Samples taken from unvaccinated people during Australia's first COVID-19 outbreak show a sustained inflammatory response suggesting that long COVID is "very different to other infections", according to the research.
The team from UNSW Sydney's Kirby Institute analysed data alongside - and collected by - St Vincent's Hospital Sydney.
The first study to describe the impact of long COVID on the immune system through laboratory analysis could lead to specific treatment for those with ongoing symptoms, the research found.
About 30 per cent of unvaccinated people who contracted COVID-19 and were part of the study experienced long symptoms.
One of them, Rick Walters from Roseville, said it was good to have scientific validation of the hardship he has been facing.
"At first, I thought I would just get better, but it became apparent that the damage to my lung was permanent, and I became quite anxious," he said.
"I have had some difficulties adjusting to my current health. COVID should not be taken lightly."
When a person becomes infected with a virus the immune system switches on to eradicate it.
"But what we're seeing with long COVID is that even when the virus has completely left the body, the immune system remains switched on," St Vincent's Hospital's head of infectious diseases Professor Gail Matthews said.
"If you measure the same thing after a standard cough or cold, which we did in this study through one of our control groups, this signal is not there.
"It's unique to sufferers of long COVID."
Multiple samples were taken from 62 patients diagnosed with COVID-19 between April and July 2020, and were analysed three, four and eight months following infection.
Those studied did not have to have severe COVID-19 to experience ongoing immunological changes, which was a surprising result according to the Kirby Institute's senior researcher Dr Chansavath Phetsouphanh.
No data was collected to determine if different variants such as Omicron would cause the same changes.
Nor is there analysis as to the role vaccination may play in reducing the risk of developing these ongoing symptoms.
"From some early international data, we are very hopeful that with a milder variant and with high vaccination rates we may see less long COVID," St Vincent's Hospital's Dr David Darley, a specialist in respiratory medicine, said.
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