Ongoing clinical research study in US children documents the rebound of endemic respiratory viruses, builds foundation for expediting future vaccines and treatments.
Courtesy: Children’s Hospital Colorado
Today, the first paper from a multi-year clinical research study was published in The Lancet Infectious Diseases: Dynamics of Endemic Virus Re-emergence in Children in the USA Following the COVID-19 Pandemic (2022-2023): A Longitudinal Immunoepidemiologic Surveillance Study and demonstrates how the approach can improve modeling to better predict future outbreaks.
The paper shares findings from a multicenter clinical research study, one of many studies that are part of the recently launched PREMISE (Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology) program, led by Daniel Douek, MD, PhD, at the National Institutes of Health’s Vaccine Research Center (VRC). This particular study is a partnership between PREMISE and clinical research sites at academic institutions led by principal investigator Kevin Messacar, MD, PhD, at the central site at University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado with additional study sites at University of North Carolina, led by site principal investigator Matthew Vogt, MD, PhD, and co-investigator Michelle Hernandez, MD, Weill Cornell Medicine and the University of Alabama at Birmingham.
Data collected during the first year of the PREMISE study, 2022-2023, shows for the first time how non-pharmaceutical interventions such as masking and distancing targeted towards SARS-CoV-2 during the pandemic also decreased circulation rates of and population immunity to common respiratory pathogens in children. The study provides new evidence-based insight into what was driving the large post-pandemic rebound in these diseases and enables more accurate predictions for the future.
The PREMISE study conducted immunologic surveillance on children younger than 10 years old, by enrolling them and following them for over a year. Through repeat blood sampling, the team could determine what children at varying young ages had immunity to and what they were susceptible to. Through respiratory sampling during illness, researchers were able to determine what infections they experienced. The data showed that most younger children lacked immunity to many normal respiratory viruses during the pandemic, suggesting they had not been exposed, as they typically would have, due to prevention measures in place. Following the lifting of pandemic measures, the level of immunity rose across all pathogens studied, reflective of the unprecedented widespread resurgence of these viruses in children post-pandemic.
While most research studies target a specific disease, samples from PREMISE were tested for many common and emerging respiratory viruses, including RSV, influenza and enterovirus D68 (EV-D68), which can cause the polio-like illness, acute flaccid myelitis. The data allowed experts to recreate past circulation patterns and model predictions for future outbreaks with greater accuracy and precision. They showed that PREMISE data from 2022-23 could be used to accurately predict the subsequent wave of disease of the emerging pathogen EV-D68 that occurred in 2024.
“Potently neutralizing anti-EV-D68 human monoclonal antibodies are finishing Phase 1 safety trials in humans, so the possibility to try to use them in children with EV-D68 infection is inching closer to reality,” said Vogt, assistant professor of Pediatrics and Microbiology & Immunology at the University of North Carolina School of Medicine in Chapel Hill. “Being able to anticipate EV-D68 outbreaks would allow for more targeted viral testing from the nose and giving the antibody as needed to try to prevent ensuing acute flaccid myelitis. An approach similar to this can prevent paralysis in mice, so while there is no guarantee it would work in humans, this certainly gives me hope,” said Vogt, who is also a co-inventor on a pending patent application for anti-EV-D68 human monoclonal antibodies.
“Four cohorts of almost 1,000 children have provided an invaluable bank of samples and data,” said lead author Dr. Hai Nguyen-Tran of CU/CHCO. “These are being used to develop ‘on the shelf’ medical countermeasures, such as antibody treatments and vaccines, for pathogens of interest. Instead of starting from scratch, this study gives us a head start to understand, predict, and prepare for future pandemics.”
Samples and data from the PREMISE study will also be used to learn which parts of viruses the human immune system attacks to become immune, so teams can better design new antibody treatments and effective vaccines to mimic this response.
“In the future, this type of immune surveillance can be used to better understand the impact of public interventions on population immunity and future waves of disease,” said Dr. Messacar. “PREMISE is a great example of a successful research partnership between NIH scientists and clinical researchers in academia, leading to concrete deliverables such as vaccine candidates and monoclonal antibodies that can directly impact public health.”
This study is funded through a subcontract with the Frederick National Laboratory for Cancer Research (FNLCR), operated by Leidos Biomedical Research (21X192QT1) in Frederick, Maryland. FNLCR funding was provided by the NIH Vaccine Research Center within NIAID.
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Children’s Hospital Colorado is one of the nation’s leading and most expansive nonprofit pediatric healthcare systems with a mission to improve the health of children through patient care, education, research and advocacy. Founded in 1908 and ranked among the best children’s hospitals in the nation as recognized by U.S. News & World Report, Children’s Colorado has established itself as a pioneer in the discovery of innovative and groundbreaking treatments that are shaping the future of pediatric healthcare worldwide. Children’s Colorado offers a full spectrum of family-centered care at its urgent, emergency and specialty care locations throughout Colorado, including an academic medical center on the Anschutz Medical Campus in Aurora, hospitals in Colorado Springs, Highlands Ranch and Broomfield, and outreach clinics across the region. For more information, visit www.childrenscolorado.org or connect with us on Facebook, Instagram and YouTube.
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Media contact: Brittany Phillips, Communications Specialist, UNC Health | UNC School of Medicine