Influenza VirusCOVID-19NCT05375006
Tropism and Pathogenesis of Influenza Virus and Coronavirus in Human Brain Explant Culture
An observational study of Influenza Virus and Coronavirus, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
Background: Influenza and coronavirus have been repeatedly causing pandemic recently. Like the Influenza A/H7N9 virus has caused five epidemics in China since its first detection in East China in 2013. Read more about this study
- Who is it for?
- Ages 1 year to 70 years
- Conditions the study is for
- Influenza Virus, Coronavirus
- How many people
- 4 participants
- Where
- 1 siteHong Kong
- Study dates
- 26 May 2022to 4 Jun 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: This study will recruit participants who will undergoing elective or emergency craniotomies for intrinsic brain lesions at Prince of Wales Hospital
Who may be able to join
- Age: > 1 year old and < 70 years old
- Undergo elective or emergency craniotomies for intrinsic brain lesions
Who cannot join
- Samples containing infected material
Trial locations and contacts
1 site in 1 country.
About this study
Background:
Influenza and coronavirus have been repeatedly causing pandemic recently. Like the Influenza A/H7N9 virus has caused five epidemics in China since its first detection in East China in 2013. In 2017, the previously low pathogenic avian influenza (LPAI) H7N9 virus underwent mutation in its haemagglutinin to give to a highly pathogenic avian influenza (HPAI) virus causing 32 human cases and potentially poses a threat to animal and human health. More recently, the SARS-CoV-2 pandemic has been heavily affecting the world. Therefore an effective risk assessment platform is urgently required for better pandemic preparation.
Read more
Hypothesis:
The tissue tropism and pathogenesis of a newly emerged infectious viruses, like the highlypathogenic influenza, like H7N9 and coronavirus, like SARS-CoV-2 would be different from that of their low pathogenic subtype and it would infect and replicate the human respiratory system more efficiently.
Because of its resistance to oseltamivir for influenza and no effective antiviral for coronavirus, investigators therefore propose to set up an novel and effective risk assessment platform for emerging infectious viruses.
Experimental Design:
The tissue tropism and viral replication kinetics of a HPAI and LP influenza and coronavirus will be determined in ex vivo cultures of human brain and compared with their LP subtype. The replication competence and innate immune responses of influenza and coronavirus will be studied and compared with other LP virus in in vitro cultures of human brain cells and human microvascular endothelial cells (HMVEC) both isolated from human brain tissues.
Expected outcomes:
HPAI influenza and coronavirus particularly SARS-CoV-2 will infect and replicate the human brain tissues and cells more efficiently than their LP subtype. Besides, HPAI influenza and SARS-CoV-2 will induce dysregulated host innate immune response than the LP subtype.
Read the detailed description
In this study, 80 subjects who will undergoing elective or emergency craniotomies for intrinsic brain lesions at Prince of Wales Hospital, will be recruited.
This is a prospective and qualitative study. There is no randomization in the study procedure nor therapeutic invention for study subjects. No investigational product is involved.
Brain tissues that are normal discarded during the operation from patients who undergo elective or emergency craniotomies for intrinsic brain lesions will be collected for this study.
A consent for operation and agreement to use of removed tissue for scientific research will be obtained prior to the procedure.
- Conditions
- Influenza Virus, Coronavirus
- Medical subject headings
- Coronavirus Infections
What is being measured
The primary outcome is the main question the study is designed to answer.
Replication kinetics of influenza virus using ex vivo cultures of human brain
Tissue fragments will be infected with 106 TCID50/mL for 1h at 37°C and then washed with 3 ml of warm PBS for three times to remove unbound virus. To determine productive viral replication from the infected biopsy specimens, supernatants of the infected cultures will be collected at 1, 24, 48 and 72hpi and virus titers will be determined by TCID50 assay. Explant cultures will be fixed in 10% formalin at 24 and 72hpi and immunohistochemistry staining (IHC) against HB65 antibody (European Veterinary Laboratories), SARS-CoV or SARS-CoV-2 viral antibody will be performed for the detection of virus-infected cells.
Measured: baseline
replication efficiency and innate immune responses of influenza virus
Cells will be infected with viruses at either MOI of 0.01 or 2 for 1h. After 1h virus adsorption, viruses will be aspirated and cells will be washed with PBS for three times, then medium will be replenished. For cells infected at MOI of 0.01, cell culture supernatant will be harvested at 1, 24, 48 and 72hpi and viral titers will be determined by TCID50 assay.
Measured: baseline
Replication kinetics of coronavirus using ex vivo cultures of human brain
Tissue fragments will be infected with 106 TCID50/mL for 1h at 37°C and then washed with 3 ml of warm PBS for three times to remove unbound virus. To determine productive viral replication from the infected biopsy specimens, supernatants of the infected cultures will be collected at 1, 24, 48 and 72hpi and virus titers will be determined by TCID50 assay. Explant cultures will be fixed in 10% formalin at 24 and 72hpi and immunohistochemistry staining (IHC) against HB65 antibody (European Veterinary Laboratories), SARS-CoV or SARS-CoV-2 viral antibody will be performed for the detection of virus-infected cells.
Measured: Baseline
replication efficiency and innate immune responses coronavirus
Cells will be infected with viruses at either MOI of 0.01 or 2 for 1h. After 1h virus adsorption, viruses will be aspirated and cells will be washed with PBS for three times, then medium will be replenished. For cells infected at MOI of 0.01, cell culture supernatant will be harvested at 1, 24, 48 and 72hpi and viral titers will be determined by TCID50 assay.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2022
- Study start26 May 2022
- Primary completion4 Jun 2025
- Study completion4 Jun 2025
Why it stopped: Discontinue collaboration with collaborator
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Influenza VirusStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- The University of Hong Kong
- Responsible party
- Principal investigator, Owen Ho KO, Chinese University of Hong Kong
- Investigators
- Owen Ho Ko, PhD, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05375006
- Sponsor's protocol ID
- 2022.120
- Acronym
- COVID-19
- Status last verified
- Oct 2026
- First submitted
- 12 May 2022
- Last updated
- 30 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tropism and Pathogenesis of Influenza Virus and Coronavirus in Human Brain Explant Culture
- ClinicalTrials.gov ID
- NCT05375006
- Acronym / sponsor ID
- COVID-19 / 2022.120
- Conditions
- Influenza Virus, Coronavirus
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Discontinue collaboration with collaborator
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Collaborators
- The University of Hong Kong
- Study start
- 26 May 2022 (actual)
- Primary completion
- 4 Jun 2025 (actual)
- Study completion
- 4 Jun 2025 (actual)
- First posted
- 16 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Influenza and coronavirus have been repeatedly causing pandemic recently. Like the Influenza A/H7N9 virus has caused five epidemics in China since its first detection in East China in 2013. In 2017, the previously low pathogenic avian influenza (LPAI) H7N9 virus underwent mutation in its haemagglutinin to give to a highly pathogenic avian influenza (HPAI) virus causing 32 human cases and potentially poses a threat to animal and human health. More recently, the SARS-CoV-2 pandemic has been heavily affecting the world. Therefore an effective risk assessment platform is urgently required for better pandemic preparation.
Hypothesis:
The tissue tropism and pathogenesis of a newly emerged infectious viruses, like the highlypathogenic influenza, like H7N9 and coronavirus, like SARS-CoV-2 would be different from that of their low pathogenic subtype and it would infect and replicate the human respiratory system more efficiently.
Because of its resistance to oseltamivir for influenza and no effective antiviral for coronavirus, investigators therefore propose to set up an novel and effective risk assessment platform for emerging infectious viruses.
Experimental Design:
The tissue tropism and viral replication kinetics of a HPAI and LP influenza and coronavirus will be determined in ex vivo cultures of human brain and compared with their LP subtype. The replication competence and innate immune responses of influenza and coronavirus will be studied and compared with other LP virus in in vitro cultures of human brain cells and human microvascular endothelial cells (HMVEC) both isolated from human brain tissues.
Expected outcomes:
HPAI influenza and coronavirus particularly SARS-CoV-2 will infect and replicate the human brain tissues and cells more efficiently than their LP subtype. Besides, HPAI influenza and SARS-CoV-2 will induce dysregulated host innate immune response than the LP subtype.
Detailed description
In this study, 80 subjects who will undergoing elective or emergency craniotomies for intrinsic brain lesions at Prince of Wales Hospital, will be recruited.
This is a prospective and qualitative study. There is no randomization in the study procedure nor therapeutic invention for study subjects. No investigational product is involved.
Brain tissues that are normal discarded during the operation from patients who undergo elective or emergency craniotomies for intrinsic brain lesions will be collected for this study.
A consent for operation and agreement to use of removed tissue for scientific research will be obtained prior to the procedure.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 1 year to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This study will recruit participants who will undergoing elective or emergency craniotomies for intrinsic brain lesions at Prince of Wales Hospital
Key inclusion criteria (2 listed)
- Age: > 1 year old and < 70 years old
- Undergo elective or emergency craniotomies for intrinsic brain lesions
Key exclusion criteria (1 listed)
- Samples containing infected material
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Replication kinetics of influenza virus using ex vivo cultures of human brain
Time frame: baseline
Tissue fragments will be infected with 106 TCID50/mL for 1h at 37°C and then washed with 3 ml of warm PBS for three times to remove unbound virus. To determine productive viral replication from the infected biopsy specimens, supernatants of the infected cultures will be collected at 1, 24, 48 and 72hpi and virus titers will be determined by TCID50 assay. Explant cultures will be fixed in 10% formalin at 24 and 72hpi and immunohistochemistry staining (IHC) against HB65 antibody (European Veterinary Laboratories), SARS-CoV or SARS-CoV-2 viral antibody will be performed for the detection of virus-infected cells.
replication efficiency and innate immune responses of influenza virus
Time frame: baseline
Cells will be infected with viruses at either MOI of 0.01 or 2 for 1h. After 1h virus adsorption, viruses will be aspirated and cells will be washed with PBS for three times, then medium will be replenished. For cells infected at MOI of 0.01, cell culture supernatant will be harvested at 1, 24, 48 and 72hpi and viral titers will be determined by TCID50 assay.
Replication kinetics of coronavirus using ex vivo cultures of human brain
Time frame: Baseline
Tissue fragments will be infected with 106 TCID50/mL for 1h at 37°C and then washed with 3 ml of warm PBS for three times to remove unbound virus. To determine productive viral replication from the infected biopsy specimens, supernatants of the infected cultures will be collected at 1, 24, 48 and 72hpi and virus titers will be determined by TCID50 assay. Explant cultures will be fixed in 10% formalin at 24 and 72hpi and immunohistochemistry staining (IHC) against HB65 antibody (European Veterinary Laboratories), SARS-CoV or SARS-CoV-2 viral antibody will be performed for the detection of virus-infected cells.
replication efficiency and innate immune responses coronavirus
Time frame: Baseline
Cells will be infected with viruses at either MOI of 0.01 or 2 for 1h. After 1h virus adsorption, viruses will be aspirated and cells will be washed with PBS for three times, then medium will be replenished. For cells infected at MOI of 0.01, cell culture supernatant will be harvested at 1, 24, 48 and 72hpi and viral titers will be determined by TCID50 assay.
Results and safety
The study was stopped early (reason given: Discontinue collaboration with collaborator). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Owen Ho Ko, PhD principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Influenza Virus and Coronavirus, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Discontinue collaboration with collaborator). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Replication kinetics of influenza virus using ex vivo cultures of human brain (time frame: baseline). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2026.