# Multi-center Evaluation of the Threat of Established and Emerging Respiratory Viral Infections in Pediatric Transplant Recipients

> **NIH NIH R01** · ARKANSAS CHILDREN'S HOSPITAL RES INST · 2021 · $675,979

## Abstract

Respiratory viral infections (RVI) have changed the world. RVI are a leading cause of infectious morbidity and
mortality in children undergoing hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT).
RVI diagnosis by qualitative PCR screening is sensitive, but unfortunately does not distinguish disease from
presence of viral nucleic acid or predict risk for progression from upper to the more severe lower respiratory tract
disease (LRTD). In the COVID-19 era, many centers now use pre-transplant RVI screening, but the implications
of detection in an asymptomatic host are unknown. Integrating quantitative viral load, viral sequencing, and/or
host immune (T cell and antibody) responses could provide novel predictive tools to stratify the risk of developing
an RVI and the progression to LRTD. Our objective is to establish a comprehensive RVI diagnostic and disease
progression predictive model in children undergoing transplantation. We propose a prospective multi-center
epidemiologic study of 2000 pediatric transplant recipients, with a nested case-control immunologic and virologic
substudy. This will be the largest study on RVI in any age group of HCT and SOT recipients. We will leverage
the Pediatric Transplant ID Network (PIDTRAN), a consortium of 21 nationwide sites and the only group
dedicated to pediatric transplant infectious diseases. We will obtain pre-transplant blood and nasal samples in
all 2000 transplant participants at enrollment and also blood at day +100 post-transplant. In Aim 1, we will
determine the prevalence of viral nucleic assay positivity using qualitative PCR and then perform quantitative
PCR (qPCR) and viral sequencing (metagenomics) on positive specimens. We hypothesize that the quantity of
respiratory viral nucleic acid or certain viral genotypes will identify patients at risk for progressive RVI. In Aim 2,
we will develop an immunological classifier to predict risk of RVI and progression to LRTD using a nested
substudy focused on three major pediatric viruses: RSV, parainfluenza virus 3, and human metapneumovirus.
We will characterize pre-transplant humoral and cellular immune responses in the subset of patients who develop
those RVIs compared with pre-transplant immunologic and day +100 post-transplant immune responses from
uninfected matched controls. The combination of host response and virologic data (qPCR and viral
metagenomics) will also be compared between RVI cases who do or do not progress to LRTD to identify
biomarkers. We hypothesize that patients with specific functional antibody response and/or specific T cell
repertoires to RVI will have superior clinical outcomes. Characterizing a comprehensive viral and host response
pre-transplant, we will learn to predict who is at risk of LRTD and needs early intervention vs. delay of transplant,
and when PCR positivity is indicative of live virus shedding and potential disease. These results will help
formulate novel evidence-based pediatric guid...

## Key facts

- **NIH application ID:** 10540605
- **Project number:** 7R01AI159684-02
- **Recipient organization:** ARKANSAS CHILDREN'S HOSPITAL RES INST
- **Principal Investigator:** JANET A ENGLUND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $675,979
- **Award type:** 7
- **Project period:** 2021-09-17 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10540605

## Citation

> US National Institutes of Health, RePORTER application 10540605, Multi-center Evaluation of the Threat of Established and Emerging Respiratory Viral Infections in Pediatric Transplant Recipients (7R01AI159684-02). Retrieved via AI Analytics 2026-06-15 from https://api.ai-analytics.org/grant/nih/10540605. Licensed CC0.

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