NCT05375006

Tropism and Pathogenesis of Influenza Virus and Coronavirus in Human Brain Explant Culture

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 80 (estimated)
• Sponsor: Chinese University of Hong Kong · Academic / Other
• Sex: All
• Age: 1 Year – 70 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Influenza Virus
• Coronavirus

Timeline

• Start date: 2022-05-26
• Primary completion: 2024-03-31
• Completion: 2024-09-30
• First posted: 2022-05-16
• Last updated: 2022-08-17

Locations

1 site across 1 country: Hong Kong