What causes long COVID?

When it comes to public health messaging about the risks of COVID infection, long COVID gets very little mention.
 
But post COVID-19 condition, as it has been officially named by the World Health Organization, can be debilitating, and affect more than one system of the body.
 
In the UK, as of 6 December 2021 prior to the widespread emergence of the Omicron variant, an estimated 1.3 million people who tested positive to COVID-19 self-reported symptoms persisting for more than four weeks post-infection. Fatigue was the most common (51%) followed by loss of smell (37%), shortness of breath (36%), and difficulty concentrating (28%).
 
Though many questions remain about long COVID, new research by UNSW’s Kirby Institute has uncovered an immune profile for the condition.
 
Published in Nature Immunology, researchers used data obtained from St Vincent’s Hospital’s ADAPT study and analysed blood samples from 62 unvaccinated Australians diagnosed with COVID-19 between April and July 2020 taken at three, four and eight months following initial infection. They then compared the results to control groups, including people who had never been exposed to COVID-19 and to those who had been infected with other coronaviruses, such as the common cold.
 
The team looked for a variety of immune biomarkers and found persistently elevated levels of type I and type III interferons – types of protein created by cells in response to the presence of a virus.
 
While these proteins generally disappear after an infection clears, in patients with long COVID, the findings show sustained inflammation detectable for at least eight months following initial infection.
 
Dr David Darley, who is a respiratory physician at St Vincent’s Hospital and a lead author on the paper, told newsGP the findings are particularly significant for GPs.
 
‘What this means is that long COVID has a true biologic basis – it’s not something that is purely psychological – it’s an actual syndrome,’ he said.
 
‘That’s what’s really important for GPs in that it’s a condition that should be taken seriously.’
 
The research is the first to describe the impact of long COVID on the immune system through analysis in a laboratory setting, with hopes that it will help the development of treatment and management of the condition.
 
A particularly interesting finding is that disease severity is not a predictor of whether someone is more likely to experience lingering symptoms, unless they have been admitted to ICU, nor is age. However, females do appear to be at greater risk than men, though the reason remains unknown.
 
More broadly, why people develop long COVID has yet to be confirmed. Though Dr Darley says there are three main hypotheses.
 
‘The COVID virus could still be lingering in the body … in a reservoir site and patients are still being exposed to COVID antigens,’ he proposed.
 
‘The second is that maybe the virus triggers some sort of autoimmune process which persists.
 
‘Or, patients could have had some viral-induced tissue injury or damage, and this is a persistent post-inflammatory response as a result.
 
‘That’s what our thinking is.’
 
Australian modelling on long COVID, released by researchers from Deakin University in December as a pre-print, estimated that a relaxation of public health measures could result in excess of 130,000 cases. That, however, was prior to the emergence of Omicron and the subsequent rise in infection rates.
 
A recent pre-print study from Israel has offered a glimmer of hope for Australia's high vaccination rates, suggesting that vaccination with at least two doses reduces the incidence of long COVID – but it again remains to be seen whether that will also be the case with Omicron.
 
‘We don’t have the data yet, but we’re speculating that we’re going see less long COVID because the immune system has already had a chance to learn what COVID is before patients get infected,’ Dr Darley said.
 
‘But I think it’s important to be honest when we don’t know and that’s our answer – we don’t know yet.’
 
Approximately one in three study participants who contracted COVID have experienced some long COVID symptoms. If the burden of long COVID were to continue at the same rate as seen with the original strain of the virus among unvaccinated cohorts, the respiratory physician says it would no doubt be a significant burden on frontline workers, in particular GPs and emergency physicians.
 
At this stage, while understanding around the condition is still in its relative infancy, Dr Darley said a comprehensive assessment is required to develop an individualised treatment plan for each patient.
 
‘So, a full assessment of their respiratory system, mental health, cognitive and rehabilitation potential,’ he said.
 
‘The main kind of treatments that we’ve been using for long COVID at St Vincent’s has really been rehabilitation; giving them a chance to work with a physiotherapist and really try to break through some of that post-viral inflammatory fatigue.
 
‘Also cognitive therapy if they’re struggling with mental health, and then really objectively assessing their lung and heart function if they need it.’
 
Currently, Dr Darley and his team are looking at data from Australia’s Delta wave to better understand the role of vaccination and reduced incidence of long COVID. But while the health system remains overwhelmed, he says further answers on long COVID may be delayed.
 
‘We’ve got thousands of healthcare workers off sick, we’ve got heaps of patients and so the ability at the moment to be doing rigorous research is actually not great,’ Dr Darley said.
 
‘We’ve got to try to get the whole system well-resourced again.’
 
GPs can access the RACGP’s ‘Caring for adult patients with post−COVID-19 conditions’ guidelines on the college website.
 
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