1. Sickle cell trait was associated with increased COVID-19 mortality and various preexisting chronic medical conditions, particularly in persons of African ancestry.

2. These findings support the inclusion of sickle cell trait as a risk factor for poor COVID-19 outcomes.

Evidence Rating Level: 2 (Good)

Study Rundown: Early studies have reported systemic and vascular consequences from COVID-19 infection. However, the association between individuals with sickle cell trait (SCT) and COVID-19 is unclear, particularly among patients of African and Hispanic ancestry. This study examined the association of SCT with preexisting conditions, COVID-19 outcome severity, and post-COVID-19 conditions. Key outcomes included COVID-19 severity derived from the World Health Organization scale and phenotypes from International Classification of Diseases codes. Among 2729 individuals with SCT and 129 848 controls, the presence of SCT was associated with more preexisting kidney conditions resulting in unfavorable outcomes following COVID-19, including increased risk of mortality and acute kidney failure. A limitation of this study was the predominance of male participants, but it did represent one of the largest African ancestry study populations in the current literature.

Click to read the study in JAMA Internal Medicine

Relevant Reading: Clinical predictors of poor outcomes in patients with sickle cell disease and COVID-19 infection

In-Depth [retrospective cohort]: This genetic association study included 2729 patients with SCT, of whom 353 had COVID-19, and 129 848 SCT-negative individuals, of whom 13 488 had COVID-19 (mean [SD] age, 64.8 [13.1] years) between March 2020 and February 2021. Overall, sickle cell trait was present in 7.8% of individuals of African ancestry and associated with preexisting chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among individuals of African ancestry, SCT was associated with an increased COVID-19 mortality (n = 3749; OR, 1.77; 95%CI, 1.13-2.77; P = .01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure, which is estimated to be a contributing factor in 20.7% of fatalities in this patient population.

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