Boston Children's Hospital has launched a two-pronged study of COVID-19 disease among children and youth up to age 25 across the country, with $2.1 million in funding from the Centers for Disease Control and Prevention.
The Overcoming COVID-19 study will perform real-time surveillance at more than 35 U.S. children's hospitals to capture data on 800 patients hospitalized with COVID-19, reporting near real-time to the CDC. It will also enroll up to 400 of these patients for detailed, prospective observation and periodic collection of respiratory and blood samples.
Our major goals are to understand why some children get very ill with COVID-19 and why most children aren't getting sick in the same numbers as adults. 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. If we can understand what protects kids, we may get clues as to why older people are so susceptible."
Adrienne Randolph, MD, MSc, senior physician in Critical Care Medicine at Boston Children's and the study's principal investigator
The prospective study will involve children and youth in intensive care units, intermediate-care units, and general hospital wards. Selected study centers will also enroll positive but asymptomatic patients, as well as patients with influenza to serve as control groups, says Randolph, whose research focuses on immunobiology of critical illness in children, particularly life-threatening infections and acute lung injury.
"We want to understand the full range of severity," says Randolph.
Many factors to be investigated
The collaborators are investigating a variety of parameters, including patients' antibody levels, other indicators of immune response, markers of inflammation, viral shedding (indicating the likelihood of infecting others), and the various treatments used for COVID-19 and their effects.
In a separate initiative at Boston Children's, via the Children's Rare Disease Cohort Initiative led by Piotr Sliz, PhD, and Shira Rockowitz, PhD, Randolph and colleagues will also conduct genetic studies looking for variations in DNA that are protective or make people more susceptible to the virus. Rather than test individual genes, these studies will examine the entire genetic code (whole-genome sequencing) or all genes that code for proteins (whole-exome sequencing).
"It's possible some children will have underlying immune deficiencies that this virus reveals," says Randolph. "But we don't want to make a lot of assumptions about the genetics, because no one really knows what might make people susceptible."
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 (viral transport media; swabs) and minimize the need for personal protective equipment (PPE) in obtaining the samples.
"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.
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. They conducted surveillance of children during the 2009 influenza A(H1N1) pandemic, also led by Randolph. The centers maintained preparedness in the interim, so were able to quickly reactivate their sites for the COVID-19 study.
Collaborators at Boston Children's Hospital 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. This study is one of several COVID-19-related studies at Boston Children's, including the development of new vaccines.
Researchers uncover key mechanisms of CRISPR gene editing