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

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  • 1 Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois;
  • 2 Lake Forest Academy, Lake Forest, Illinois;
  • 3 CSS LLC, Chicago, Illinois;
  • 4 Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois;
  • 5 Center for Molecular Medicine, NorthShore University HealthSystem, Evanston, Illinois;
  • 6 Department of Medicine, NorthShore University HealthSystem, Evanston, Illinois
  • 7 Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, Illinois;
  • 8 Department of Pediatrics, NorthShore University HealthSystem, Evanston, Illinois

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.

Author Notes

* Address correspondence to Jianfeng Xu, NorthShore University HealthSystem, 1001 University Place, Evanston, IL 60201. E-mail: jxu@northshore.org

Disclosure: All authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. The UKB was approved by North West–Haydock Research Ethics Committee (REC reference: 16/NW/0274; IRAS project ID: 200778). UKB data were accessed through a Material Transfer Agreement under Application Reference Number 50295. This study was performed in accordance with the Declaration of Helsinki. All UKB participants provided their informed consent before any data/samples were collected. The data used in this study are available in the UK Biobank, a publicly available repository. Data were accessed through a Material Transfer Agreement under Application Reference Number 50295. For additional information, please feel free to contact the corresponding author.

Authors’ addresses: W. Kyle Resurreccion, Zhuqing Shi, Jun Wei, Chi-Hsiung Wang, Rong Na, S. Lilly Zheng, Brian T. Helfand, and Jianfeng Xu, Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, IL, E-mails: wresurreccion@northshore.org, shizhuqing1991@hotmail.com, weijun19992019@gmail.com, cwang@northshore.org, narong.hs@gmail.com, szheng@northshore.org, brianhelfand@gmail.com, and jxu@northshore.org. Joseph Hulsizer, Lake Forest Academy, Lake Forest, IL, E-mail: joerig4@gmail.com. Clay Struve, CSS LLC, Chicago, IL, E-mail: clay@csstrading.com. Brian T. Helfand and Jianfeng Xu, Department of Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL, E-mails: brianhelfand@gmail.com and jxu@northshore.org. Janardan Khandekar, Center for Molecular Medicine, NorthShore University HealthSystem, Evanston, IL, E-mail: jkhandekar@northshore.org. Liana Billings, Department of Medicine, NorthShore University HealthSystem, Evanston, IL, and Department of Medicine, University of Chicago Pritzker School of Medicine, Chicago, IL, E-mail: lbillings@northshore.org. Michael S. Caplan, Department of Pediatrics, NorthShore University HealthSystem, Evanston, IL, E-mail: mcaplan@northshore.org.

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