Association of Sickle Cell Trait with Risk and Mortality of COVID-19: Results from the United Kingdom Biobank

  1. W. Kyle Resurreccion
  2. Joseph Hulsizer
  3. Zhuqing Shi
  4. Jun Wei
  5. Chi-Hsiung Wang
  6. Rong Na
  7. S. Lilly Zheng
  8. Clay Struve
  9. Brian T. Helfand
  10. Janardan Khandekar
  11. Liana Billings
  12. Michael S. Caplan
  13. Jianfeng Xu

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Abstract

Sickle cell trait (SCT) carriers inherit one copy of the Glu6Val mutation in the hemoglobin gene and is particularly common in Black individuals (5–10%). Considering the roles of hemoglobin in immune responses and the higher risk for coronavirus disease (COVID-19) among Black individuals, we tested whether Black SCT carriers were at increased risk for COVID-19 infection and mortality according to the United Kingdom Biobank. Among Black individuals who were tested for COVID-19, we found similar infection rates among SCT carriers (14/72; 19.7%) and noncarriers (167/791; 21.1%), but higher COVID-19 mortality rates among SCT carriers (4/14; 28.6%) than among noncarriers (21/167; 12.6%) (odds ratio [OR], 3.04; 95% confidence interval [CI], 0.69–11.82; P = 0.12). Notably, SCT carriers with preexisting diabetes had significantly higher COVID-19 mortality (4/4; 100%) than those without diabetes (0/10; 0%; (OR, 90.71; 95% CI, 5.66–infinite; P = 0.0005). These findings suggest that Black SCT carriers with preexisting diabetes are at disproportionally higher risk for COVID-19 mortality. Confirmation by larger studies is warranted.

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  1. Version published to 10.4269/ajtmh.20-1657
  2. ScreenIT

    SciScore for 10.1101/2020.07.02.20145359: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    One limitation of this study is the relatively small sample size. However, this study represents one of the largest available compared to other published papers and case series that study the association between COVID-19 and SCD/SCT.[7-9] Another limitation is the lack of detailed clinical information on COVID-19 symptoms and treatment. This limits our ability to perform a more comprehensive analysis. Nevertheless, due to the novel and emergent status of this pandemic, more data will likely become available for additional analysis in future studies to address both limitations of this study. In conclusion, in this first association test between SCT and COVID-19 from a population-based cohort, we find Blacks had significantly higher rates than Whites for COVID-19 infections. The age at COVID-19 infection and death in Blacks were also significantly younger than Whites. Among Blacks, SCT carriers had similar COVID-19 infection rates but a trend of higher, albeit not statistically significant, death rate than non-SCT carriers. Independent larger/more diverse datasets are required to confirm these findings and to expand our knowledge of the association between SCT carriers with COVID-19 susceptibility and severity.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  3. Version published to 10.1101/2020.07.02.20145359v1 on medRxiv