antiviral response, Pathways, PRS, interquartile range, Factor, adjusted odds ratio, 95% CI, individual, participant, enrolment, men, European, socio-demographic, genetic risk factor, lowest, IMPROVE, greater, highest, identify, develop, reported, conducted, was performed, median, diagnosed with COVID-19, single-nucleotide, 【제목키워드】 severe COVID-19, risk factor,