New study paves the way for more effective COVID-19 research and treatment

A Melbourne-led study, involving researchers from the Royal Melbourne Hospital (RMH), suggests that a primary tissue culture model is more effective at recreating the human experience of COVID-19, leading to more accurate treatments for the condition.

The air-liquid-interface (ALI) human nose epithelium (HNE) culture system, a replica of the key features of human tissue, was found to be effective at recreating authentic human SARS-CoV-2 infection without the need to collect invasive human respiratory tissue samples.

The study also highlighted that ALI-HNE is more accurate than the “workhorse” of tissue samples typically used in virus research – Vero cells.

Derived from African Green Monkey kidney epithelium in the mid-1960s, Vero cells have recently been shown to be less effective for screening COVID-19 treatments.

The highly controversial proposed COVID-19 treatment, hydroxychloroquine was found to be very effective at combating the infection in Vero cells, yet showed no benefit in human trials. Subsequent testing in primary human respiratory cells showed that the drug did not stop infection, hence the failed clinical trials.

Medical Scientist and Researcher at the Victoria Infectious Diseases Laboratory (VIDRL) at the Royal Melbourne Hospital and the Department of Infectious Diseases, Melbourne Medical School, University of Melbourne, Professor Elizabeth Vincan, says the ALI-HNE study stressed the need to use this new tissue culture when developing new treatments for COVID-19.

“In a time when the global urgency to uncover new treatments to combat the COVID-19 pandemic, we’re glad we could conclude that ALI-HNE is a robust tissue culture model of SARS-CoV-2 infection that faithfully replicates key features of the human nose,” she said.

Professor Vincan said the study also uncovered a bonus benefit of using ALI-HNE. It was able to identify the difference between the Wuhan strain (VIC01) and the Delta variant of SARS-CoV-2.

“Wuhan strain infected organoids look the same as the uninfected – no obvious damage. In stark contrast, the damage from the Delta virus was quite striking. Dr Bang Tran in my lab who did the microscopy said the ALI-HNE looked battered after infection with Delta."

“It caused cells to fuse together, damaging the epithelium, which most likely underlies shedding more virus from the nose and the consequent high transmissibility – hence the ALI-HNE serve as an excellent model to nut out differences in transmissibility. The nose is the first tissue infected and we can learn a lot in this model about how to stop or control transmission,” she added.

To establish ALI-HNE, turbinate brush samples were collected from adult and child donors, in the same way that we collect samples for polymerase chain reaction (PCR) diagnostic tests.

The stem cells (basal cells) in the brush sample were expanded and seeded into special tissue culture plates. Over three to four weeks, the basal cells form three-dimensional tissue that has the same cell types as the nose.

Once mature, they are infected with different variants of SARS-CoV-2. The non-invasive samples that are required means variants could be screened as they emerge using a biobank of basal progenitors.

Published in the International Journal of Molecular Sciences, ALI-HNE data has shown that this model can be used for further research into new variants.

“In the coming weeks the team will be looking at Omicron infection of ALI-HNE,” said Prof Vincan. “Early studies have shown that the Omicron variant infects the nose better than Delta but does not infect the lung as well. This might explain why it is more transmissible and less likely to cause severe illness.

“So ALI-HNE samples are delivering what they promised – which is a good model of transmissibility,” she added.

This work was made possible with the generous donation from the Kim Wright foundation.