Why are children largely spared from COVID-19 — and why do a few become extremely sick? To find out, Boston Children’s Hospital launched a national study in April to perform real-time surveillance at more than 35 U.S. children’s hospitals. In May, when multi-system inflammatory syndrome in children (MIS-C) began appearing, that still-mysterious condition was added to the agenda.
Called Overcoming COVID-19, the study has $2.1 million in funding from the Centers for Disease Control and Prevention. It will capture real-time data on 800 children and youth up to age 25 hospitalized with COVID-19, in search of factors that increase vulnerability to the novel coronavirus — but also what protects the vast majority of kids.
A separate study, IMPACC, is using proteomics, metabolomics, and other methods to study immune responses in up to 2,000 adults hospitalized with COVID-19.
“Based on what we know about other viruses, such as influenza, we would expect children to be the first to get sick and have more severe disease,” says Adrienne Randolph, MD, MSc, a senior physician in Critical Care Medicine at Boston Children’s and the study’s principal investigator. “If we can understand what protects kids, we may get clues as to why older people are so susceptible.”
The prospective study will track children and youth in intensive care units, intermediate-care units, and general hospital wards. Selected study centers will enroll patients who are COVID-19-positive but have no symptoms, as well as patients with influenza, who will serve as a control group.
“We want to understand the full range of severity,” says Randolph.
Of the 800 patients tracked, the study will enroll up to 400 for detailed, prospective observation and periodic collection of respiratory and blood samples. These will be used to investigate a variety of parameters, including antibody levels, other indicators of immune response, markers of inflammation, viral shedding (indicating the likelihood of infecting others), and the effects of various treatments used for COVID-19.
Genetic studies and a COVID-19 ‘biobank’ for children
Meanwhile, Randolph is leading a separate initiative at Boston Children’s that will conduct genetic studies looking for variations in DNA that either protect people from COVID-19 disease or make them more susceptible. Through the Children’s Rare Disease Cohort Initiative led by Piotr Sliz, PhD, and Shira Rockowitz, PhD, the study will sequence patients’ entire genome or the smaller group of genes that code for proteins (exome).
“It’s possible some children will have underlying immune deficiencies that this virus reveals,” says Randolph, whose research has long focused on the immunobiology of critical illness in children, particularly life-threatening infections and acute lung injury. “But we don’t want to make a lot of assumptions about the genetics, because no one really knows what might make people susceptible.”
We’re trying to do this is a very coordinated, thoughtful way to be safe and ethical, and at the same time move rapidly to answer a lot of important questions.”— Adrienne Randolph
Through the same hospital initiative, called Taking on COVID-19 Together, Boston Children’s is creating a biobank of samples from its own patients that investigators can submit applications to access. The goal is to avoid overburdening patients, conserve testing supplies (such as viral transport media and swabs), and minimize the need for personal protective equipment (PPE) in obtaining the samples.
Tapping an existing pediatrics network
The centers involved in the CDC-funded study are part of the long-standing Pediatric Acute Lung Injury and Sepsis Investigator’s (PALISI) network founded by Randolph in 2002. These centers conducted surveillance of children during the 2009 influenza A(H1N1) pandemic, also led by Randolph. They maintained preparedness in the interim, so were able to quickly reactivate their sites for the COVID-19 study.
Collaborators at Boston Children’s include Kristin Moffitt, MD, an expert in infectious disease; Benjamin Raby, MD, MPH, chief of Pulmonary Medicine; Janet Chou, MD, director of the Primary Immunodeficiency and Immunogenomics programs; and Nira Pollock, MD, PhD, of the Infectious Diseases Diagnostic Laboratory.
“We’re trying to do this is a very coordinated, thoughtful way to be safe and ethical and at the same time move rapidly to get information to answer a lot of important questions,” says Randolph.
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