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Interplay between demographic, clinical and polygenic risk factors for severe COVID-19.

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  • معلومة اضافية
    • المصدر:
      Publisher: Oxford University Press Country of Publication: England NLM ID: 7802871 Publication Model: Print Cited Medium: Internet ISSN: 1464-3685 (Electronic) Linking ISSN: 03005771 NLM ISO Abbreviation: Int J Epidemiol Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: [London] Oxford University Press.
    • الموضوع:
      COVID-19*/epidemiology ; COVID-19*/genetics; Humans ; Male ; Antiviral Agents ; COVID-19 Testing ; Demography ; Immunosuppressive Agents ; Interleukin-10 ; Ligases ; Risk Factors ; SARS-CoV-2
    • نبذة مختصرة :
      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.
      (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)
    • Grant Information:
      MC_PC_17228 United Kingdom MRC_ Medical Research Council; MC_QA137853 United Kingdom MRC_ Medical Research Council; MR/N011775/1 United Kingdom MRC_ Medical Research Council; MC_PC_19042 United Kingdom MRC_ Medical Research Council
    • Contributed Indexing:
      Keywords: COVID-19; epidemiology; polygenic risk score; risk prediction
    • الرقم المعرف:
      0 (Antiviral Agents)
      0 (Immunosuppressive Agents)
      130068-27-8 (Interleukin-10)
      EC 6.- (Ligases)
    • الموضوع:
      Date Created: 20220630 Date Completed: 20221028 Latest Revision: 20230802
    • الموضوع:
      20240829
    • الرقم المعرف:
      PMC9278202
    • الرقم المعرف:
      10.1093/ije/dyac137
    • الرقم المعرف:
      35770811