About 5 to 10 percent of people infected with COVID-19 go on to suffer long COVID, with symptoms lasting three months or more.
Researchers have proposed several biological mechanisms .
However, in a perspective article published in the latest Medical Journal of Australia, we argue that much, if not all, of Long COVID appears to be due to the persistence of the virus itself in the body.
Since the start of the COVID-19 pandemic, it has been recognized that in some people, SARS-CoV-2 – or at least remnants of the virus – can remain in various tissues and organs for long periods of time. This theory is known as “viral persistence.”
Although the long-term presence of residual viral fragments in some people’s bodies is now well established, what remains less certain is whether the living virus itself, and not just old virus fragments, persists – and if so, if that’s what’s causing the long lifespan. COVID.
This distinction is crucial because live viruses can be targeted by specific antiviral approaches, unlike “dead” viral fragments.
Viral persistence has two important implications:
- When it occurs in some highly immunocompromised people, it is thought to cause new variants with significantly different appearances, such as JN.1;
- It has the potential to continue to cause symptoms in many people in the wider population, well beyond the acute illness. In other words, Long COVID could be caused by a long infection.
What does the research say?
While there are no studies confirming that a lingering virus is the cause of Long COVID, several recent key papers collectively make compelling arguments.
In February, a study published in Nature found that a high number of people with mild COVID-19 symptoms had prolonged periods of shedding the virus’s genetic material, called viral RNA, from their airways.
Those who had persistent shedding of this viral RNA – which almost certainly represents the presence of a live virus – were at higher risk of Long COVID.
Other key papers detected replication of viral RNA and proteins in patients’ blood fluid years after their initial infection, a sign that the virus likely replicates for long periods in certain hidden reservoirs in the body, including maybe blood cells.
Another study detected viral RNA in ten different tissue sites and blood samples 1 to 4 months after acute infection. This study found that the risk of long COVID (measured four months after infection) was higher in people with persistent positive viral RNA.
The same study also gave clues as to where the lingering virus resides in the body. The gastrointestinal tract is a site of considerable interest as a long-term viral hiding place.
Earlier this week, further evidence of a persistent virus increasing the likelihood of Long COVID was released as part of the RECOVER initiative, a collaborative research project that aims to address the impacts of Long COVID.
However, formal proof that a virus capable of replicating itself can persist for years in the body remains elusive. Indeed, isolating the living virus from the reservoirs inside the body where the virus “hides” is technically difficult.
In their absence, we and other scientists argue that the accumulated evidence is now compelling enough to galvanize action.
What should happen next?
The obvious response to this situation is to accelerate trials of antivirals known for the prevention and cure of Long COVID.
This should include more left-field therapies, such as the diabetes drug metformin. This presents a possible double advantage in the context of Long COVID:
- Its antiviral properties, which have demonstrated surprising effectiveness against Long COVID;
- As a potential therapeutic in the treatment of fatigue-related impairments.
However, another major focus should be the development of new drugs and the creation of clinical trial platforms for rapid testing.
Science has discovered exciting treatment options. But translating this information into clinically usable forms poses a significant hurdle that requires government support and investment.
Demystifying and preventing Long COVID
The notion of “long infection” as a contributor, or even driver, of Long COVID is a powerful message.
This could help demystify the disease in the eyes of the wider community and increase awareness among the general public as well as healthcare professionals.
This should help raise community awareness of the importance of reducing reinfection rates. This is not just your first infection, but every subsequent COVID-19 infection carries a risk of Long COVID.
Long COVID is common and is not limited to people at high risk of severe acute illness, but affects all age groups. In one study, the highest impact was on people aged 30 to 49.
So, for now, we all need to reduce our exposure to the virus with the tools available, a combination of:
- Clean indoor air is approaching. In its simplest form, this means being aware of the importance of well-ventilated indoor spaces, opening windows, and improving air circulation as COVID-19 spreads through the air . More sophisticated ways to ensure indoor air safety involve monitoring the quality and filtering the air in spaces that cannot be easily ventilated naturally.
- Use high-quality masks (well-fitted and do not easily let in air, such as N95-style masks) in environments where you do not have confidence in indoor air quality and/or are crowded .
- Test, so you know when you are positive. Then, if you are eligible, you will be able to receive treatment. And you can be vigilant by protecting those around you with masks, staying home when possible and ventilating spaces.
- Stay up to date with COVID-19 booster doses. Vaccines reduce long COVID and other post-COVID complications.
Hopefully one day there will be better treatments and even a cure for COVID-19. But in the meantime, increased awareness of the biomedical underpinnings of Long COVID should prompt clinicians to take patients more seriously when trying to access already existing treatments and services.
Brendan Crabb is the Director and CEO of the Burnet Institute. Gabriela Khoury is thematic lead for antiviral immunity at the Burnet Institute. Michelle Scoullar is a senior researcher at the Burnet Institute.
