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

Award Number: R01AI159684
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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 RVI or disease progression. In Aim 2, we will develop and validate an immunological classifier to predict risk of RVI and progression to LRTD in 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 qualitative or quantitative antibody responses 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 RVI and LRTD and needs early intervention vs. delay of transplant, and when PCR positivity is indicative of potential disease. These results will allow us to generate novel evidence-based pediatric guidelines for personalized clinical management of children undergoing transplant, and also inform future antiviral and vaccine studies in these high-risk patient populations.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $1 )
2024	2024	ARKANSAS CHILDREN'S RESEARCH INSTITUTE	13 CHILDREN'S WAY	LITTLE ROCK	AR	72202	PULASKI	USA	Allergy and Infectious Diseases Research	000	5	8/23/2024	NON-COMPETING CONTINUATION	$1
														Subtotal = $1

Issue Date FY: 2023 ( Subtotal = $842,739 )
2023	2023	ARKANSAS CHILDREN'S RESEARCH INSTITUTE	13 CHILDREN'S WAY	LITTLE ROCK	AR	72202	PULASKI	USA	Allergy and Infectious Diseases Research	003	4	8/15/2023	NON-COMPETING CONTINUATION	$842,739
2023	2022	ARKANSAS CHILDREN'S RESEARCH INSTITUTE	13 CHILDREN'S WAY	LITTLE ROCK	AR	72202	PULASKI	USA	Allergy and Infectious Diseases Research	000	3	4/28/2023	NON-COMPETING CONTINUATION	$0
2023	2021	ARKANSAS CHILDREN'S RESEARCH INSTITUTE	13 CHILDREN'S WAY	LITTLE ROCK	AR	72202	PULASKI	USA	Allergy and Infectious Diseases Research	002	2	5/15/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$219,796
2023	2021	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Allergy and Infectious Diseases Research	001	1	5/15/2023	NEW	-$219,796
														Subtotal = $842,739

Issue Date FY: 2022 ( Subtotal = $898,281 )
2022	2022	AR CHILDRENS HOSPITAL RESEARCH INSTITUTE	13 CHILDRENS WAY STE 842	LITTLE ROCK	AR	72202	PULASKI	USA	Allergy and Infectious Diseases Research	002	3	8/17/2022	NON-COMPETING CONTINUATION	$845,245
2022	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Allergy and Infectious Diseases Research	000	1	2/25/2022	NEW	-$622,943
2022	2021	AR CHILDRENS HOSPITAL RESEARCH INSTITUTE	13 CHILDRENS WAY STE 842	LITTLE ROCK	AR	72202	PULASKI	USA	Allergy and Infectious Diseases Research	001	2	2/25/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$675,979
														Subtotal = $898,281

Issue Date FY: 2021 ( Subtotal = $885,241 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Allergy and Infectious Diseases Research	000	1	9/17/2021	NEW	$885,241
														Subtotal = $885,241

Grand Total All Awards = $2,626,262

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

Award Number: R01AI159684

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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