key: cord-1054087-nngagjsm
authors: Clift, Ashley Kieran; Saatci, Defne; Coupland, Carol A.C.; Dambha-Miller, Hajira; Hippisley-Cox, Julia; Tan, Pui San; Patone, Martina
title: Sickle Cell Disorders and Severe COVID-19 Outcomes: A Cohort Study
date: 2021-07-20
journal: Ann Intern Med
DOI: 10.7326/m21-1375
sha: 24580ad433912463835df48c3e72013d199ba55d
doc_id: 1054087
cord_uid: nngagjsm

nan

[CI, 1.36 to 4.75]) (Figure) . E-values for HRs for COVID-19related hospitalization and death were 7.69 (lower limit of the CI, 5.41) and 4.54 (lower limit of the CI, 2.06), respectively, suggesting robustness to residual confounding.

Persons with sickle cell trait had 98 (0.38%) hospitalizations and 50 (0.19%) deaths. In the cohort, sickle cell trait was also associated with higher risks for COVID-19-related hospitalization (HR, 1.38 [CI, 1.12 to 1.70]) and death (HR, 1.51 [CI, 1.13 to 2.00]). E-values for COVID-19-related hospitalization and death were 2.1 (lower limit of the CI, 1.49) and 2.39 (lower limit of the CI, 1.51), respectively.

Discussion: Our analysis estimated a 4-fold increased risk for COVID-19-related hospitalization and a 2.6-fold increased risk for COVID-19-related death for sickle cell disease. Sickle cell trait was also associated with increased risks for both outcomes, albeit to a lesser extent. Several aspects of sickle cell phenotypes overlap with the pathophysiology of severe COVID-19 (1, 2), which could be relevant mechanisms worthy of further study, as should the directionality of infection and sickle crisis.

Study limitations include the potential underdiagnosis of sickle cell trait in the population, the rarity of outcomes limiting extended adjustments and sickle subtype-specific or age-or sex-specific analyses, the lack of information on symptoms or presentation, and that the HRs do not possess a direct causal interpretation.

Given that sickle cell disease affects approximately 15 000 persons in the United Kingdom, 100 000 persons in the United States, and 8 million to 12 million persons globally, we believe our results are relevant to policymakers and decision making about vaccination prioritization for potentially high-risk groups. Episode Statistics data and civil registration data used in this analysis are reused by permission from NHS Digital, which retains the copyright. This study was undertaken as part of a larger project, which is detailed at www.qresearch.org/research/approved-research-programs-and-projects /quantifying-the-association-between-covid-19-ethnicity-and-mortality-a-cohortstudy-across-three-uk-national-databases. Cause-specific Cox regression models were stratified by individual general practice and adjusted for age (restricted cubic spline with 5 knots), sex, and self-reported ethnicity (White, South Asian, Black, and other [including Chinese, multiracial, and Arab]). We did post hoc analyses restricted to those with sickle cell disorders. For COVID-19-related hospitalization, compared with persons with sickle cell trait, those with sickle cell disease had an adjusted HR of 3.00 (95% CI, 1.99 to 4.52). For COVID-19-related death, persons with sickle cell disease had an adjusted HR of 1.37 (CI, 0.62 to 3.02) compared with those with sickle cell trait. HR = hazard ratio.

Sickle cell disease

Intravascular hemolysis and the pathophysiology of sickle cell disease

COVID-19 infection and sickle cell disease: a UK centre experience

Coronavirus disease among persons with sickle cell disease

Prognosis of patients with sickle cell disease and COVID-19: a French experience

Parameter Persons Without Sickle Cell Disorders, n (column %)

Persons With Sickle Cell Disease, n (column %)

Information Systems) practices that contribute to the database as well as the University of Nottingham and University of Oxford for expertise in establishing, developing, and supporting the QResearch database. QResearch acknowledges funding from the Nottingham Biomedical Research Centre funded by the National Institute for Health Research. The data on SARS-CoV-2 reverse transcriptase polymerase chain reaction tests were used with permission from Public Health England. The Hospital