Immune response against "bystander" virus, not SARS-CoV-2, may cause long Covid: Study

Immune inflammatory reaction not against COVID-19, but against a common, harmless, dormant "bystander" virus present in the body, driving a cytokine storm, may be behind long Covid, a new research has found.

Analysing Covid-patients' blood samples, researchers found that 3 months after being hospitalised for severe infection, there was no rapid increase in the immune cells targeting SARS-CoV-2, but an increase in those targeting the dormant Cytomegalovirus (CMV). CMV is usually harmless but can stay in your body for life once infected with it.

The finding indicated that the prolonged inflammation at 3 months in severe patients may not be driven by SARS-CoV-2 but instead may be "bystander driven".

"Long Covid occurs in one out of ten COVID-19 cases, but we still don't understand what causes it.

"Several theories proposed include whether it might be triggered by an inflammatory immune response towards the virus that is still persisting in our body, sending our immune system into overdrive or the reactivation of latent viruses such as human cytomegalovirus (CMV) and Epstein Barr virus (EBV)," said Laura Rivino, senior lecturer at the University of Bristol, UK, and the study's lead author.

The researchers analysed blood samples of 63 patients hospitalised for mild, moderate or severe COVID-19 infection at the start of the pandemic when vaccines were not available.

The study also found patients with severe COVID-19 to display a higher number of long Covid symptoms compared to mild and moderate patients, even as the team's analysis revealed no direct association between long Covid symptoms and Covid-related immune inflammatory responses.

Further, 79 per cent of all the patients reported at least one ongoing long Covid symptom with breathlessness and excessive fatigue being the most common, the study published in the journal eLife said.

The significant dysfunction found in the immune profiles of severe patients at 3 months indicated that inflammation may persist even for months post-recovery, even though results showed the inflammation in these patients to resolve over time.

At 12 months, the researchers found, both the immune profiles and inflammatory levels of patients with severe disease were similar to those of mild and moderate patients.

"Our findings suggest that prolonged immune activation and long Covid may correlate independently with severe COVID-19.

"Larger studies should be conducted looking at both a larger number of patients, including if possible vaccinated and non-vaccinated COVID-19 patients, and measuring a larger range of markers and cytokines.

"Understanding whether inflammation and immune activation associate with long Covid would allow us to understand whether targeting these factors may be a useful therapy for this debilitating condition," said Rivino.