New research finds immune inflammatory response not the cause of long COVID

Long Covid is not caused by an immune-inflammatory reaction to COVID-19, University of Bristol-led research finds. Emerging data demonstrate that immune activation may persist for months after COVID-19. To investigate this, the Bristol team collected and analyzed immune responses in blood samples from 63 patients hospitalized with mild, moderate or severe COVID-19 at the start of the pandemic and before vaccines were available.

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.

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.

Reference: Prolonged T-cell activation and long COVID symptoms independently associate with severe COVID-19 at 3 months, eLife, DOI 10.7554/eLife.85009