When PA Research Foundation supporters give to help patients and advance research, they might not know they’ve potentially helped to redefine how society will tackle Covid-19.
PA Hospital based lung cancer researcher Dr Arutha Kulasinghe is on the frontlines of the battle to understand and overcome Covid-19 and its impact on our lives, and his cancer work, made possible by PA Research Foundation donors has been crucial to his studies in Covid-19.
Collaborating with researchers here and overseas in a study that examined the lung tissues and over 1000 blood and nasal swabs from Covid-19 positive patients, Dr Kulasinghe and his colleagues identified a genetic marker called IFI27 (interferon alpha inducible protein) in both the lung tissue and blood of people with Covid-19.
The finding is a game changer in the battle against Covid-19 because the IFI27 marker can be used to identify how severe the virus is likely to be in Covid-19 patients and signal whether they need to be hospitalised or are able to quarantine at home. The research has led Sydney based company SpeeDx to begin development of a blood test that could be used by an infected person, early on in their symptoms, as a guide to how bad their infection will be.
“IFI27 is an immunological anti-viral response and was discovered in the lung tissue using spatial transcriptomics, where we mapped the cell types and genes in the lungs of Covid-19. This work was intricately performed under the guidance of Dr Caroline Cooper from the pathology department at the PA,” Dr Kulasinghe said.
“Dr Cooper identified the cell types in the lungs and then we liberated the genes from those cell types. This enabled us to understand the types of cells that were infected by the SARS-CoV-2 virus and understand the genes which were being expressed.”
“We could see visually where the virus was localising, so we knew the cell types that were being infected, then when we compared the Covid-19 lungs to that of healthy lungs of non-Covid-19 related deaths and deaths from the 2009 H1N1 influenza pandemic. By comparative mapping of cell types and the genes between the disease states, we could see that IFI27 was really highly expressed in the Covid-19 patients.
“That was one of the first signs that something was going on in the tissue that was making this gene peak. At the time we were oblivious to what the gene was, we just knew it was involved in the interferon pathway.
Dr Arutha Kulasinghe is a lung cancer and Covid-19 researcher based on the PA Hospital campus.
“My background is in cancer biology, so luckily we had leading virologists (Dr Kirsty Short, UQ), immunologists (Prof Gabrielle Belz, Dr Fernando Guimaraes) and computational biologists (Prof Melissa Davis) on the call. Kirsty knew that IFI27 was elevated in the blood of COVID-19 patients, but these findings had not been tied back to the tissue level yet. Our study now provides first evidence of this in the lungs of COVID-19 patients.
The finding allowed the team to then do further research which highlighted that IFI27 was much higher in patients who ended up with severe cases of Covid-19.
“We looked at about 1000 patients from Brazil, Chile, Denmark, Iran and the US, and we asked how does IFI27 differ really early on in mild, moderate and severe Covid-19 patients, and we could see that it in severe cases the levels were quite high early on in disease onset. We could see that patients that had really high IFI27 levels, typically within the first few days of infection, went on to do really poorly and had severe Covid-19.”
With the idea of Covid normal becoming more commonplace and the realisation we will have to live with the virus, Dr Kulasinghe and his fellow researchers are excited about the impact that a blood test will have for patient triage.
“We’re hoping to develop this as a companion diagnostic test. There are two major questions if you get sick in the future, 1) is this COVID-19, which hopefully rapid antigen tests will tell and 2) how sick will I get, do I need to seek medical attention, will I need hospitalization? Our test will potentially help you answer that second part of that, based off the IFI27 levels,” he said.
“If it’s measured within the first few days of symptom onset, we can accurately predict how severe your Covid-19 is going to get, which is useful in the triaging of patients.
“In a remote setting if you have 100 patients you can’t send them all to hospital but if you’re able to say these 10 patients need to be monitored, they may need to be hospitalised and they might need ventilation, whereas the other 90 can stay home and home quarantine based off the expression of this gene, that’s really useful.”
Dr Kulasinghe said the PA Foundation’s donors played a major role in allowing the work to get to the point where a commercial team could start to develop the blood test which could be available in 2022.
“We were already looking at lung cancer tissues, so the lungs of Covid-19 patients wasn’t a stretch for us to profile. We used our knowledge gained in lung cancer through the PA funding in 2020 and 2021 in developing our methodology,” he said.
“We already had the team working together for lung cancer, which included clinicians, scientists, pathologists, immunologists and bioinformaticians. Our methodologies and workflows had been optimized to profile tissues, so when we had Covid-19 samples, we could apply these methods efficiently.
“The funding from the PA Foundation was critical because we wouldn’t have developed the methodologies to be able to apply it to a different disease model.”
You can donate to support vital research by Dr Kulasinghe and his colleagues at the PA Hospital campus here.
You can read the latest publication on this research here.