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)." 

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-19 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. 

Importantly, 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" i.e. driven by cytokines. 

Read the full University of Bristol news item

Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months' by Marianna Santopaolo, Michaela Gregorova, Laura Rivino et al. in eLife [open access]