SCD and SCT tied to worse COVID-19 outcomes in pooled analysis

Mortality, hospital rates reported higher in those with the disease and trait

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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People with sickle cell disease (SCD) or sickle cell trait (SCT) face an increased risk of hospitalization and mortality following infection with SARS-CoV-2, the virus that causes COVID-19, compared with the general population, according to a pooled analysis of published studies.

Researchers also noted that kidney complications after COVID-19 infection were more likely among those with the trait than in those without it or the disease.

“Further research and ongoing collaborations are needed to better understand the complex interplay between SCD, SCT, and social determinants of health when evaluating vulnerabilities to emerging health threats,” the researchers wrote.

Details of the pooled analysis were reported in the study “COVID-19 outcomes in patients with sickle cell disease and sickle cell trait compared with individuals without sickle cell disease or trait: a systematic review and meta-analysis,” published in the journal eClinicalMedicine.

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People with sickle cell disease carry mutations in both copies of the HBB gene, one inherited from each parent, leading to the production of an abnormal version of hemoglobin, which is the protein that transports oxygen in red blood cells. The defective protein causes red blood cells to adopt a sickle shape and become rigid and sticky, making them more prone to obstruct blood vessels and restrict blood flow to tissues and organs.

People who carry a single mutated copy of the HBB gene are considered to have sickle cell trait. Although these people usually do not show any diseases symptoms, they may have some sickling of red blood cells under low-oxygen conditions.

“Carriers of the sickle cell trait have only one of the altered, recessive genes from their parents and don’t develop sickle cell disease,” Stéphanie Forté, MD, the study’s corresponding author from the Université de Montréal, said in a university press release. “Nevertheless, this group is at risk and should be monitored and prioritized when it comes to public health measures, like vaccination.”

COVID-19 is most known for its impact on lung function, but it has also been associated with damage to blood vessels and abnormal blood clot formation.

However, studies investigating the risk of worse COVID-19 outcomes in people with sickle cell disease and trait have generated mixed results. In fact, some studies suggest that disease patients experience a milder COVID-19 course.

Compiling the meta-analysis

When faced with conflicting studies, Forté and colleagues in Brazil decided to conduct a meta-analysis, in which multiple published studies are pooled together to derive overall conclusions.

The meta-analysis included 22 studies. Overall, these studies looked at 1,892 people with sickle cell disease, 8,677 with the trait, and a group of 1,653,369 individuals without either of them who were used for comparison.

“There are an estimated 1,500 to 1,800 people with sickle cell disease in Quebec,” Forté said. “Although it is not frequently talked about, it is the most common rare disease in Canada.”

A pooled analysis of 15 of the studies found no significant difference in all-cause mortality, or death by any cause, between people with and without SCD and SCT after cases of COVID-19. The results were similar when studies assessing COVID-19-related deaths specifically were pooled.

Researchers then conducted a pooled analysis of eight studies that adjusted for the so-called confounding factors that may have influenced the results, such as sex, age, weight, and coexisting medical conditions. Here, patients with sickle cell disease and trait were found to have a relative 86% greater risk of death after COVID-19, compared with those without either condition.

“We concluded that compared with patients who do not have SCD or SCT, the presence of either of these two conditions carries a similarly increased risk of mortality,” the researchers wrote.

An unadjusted pooled analysis of three studies that included 387 Black people with the trait demonstrated that they had a 73% increased mortality rate compared with Black individuals without either condition.

Across nine studies, hospitalization rates were 8.27 times higher among disease patients than in those without the disease or the trait. This result was not seen in individuals with the trait, however. When adjusted for cofounders, however, the hospitalization rate was 5.44 times higher for patients with the disease and 31% higher for those with the trait.

Regarding admission to intensive care units, no significant differences were seen between patients with sickle cell disease and the general population. Likewise, people with the disease and the trait were not at an increased risk of respiratory failure or requiring invasive breathing support, compared with individuals without sickle cell disease or trait.

Three pooled studies found people with the trait had a 61% increased risk of developing kidney complications following COVID-19 infection compared with the non-SCT/SCD group.

After having COVID-19, 24.2% of sickle cell disease patients developed acute chest syndrome, a serious lung condition that causes fever, chest pain, and breathing difficulties. About 25% required blood transfusions, and 23.1% developed painful vaso-occlusive crises. Shortness of breath, pneumonia, and fever were reported in 37.8% of the disease patients.

“The current data suggest that individuals with SCD and SCT had similarly increased COVID-19 mortality rates compared with individuals without SCD/SCT,” the scientists wrote.