Could Deep Immune Profile of Pediatric COVID-19 Patients Aid Understanding of Adult Disease?

Researchers used deep immune profiling to examine the immune states of patients with COVID-19 and those with multiystem inflammatory syndrome in children.

The findings:

Researchers at Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania found that children with multisystem inflammatory syndrome in children (MIS-C), a novel SARS-CoV-2 associated inflammatory syndrome, have highly activated immune systems that in many ways are more similar to those of adults with severe COVID-19.

Children with MIS-C had highly elevated T cells, particularly CD8 T cells, and a highly activated vascular patrolling CD8 T cell subset. These vascular patrolling CD8 T cells have a proposed role in the control of persisting or reactivating viral infection, as well as implications in cardiovascular disease, which may be related to the vascular symptoms observed in patients with MIS-C. The elevation of CD8 T cells exceeded that of pediatric patients with acute COVID-19 and most adults with COVID-19, but the level of CD8 T cells dropped in MIS-C patients in conjunction with clinical improvement.

Why it matters:

While pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and milder disease than in adults, a subset of children present with MIS-C, a condition that can lead to vascular complications and shock. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. The findings provide a broad immunologic foundation for a better understanding of pathogenesis and recovery in MIS-C with potential implications for adult disease.

Who conducted the study:

Among the four first authors was Laura Vella, MD, PhD, attending physician in the Division of Infectious Diseases at CHOP, who was joined by numerous CHOP colleagues and Penn collaborators, including senior author E. John Wherry, director of the Penn Institute for Immunology.  

How they did it:

Researchers used deep immune profiling to examine the immune state in pediatric COVID-19 and MIS-C. They collected blood from patients admitted to CHOP from April through June of 2020, performing high dimensional flow cytometry in parallel with samples from adult patients with COVID-19, adults who had recovered from COVID-19, and healthy adults. Cellular analyses for the pediatric patients were paired with serologic and plasma cytokine data and integrated with clinical and laboratory information. 

Quick thoughts:

“We started collecting samples from children before MIS-C — since adults [with COVID-19] were doing very poorly and children were faring much better — it would be interesting to know whether their immune systems look the same or different,” Dr. Vella said. “What is fascinating is that in pediatric patients [with MIS-C], the most distinct difference for them compared to pediatric COVID-19 and compared to adult COVID-19, is their marked activation of vascular patrolling CD8+ T cells. When it comes to T cell activation, children with MIS-C look more like severely ill adults than like other pediatric patients with COVID-19.”

What’s next:

Dr. Vella noted that the immune reactions of children with COVID-19 are similar to mildly ill adults, which suggests there are other features in adult severe disease. In addition, this exploration highlights the idea that enhanced understanding of COVID-19 in both children and in adults can inform the treatment of both patient populations.

The authors note that pediatric studies are often limited by a smaller number of subjects available for analysis, and larger cohorts in future studies will be more informative. Another limitation of the study is the heterogeneity in treatments received before blood draws and the timing of the sample availability relative to symptom onset. An understanding of patients’ immune state before immune modulation will help to more accurately define the immunologic features of MIS-C. Comparing and contrasting the immune system in distinct clinical presentations of SARS-CoV-2 infection will help guide precision immunotherapeutics in children and elucidate the pathology of severe disease in diverse COVID-19 patient populations.

Where the study was published:

The paper appears in Science Immunology.