Down Syndrome Associated With Higher COVID-19 Risk in Pediatric Patients With Hematologic Malignancies

Insights From the 64th American Society of Hematology Annual Meeting & Exposition

Jennifer Wilkes, MD, MSCE, discusses her research exploring the risk of COVID-19 infection and complications in pediatric patients with hematologic malignancies and Down syndrome.

What inspired your recent research on children with Down syndrome and hematologic malignancies?

We had a clinical question regarding tixagevimab/cilgavimab, or Evusheld, which is a prophylactic measure for patients older than 12 years of age to help prevent or mitigate COVID-19. Since we were given Evusheld as a limited resource from the state, we were trying to figure out how to prioritize our patient population in terms of their risk of COVID-19 complications. 

The literature and supportive care research from the Children’s Oncology Group and other organizations indicated patients with Down syndrome and hematologic malignancies were at higher risk of infections. This patient population is also at higher risk for viral infections in stages of treatment during which other patient populations may not be as severely immunocompromised. We knew this patient population was at risk, but we did not have any data on their actual risk of COVID-19 infection, their COVID-19 infection history, and their infection trajectory to see if this was a patient population for whom we should particularly target protective measures. 

I reached out to our coinvestigators who had been collecting data for the Pediatric Oncology COVID-19 Case Report. I asked them if we could conduct a secondary analysis to understand whether we needed to focus more of our efforts on targeting the pediatric population with Down syndrome for supportive COVID-19 care.

Thank you for that background, Dr Wilkes. Can you discuss your study’s design and participants?

This was a retrospective cohort study of patients with Down syndrome who had acute lymphocytic leukemia, acute myeloid leukemia, and some other rare hematologic malignancies. With registry data, people are actively sending information in, so there is the potential for error in terms of which patients are included and excluded, but at the same time, it means people are volunteering information about their patients both on and off of clinical trial. The goal was to conduct a descriptive analysis to compare patients who had Down syndrome with those who did not, within groups who had the same hematologic malignancy. 

We sought to understand patients’ care utilization, including hospitalization in the intensive care unit (ICU) and respiratory support. The investigators used multifactorial analysis to determine the odds these patients would need supportive care measures, so we could prognosticate whether there would be a mitigating effect in prioritizing preventive measures such as vaccination and prophylactic antibody therapy.

Can you walk through some of the findings? Did you find any outcomes surprising?

I do not think many of us found the findings surprising. This study validated what we were seeing clinically. 

It was significantly more likely for a patient with Down syndrome and hematologic malignancy to be hospitalized than a peer without Down syndrome. Patients with Down syndrome were also more likely to have an ICU admission and to change their therapy. It is hard to delineate what “change of therapy” means, whether it was a delay or deviation from standard care, but there was a higher likelihood of changing therapy in this setting.

In addition, patients with Down syndrome were more likely to require vasopressor and respiratory support. This did not necessarily mean intubation, but rather, these patients required oxygen more frequently than patients who did not have Down syndrome. Interestingly, patients with Down syndrome did not need other types of supportive care as frequently, such as extracorporeal membrane oxygenation or dialysis. 

How do you think your findings can inform care for patients with Down syndrome and hematologic malignancies?

This is important information to provide to practitioners over time so they can counsel patients early in their treatment about the risk of hospitalization and side effects, particularly with COVID-19. We also must consider appropriate timing for vaccination, as well as prioritization for prophylactic antibodies if available. Although this is a small patient population, perhaps we should have additional analyses and larger population-based studies regarding the use of prophylaxis like Evusheld.

In addition, this patient population should be considered beyond the hematologic malignancy setting. We should look at this population’s risk of COVID-19 complications in the pediatric and general settings, particularly if patients are at risk for pulmonary hypertension, so we can understand whether risk decreases or increases over time.

Do you and your colleagues intend to expand upon this research going forward?

We plan to provide additional information about this patient population in a larger manuscript. We will continue to use this type of data to understand changes over time as different strains emerge. Registry data is wonderful and allows us to collect the initial data to investigate, but we probably need a different mechanism to understand how to intervene moving forward, so that research will need to be conducted differently. 

Is there anything else we have not mentioned yet that you would like to add?

One nice part about this type of research group is that it was grassroots-supported during the pandemic. This research was inspired by a group of female physicians talking about what they were seeing clinically and realizing there was not a great forum to have a discussion. We would love to continue collaborating postpandemic as everything settles down.