University Of New South Wales: Despite the uncertainty, there is hope for long COVID patients

As the world came to grips with the news of the pandemic unfolding in early 2020, online chatter among patients who were experiencing lingering symptoms after contracting COVID-19 began to spring up on social media.

The term ‘long COVID’ was first used by Dr Elisa Perego in Lombardy, Italy as a Twitter hashtag in May 2020 to describe her experience of COVID-19 infection as cyclical, progressive, and multiphasic. In other words, it was taking longer than anticipated for her to recover with symptoms that would come and go.

Further evidence of COVID-19 survivors experiencing similar long-term symptoms resulted in support groups popping up on other social media platforms such as Facebook.

To date, the World Health Organisation (WHO) estimates one in 10 people who have had the virus continues to feel unwell after 12 weeks. While the WHO uses the term ‘post-COVID-19′ to describe lingering symptoms after initial infection from contracting the SARS-CoV-2 virus, their definition states this condition occurs usually three months from the onset of COVID-19 with symptoms that last for at least two months and cannot be explained by an alternative diagnosis.

“I think we’re still learning a lot about long COVID. But we’ve come a long way from where we were in mid-2020, which is when long COVID first started to be talked about especially among patients themselves to start off with. The medical and research community caught up with what was going on, on social media, with patients realising they were taking a long time to recover, and experiencing a wide range of symptoms, some months after having an initial COVID-19 infection,” explains Professor Gail Matthews who is head of the Therapeutic Vaccine and Research Program at the Kirby Institute, UNSW Sydney and an Infectious Diseases physician at St Vincent’s Hospital, Sydney.

The first Australian long COVID study
“The ADAPT study is interesting because we commenced that research very soon after the beginning of the pandemic around April 2020 and we were able to get it going quickly through a major collaborative effort within St. Vincent’s Hospital in Sydney. We started following people who had COVID-19 infections at the time, but we didn’t know there was anything like long COVID,” says Prof Matthews.

As the team began to follow their patients, the researchers soon became aware a proportion of people in the study – about 30 per cent of people who were managed in the community – were not recovering at four months post-infection.

“And in fact, that group had still not recovered at eight months post-infection. So, that was the first important recognition of long COVID occurring in Australia. We were seeing similar reports coming out of the US and the UK, but ADAPT was the first Australian study to really document very clearly that this was an issue,” explains Prof Matthews.

The most common symptoms patients displayed included persistent fatigue; respiratory symptoms such as a persistent cough; shortness of breath, particularly in patients who were in hospital with pneumonia or in ICU; brain fog and difficulty concentrating. Some patients experienced high heart rates that didn’t settle.

“But really, there’s a whole range of symptoms. In fact, up to 100 different symptoms have been described as part of the long COVID spectrum. Some of our patients who’ve been very unwell when they’ve been in hospital with COVID-19 have certainly taken a long time to recover. It could be because they’ve got scarring in their lungs, or just because they’ve been very sick in hospital. And that’s not too surprising.

“But we also see many people with long COVID, who, in fact, were never hospitalised. They may have had some symptoms at home, but they were managed in the community. It was not severe enough to go to hospital, but they still have symptoms some months afterwards,” explains Prof Matthews.

“This is only one piece of a big puzzle. We haven’t found the answer to long COVID, but what we have found is a signal,” says Professor Gail Matthews. Photo: Richard Freeman/UNSW

Immune cells still activated in long COVID patients
The ADAPT study looks at a range of different outcomes in patients including neurological function, cardiac function, respiratory function, and mental health. But one important finding the study revealed was that immune cells were still activated in long COVID patients who still displayed symptoms.

“The long COVID patients were showing abnormal immune signals at about eight months post-infection. And we wouldn’t expect to see that in somebody who had recovered from a viral illness. So this was an important finding, because it showed unequivocally, that biologically, people who had long COVID were different from those who’d had COVID and fully recovered,” explains Prof Matthews.

“This is only one piece of a big puzzle. We haven’t found the answer to long COVID, but what we have found is a signal. And what that means is, when you have influenza, or any viral illness, your immune system switches on and it produces several signals, called cytokines – markers in the blood – which tell your immune system, there’s a problem, there’s a virus here. And that’s often what’s responsible for some of the symptoms we get when we’re sick such as fever or feeling unwell.”