Clinical Characteristics of Sickle Cell Patients May Predict COVID-19 Severity

Caterina Minniti, MD

Although severity of coronavirus disease 2019 (COVID-19) is varied among patients with sickle cell disease (SCD), there may be clinical predictors of poor outcomes.

A new study described clinical patterns associated with high disease severity and, ultimately, death.

A team, led by Caterina Minniti, MD, Division of Hematology, Monefiore Health Systems, evaluated pediatric and adult patients across 5 academic centers in the United States.

They included those living with sickle cell disease and COVID-19, as confirmed by polymerase chain reaction testing of a nasopharyngeal sample.

All COVID-19 testing had occurred between February 16–May 8 2020.

"The overarching aim of the current report was to add granularity to our understanding of the impact of COVID-19 infection on clinical outcomes in patients with SCD to inform best approaches to prevention and care," Minniti and colleagues explained.

Sickle Cell Disease and COVID-19: Identifying Risk Factors

Overall, the team evaluated a total of 66 infected patients with sickle cell disease.

All patients represented ages between 8 months – 69 years (median age, 34). There were 9 pediatric patients—defined up to age 21. 

Further, the majority of the total population was female (55%), and 88% self-identified as Black. Up to 71% had HbSS or HbSβ⁰ thalassemia genotypes.

Extensive clinical data were gathered, in addition to demographics, medical history and medication use. 

Inpatient medication and treatments, including noninvasive or invasive ventilation and hemodialysis were included in the analysis, as well as such outcomes as length of hospitalization, need for intensive care, and mortality.

A history of acute chest syndrome was the most common pre-existing comorbidity, which was observed in as many as 62% of patients. The second-most common comorbidity was chronic kidney disease (33%).

Minniti and team reported that 75% of all patients required hospitalizations, while mortality was recorded in 10.6% of the population.

As such, patients with chronic kidney disease were more likely to be hospitalized. Furthermore, acute chest syndrome occurred in 60% of all those who were hospitalized and in all of those who had died.

“Older age and histories of pulmonary hypertension, congestive heart failure, chronic kidney disease, and stroke were more prevalent in patients who died, as were higher creatinine, lactate dehydrogenase, and D-dimer levels,” the team noted.

Individuals with pulmonary hypertension and COVID-19 were considered at highest risk for morbidity; furthermore, deaths occurred in those who were not taking hydroxyurea or any sickle cell disease-modifying therapy.

The investigators also reported anticoagulation for inpatients was used twice less frequently in patients who died.

"The inflammatory, hypercoagulable, and vasculopathic milieu present in patients with SCD, especially as they age, likely predisposes these patients to thrombosis if other risk factors are present," Minniti and colleagues indicated.

"Although our results were not significant, we would favor the use of at least prophylactic anticoagulation for SCD patients with COVID-19," they advised.

Investigator Perspectives

"We cannot definitively state that the overall mortality is higher in patients with SCD, although our case fatality rate was approximately 10% compared with the approximate 3% in the general population, despite a mediate age of 34 years," Minniti and colleagues reported.

The investigators urged close follow-up of all SCD patients with COVID-19 after initial presentation, even if initially presenting with mild disease. 

They also called for aggressive evaluation of SCD patients with end-organ disease, especially pulmonary hypertension, congestive heart failure and chronic kidney disease, irrespective of hemoglobin genotype.

Further, Minniti and colleagues noted that an abnormal chest radiograph consistent with acute coronary syndrome was more common in those requiring hospitalization, and present in all who died. 

They therefore suggested that this should be part of the diagnostic evaluation for all SCD patients presenting with COVID-19-like symptoms.

"Finally, we remain concerned about the impact of social determinants of health and health care disparities on the observed outcomes," Minniti and colleagues commented.

"The limited use of biologics and novel therapeutics in our cohort—only 2 patients received tocilizumab—is striking, as is the fact that almost 50% of patients were on no SCD-modifying therapies, particularly hydroxyurea, which likely increases their risk of acute coronary syndrome from COVID-19," they pointed out.

The study, “Clinical predictors of poor outcomes in patients with sickle cell disease and COVID-19 infection,” was published online on Blood Advances.