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The objective of the VIRCHILLD project is to identify age-related modifications of the bronchial epithelium physiology that account for differences in the response and susceptibility to respiratory viruses. Epidemiology and cell-based data show that respiratory virus infections differentially affect children, adults or the elderly populations.
The current worldwide pandemic of SARS-CoV-2 clearly highlighted this notion with a large part of the deaths occurring in the elderly population and very few deaths amongst children. This may be linked to a decreased transmission and/or viral load with SARS-CoV-2 in children compared to adults and elderly. Less in the public eye is the observation that other major respiratory virus targeting the bronchial epithelium (BE) such as rhinovirus (RV) and adenovirus (AdV) cause important clinical feature in children and have a much lower incidence in adults and the elderly populations, which is the opposite to the situation with SARS-CoV-2. Based on this remarkable discrepancy between respiratory viruses the investigators hypothesize that intrinsic age-controlled properties of the respiratory epithelium under resting physiological conditions determine virus susceptibility and virus propagation.
The objective of the VIRCHILLD project is to identify age-related modifications of the bronchial epithelium physiology able to explain differences in the response to respiratory viruses. Several epidemiological and cell-based data have demonstrated that respiratory virus infections differentially affect children, adults or the elderly populations. Perhaps, this difference has been put most notably into the spotlight by the current worldwide pandemic of SARS-CoV-2 with a large part of the deaths occurring in the elderly population whereas very few deaths amongst children have been recorded. According to some studies, this could be linked to a decreased transmission and/or viral load with SARS-CoV-2 in children compared to adults and elderly. What is less in the public eye is the observation that other major respiratory virus targeting the bronchial epithelium such as rhinovirus and adenovirus cause important clinical feature in children and have a much lower incidence in adults and the elderly populations, which is the opposite to the situation with SARS-CoV-2. Based on this remarkable discrepancy between respiratory viruses the investigators hypothesize that intrinsic age-controlled properties of the respiratory epithelium under resting physiological conditions determines virus susceptibility and virus propagation. Such hypothesis is supported by the literature and our own strong preliminary data. A highly complementing consortium composed of experts in lung physiology, pulmonary transcriptomic, respiratory viruses and ultrastructure analysis will address the question. The investigators will use three major respiratory pathogens (AdV, RV and SARS-CoV-2) to infect reconstituted fully functional respiratory epithelium obtained from children, adults and elderly and study parameters of virus infection and epithelial response. This project should highlight specific therapeutic targets against respiratory viruses with a high prevalence in children such as rhinovirus and adenoviruses to increase the therapeutic arsenal of clinician against those infections.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| children | Experimental | reconstituted fully functional respiratory epithelium obtained from children (0 -18 years old) |
|
| adults | Experimental | reconstituted fully functional respiratory epithelium obtained from adults (18 to 60 years old) |
|
| elderly | Experimental | reconstituted fully functional respiratory epithelium obtained from adults (over 60 years old) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SARS-CoV-2 | Biological | Circulating strains of SARS-CoV-2 (including variants of concern) were already collected, cultured and purified. The Wuhan reference strain will be used in the VIRCHILLD study to infect cells. |
| Measure | Description | Time Frame |
|---|---|---|
| number of viral particles - Rhinovirus - Children -24 | number of viral particles produced at the apical level after 24 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from children | after 24 hours of infection |
| number of viral particles - Adenovirus - Children -24 | number of viral particles produced at the apical level after 24 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from children | after 24 hours of infection |
| number of viral particles - SARS-CoV-2 - Children-24 | number of viral particles produced at the apical level after 24 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from children | after 24 hours of infection |
| number of viral particles - Rhinovirus - Adults-24 | number of viral particles produced at the apical level after 24 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from adults | after 24 hours of infection |
| number of viral particles - Adenovirus - Adults-24 | number of viral particles produced at the apical level after 24 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from adults | after 24 hours of infection |
| number of viral particles - SARS-CoV-2 - Adults-24 | number of viral particles produced at the apical level after 24 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from adults |
| Measure | Description | Time Frame |
|---|---|---|
| number of viral particles - Rhinovirus - Children-48 | number of viral particles produced at the apical level after 48 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from children | after 48 hours of infection |
| number of viral particles - Rhinovirus - Children-72 |
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Inclusion Criteria:
For pediatric patients requiring research-specific bronchial brushing:
For pediatric patients whose bronchial brushing will be carried out as part of their care and for those whose surgical waste will be collected for research:
For adult patients:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Thomas TRIAN, PhD | Contact | 05 55 47 30 27 50 | thomas.trian@u-bordeaux.fr | |
| Aurore CAPELLI, PhD | Contact | 0557820877 | aurore.capelli@chu-bordeaux.fr |
| Name | Affiliation | Role |
|---|---|---|
| Michael FAYON, MDPhD | University Hospital, Bordeaux | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bordeaux University Hospital | Recruiting | Bordeaux | 33076 | France |
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| ID | Term |
|---|---|
| D000257 | Adenoviridae Infections |
| ID | Term |
|---|---|
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| Adenovirus (AdV) | Biological | Infection with C-type viruses (e.g. HAd-C5) using bronchial epithelium from adult donors |
|
| Rhinovirus | Biological | RV is a member of the picornaviridae family; small non-enveloped viruses with a single strand positive RNA genome protected by an icosahedral capsid. They are divided in more than 160 serotypes classed in subtype A, B and C. RV-A and RV-C infections will be used in the VIRCHILLD study |
|
| No Intervention | Biological | no infection |
|
| after 24 hours of infection |
| number of viral particles - Rhinovirus - elderly-24 | number of viral particles produced at the apical level after 24 hours of infection ( Rhinovirus) by epithelia reconstituted in-vitro from samples from elderly people | after 24 hours of infection |
| number of viral particles - Adenovirus - Elderly-24 | number of viral particles produced at the apical level after 24 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from elderly people. | after 24 hours of infection |
| number of viral particles - SARS-CoV-2 - Elderly-24 | number of viral particles produced at the apical level after 24 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from elderly people. | after 24 hours of infection |
number of viral particles produced at the apical level after 72 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from children |
| after 72 hours of infection |
| number of viral particles - Rhinovirus - Children-96 | number of viral particles produced at the apical level after 96 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from children | after 96 hours of infection |
| number of viral particles - Rhinovirus - Children-168 | number of viral particles produced at the apical level after 168 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from children | after 168 hours of infection |
| number of viral particles - Adenovirus - Children -48 | number of viral particles produced at the apical level after 48 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from children | after 48 hours of infection |
| number of viral particles - Adenovirus - Children -72 | number of viral particles produced at the apical level after 72 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from children | after 72 hours of infection |
| number of viral particles - Adenovirus - Children -96 | number of viral particles produced at the apical level after 96 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from children | after 96 hours of infection |
| number of viral particles - Adenovirus - Children -168 | number of viral particles produced at the apical level after 168 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from children | after 168 hours of infection |
| number of viral particles - SARS-CoV-2 - Children-48 | number of viral particles produced at the apical level after 48 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from children | after 48 hours of infection |
| number of viral particles - SARS-CoV-2 - Children-72 | number of viral particles produced at the apical level after 72 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from children | after 72 hours of infection |
| number of viral particles - SARS-CoV-2 - Children-96 | number of viral particles produced at the apical level after 96 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from children | after 96 hours of infection |
| number of viral particles - SARS-CoV-2 - Children-168 | number of viral particles produced at the apical level after 168 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from children | after 168 hours of infection |
| number of viral particles - Adenovirus - Adults-48 | number of viral particles produced at the apical level after 48 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from adults | after 48 hours of infection |
| number of viral particles - Adenovirus - Adults-72 | number of viral particles produced at the apical level after 72 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from adults | after 72 hours of infection |
| number of viral particles - Adenovirus - Adults-96 | number of viral particles produced at the apical level after 96 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from adults | after 96 hours of infection |
| number of viral particles - Adenovirus - Adults-168 | number of viral particles produced at the apical level after 168 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from adults | after 168 hours of infection |
| number of viral particles - Rhinovirus - Adults-48 | number of viral particles produced at the apical level after 48 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from adults | after 48 hours of infection |
| number of viral particles - Rhinovirus - Adults-72 | number of viral particles produced at the apical level after 72 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from adults | after 72 hours of infection |
| number of viral particles - Rhinovirus - Adults-96 | number of viral particles produced at the apical level after 96 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from adults | after 96 hours of infection |
| number of viral particles - Rhinovirus - Adults-168 | number of viral particles produced at the apical level after 168 hours of infection (Rhinovirus) by epithelia reconstituted in-vitro from samples from adults | after 168 hours of infection |
| number of viral particles - SARS-CoV-2 - Adults-48 | number of viral particles produced at the apical level after 48 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from adults | after 48 hours of infection |
| number of viral particles - SARS-CoV-2 - Adults-72 | number of viral particles produced at the apical level after 72 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from adults | after 72 hours of infection |
| number of viral particles - SARS-CoV-2 - Adults-96 | number of viral particles produced at the apical level after 96 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from adults | after 96 hours of infection |
| number of viral particles - SARS-CoV-2 - Adults-168 | number of viral particles produced at the apical level after 168 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from adults | after 168 hours of infection |
| number of viral particles - Rhinovirus - elderly-48 | number of viral particles produced at the apical level after 48 hours of infection ( Rhinovirus) by epithelia reconstituted in-vitro from samples from elderly people | after 48 hours of infection |
| number of viral particles - Rhinovirus - elderly-72 | number of viral particles produced at the apical level after 72 hours of infection ( Rhinovirus) by epithelia reconstituted in-vitro from samples from elderly people | after 72 hours of infection |
| number of viral particles - Rhinovirus - elderly-96 | number of viral particles produced at the apical level after 96 hours of infection ( Rhinovirus) by epithelia reconstituted in-vitro from samples from elderly people | after 96 hours of infection |
| number of viral particles - Rhinovirus - elderly-168 | number of viral particles produced at the apical level after 168 hours of infection ( Rhinovirus) by epithelia reconstituted in-vitro from samples from elderly people | after 168 hours of infection |
| number of viral particles - Adenovirus - Elderly-48 | number of viral particles produced at the apical level after 48 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from elderly people. | after 48 hours of infection |
| number of viral particles - Adenovirus - Elderly-72 | number of viral particles produced at the apical level after 72 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from elderly people. | after 72 hours of infection |
| number of viral particles - Adenovirus - Elderly-96 | number of viral particles produced at the apical level after 96 hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from elderly people. | after 96 hours of infection |
| number of viral particles - Adenovirus - Elderly-168 | number of viral particles produced at the apical level after 168hours of infection (Adenovirus) by epithelia reconstituted in-vitro from samples from elderly people. | after 168 hours of infection |
| number of viral particles - SARS-CoV-2 - Elderly-48 | number of viral particles produced at the apical level after 48 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from elderly people. | after 48 hours of infection |
| number of viral particles - SARS-CoV-2 - Elderly-72 | number of viral particles produced at the apical level after 72 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from elderly people. | after 72 hours of infection |
| number of viral particles - SARS-CoV-2 - Elderly-96 | number of viral particles produced at the apical level after 96 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from elderly people. | after 96 hours of infection |
| number of viral particles - SARS-CoV-2 - Elderly-168 | number of viral particles produced at the apical level after 168 hours of infection (SARS-CoV-2 ) by epithelia reconstituted in-vitro from samples from elderly people. | after 168 hours of infection |