Philadelphia—The presence of sickle cell trait (SCT) should be considered an adverse prognostic factor for COVID-19, according to a new study.

The genetic association study of 2,729 adults with SCT and 129,848 who were SCT negative, published in the Journal of the American Medical Association Internal Medicine, determined that SCT patients had a range of preexisting kidney conditions that were associated with unfavorable outcomes following infection with SARS-CoV-2. The most serious was an increased risk of mortality and acute kidney failure following COVID-19, according to researchers and colleagues from the University of Pennsylvania Department of Medicine and the Corporal Michael J. Crescenz Veterans' Affairs Medical Center, both in Philadelphia.

SCT is defined as the presence of one hemoglobin beta sickle allele (rs334-T) and one normal beta allele. It affects millions in the U.S., especially those of African and Hispanic ancestry. Until now, however, the association of SCT with COVID-19 was unclear.

The study team sought to assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP), including an analysis of the severity and sequelae of COVID-19.

To do that, researchers focused on COVID-19 clinical data of 2,729 SCT patients, of whom 353 had COVID-19, as well as 129,848 SCT-negative individuals, of whom 13,488 had COVID-19. Data for the study were collected between March 2020 and February 2021.

Of the 132,577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years, according to the authors, who advise that SCT 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.

"Sickle cell trait was found to be associated with increased COVID-19 mortality in individuals of African ancestry (n = 3749; odds ratio, 1.77; 95% CI, 1.13-2.77; P = .01). In the 60 days following COVID-19 and 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," the researchers pointed out, adding, "In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity."

Background information in the study states that the U.S. incidence estimate for SCT was 73.1 cases per 1,000 Black newborns, 6.9 cases per 1,000 Hispanic newborns, and 3.0 cases per 1,000 white newborns.

"Although largely considered a benign condition, SCT has been associated with increased risk for adverse outcomes ranging from rare complications of exertion-related injuries and renal medullary carcinoma to more common medical conditions such as chronic kidney disease and venous thromboembolism," the authors explained.

The authors added, "The CDC has advised that patients with SCD be regarded as highly susceptible to COVID-19. However, this cautionary advice does not extend to individuals with SCT."

Even though SCT affects more than 3 million people in the U.S. and 300 million people globally, limited data exist on the association between SCT and COVID-19 outcomes. The researchers said they used the Million Veteran Program data because it has clinical information pre-COVID-19 and post-COVID-19 for SCT in more than 658,582 veterans.

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