COVID-19 Severity Variable in Sickle Cell Populations

Babak Sayad, MD, MPH

A new review characterized COVID-19 outcomes in patients with sickle cell disease (SCD), particularly noting the separate experiences in both children and adults.

“Since SCD patients (1) have underlying pathophysiology of chronic inflammation with increased risk of thrombosis, (2) are immunocompromised due to auto-infarction of their spleen or surgical splenectomy and especially prone to infectious diseases and acute chest syndrome (ACS), and (3) have the comorbidities and secondary organ dysfunction, there is concern about susceptibility and COVID-19 severity in these patients.” the investigators wrote.

The team, led by Babak Sayad, MD, MPH, of Kermanshah University of Medical Sciences, evaluated available literature through January 21, 2021 and published papers, in addition to an international and US registry of SCD patients with confirmed COVID-19.

The goal of the team was analyze susceptibility of SCD patients to COVID-19, further accounting for age, SCD genotype, hydroxyurea usage, and other clinical characteristics.

COVID-19 in Children

Children with SCD and generally had a mild clinical course of COVID-19, as per data extracted from literature and registries.

According to various case series of American pediatric children, COVID-19 was not considered severe for those with HbSS who developed acute chest syndrome. 

A multicenter study from France showed there were no deaths among 12 SCD inpatients hospitalized for COVID-19. All patients had SS/Sβ⁰-thalassemia genotypes. Similarly, no deaths were reported among 5 cases reported, 3 of which were on hydroxyurea treatment.

However, in a report of the national survey of United Kingdom, 1 death was reported among 10 patients <20 years of age.

The international SCD registry, updated as of April 2, 2021, recorded 1 death (0.3%) among 65 SCD patients <19 years with COVID-19. The death rate was 2.1% (2/94) based on published papers.

Additionally, 9 out of 40 (22.5%) pediatric ended up in the ICU, according to published papers, while 23 out of out of 365 (6.3%) were reported in the ICU accprdomg to the international registry.

The most commonly reported symptoms for children were pain and pneumonia/ACS.

COVID-19 in Adults

Sayad and colleagues noted that older patients with pre-existing multiple organ damage were at a higher risk of morbidity and mortality due to COVID-19. However, hemoglobin genotype and gender seemed not to be not associated with the severity of COVID-19.

Overall, disease severity was notably variable and generally moderate in the adult populations.

For example, in the Surveillance Epidemiology of Coronavirus (COVID-19) Under Research Exclusion (SECURE)-SCD registry, among 134 SCD patients, the ICU admission rate was 11% and mortality rate was 7%. Patients with a milder SCD genotype demonstrated higher mortality compared to those with a more severe genotype

A report of 24 SCD patients from the United States showed an overall mild clinical course of COVID-19, low rate of intubations, ICU admission, and mortality. Interestingly, none of the patients had received hydroxyurea therapy, although other studies and reports have demonstrated potential protective effects.

The death rate was 31 out of 409 (7.6%) in published papers versus 18 out of 390 (4.6%) in the international SCD registry.

And further, the most common symptoms for adults were pneumonia/ACS, as well as pain, cough, fever, myalgia, shortness of breath, and chills.

Of course, a simple characterization of SCD patient responses to COVID-19 is unlikely at the moment.

“To explain COVID-19 outcome in SCD patients, the possible benefits of hydroxyurea therapy could be considered,” Sayad and colleagues concluded.

“The obtained results should be interpreted considering low cases from sub-Saharan people, younger age of SCD patients compared to general population, a bias toward registry of the more severe form of disease, the effect of pre-existing comorbidities with multisystem organ damage, and the role of health socio-economic determinants,” they cautioned.