Individuals with sickle cell trait experience worse COVID-19 outcomes, a new study finds. Kidney conditions appear to be major contributors.
Sickle cell trait is the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele. In the United States, sickle cell trait affects 73.1 Black, 6.9 Hispanic, and 3.0 White newborns per 1000, according to background information.
In the Million Veteran Program (90% male), 2729 adults had sickle cell trait and 129,848 did not. In the groups with and without sickle cell trait, 353 and 13,488 contracted COVID-19, respectively.
Sickle cell trait affected 7.8% of veterans of African ancestry and 1% of veterans of Hispanic ancestry. Among 30,949 African Americans in the program, sickle cell trait was significantly associated with 1.8-fold increased odds of COVID-19 mortality, Chiuh-Wen Luoh, MD, PhD, of VA Portland Health Care System, and colleagues reported in JAMA Internal Medicine. Patients with sickle cell trait also had significant 1.4-fold increased odds of developing acute kidney failure within 60 days of COVID-19 infection. According to a counterfactual mediation framework, approximately 20.7% of the total effect of sickle cell trait on COVID-19 death was attributable to acute kidney failure.
Sickle cell trait was associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Yet a history of these conditions explained only a fraction of the increased risk for post-COVID-19 acute kidney failure, the investigators noted.
“In individuals with sickle cell trait, sickling due to low oxygenation tension in the kidneys may cause kidney dysfunction, which can be exacerbated by COVID-19, in addition to other potential mechanisms,” Dr Luoh’s team explained.
According to the investigators, sickle cell trait may be an adverse prognostic factor for COVID-19 and warrants tailored interventions.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Verma A, Huffman JE, Gao L, et al. Association of kidney comorbidities and acute kidney failure with unfavorable outcomes after COVID-19 in individuals with the sickle cell trait. JAMA Intern Med. Published online June 27, 2022. doi:10.1001/jamainternmed.2022.2141