Novel immunologic surveillance study provides new insights into post-pandemic return of respiratory viruses
Ongoing clinical research study in US children documents the rebound of endemic respiratory viruses, builds foundation for expediting future vaccines and treatments
Children's Hospital Colorado
AURORA, Colo. (Aug. 7, 2025) – The first paper from a multi-year clinical research study has been 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 Dr. Daniel Douek at the National Institutes of Health’s (NIH) Vaccine Research Center (VRC). 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.
This study is a partnership between PREMISE and clinical research sites at academic institutions led by principal investigator Kevin Messacar, MD, PhD, infectious disease specialist at Children's Hospital Colorado, 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, Weill Cornell Medicine and the University of Alabama at Birmingham.
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 after the end of the 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.
“Four cohorts of almost 1,000 children have provided an invaluable bank of samples and data,” said lead author Hai Nguyen-Tran, MD, infectious disease specialist at Children's Hospital Colorado and assistant professor at University of Colorado School of Medicine. “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, who is also a professor at University of Colorado School of Medicine. “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 fully funded by a subcontract with Frederick National Laboratory for Cancer Research (FNLCR), currently operated by Leidos Biomedical Research, Inc. through Agreement 21X192QT1. FNLCR funding was provided by the NIH Vaccine Research Center within NIAID. The total project funding is $7.98 million over five years. No financing for this project was supplied by nongovernmental sources.
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ABOUT CHILDREN’S HOSPITAL COLORADO
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.
Journal
The Lancet
Subject of Research
People
Article Title
Dynamics of endemic virus re-emergence in children in the USA following the COVID-19 pandemic (2022–23): a prospective, multicentre, longitudinal, immunoepidemiological surveillance study
Article Publication Date
6-Aug-2025
Immunological study provides new insights into post-pandemic return of respiratory viruses
COVID-19 prevention methods such as masking and social distancing also suppressed the circulation of common respiratory diseases, leaving young children lacking immunity to pathogens they otherwise would have been exposed to, a new multi-center clinical research study reveals. The investigators say their findings help explain the large post-pandemic rebound in these diseases and enable more accurate predictions for the future.
The study, published Aug. 6 in The Lancet Infectious Diseases and funded by the National Institutes of Health, followed 174 children under the age of 10 from 2022-2023 across four academic medical centers across the country: Weill Cornell Medicine; University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado; University of North Carolina; and the University of Alabama at Birmingham. Through repeat blood sampling and respiratory sampling during illness, the investigators gauged the children’s level of immunity to many common and emerging respiratory viruses, such as RSV, influenza and enterovirus D68 (EV-D68), which can cause the polio-like illness acute flaccid myelitis.
The findings, among the first from the National Institutes of Health’s PREMISE (Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology) Program, showed that most young 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. Enrolled children received routine medical care while participating in the observational study. 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.
“PREMISE is a one-of-a-kind study as we followed very young children, with their parents’ consent, over a year for longitudinal sample collection, affording us the unique opportunity to assess immunity due to primary infection, re-exposure and even vaccination, during a time when mask requirements and other non-pharmaceutical interventions were lifted,” said co-first author Dr. Perdita Permaul, section chief of pediatric allergy and immunology, associate professor of clinical pediatrics and trial principal investigator at Weill Cornell Medicine.
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.
“Findings from our study successfully demonstrate the utility of longitudinal immunologic surveillance in children, particularly young, immunologically naïve unexposed children, to help model the behavior of endemic viruses,” said Dr. Permaul, who is also an Englander Clinical Scholar at Weill Cornell Medicine and a pediatric allergist and immunologist at NewYork-Presbyterian Komansky Children’s Hospital of Children’s Hospital of New York.
Investigators have so far evaluated nearly 1,000 children through PREMISE, based at NIH’s Vaccine Research Center, providing a treasure-trove of sampling and data that can be used to learn which parts of viruses the human immune system attacks to develop immunity. This information may enable teams to better design new antibody treatments and effective vaccines to mimic this response.
“This approach allows for the rapid development of vaccine and monoclonal antibody therapeutics for pathogens of interest in children,” Dr. Permaul said. “Future analysis of blood samples collected from almost 1,000 children enrolled in PREMISE includes pathogen-specific T and B cell responses. Longitudinal immune surveillance in young children is an important tool for informing public health planning, assessing the effectiveness of pharmacologic and non-pharmacological interventions, developing ‘on the shelf’ therapeutics and mitigating overall disease burden.”
This study is fully funded by a subcontract with Frederick National Laboratory for Cancer Research (FNLCR), currently operated by Leidos Biomedical Research, Inc. through Agreement 21X192QT1. FNLCR funding was provided by the NIH Vaccine Research Center. The total project funding is $7.98 million over five years. No financing for this project is supplied by nongovernmental sources.
A version of this story first appeared on Children’s Hospital Colorado’s Newsroom.
Journal
The Lancet Infectious Diseases
Article Publication Date
6-Aug-2025
Cost-effectiveness of 2023-2024 COVID-19 vaccination in US adults
JAMA Network Open
About The Study:
In this modeling study, economic favorability of COVID-19 vaccination varied by age. Cost-effectiveness results for individuals in the 2 older age groups were favorable and generally robust to changes in parameter inputs, while results for the younger age group were sensitive to parameter input changes. As the evidence base for COVID-19 vaccination and burden of illness evolves, it may be important to continue to update and revise the economic evaluation of vaccination. The Advisory Committee on Immunization Practices considered these results in its decision to recommend vaccination with the 2023 to 2024 COVID-19 mRNA vaccines.
Corresponding Author: To contact the corresponding author, Lisa A. Prosser, PhD, email lisapros@umich.edu.
To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/
(doi:10.1001/jamanetworkopen.2025.23688)
Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.
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About JAMA Network Open: JAMA Network Open is an online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.
Journal
JAMA Network Open
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