Pain, Comorbidities Increase Risk of Severe COVID-19 in Patients with SCD

Research published in Blood Advances found patients with sickle cell disease (SCD) and a history of pain and renal and heart/lung comorbidities have a higher risk of severe COVID-19 illness and worse outcomes related to the virus.

Pending further validation, these characteristics fill a significant knowledge gap and could be used to identify patients with SCD most at risk of developing serious COVID-19, according to researchers led by Lana Mucalo, MD, from the Medical College of Wisconsin.

During the ongoing COVID-19 pandemic, mounting evidence has come to support an association between the presence of comorbidities and an increased risk of hospitalization. Comorbidities most linked to hospitalization for severe COVID-19 include diabetes, hypertension, cardiovascular disease (CVD), cerebrovascular disease, chronic obstructive pulmonary disease, obesity, and malignancy.

Previous research has also found that patients with SCD tend to have a higher prevalence of viral infections compared with the general population. To investigate the factors associated with hospitalization and severe COVID-19 disease in patients with SCD, the investigators evaluated a set of data on pediatric and adult patients with SCD who were registered in the international SECURE-SCD (Surveillance Epidemiology of Coronavirus [COVID-19] Under Research Exclusion for Sickle Cell Disease) Registry, which relied on health care providers to report confirmed COVID-19 cases in patients with SCD.

The analysis included 364 children and 386 adults with SCD and COVID-19 who were reported in the registry between March 2020 and March 2021.

In addition to the primary outcome of hospitalization and severe COVID-19 illness, the investigators assessed the prevalence of pain as a presenting symptom.

Most children (90.7%) and adults (83.9%) in the study were Black. At baseline, the median age was 11 in children and 31 in adults. More than half of children (55.8%) and just under half of adults (49.5%) were treated with hydroxyurea. Penicillin was the second most prevalent SCD therapy taken by children (34.6%).

Emergency department visits were reported in 59.1% of children and 79.5% of adults. Approximately 40% of children and 60% of adults were hospitalized.

At baseline, 56.3% of children and 54.9% of adult patients had mild COVID-19 severity, while 25.5% of children and 10.4% of adults had asymptomatic COVID-19. Severe COVID-19 was reported in 7.1% and 14.2% of children and adults, respectively. Additionally, 1.1% of children and 2.8% of adults had critical COVID-19.

A prior acute care visit for pain was the most prevalent SCD-related comorbidity in both children (55.5%) and adults (78.8%). Asthma was the most common comorbidity not related to SCD (23.9% and 15.3%). Other common non-SCD comorbidities included anxiety, depression, and behavioral problems in children, as well as CVD and hypertension in adults.

In an adjusted analysis, the researchers found that children were 2.15 times more likely to be hospitalized for COVID-19 if they had frequent prior acute care visits for pain (p<0.0001). Children were also 1.61 times more likely to be hospitalized if they had SCD-related heart/lung comorbidities (p=0.0001). Adults were 1.78 times more likely to be hospitalized for COVID-19 if they had frequent prior acute care visits for pain (p=0.002).

Additionally, children had a 3.09 times higher risk of developing serious COVID-19 illness if they had a history of pain (p=0.009). Children with SCD-related heart/lung comorbidities had a 1.76 times higher likelihood of severe COVID-19 (p=0.03), while those with SCD-renal comorbidities had a 3.67 times higher likelihood of serious illness (p<0.0001). The likelihood of severe COVID-19 was 1.94 times higher in adults with a history of pain (p=0.02).

The overall mortality rate was 2.5%, with one death among children and 18 deaths in the adult cohort. During COVID-19 illness, a high proportion of both children and adults reported pain as the most common presenting symptom (35.2% vs. 67.4%, respectively). Acute chest syndrome was the second-most common presenting symptom during illness (14.8% vs. 28.5%).

The authors report no relevant conflicts of interest.


Mucalo L, Brandow AM, Dasgupta M, et al. Comorbidities are risk factors for hospitalization and serious COVID-19 illness in children and adults with sickle cell disease. Blood Adv. 2021;5:2717-2724.