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Course: Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait

CME Credits: 1.00

Released: 2022-06-27

Key Points

Question Is the presence of sickle cell trait (SCT) associated with worse outcomes of COVID-19?
Findings In this genetic association study of 2729 persons with SCT and 129,848 who were SCT negative, individuals with SCT had a number of preexisting kidney conditions that were associated with unfavorable outcomes following COVID-19. The presence of SCT was associated with increased risk of mortality and acute kidney failure following COVID-19.
Meaning Results strongly support the inclusion of SCT as an adverse prognostic factor for COVID-19.

Abstract

Importance Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the association of SCT with COVID-19 is unclear.
Objective To assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP) and to assess the severity and sequelae of COVID-19.
Design, Setting, and Participants COVID-19 clinical data include 2729 persons with SCT, of whom 353 had COVID-19, and 129,848 SCT-negative individuals, of whom 13,488 had COVID-19. Associations between SCT and COVID-19 outcomes were examined using firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification. Data for the study were collected between March 2020 and February 2021.
Exposures The hemoglobin beta S (HbS) allele (rs334-T).
Main Outcomes and Measures This study evaluated 4 COVID-19 outcomes derived from the World Health Organization severity scale and phenotypes derived from International Classification of Diseases codes in the electronic health records.
Results Of the 132,577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years. Sickle cell trait was present in 7.8% of individuals of African ancestry and associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among the 4 clinical outcomes of COVID-19, SCT was associated with an increased COVID-19 mortality in individuals of African ancestry (n?=-3749; odds ratio, 1.77; 95% CI, 1.13 to 2.77; P?=?.01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. A counterfactual mediation framework estimated that on average, 20.7% (95% CI, -3.8% to 56.0%) of the total effect of SCT on COVID-19 fatalities was due to acute kidney failure.
Conclusions and Relevance In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity.


Educational Objective
To identify the key insights or developments described in this article


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