# Impact of SARS-CoV-2 infection on respiratory viral immune responses in children with and without asthma

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $799,479

## Abstract

PROJECT SUMMARY
SARS-CoV-2 infections in children are mostly milder and less lethal than in adults. This lower
incidence of relevant disease associated with SARS-CoV-2 has surprisingly also been observed
for children with asthma, the most common chronic respiratory and inflammatory disease in
children. As social distancing and masks have dramatically but temporarily decreased the
spread of common viral respiratory infections, this created the positive effect of a significant
decrease of viral-triggered asthma in children. The growing prevalence of SARS-CoV-2 infection
in children and the resurgence of non-SARS-CoV-2 respiratory viral infections make it critical
and timely to understand how SARS-CoV-2 infection shapes respiratory outcomes and immune
responses to other respiratory viruses and the upcoming SARS-CoV-2 vaccines.
In addition to a strong genetic predisposition, asthma is strongly linked to viral respiratory
infections, and infectious stimuli can have long-term epigenetic consequences that shape
immune responses to subsequent infections. We propose that a common genetic variation that
alters sphingolipid levels in children with asthma may also result in limited pathogenesis of
SARS-CoV-2 in children with asthma. This proposal aims to test the hypothesis is that common
genetic variation in asthma moderate age-dependent outcomes and immune responses to
SARS-CoV-2 infection and vaccines utilizing an NYC pediatric asthma cohort that was started
early in the pandemic. This cohort is uniquely suited to the hypothesis as it (1) includes children
of all ages with and without asthma; (2) is enriched for children from ethnic, racial, and
socioeconomic backgrounds associated with health disparities and high exposure to SARS-
CoV-2; and (3) has already enrolled more than three hundred with a high antibody positivity rate
since May 2020. The availability of detailed questionnaire data on asthma and SARS-CoV-2
exposure, biospecimen that include blood (including stored PBMC), and nasal samples will
enable us to address these three Specific Aims, to (1) determine the age-dependent effect of
SARS-CoV-2 infection on subsequent respiratory health in asthmatic children; (2) define the
epigenetic and transcriptomic effect of SARS-CoV-2 infection on hematopoietic stem cells,
and (3) define the effects of common genetic asthma risk alleles on responses to SARS-CoV-2
infection of nasal epithelial cells and subsequent infection with respiratory syncytial virus and
rhinovirus. These studies will be supported by a team with expertise in viral immunology,
pediatric asthma, and epigenetics of immune responses and will inform on age- and disease-
specific impact and mechanisms of SARS-CoV-2 and common respiratory viruses in children.

## Key facts

- **NIH application ID:** 10876498
- **Project number:** 5R01AI173504-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Stefan Worgall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $799,479
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876498

## Citation

> US National Institutes of Health, RePORTER application 10876498, Impact of SARS-CoV-2 infection on respiratory viral immune responses in children with and without asthma (5R01AI173504-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10876498. Licensed CC0.

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