Study examines viral load, immune response, hyperinflammation in pediatric COVID-19

Children play a larger role in the community spread of the novel coronavirus (COVID-19) than previously thought, according to new research from Massachusetts General Hospital (MGH) in Boston published in The Journal of Pediatrics.

In the study, of 192 children ages 0-22 years old, 49 children tested positive for SARS-CoV-2, and an additional 18 children had late-onset COVID-19-related illness. The infected children were shown to have a significantly higher level of virus in their airways than hospitalized adults in intensive care units for COVID-19 treatment.

Transmissibility or risk of contagion is greater with a high viral load, the researchers said. Even when children exhibit symptoms typical of COVID-19, like fever, runny nose, and cough, they often overlap with common childhood illnesses, including influenza and the common cold. This confounds an accurate diagnosis of COVID-19, the illness derived from the SARS-CoV-2 coronavirus, according to Lael Yonker, MD, lead author of the study and director of the MGH Cystic Fibrosis Center.  

Along with viral load, researchers examined expression of the viral receptor and antibody response in healthy children, children with acute SARS-CoV-2 infection and a smaller number of children with Multisystem Inflammatory Syndrome in Children (MIS-C).

Findings from nose and throat swabs and blood samples carry implications for the reopening of schools, daycare centers, and other locations with a high density of children and close interaction with teachers and staff members, the researchers said.

"Kids are not immune from this infection, and their symptoms don't correlate with exposure and infection," says Alessio Fasano, MD, senior author of the study and director of the Mucosal Immunology and Biology Research Center at MGH, in a statement. "During this COVID-19 pandemic, we have mainly screened symptomatic subjects, so we have reached the erroneous conclusion that the vast majority of people infected are adults. However, our results show that kids are not protected against this virus. We should not discount children as potential spreaders for this virus."

The researchers note that although children with COVID-19 are not as likely to become as seriously ill as adults, as asymptomatic carriers or carriers with few symptoms attending school, they can spread infection and bring the virus into their homes. This is a particular concern for families in certain socio-economic groups, which have been harder hit in the pandemic, and multi-generational families with vulnerable older adults in the same household. In the study, 51 percent of children with acute SARS-CoV-2 infection came from low-income communities compared to 2 percent from high-income communities.

In the study, the researchers also challenge the current hypothesis that because children have lower numbers of immune receptors for SARS-CoV2, this makes them less likely to become infected or seriously ill. Data from the group show that although younger children have lower numbers of the virus receptor than older children and adults, this does not correlate with a decreased viral load. According to the study, this finding suggests that children can carry a high viral load, meaning they are more contagious, regardless of their susceptibility to developing COVID-19 infection.

Additionally, the researchers also studied immune response in MIS-C, a multi-organ, systemic infection that can develop in children with COVID-19 several weeks after infection. Complications from the accelerated immune response seen in MIS-C can include severe cardiac problems, shock, and acute heart failure.

Understanding MIS-C and post-infectious immune responses from pediatric COVID-19 patients is critical for developing next steps in treatment and prevention strategies, according to the researchers. Early insights into the immune dysfunction in MIS-C should prompt caution when developing vaccine strategies, said Yonker.

As pediatricians, both Yonker and Fasano are constantly fielding questions from parents about the safe return of their children to school and daycare. They agree that the most critical question is what steps the schools will implement "to keep the kids, teachers, and personnel safe." Recommendations from their study, which includes 30 co-authors from MGHfC, MGH, HMS, Massachusetts Institute of Technology, Brigham and Women's Hospital, and Harvard T.H. Chan School of Public Health, include not relying on body temperature or symptom monitoring to identify SARS-CoV-2 infection in the school setting.

The researchers emphasize infection control measures, including social distancing, universal mask use (when implementable), effective hand-washing protocols and a combination of remote and in-person learning. They consider routine and continued screening of all students for SARS-CoV-2 infection with timely reporting of the results an imperative part of a safe return-to-school policy.

"This study provides much-needed facts for policymakers to make the best decisions possible for schools, daycare centers and other institutions that serve children," said Fasano. "Kids are a possible source of spreading this virus, and this should be taken into account in the planning stages for reopening schools."

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