Breathlessness, brain fog and fatigue are symptoms of long Covid that remain difficult to explain – but a group of leading microbiologists think they may have discovered an important clue to understanding the origins of the condition.
They suggest long Covid symptoms stem from additional infections that occur alongside SARS-CoV-2.
Long Covid has affected as many as 400 million people worldwide, causing a wide range of symptoms that can range from mild impairment to severe disability. It can affect the brain, heart, lungs and the digestive system.
Yet, there are no proven treatments for long Covid because the underlying cause remains unknown.
A review published in the journal eLife by 17 experts, suggests infections that were acquired before or during Covid may be to blame for the persistent symptoms.
“This is an aspect of long Covid that is not talked about a lot,” said Maria Laura Gennaro, a microbiologist at the Rutgers New Jersey Medical School.
Researchers studied existing reviews to argue infections beyond Covid could be critical players in long Covid.
One virus is the Epstein-Barr virus (EBV), which is carried by about 95 per cent of adults, typically without symptoms, until an immune disruption such as Covid awakens the dormant virus.
One study in the review found that two-thirds of people with long Covid showed signs of recent EBV activity, and those with more symptoms had higher antibody levels. Later research linked EBV reactivation to long Covid hallmarks such as fatigue and cognitive problems.
Another potential culprit is Tuberculosis (TB) and about a quarter of the world’s population carries a latent form of TB.
There is some evidence to suggest Covid can deplete the immune cells that normally keep it dormant and trigger reactivation. It’s also thought a TB infection would worsen Covid outcomes.
If these co-infections hit before Covid they could leave the immune system compromised, during acute illness it could compound tissue damage and after Covid it could exploit immune dysfunction.
Researchers suggested antibiotics and antivirals could be repurposed to target underlying infections, but they admit although the associations they discuss are biologically plausible, they are still speculative. No one has established a causal link between any co-infection and long Covid.
“Everyone has heard it a million times, but it bears repeating: Correlation doesn’t equal causation,” Dr Gennaro said.
She said proving the hypothesis would require large epidemiological studies and animal experiments, which is complicated by the absence of good animal models for long Covid.
The authors suggest that effective treatment may require looking beyond Covid itself.