NEWS

Research from recent issues of Blood Advances

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 ( HbSb ⁰ ), which the investigators indicated reflected the typical distribution in North America .

A history of acute coronary syndrome was the

TABLE . Clinical Variables of Hospitalized Patients Who Died

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 %).

— Caterina Minniti , MD

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 %).

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 .

References Minniti CP , Zaidi AU , Nouraie M , et al . Clinical predictors of poor outcomes in patients with sickle cell disease and COVID-19 infection . Blood Adv . 2021 ; 5:207-215 .

26 ASH Clinical News March 2021