Kids With Cancer More Likely to Develop Severe COVID

Children and adolescents with cancer and SARS-CoV-2 infection were more likely to develop severe and critical cases of COVID-19 compared with the general pediatric population, according to a global cohort study.

Of children with cancer who contracted COVID-19, 20% developed severe or critical disease compared with 1% to 6% of children without cancer as noted in other studies, reported Sheena Mukkada, MD, of St. Jude Children’s Research Hospital in Memphis, and colleagues.

Pediatric cancer patients with COVID-19 were also more likely to be hospitalized and die compared with children in the general population, they noted in Lancet Oncology.

The study authors created the Global Registry of COVID-19 in Childhood Cancer, which includes data from 131 institutions in 45 countries on laboratory-confirmed SARS-CoV-2 infections in children and adolescents (under 19 years of age) with cancer and those who had received hematopoietic stem cell transplantation.

“The results clearly and definitively show that children with cancer fare worse with COVID-19 than children without cancer,” Mukkada said in a press release. “This global collaboration helps clinicians make evidence-based decisions about prevention and treatment, which, unfortunately, remain relevant as the pandemic continues.”

From April 15, 2020 to Feb. 1, 2021, the registry captured data on 1,520 pediatric cancer patients with COVID-19. Of these patients, 1,500 were included in the study, and 1,319 completed a 30-day follow-up.

About half of SARS-CoV-2 infections (49.1%) occurred in patients with a diagnosis of acute lymphoblastic lymphoma or acute lymphoblastic leukemia, while 24.2% occurred in those with extracranial solid tumors. Comorbidities were documented in 17.1% of patients, the most common of which was the receipt of high-dose steroids within the previous 14 days.

While a majority of patients either remained asymptomatic (35%) or had mild/moderate infections (45%), 19.9% developed severe or critical infections — a composite measure that included the anatomical level of respiratory tract involvement, respiratory support level, the requirement of higher level of care for any reason, and COVID-19-associated mortality.

Patients with hematologic malignancies accounted for most of the severe or critical cases (80.3%). For patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy or therapy for relapsed or refractory disease, and in those in the maintenance or continuation phase of therapy.

About 67% of patients were hospitalized, and 17.5% required transfer to a higher level of care.

There were 83 (6.3%) deaths in the study population, 50 of which were attributed to COVID-19. The median time to death attributed to COVID-19 was 8 days.

While this was considerably lower than the rates reported in adults with cancer, Mukkada and colleagues noted that it was “disproportionately high compared with 0.01-0.70% mortality in cohorts of general pediatric patients.”

While more than half of cases were reported in upper middle-income countries, 41.7% of severe or critical cases were observed in low- and lower-middle-income countries compared with 16.5% in upper-middle-income countries and 7.4% in high-income countries.

Multivariable analysis demonstrated that there were several factors associated with severe or critical illness, including:

• Low-income or lower-middle-income countries (OR 5.8, 95% CI 3.8-8.8)
• Upper-middle-income countries (OR 1.6, 95% CI 1.2-2.2)
• Ages 15-18 years (OR 1.6, 95% CI 1.1-2.2)
• Absolute lymphocyte count ≤300 cells per mm³ (OR 2.5, 95% CI 1.8-3.4)
• Absolute neutrophil count ≤500 cells per mm³ (OR 1.8, 95% CI 1.3-2.4)
• Intensive treatment (OR 1.8, 95% CI 1.3-2.3)

Chemotherapy was withheld in 44.6% of patients receiving active therapy, noted Mukkada and colleagues, and some modification to therapy occurred in 55.8% of patients on active therapy. Treatment modification was associated with upper-middle-income countries (OR 0.5, 95% CI 0.3-0.7), other hematologic malignancies (OR 0.5, 95% CI 0.3-0.8), the presence of COVID-19 symptoms (OR 1.8, 95% CI 1.3-2.4), and the presence of comorbidities (OR 1.6, 95% CI 1.1-2.3).

The authors acknowledged that their study had several limitations, including the fact that since they used a hospital-based registry approach, it prohibited them from making any population-level conclusions. In addition, the requirement of laboratory confirmation of COVID-19 infection may have contributed to an underrepresentation of reports from lower-income settings where diagnostic testing may have been less available.