Long COVID, which affects millions of people worldwide, is not caused by an immune-inflammatory reaction to COVID-19, according to research.

Studies show that around 10-20 per cent of people infected by SARS-CoV-2 may go on to develop symptoms that can be diagnosed as long COVID.

In the study, published in the journal eLife, researchers found there was no rapid increase in immune cells targeting SARS-CoV-2 at three months. 

But T-cells targeting the persistent and dormant Cytomegalovirus (CMV) -- a common virus that is usually harmless but can stay in your body for life once infected with it -- did show an increase at low levels. 

This indicates that the prolonged T-cell activation observed at three months in severe patients may not be driven by SARS-CoV-2 but instead may be "bystander driven” that is, driven by cytokines.

"Our findings suggest that prolonged immune activation and long COVID may correlate independently with severe COVID-19," said lead author Dr Laura Rivino, Senior Lecturer at the University of Bristol’s School of Cellular and Molecular Medicine.

"Larger studies should be conducted looking at both a larger number of patients, including if possible vaccinated and unvaccinated COVID-19 patients, and measuring a larger range of markers and cytokines. Understanding whether inflammation and immune activation are associated with long COVID would allow us to understand whether targeting these factors may be a useful therapy for this debilitating condition,” Dr Rivino said.

To find out whether persistent immune activation and ongoing inflammation response could be the underlying cause of long COVID, the team collected and analysed immune responses in blood samples from 63 patients hospitalised with mild, moderate or severe COVID at the start of the pandemic and before vaccines were available. 

The team then tested patients’ immune responses at three months and again at eight and 12 months post-hospital admission. 

Of these patients, 79 per cent (82 per cent, 75 per cent, and 86 per cent of mild, moderate, and severe patients, respectively) reported at least one ongoing symptom with breathlessness and excessive fatigue being the most common.

The team found patients’ immune responses at three months with severe symptoms displayed significant dysfunction in their T-cell profiles indicating that inflammation may persist for months even after they have recovered from the virus. 

Reassuringly, results showed that even in severe cases inflammation in these patients resolved in time. At 12 months, both the immune profiles and inflammatory levels of patients with severe disease were similar to those of mild and moderate patients.

Patients with severe COVID were found to display a higher number of long COVID symptoms compared to mild and moderate patients. 

However, further analysis by the team revealed no direct association between long COVID symptoms and immune-inflammatory responses, for the markers that were measured, in any of the patients after adjusting for age, sex and disease severity.