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COVID-19 patients with sickle cell trait (SCT) were prone to poor outcomes that appeared to be driven in part by kidney dysfunction, a genetic association study suggested.

Among U.S. veterans of African ancestry, SCT was tied to a higher chance of COVID-related mortality versus those without the trait (OR 1.77, 95% CI 1.13-2.77). The presence of either sickle cell anemia or another SCT-related condition was linked with more than 93-times higher odds of severe COVID-19 illness (OR 93.17, 95% CI 78.60-110.44), according to Shiuh-Wen Luoh, MD, PhD, of the VA Portland Health Care System in Oregon, and colleagues.

Moreover, those with SCT saw a significantly higher incidence of acute kidney failure in the 60 days following COVID-19 infection (OR 1.40, 95% CI 1.09-1.90), Luoh's group reported in .

The researchers determined that this increase in acute kidney failure drove approximately 20.7% of the total effect that SCT appeared to have on COVID mortality.

Even among a subset of patients with stable or normal kidney function prior to testing positive for SARS-CoV-2 infection, SCT was still significantly linked with a higher odds for declining kidney function following COVID-19 (OR 1.77, 95% CI 1.16-2.67).

It appears that for individuals with SCT, "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," the investigators said.

Prior studies had linked sickle cell disease -- and SCT, to a lesser degree -- to COVID-related hospitalizations and deaths.

"Our findings support the inclusion of SCT as an adverse prognostic factor for COVID-19 and development of SCT-tailored interventions," Luoh and colleagues suggested, adding that their work has broad implications for both the detection and clinical management of SCT.

Their present study relied on data from the Million Veteran Program that included electronic health records pulled from Veterans Affairs medical centers from the start of the pandemic through March 2021.

There were 132,577 U.S. adults included, with a mean age of 64.8 years and predominantly male. Among this cohort, 7.8% of adults with African ancestry had SCT, defined as the presence of one hemoglobin beta S allele (rs334-T).

SCT was also present in 1% of study participants with Hispanic ancestry, but this group was too small to assess outcomes.

People with SCT were especially likely to develop severe COVID-19 illness if they had preexisting conditions such as:

• Chronic kidney disease: OR 1.45 (95% CI 1.36-1.55)
• Type 2 diabetes with kidney complications: OR 1.33 (95% CI 1.23-1.43)
• Pulmonary embolism: OR 1.43 (95% CI 1.27-1.60)
• Pulmonary heart disease: OR 1.30 (95% CI 1.19-1.42)
• Hypertensive kidney disease: OR 1.19 (95% CI 1.12-1.26)

Hemoglobin C allele rs33930165-T -- present in about 1.7% of people with African ancestry -- was not linked with poor COVID outcomes nor kidney complications after infection, Luoh's group reported.

Study authors acknowledged that they did not analyze COVID outcomes of people with sickle cell disease, a cohort that is precluded from enlisting in the armed forces.

Additionally, their analysis was potentially affected by residual confounding and misclassification.

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