Study Suggests Sickle Cell Trait as an Adverse Prognostic Factor for COVID-19

A team of investigators conducted a study to determine if the presence of sickle cell trait (SCT) was associated with worse outcomes of COVID-19. An increased risk of mortality and acute kidney failure was observed in patients with SCT after experiencing COVID-19.

Further understanding of the relationship between SCT and the prepandemic health conditions in individuals of the Million Veteran Program (MVP), as well as the assessment of the severity and consequence of COVID-19 were the research motivations.

According to the results, individuals with SCT who previously had COVID-19 also had various preexisting kidney conditions that were associated with poor outcomes.

"Our findings support the inclusion of SCT as an adverse prognostic factor for COVID-19 and development of SCT-tailored interventions. Our work has broad implications for the detection and clinical management of SCT," investigators wrote.

The Analyses

Lead author, Anurag Verma, PhD, Corporal Michael J. Crescenz VA Medical Center, included 2729 individuals with sickle cell trait, and 129,848 indiviudals who did not have the trait in this genetic association study. Of those with SCT, 353 had COVID-19, and 13,488 who were SCT-negative had experienced COVID-19.

The aim was to identify any associations between SCT and COVID-19 outcomes. To examine this, investigators implemented firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification.

More specifically, 4 COVID-19 outcomes were evaluated in regard to the World Health Organization (WHO) severity scale. Phenotypes were then derived from codes in the electronic records of International Classification of Disease.

The Results

It was revealed that sickle cell trait correlated with increased COVID-19 mortality and as well as multiple preexisting chronic medical conditions in individuals of African ancestry.

Among the 132 577 MVP participants with COVID-19, data displayed the mean age at the index date was 64.8 (standard deviation: 13.1) years and 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.

When the 4 clinical outcomes of COVID-19 we're assessed, 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).

Additionally, investigators reported that the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. An estimation by counterfactual mediation framework showed 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.

"In this genetic association study, SCT was associated with increased COVID-19 mortality and a number of preexisting chronic medical conditions in African ancestry individuals. Our findings support the inclusion of SCT as an adverse prognostic factor for COVID-19 and development of SCT-tailored interventions. Our work has broad implications for the detection and clinical management of SCT," investigators concluded.

The study, "Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait" was published in JAMA Internal Medicine.