Pediatric disease modeling for long COVID
Background | Project description | Project outcomes | Related links
Performer: Children’s Hospital Los Angeles (CHLA)
Principal Investigator: Senta Georgia, PhD
Initial contract value: $559,428
Contract modification value: $1,715,878 (June 2023)
Project dates: June 2022 – June 2024
People infected with SARS-CoV-2 (the virus that causes COVID-19) typically recover within a few days or weeks. However some individuals have long-term effects that persist for multiple weeks, months, or even years; this is known as post-COVID conditions (PCC) or long COVID. In such cases, people experience both obvious and subtle long-term health consequences after recovering from the active infection.
While PCC occurs more frequently in people who have had severe COVID-19 illness, individuals experiencing these health consequences are not limited those who were the sickest. These effects manifest in patients across the full spectrum of COVID-19 severity and ages, including children.
At this time, it is not possible to identify patients who will develop PCC during the active phase of COVID-19 infection. If it were possible to identify patients who are more susceptible to suffering long-term health consequences of SARS-CoV-2 infection, then it may be possible to mitigate those outcomes with medical interventions. While considerable efforts have gone into understanding how COVID-19 affects the body in adults, much less is known about how COVID-19 affects children, and how those effects manifest into long-term health consequences of COVID-19 infection.
Children’s Hospital Los Angeles (CHLA) will take a holistic approach to understanding how early inflammatory and tissue responses can predict long-term health consequences of COVID-19 in children. Specifically, this project will leverage the National Institutes of Health NIH RECOVER initiative to study clinical cohorts of children to try to identify a COVID-19-specific inflammatory and tissue damage disease signature. This project also seeks to identify potential biomarkers that correlate to a COVID-19-specific inflammatory and tissue damage disease signature during the disease course.
Ultimately, the primary goal is to produce a predictive model that will forecast whether a patient is more likely to experience long-term health effects after COVID-19. The model will be built by integrating data on immune system responses, organ injury, and clinical outcomes in individual patients, which will be adapted and refined to address emergent scientific and research needs in the future. Provided that the model is successful, therapeutics against identified targets could then be tested to discern if modulating target activity improves disease outcomes.
CHLA will be collaborating with the following partners to achieve the project’s outcomes:
- University of Southern California
- Stanford University
- University of California Los Angeles
CHLA will integrate molecular and clinical assessments of pediatric patient samples to develop a model that can predict whether a child is more likely to have long-term negative outcomes from COVID-19. The integrated data includes the following high-content data sets:
- Serum proteomics analysis to profile COVID-19-induced inflammation
- Cell-free serum DNA methylation analysis of COVID-19-induced cell death
- Comprehensive clinical profiling from electronic medical records
By collecting and integrating these data sets, the base year of this project will result in a detailed molecular/clinical assessment on the potential role of obesity in increasing the severity of long-term negative outcomes from SARS-CoV-2 infection in children.
In June 2023, FDA awarded a contract option phase. Under the option, CHLA will continue development of the long COVID model, including evaluation and data integration from adults. Objectives include:
- Detailed molecular and clinical assessment on the role of obesity in increasing the severity of negative outcomes from SARS-CoV-2 infection in adults
- List of biomarkers that correlate to the long-term impacts on tissue-specific injury post-COVID-19 infection in adults and children with molecular analysis of how the biomarker induces cellular injury
- Comparative analysis of the inflammatory and tissue specific injuries induced in pediatric and adult patients infected by SARS-CoV-2
This project is funded through the MCMi Regulatory Science Extramural Research program.