The Lancet Infectious Diseases Journal Publishes PREMISE Study on Post-Pandemic Childhood Illness Trends

How can immune surveillance in children teach us about outbreaks and prepare us for the next pandemic?

A landmark study led by infectious disease specialists at Children’s Hospital Colorado was published in The Lancet Infectious Diseases journal. The paper, “Dynamics of Endemic Virus Re-Emergence in Children in the USA Following the COVID-19 Pandemic (2022-2023): A Longitudinal Immunoepidemiologic Surveillance Study,” is the first from a multi-year pilot study run through the national Pandemic REsponse REpository through Microbial and Immune Surveillance and Epidemiology (PREMISE) initiative. PREMISE is a program led by Daniel Douek, MD, PhD, of the National Institutes of Health’s Vaccine Research Center (VRC), which offers a new framework for preparing for outbreaks through longitudinal immune surveillance.

By continuously monitoring immune responses and circulating pathogens, the program works to improve our understanding of emerging and re-emerging pathogens dynamics to better and more effectively prepare for future potential threats.

In partnership with clinical research sites, the PREMISE pilot study initially focused on Enterovirus D68 (EV-D68), a virus that causes cyclical outbreaks of asthma-like respiratory disease and acute flaccid myelitis (AFM). Researchers also evaluated 15 other respiratory viruses. The primary research site was based out of the University of Colorado Anschutz Medical Campus and Children’s Colorado.

Led by principal investigator Kevin Messacar, MD, and first author Hai Nguyen-Tran, MD, the study highlights how real-time surveillance in children can enhance disease modeling and improve public health preparedness for future outbreaks.

Data collected from the first year of the study show how non-pharmaceutical interventions (NPIs) targeted to decrease circulation of SARS-CoV-2 during the COVID-19 pandemic, such as masking and social distancing, significantly reduced the circulation of other common respiratory viruses in children. This widespread reduction in viral exposure led to lower population immunity in children and contributed to a large, post-pandemic resurgence of these diseases, including EV-D68.

Researchers conducted longitudinal immune surveillance by enrolling children 10 years old and younger and following them over the course of a year. By analyzing repeated blood samples, the team was able to identify which pathogens children had developed immunity to and which they remained susceptible to. Results confirmed that younger children had little to no immunity to many routine respiratory viruses during the pandemic and then developed increase levels of immunity as NPIs were lifted, corresponding to the unprecedented surge in viral infections seen post-pandemic. The data enabled researchers to not only reconstruct past viral circulation, but also more accurately model future outbreaks with greater precision. 

“I hope what this study really shows is the importance of doing research,” Dr. Nguyen-Tran says. “Studies like this are just so important to the health of children and the health of a community. This kind of work helps us better prepare for the next pandemic, so we’re not in the same place again.”

The team used immune surveillance in children to show how pandemic-era public health measures delayed exposure to common respiratory viruses, and how lifting those measures led to a re-emergence of infections. By tracking antibodies over time, researchers demonstrated that immune data can dramatically improve outbreak modeling, helping hospitals, health agencies and policymakers better prepare for future outbreaks.

“Everybody remembers the COVID pandemic — and nobody wants to relive it,” Dr. Nguyen-Tran says. “Knowing that pandemics and viral surges are inevitable, the goal of PREMISE is figuring out how we can be better prepared next time, and how we can respond effectively.”

Dr. Nguyen-Tran hopes the publication of the study will inspire further research and continued support and funding, particularly for junior investigators. “I started this work when I was a fellow, and Dr. Messacar was my mentor,” she says. “Now, seeing it published in The Lancet Infectious Diseases is just incredible. It really highlights the importance of the work we’re doing and the collaboration behind it — from scientists to clinical researchers to modelers. I wouldn’t be where I am as a researcher without that mentorship and experience.”

As the PREMISE program expands to include more pathogens and populations, this study sets a precedent for how immune surveillance can shape faster, smarter responses to future pandemics. Beyond improving outbreak predictions, PREMISE samples are also being used to study which parts of viruses the immune system targets, informing the development of next-generation vaccines and monoclonal antibody therapies.