The story of Long COVID
How the REACT and PHOSP studies uncovered the phenomenon of Long COVID — and how do we help those still suffering the aftereffects of COVID-19?
Cast your mind back to the start of 2020, as a strange new disease swept across the world. We all quickly learned its name — COVID-19 — as well as the identity of the coronavirus that caused it, SARS-CoV-2.
During the first wave, we had plenty of data on hospitalisations and deaths across the UK, but nobody knew how many people in the general population were infected with the virus or how sick it was making them.
“Back then, there wasn’t really any testing available, except for patients admitted into hospital,” explains Helen Ward, Professor of Public Health at Imperial College London. “The research community and the Government quickly realised we needed to get a handle on what was going on in the community, outside from the hospitalisations and deaths, and that we had to move fast to get a study off the ground.”
In a matter of weeks, Ward and her colleagues had put together the protocol and funding for the Real-time Assessment of Community Transmission (REACT) study to look at the extent of coronavirus infection across England. Thousands of randomly-selected households were sent PCR swab testing kits, together with detailed questionnaires asking about symptoms and duration of illness. The study team later added fingerprick blood tests to look for antibodies against the virus that would indicate a previous infection.
As repeated rounds of REACT surveys ran through the spring and summer of 2020, an unsettling spectre began to emerge out of the data: Long COVID.
A serious health problem emerges
“The perception at the beginning of the pandemic was that you were either unaffected, mildly to moderately ill, or you’d get very sick and maybe die,” says Ward. “But we started to accumulate data showing that for some people there is a long tail of symptoms where they become ill with COVID and remain unwell for many weeks or even months.”
At the same time, people who were still dealing with symptoms long after first catching COVID started to find each other on the internet to swap stories and suggestions for how to get better. The phenomenon quickly became known as Long COVID — a condition that is now broadly accepted as experiencing symptoms for three months or more after the initial infection.
The stories quickly stacked up from people suffering breathlessness, fatigue, ‘brain fog’, aches and pains and other symptoms many months after their initial bout of COVID-19. There was also plenty of frustration about the lack of knowledge about the condition or how best to treat it.
In search of answers, the REACT team launched a specific Long COVID study in March 2021, aiming to describe the varied experiences of people in the general community who have had COVID and its aftermath.
The results were stark. More than 2 million people in the UK could be living with Long COVID, with women and people who smoke or are overweight or obese most at risk, along with people living in more deprived areas.
The data also showed that there were two main ‘types’ of Long COVID. Around a quarter of people have lingering respiratory symptoms such as breathing problems and chest pain, while the majority suffer more general issues such as fatigue, muscle aches and problems sleeping.
The post-hospitalisation long haul
While the REACT team was studying the impact of Long COVID in the general population, Chris Brightling, Clinical Professor in Respiratory Medicine at the University of Leicester, focused his attention on outcomes for the most severely ill COVID patients admitted to hospital.
“We know that some viruses can cause long-term health problems, and the SARS outbreak in the early 2000s led to a variety of long term health issues, such as persistent breathlessness and fatigue,” Brightling says. “The scale of the emerging pandemic and the first wave of hospitalisations made us realise this was likely to be a serious problem that we would need to address.”
In response, Brightling and his team launched the Post-Hospitalisation COVID study (PHOSP), the first study of its kind to follow up the long term health of people lucky enough to survive a spell in hospital with COVID-19.
The first patients were recruited in mid-August 2020 and there are now more than 7,000 participants from around 80 hospitals. Nearly 3,000 of them have undergone detailed assessments and tests to measure all kinds of aspects of their health, from lung and heart function to immune molecules in their blood, with long-term follow-up made easy by securely linking to the data held in their NHS records.
“We want to understand how the course of someone’s initial illness and the treatments they receive in hospital relate to the downstream impacts on their health, and dig into the underlying biological mechanisms responsible,” he says. “And, of course, we want to know what we can do next for these patients with the aim of helping them improve their lives.”
First released as a preprint in March 2021 and formally published in the journal Lancet Respiratory Medicine in October, the first results from PHOSP show that many people are living with lingering health problems after being hospitalised with COVID-19.
“Unfortunately, while these patients did make it out of hospital, their recovery was worse than expected — fewer than three in ten people reported that they felt completely well again a year after leaving hospital, and the rest were still experiencing an average of nine symptoms,” says Rachael Evans, Associate Professor at the University of Leicester and one of the lead authors of the paper.
“Importantly, this isn’t just related to being admitted to intensive care or having other underlying health conditions — there’s something else to do with the SARS-CoV-2 virus itself as well.”
“This is a very nasty coronavirus, so it’s not surprising we’re seeing such a range of long term effects,” adds Ward. “Not only does it affect the lungs and heart, we know from detailed studies that it infects multiple organ systems including the brain, where we think it’s directly causing issues like memory problems, brain fog, depression and anxiety.”
How do we treat Long COVID?
As well as cataloguing the scale and scope of Long COVID in different groups of patients, PHOSP and REACT Long-COVID are aiming to discover how best to treat this emerging long-term health condition.
Both studies are carrying out detailed genetic and molecular analysis on patient samples, looking for clues that might help to explain what’s going on within the body and point towards treatments that are likely to help. At the same time, there is an urgent need to help these individuals now to improve their wellbeing and quality of life.
“We’re running a rehabilitation study as part of PHOSP, working closely with patients to make sure we’re really addressing the right issues that affect them — for example, we’re looking at how to help people with muscle pains and fatigue, and we’re also looking at how best to support people experiencing mental health problems and brain fog,” Evans explains.
“We also need a proactive healthcare system that is following up people who’ve been seriously ill with COVID-19, following them up to see how they’re doing rather than waiting until they go to their GP, and that is holistic across mental as well as physical health.”
The long shadow of Long COVID
In addition to the lingering symptoms of Long COVID, there are concerns that other long term impacts of coronavirus infection could emerge in the future.
“When you have a respiratory infection like COVID-19, there’s a risk that it can set off a chain of events that eventually leads to irreversible lung scarring, known as fibrosis,” explains Gisli Jenkins, Professor of Thoracic Medicine at Imperial College London. “This isn’t obvious immediately and the time lag from the initial damage to observable fibrosis can be anything from five to 25 years, so we have no idea of what the scale of this problem might be in the future.”
Previous research has shown that the chances of developing lung fibrosis in response to damaging events like infections are strongly influenced by an individual’s underlying genetic makeup.
“If basically everybody ends up catching COVID-19, a significant proportion are going to have genetic variations that put them at greater risk,” Jenkins warns.
“We urgently need to identify the people who are most likely to go on to develop fibrosis, so we can monitor them and find ways of slowing down the progression.”
Jenkins and his team are running two studies aimed at answering these pressing questions: XMAS — which is using xenon MRI scans to look for early signs of lung damage — and POSTCODE, a detailed biological investigation of samples taken from the lungs of people with post-COVID lung problems.
“We know that other viral infections can have long term problems that pop up years later, so it’s vital that we monitor this cohort of people,” he says. “With such huge numbers infected in the UK over the course of the pandemic so far, there could be a huge impact on the nation’s health, wellbeing and productivity in the years ahead.”
What can we expect for Long COVID in the future?
As the UK vaccination programme reaches a high level of coverage and restrictions lift, we can hope to look towards some kind of normality returning.
But even now, two years after the first UK case of COVID-19 was identified, many thousands of people are still catching the virus and hundreds are being hospitalised every week, suggesting that it’s premature to think that Long COVID will soon be a thing of the past.
“We would be brave to say that in a year everyone will be fine — the truth is we just don’t know, and we’d be wise to be cautious about the long term health impacts of the virus,” cautions Ward.
“I hope that vaccination will reduce the incidence and duration of Long COVID going forward, and that future variants are less severe, but we’re still talking about hundreds of thousands of people with debilitating chronic illness that might last for years — that’s going to be a really big issue for them and for society.”
While the potential future burden of Long COVID is concerning, there are signs that the worst of the infections might be over.
“Obviously, the best way to avoid Long COVID is to avoid catching COVID-19 in the first place. but the good news is that vaccines seem to be making a big impact in reducing Long COVID cases,” says Jenkins. “It also looks like Omicron doesn’t infect the lungs in the same way as previous variants, which should hopefully mean less scarring in the future.”
Still, he warns, this doesn’t mean that we can completely forget about Long COVID as we move towards a post-pandemic future.
“In a few years’ time everyone will want to forget about COVID-19 — it’s been a harrowing period for everybody with the social isolation, stress, grief and disruption to people’s lives, so people are going to want to put it out of their minds and move on. But there are going to be real long term health impacts for potentially tens of thousands of people, so we need to be prepared and figure out who they are, reassure the vast majority that they will get better, and monitor and protect those who might not.”
Want to know more?
If you’re a UK taxpayer, your contributions help fund the REACT Long COVID, PHOSP, XMAS and POSTCODE studies, via UK Research and Innovation — the UK’s largest public funder of research — and the Medical Research Council. REACT-LC and PHOSP are funded in conjunction with NIHR. You can read more about what we do here, and more about NIHR here.
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