Comorbidities are risk factors for hospitalization and serious COVID-19 illness in children and adults with sickle cell disease

Abstract

Patients with sickle cell disease (SCD) are at high risk of developing serious infections, therefore, understanding the impact that severe acute respiratory syndrome coronavirus 2 infection has on this population is important. We sought to identify factors associated with hospitalization and serious COVID-19 illness in children and adults with SCD.We established the international SECURE-SCD Registry to collect data on patients with SCD and COVID-19 illness. We used multivariable logistic models to estimate the independent effects of age, sex, genotype, hydroxyurea, and SCD-related and -nonrelated comorbidities on hospitalization, serious COVID-19 illness, and pain as a presenting symptom during COVID-19 illness. As of 23 March 2021, 750 COVID-19 illness cases in patients with SCD were reported to the registry. We identified history of pain (relative risk [RR], 2.15; P < .0001) and SCD heart/lung comorbidities (RR, 1.61; P = .0001) as risk factors for hospitalization in children. History of pain (RR, 1.78; P = .002) was also a risk factor for hospitalization in adults. Children with history of pain (RR, 3.09; P = .009), SCD heart/lung comorbidities (RR, 1.76; P = .03), and SCD renal comorbidities (RR, 3.67; P < .0001) and adults with history of pain (RR 1.94, P = .02) were at higher risk of developing serious COVID-19 illness. History of pain and SCD renal comorbidities also increased risk of pain during COVID-19 in children; history of pain, SCD heart/lung comorbidities, and female sex increased risk of pain during COVID-19 in adults. Hydroxyurea showed no effect on hospitalization and COVID-19 severity, but it lowered the risk of presenting with pain in adults during COVID-19.

COVID-19 and Hemoglobinopathies: A Systematic Review of Clinical Presentations, Investigations, and Outcomes

“…Up-regulation of ACE-2 expression in COPD, and delayed innate antiviral immune response in asthma (45) are mechanisms that possibly explain the higher risk of severe COVID-19 infection and mortality among those with respiratory comorbidities (40). Several studies have found that SCD patients with heart and lung comorbidities were at higher risk of severe COVID-19 infections (46,47). Similarly, the mortality rate among thalassemia patients with cardiovascular comorbidities was significantly higher when compared to its counterpart without underlying cardiovascular disease (48).…”

“…Several studies have found that SCD patients with heart and lung comorbidities were at higher risk of severe COVID-19 infections ( 46 , 47 ). Similarly, the mortality rate among thalassemia patients with cardiovascular comorbidities was significantly higher when compared to its counterpart without underlying cardiovascular disease ( 48 ).…”

Prognostic factors associated with COVID-19 related severity in sickle cell disease

“…In regard to risk factors for COVID-19 related severity, the only variable that held up to MVA for the outcome of hospitalization was admission Hb; this is consistent with previous findings of a significant Hb decrease from baseline for SCD patients requiring hospitalization [1] and studies that reported Hb as a strong predictor of COVID-19 related severity or mortality in the general population [16] , [24] , [25] For the outcome of ICU admission, 3 variables remained significant in the MVA: HCW employment, HU use, and immature granulocyte count on admission. HCW employment has not been previously reported as a risk factor in SCD ICU admission but has been associated with COVID-19 morbidity in the general US population as well as comprehensive meta-analysis [13] , [14] .. HU use has been reported to reduce morbidity in SCD in one report [1] but not others [10] , [21] . It is biologically plausible that HU might decrease morbidity from COVID-19 infection due to reduction of coagulation and neutrophil and endothelial cell activation [26] , [27] , [28] .…”

“…Since COVID-19 infection may precipitate or exacerbate SCD-related complications [8] , [10] , [21] , complications were classified as SCD-related or COVID-19-related as per Table 2 ; outpatients had no complications. Of the 15% (4 of 27) adults who experienced COVID-19 complications, all went to the ICU and required intubation, whereas no children had COVID-19 related complications.…”

“…Despite possible increased COVID-19 disease severity in SCD, one large study did not show an increased fatality rate in SCD [4] . Patient variables associated with increased clinical severity of COVID-19 infection in SCD patients include older age [1] , [9] , comorbidities [1] , [8] , [9] , [10] , not being on hydroxyurea (HU) [1] , [9] , history of stroke [2] , [8] and black race [5] . Non-SCD studies show similar risk factors such as older age [11] , [12] , comorbidities [11] , [12] , as well as being a health care worker (HCW) [13] , [14] .…”