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Sickle cell disease (SCD) was associated with a significantly increased risk of COVID-19-related hospitalization and death in adults, U.K. researchers found.

Their cohort study showed that having SCD quadrupled a person's risk for COVID-19-related hospitalization (HR 4.11, 95% CI 2.98-5.66), and more than doubled the risk of death (HR 2.55, 95% CI 1.36-4.75), reported Ashley Kieran Clift, MBBS, of the University of Oxford, and colleagues from the International Investigator Group for Ethnicity and COVID-19.

The team also found that was associated with an increased risk for both outcomes.

The cohort study, published as a research letter in the , included 12.3 million individuals (ages up to 100) in a primary care database covering about a fifth of the English population. Follow-up was from Jan. 24, 2020 to Sept. 30, 2020 for hospitalization, and to Jan. 18, 2021 for death.

The objective of the study, the team explained, was to determine hazard ratios for COVID-19-related hospitalization and death for SCD (genotypes SC, SD, or SE; sickle cell anemia; thalassemia with hemoglobin S; sickle thalassemia; or not otherwise specified) and sickle cell trait.

A total of 5,059 individuals in the cohort had SCD (0.04%) and 25,682 (0.21%) had sickle cell trait. There were very few COVID-19-related hospitalizations in children with SCD (i.e., "fewer than five"), and no deaths. However, adults with SCD had 40 hospitalizations (0.79%), and 20 (0.20%) died.

Sickle cell trait was associated with an increased risk of COVID-19 hospitalization and death, but to a lesser degree, the researchers reported. There were 98 (0.38%) hospitalizations and 50 (0.19%) deaths among persons with sickle cell trait, and the trait was therefore associated with higher risks for COVID-19-related hospitalization (HR 1.38, 95% CI 1.12-1.70) and death (HR 1.51, 95% CI 1.13-2.00).

Clift and co-authors also performed post-hoc analyses of patients with SCD and found that compared with persons with sickle cell trait, those with SCD had an adjusted HR of 3.00 (95% CI 1.99-4.52) for COVID-19 hospitalization, while risk for COVID-19-related death was not significantly different.

"Given that sickle cell disease affects approximately 15,000 persons in the United Kingdom, 100,000 persons in the United States, and 8 million to 12 million persons globally, we believe our results are relevant to policymakers and decision making about vaccination prioritization for potentially high-risk groups," the researchers concluded.

Sophie Lanzkron, MD, MHS, of Johns Hopkins Medicine in Baltimore, who was not involved with the research, commented: "It isn't all that surprising that people end up getting admitted to the hospital when they have a SARS-CoV-2 infection and sickle cell disease, because we know that infection triggers crisis, and that's what our experience has been at Johns Hopkins."

"The real question regards mortality," she told MedPage Today. "In our experience here we've seen almost 70 people with COVID and -- luckily -- no one has died from it. If it does increase mortality in sickle cell disease over everyone else, why does it?"

Lanzkron suggested that some of the increased mortality may be due to the fact that persons with SCD have a lot of end organ disease and are already at risk for poor outcomes.

"The other aspect is that people with COVID will get dexamethasone if they are hypoxic, and those of us who care for patients with sickle cell disease know that dexamethasone can trigger crises and make people worse," she added. "At Johns Hopkins we've been very cautious with patients regarding use of steroids, and if they are that sick we usually transfuse them and then feel comfortable giving them steroids."

"So is the increased risk of mortality a question of quality of care for people with sickle cell disease, recognizing that they are going to need more aggressive therapy and that the potential use of steroids can worsen crisis and make people quite sick?" she asked. "Where did these patients get their care? Were they seen in an institution that has SCD expertise? I don't think we know that."

Results of the new study mirror those of previous studies looking at the association of SCD and COVID-19 outcomes. For example, a study presented at the 2020 American Society of Hematology virtual meeting found that after adjusting for age, Black individuals with SCD had a 6.2 times greater risk of COVID-related mortality compared with the general Black population.

And a July 2021 study showed that patients with SCD with a history of disease-related comorbidities were at a greater risk for worse COVID-19 outcomes.

Clift and co-authors said limitations for their study include the potential underdiagnosis of sickle cell trait in the population, the rarity of outcomes limiting extended adjustments and sickle subtype-specific or age/sex-specific analyses, the lack of information on symptoms or presentation, and that the hazard ratios do not have a direct causal interpretation.

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