# Human rhinovirus infection and susceptibility to SARS-CoV-2 infection and symptomatic disease

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $224,548

## Abstract

ABSTRACT
 Children tend to experience more frequent asymptomatic infections and milder illnesses associated
with SARS-CoV-2 infections than adults, but the reasons for these age-associated differences are unclear.
While typical patterns of respiratory syncytial virus, influenza, and other viruses were markedly disrupted
during the early pandemic, human rhinoviruses (HRVs) remained prevalent. Unlike other respiratory viruses,
HRVs, consisting of species A, B, and C, are detected frequently year-round, and HRV infection is often
asymptomatic, especially in children, who frequently undergo frequent re-infections with new HRV strains. The
immunological consequences of these frequent HRV reinfections are unclear. Studies have suggested a role
for HRV infection in rendering individuals less susceptible to infection with heterologous respiratory viruses,
including SARS-CoV-2, with recent studies reporting that infection with HRV may trigger interferon responses
that block SARS-CoV-2 replication and reduce SARS-CoV-2 transmission.
 While insightful, many prior observations of HRV interference with SARS-CoV-2 or other viruses are
derived from ecological studies or animal models of infection, in which the experimental conditions are closely
controlled. Observations from individuals in real-world conditions with detailed information on the sequence of
infections, specimen collection prior to development of symptoms, and clinical features of illness are scarce.
We aim to overcome these limitations by leveraging an intensive case-based longitudinal SARS-CoV-2
household surveillance platform, with daily nasal sampling and symptom assessment for 14 days following a
positive test of the index SARS-CoV-2 case, to test the innovative hypothesis that interactions between HRV
and SARS-CoV-2 may reduce the risk of symptomatic SARS-CoV-2 infection, reduce clinical symptoms among
symptomatic infected individuals, and reduce transmission of SARS-CoV-2 in humans. We further hypothesize
that these interactions may be HRV species-specific. We propose to build upon supportive experimental and in
vitro studies to evaluate the clinical relevance of HRV and SARS-CoV-2 interactions in real-world settings by
studying two Specific Aims: 1) To test the hypothesis that prevalent HRV infections reduce susceptibility
to SARS-CoV-2 infection among exposed household members, and 2) To test the hypothesis that
prevalent HRV infection reduces the risk of symptomatic infection or reduces symptom intensity upon
SARS-CoV-2 infection. By assessing the impact of HRV co-infection on the individual variability observed in
SARS-CoV-2 susceptibility to infection and disease severity, findings from the proposed study may yield new
insights into ARI pathogenesis and development of enhanced prevention strategies.

## Key facts

- **NIH application ID:** 10891725
- **Project number:** 5R21AI178568-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** CARLOS G GRIJALVA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $224,548
- **Award type:** 5
- **Project period:** 2023-07-20 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891725

## Citation

> US National Institutes of Health, RePORTER application 10891725, Human rhinovirus infection and susceptibility to SARS-CoV-2 infection and symptomatic disease (5R21AI178568-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10891725. Licensed CC0.

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