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Principal Investigator: CARLOS G GRIJALVA
Organization: VANDERBILT UNIVERSITY MEDICAL CENTER
Fiscal Year: 2024
Award: $224,548
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><Adult><Adult Human><Age><Airway infections><Animal Model><Animal Models and Related Studies><Attenuated><COVID crisis><COVID epidemic><COVID pandemic><COVID-19><COVID-19 crisis><COVID-19 epidemic><COVID-19 era><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 infection><COVID-19 pandemic><COVID-19 period><COVID-19 predisposition><COVID-19 public health crisis><COVID-19 susceptibility><COVID-19 transmission><COVID-19 virus><COVID-19 virus infection><COVID-19 virus transmission><COVID-19 vulnerability><COVID-19 years><COVID19 infection><COVID19 virus><CV-19><Cell Body><Cells><Cessation of life><Child><Child Youth><Children (0-21)><Circulation><Clinical><CoV-2><CoV2><Coronavirus Infectious Disease 2019><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Death><Development><Disease><Disorder><Experimental Models><Frequencies><Grippe><Health><History><Hospital Admission><Hospitalization><Household><Human><IFN><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><In Vitro><Individual><Infection><Inflammatory><Influenza><Interferons><Kinetics><Long-term cohort><Longitudinal cohort><Longterm cohort><Measures><Mediating><Modern Man><Nasal><Nasal Passages Nose><Nose><Pathogenesis><Pattern><Phase><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Predisposition><Preventative strategy><Prevention strategy><Preventive strategy><Recording of previous events><Reporting><Respiratory Infections><Respiratory System, Nose, Nasal Passages><Respiratory Tract Infections><Respiratory syncytial virus><Rhinovirus><Rhinovirus infection><Risk><Risk Reduction><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 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respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 epidemic><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 inhibitor><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome coronavirus 2 predisposition><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vulnerability><Severe acute respiratory syndrome related corona virus 2><Severity of illness><Study models><Subgroup><Susceptibility><Symptoms><Testing><Transmission><Vaccination><Viral><Viral Interference><Viral Shedding><Virus><Virus Shedding><Work><Wuhan coronavirus><adulthood><age associated><age associated difference><age based difference><age correlated><age dependent><age dependent difference><age dependent variation><age difference><age linked><age related><age related difference><age related variation><age specific><age specific difference><ages><alleviate symptom><ameliorating symptom><attenuate><attenuates><block SARS-CoV-2><block severe acute respiratory syndrome coronavirus 2><case-based><chronic infection><clinical relevance><clinically relevant><co-infection><coinfection><coronavirus disease 2019><coronavirus disease 2019 crisis><coronavirus disease 2019 epidemic><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 infection><coronavirus disease 2019 pandemic><coronavirus disease 2019 public health crisis><coronavirus disease 2019 transmission><coronavirus disease 2019 virus><coronavirus disease 2019 virus transmission><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease pandemic><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 pandemic><coronavirus disease-19 virus><coronavirus infectious disease-19><decrease symptom><developmental><differ by age><difference across age><difference in age><disease severity><experience><experiment><experimental research><experimental study><experiments><fewer symptoms><hCoV19><histories><indexing><individual heterogeneity><individual variability><individual variation><infected with COVID-19><infected with COVID19><infected with Rhinovirus><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inhibit SARS-CoV-2><inhibit severe acute respiratory syndrome coronavirus 2><innovate><innovation><innovative><insight><interfering virus><kids><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><member><model of animal><nCoV2><pandemic><pandemic disease><persistent infection><predisposed to Coronavirus disease 2019><prevent><preventing><reduce risk><reduce risks><reduce symptoms><reduce that risk><reduce the risk><reduce these risks><reduces risk><reduces the risk><reducing risk><reducing the risk><relieves symptoms><respiratory><respiratory virus><response><risk-reducing><sample collection><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 transmission><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><social role><socio-demographic factors><sociodemographic factors><specimen collection><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><symptom alleviation><symptom reduction><symptom relief><symptomatic COVID-19><symptomatic COVID19><symptomatic SARS-CoV-2 infection><symptomatic coronavirus disease 2019><transmission process><transmitted COVID-19><transmitted SARS-CoV-2><transmitted coronavirus disease 2019><transmitted severe acute respiratory syndrome coronavirus 2><variation by age><vulnerable to COVID-19><vulnerable to Coronavirus disease 2019><vulnerable to SARS-CoV-2><vulnerable to Severe acute respiratory syndrome coronavirus 2><youngster>