# Immunobiology of Influenza Virus-related Critical Illness in Young Hosts

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $1,267,324

## Abstract

ABSTRACT
Influenza virus is a persistent global menace that every year infects an estimated 5-10% of adults and 20-30%
of children worldwide causing over 500,000 influenza-related deaths. Most annual influenza infections are in
the very young, the elderly, and in individuals with chronic health conditions such as asthma. However,
recurrent influenza pandemics caused by the emergence and spread of highly pathogenic novel influenza A
strains, such as occurred in 2009, disproportionately causes severe illness in healthy children and younger
adults. This study of life-threatening influenza virus lower respiratory tract infection (LRTI) in young hosts is
designed by an established multidisciplinary group of investigators to better understand how host innate and
adaptive immunity to influenza virus is associated with disease susceptibility, severity and clinical outcomes.
In the Pediatric Intensive Care Influenza (PICFLU1) study, we hypothesized that infection with the influenza
virus triggers hypercytokinemia and immune dysregulation in a genetically susceptible host resulting in severe
life-threatening infection. Confirming our hypothesis, in PICFLU1 (AI084011, enrolling 2008-2016), we
identified a hyperinflammatory phenotype coexisting with innate immunosuppression; both were associated
with mortality. We also identified associations between functional variants in IFITM3 and MBL2 with pediatric
influenza-related death. In the Immunobiology of Influenza Virus-Related Critical Illness in Young Hosts study
(PICFLU2, enrolling 2020-2025), we test the hypothesis that distinct severe influenza LRTI phenotypes –
defined by host immunobiology – can be identified for targeted preventive and therapeutic
interventions. In this study we aim to: 1. Identify biomarkers in children with severe influenza LRTI that can be
used for prognostic stratification and predictive enrichment in future immunomodulatory clinical trials; 2.
Determine if pre-existing strain specific immunity to influenza virus protects against life-threatening disease
and influences viral shedding and disease severity; and 3. Identify genes essential for anti-viral immunity
and/or containment that explain host susceptibility to severe influenza infection or its outcome. To achieve
these aims, we will enroll 600 additional children and young adults with confirmed influenza infection (300
intensive care unit and 300 ward or outpatient) across 35 PICFLU sites. Across PICFLU studies (2008-2025)
we will have DNA on ~1,000 young hosts infected with influenza virus to identify important endophenotypes for
risk stratification and predictive enrichment in future clinical trials targeting prevention of and more rapid
recovery from severe influenza-related disease. Identified influenza virus susceptibility and severity genes are
potential “druggable targets” for immune modulation. Our findings could personalize the care of young
individuals with severe influenza infection based on distinct immunobiologic ho...

## Key facts

- **NIH application ID:** 10055872
- **Project number:** 1R01AI154470-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Adrienne G Randolph
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,267,324
- **Award type:** 1
- **Project period:** 2020-09-18 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10055872

## Citation

> US National Institutes of Health, RePORTER application 10055872, Immunobiology of Influenza Virus-related Critical Illness in Young Hosts (1R01AI154470-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10055872. Licensed CC0.

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