Patients with sickle cell disease (SCD) have poor outcomes associated with COVID-19, particularly if they are older or present with end organ damage, acute kidney disease, increased serum creatinine, and elevated lactate dehydrogenase and D-dimer levels, according to a study published in Blood Advances.
“Patients with SCD are considered immunocompromised and have a higher risk of exposure to COVID-19 because of frequent hospitalizations and encounters within the emergency department, day hospitals, and specialty clinics,” lead study author Caterina Minniti, MD, of the Albert Einstein College of Medicine in New York, told ASH Clinical News. Dr. Minniti suggests that clinicians could reduce patients’ risk of COVID-19 and poor outcomes by increasing the use of telehealth to avoid encounters with the health system, in addition to writing preemptive refills of narcotics and other medications.
In this study, researchers prospectively collected outcomes data for 66 pediatric and adult patients with SCD and confirmed COVID-19 infection from academic centers in Boston, New York City, Chicago, and Detroit.
The median age of the study population was 34 years and ranged between 8 months and 69 years. In terms of race and ethnicity, approximately 88% of patients self-identified as Black and 15% self-identified as Hispanic. A total of 47 patients (71%) had homozygous hemoglobin S (HbSS) or hemoglobin S/beta-thalassemia genotypes (HbSb0), which the investigators indicated reflected the typical distribution in North America.
A history of acute coronary syndrome was the most common preexisting comorbidity in this cohort (62%), followed by chronic kidney disease (CKD; 33%). Approximately 6% of patients had end-stage renal disease prior to COVID-19 diagnosis. Other pre–COVID-19 conditions in the study population included venous thromboembolism (29%), pulmonary hypertension (21%), stroke (18%), and surgical splenectomy (18%).
More than half of patients (n=34) received at least one SCD-specific therapy, including hydroxyurea (42%), chronic transfusion (8%), and a newer therapy such as L-glutamine, voxelotor, and crizanlizumab (20%).
“Patients with SCD are considered immuno-compromised and have a higher risk of exposure to COVID-19.”
—Caterina Minniti, MD
Most patients with SCD and COVID-19 in this study required hospitalization (75%). A significantly greater proportion of patients who were hospitalized had CKD (20% vs. 13%; p=0.013) and a higher white blood cell count (p=0.019).
In an age-adjusted logistic regression analysis, presence of CKD increased one’s risk of hospitalization (odds ratio [OR] = 9.1; p=0.02). Variables predictive of a high risk of hospital admission in a stepwise variable selection included male sex (OR=4.5; 95% CI 1.2-17.3; p=0.03) and CKD (OR=15.5; 95% CI 1.8-129.2; p=0.012).
The mortality rate was 10.6% in the overall population, with four deaths occurring during the initial COVID-19 infection presentation. Individuals who died had the following genotypes: HbSS (n=4), hemoglobin SC disease (n=2), and HbSb+ (n=1). A slight minority of deaths occurred in female patients (43%). The median age in the sample of patients who died was 53 years, which was significantly greater than the overall cohort’s median age of 31 (p<0.001).
Patients with SCD and COVID-19 who died were more likely to present with pulmonary hypertension (p=0.001), stroke (p=0.021), CKD (p=0.034), and congestive heart failure (p=0.013). Every patient who died had evidence of acute coronary syndrome (p=0.035), while pain was less frequent at presentation in these patients (p=0.025).
Increased mortality was significantly associated with a history of pulmonary hypertension in an age-adjusted logistic regression analysis (OR=8.1; 95% CI 1.1-61.0; p=0.042).
None of the patients who died took hydroxyurea or a disease-modifying therapy at baseline, the authors noted, compared with 47% of patients in the survival cohort. Other clinical variables associated with mortality are presented in the TABLE.
A limitation of this study included its small sample size, which the investigators said prevented them from drawing firm conclusions about the higher mortality rate in patients with SCD.
To optimize outcomes for patients with SCD and COVID-19, Dr. Minniti added that clinicians should use hydroxyurea aggressively with the intent to reach the maximum tolerated dose. “I recommend using other disease modifiers now available to avoid or decrease progression of end-organ damage, hemolysis, anemia, and frequency of vaso-occlusive crisis,” she noted, “and use vaccinations as appropriate.” Patients may also require vitamin D replenishment and clinicians should perform aggressive monitoring for deep vein thrombosis and pulmonary embolism.
Study authors report no relevant conflicts of interest.