Hidden behind St Vincent's hospital in Sydney there's an unassuming grey building where some extraordinary research is happening.
It's here that the detailed medical data of 128 of Australia's COVID veterans — who caught the original Alpha strain in early 2020 — is being picked apart and exhaustively analysed.
The hope is that by tracking this cohort over years, Australia might contribute to the international effort to understand this fiendish virus and its short and long-term effects.
And the team has found something startling.
Cognitive decline widespread
Around one quarter of the ADAPT study's participants were experiencing noticeable cognitive decline a year after getting COVID.
And, some sort of cognitive decline was recorded in almost all of the participants, regardless of the severity of the initial infection.
"When we look over time, across the 12 months of the study, we see that even the people who have performance within a normal expectation do also have a mild cognitive decline," says neuropsychologist and associate professor Lucette Cysique.
Dr Cysique is the lead author of a yet to be published research paper based on data from the ADAPT study — a collaboration between St Vincent's Hospital, the Kirby Institute and the University of NSW.
She says the unpublished research suggests the cognitive impact of COVID may be more widespread and longer-lived than previously thought.
And their research is shedding light on how exactly this occurs.
"The immune system reacts first with the virus … tries to basically get rid of the virus," she says.
"Then it goes a little bit into overdrive and this overdrive does not fully calm down."
Dr Cysique points to a chart on a computer screen in which a metabolic marker known as the kynurenine pathway is tracked among the ADAPT study participants.
It shows that the pathway has been agitated by the coronavirus in a similar way to how inflammation is caused by viruses such as HIV.
"I think we're seeing something a bit akin here, where this low level of inflammation is more and more understood as being able to traffic to the brain, or even being within the brain and affecting those regions of the brain where we process information that demand speed, extra attention and extra cognitive demands."
Dr Cysique emphasises that the cognitive decline recorded among most participants in the study is mild and they may not even notice it.
The study is relatively small and only includes unvaccinated people infected with the early Alpha strain of COVID-19. Most had mild to moderate infections and only 9 per cent were hospitalised with the disease. No participant was entirely asymptomatic.
However, the research may help us to understand the so-called "brain fog" that many with long COVID complain of.
And here at St Vincent's hospital, there's no shortage of them.
'All I could do is lie in bed'
Across the road from Dr Cysique's research lab, inside St Vincent's Hospital, is Australia's first long COVID clinic.
Twenty-one-year-old Aston Brown is one of those presenting with ongoing symptoms including brain fog.
"If I did any sort of work [after my infection], even if that was just sitting down in front of a computer … I couldn't think straight … all I could do was lie in my bed and look at the ceiling."
Before he caught COVID, Aston was a keen bushwalker and runner, rode his bike all over Sydney, and played club rugby when he wasn't working or studying at Uni.
Five months later he's still struggling to exercise and concentration remains an issue.
"A few days ago, I went for a couple of laps around the local oval, which was the first time I've been running all year."
"I'm still pretty, pretty cautious about what I'm doing. And the big worry is that I do too much and then I go backwards."
Unlike the ADAPT participants in Dr Cysique's study, Aston was double vaccinated when he caught COVID in January. But this didn't spare him the enduring brain fog.
"It's concerning, I think … It pretty much shows that no-one is safe from the possible longer term impacts of COVID."
Inside the clinic
Australia's first multi-disciplinary long COVID clinic is not much to look at.
It's just a bunch of rooms on either side of two hallways buried out the back of the outpatients area of St Vincent's. It opened in March.
But behind the closed doors of those hallways people are grieving the lives they have lost.
"I just want my old life back and I don't know when I'm going to get that back," says 60-year-old Karen Henry.
"I want to be able to go out and go for walks, or go and play golf if I want to play golf, or go and visit friends and go out for dinner. But at the moment, I can't."
Karen has multiple sclerosis and because of allergies is unable to take medication for it. But since she got COVID in January, she's not even been able to do the things her MS allowed.
"This is a big effort to come in here today and this will wipe me out for the next few days. It could even be a week where I won't be able to do anything."
Respiratory specialist Anthony Byrne is the physician examining Karen Henry behind that closed door.
For the doctors at the St Vincent's long COVID clinic, teasing out where underlying medical conditions end and long COVID begins is a key challenge.
"Karen's a complex patient, but that's not uncommon for the sort of patients that we see in the clinic," says Dr Byrne.
"We've been treating patients for a while, but this is very much a learning experience for us as well to know what works and what doesn't."
St Vincent's long COVID clinic offers comprehensive, multidisciplinary treatment. Respiratory and rehabilitation specialists are part of the team, along with a neurologist, a psychologist and a physiotherapist.
Prospective patients apply to the clinic through their GPs, which can occasionally be a roadblock, says Elli Asgary, the clinical nurse consultant who processes the admissions.
"Some doctors do not believe in long COVID, so they find it very hard to get the referral from their own GP. So they have to change their GP to get the referral."
The respiratory specialist Dr Byrne is surprised by this scepticism.
"Sometimes if you're not the person with the symptom, it can be easy to brush it off as ‘Well, you know, just get over it,'" he says.
"[But] when you see enough of these patients, you realise that they have these symptoms that they're not making up. They're legitimate symptoms."
He says up to 100 symptoms have been linked with long COVID, but the most commonly reported are fatigue, cognitive difficulties, breathing problems, heart palpitations and lasting changes to taste and smell.
Dr Byrne says COVID is "not just any virus".
"It's a really inflammatory virus … It causes systemic inflammation. That inflammation is in blood vessels. They affect the liver, the heart, the kidneys, the brain. They just go around the body everywhere, because the blood obviously goes everywhere within the body."
A recent patient at the clinic was a fit young man in his 30s who contracted a mild case of COVID in January. He still suffers from fatigue and an inability to concentrate.
A scan, ordered five months after his initial infection, revealed he has two blood clots on his lungs.
"Which is a life-threatening condition, you know, potentially," says Dr Byrne.
'Are you serious?'
"Ha ha ha — are you serious?"
That's the response from one the United States's leading long COVID researchers, Ziyad Al-Aly, to the question of whether it exists.
"Long COVID is absolutely real. And long COVID is not even a small problem. It's a serious, serious public health crisis," he says.
Dr Al-Aly is a clinical epidemiologist at Washington University in St Louis, Missouri and the chief of research for the St Louis Health Care System.
He's also part of a panel tasked by the White House to recommend a national response to long COVID.
"There are millions of people in the US, millions of people in the UK. You know, quite a number of people in Australia will be affected with long COVID."
"Some of these people will not be able to return to work, will not be able to maintain employment."
Dr Al-Aly was lead researcher on a study of a vast trove of US military veteran medical data which suggests that vaccination provides minimal protection against long COVID.
"Vaccines reduce, but only modestly, by 15 per cent, the risk of long COVID," he says.
"They reduce the risk of long COVID, but do not eliminate the risk."
A recent report from the Centers for Disease Control in the United States found that around 20 per cent of people who had COVID later had symptoms that could be attributed to long COVID.
Dr Al-Aly says that statistic would also apply to Australia, meaning well over a million Australians could be affected, whether they're aware of it or not.
Back in the clinic
Back in the long COVID clinic, Aston Brown is getting some elementary instruction in tai chi from physiotherapist Irina Grassi.
"The first one is opening your chi. So you normally step to the left and you're going like this, breathing in and slowly breathing out."
Ms Grassi says there's "a lot of evidence that tai chi is helpful for people both psychologically and physically."
"There's a big emphasis on coordinating the breath with movement, which can help facilitate a relaxation response," she says.
In a shared journey with their patients, the clinic is throwing everything at long COVID, tackling each symptom as it presents.
Its patients, like young Aston Brown, are appreciative that their symptoms are being taken seriously.
"There's no magic cure for this thing, unfortunately," he says.
"But that's all right. Coming here, I just know that I'm getting the best possible advice and the best possible care."
Aston's feeling a lot better after a few months of treatment. But he still has concerns.
"There's no ideas about how long it would go on for, or whether there'll be permanent impacts."
"There's a lot of unknowns and that's the scary part of it."
However, Dr Cysique says their research based on the ADAPT study could offer fresh hope for future treatments.
"There is a potential pathway for treatment, because there are currently clinical trials to modulate the kynurenine pathway, for example."
That's the pathway to the brain that's agitated by the coronavirus in a similar way to HIV.
She says drugs may be an option to suppress the body's overactive immune response.
Dr Byrne explains that normally with a syndrome that affects multiple organs, "rheumatologists would put [patients] on immunosuppressive medications to suppress that immune response".
"Whether that could be possible for some people suffering long COVID is at this point unclear, but I think it is something that we need to research and look at doing specific clinical trials [for]."
For now, those with long COVID have to deal with what current medicine has to offer, drawing on multiple disciplines and treating each symptom as it arises.
Around the country, most treatment of long COVID is still focused on the condition as a respiratory illness, according to Dr Byrne.
However, other states now have dedicated long COVID clinics with some taking a multidisciplinary approach.
He believes that the holistic approach practised by St Vincent's is vital.
"Being sort of both rehab and respiratory, psychology, physio, I think is a little bit unique."
"I'm hopeful that other hospitals, tertiary hospitals, will be able to develop that sort of model."
