Clinical trial NCT05375006: Tropism and Pathogenesis of Influenza Virus and Coronavirus in Human Brain Explant Culture
Official title: Tropism and Pathogenesis of Influenza Virus and Coronavirus in Human Brain Explant Culture
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Influenza Virus
Coronavirus
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
Collaborators: name: The University of Hong Kong
First posted: 2022-05-16
Enrollment: 80
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will recruit participants who will undergoing elective or emergency craniotomies for intrinsic brain lesions at Prince of Wales Hospital

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

1. Age: \> 1 year old and \< 70 years old
2. Undergo elective or emergency craniotomies for intrinsic brain lesions

Exclusion Criteria:

a. Samples containing infected material

Primary outcomes:
measure: Replication kinetics of influenza virus using ex vivo cultures of human brain
timeFrame: baseline
measure: replication efficiency and innate immune responses of influenza virus
timeFrame: baseline
measure: Replication kinetics of coronavirus using ex vivo cultures of human brain
timeFrame: Baseline
measure: replication efficiency and innate immune responses coronavirus
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
state: NT
Study officials:
affiliation: Chinese University of Hong Kong
name: Owen Ho Ko, PhD
role: PRINCIPAL_INVESTIGATOR
References: