Overactivation of the immune system leading to circulation of inflammatory proteins around the body contributes to the development of Long Covid, and could be targeted to provide treatments for patients.

Cardiff University research has uncovered biological markers that could be targeted by repurposing medication to treat Long Covid.

The research conducted extensive analysis of plasma samples obtained from a large cohort of healthy post-Covid individuals and non-hospitalised patients with Long Covid. They found that the complement system, a system that plays a crucial part of the immune system, consisting of a group of proteins that work together to enhance the function of antibodies and immune cells, was commonly overactivated in those with Long Covid.

Paul Morgan, Professor of complement biology, Division of Infection and Immunity, said “The covid-19 pandemic has left a global legacy of ill health, with long covid estimated to affect up to 1.9 million people in the UK. Long covid can last for months or years after the triggering infection and is associated with diverse symptoms including brain fog, chest pain, breathlessness, fatigue, and sensory problems. The causes of this disease remain largely unknown, emerging evidence suggests an important role for chronic inflammation.

“In this research, we show overactivation of the complement system in long covid. Complement system dysregulation is a common feature of acute and chronic inflammatory diseases and a major driver of inflammation. Therefore, we could use this information not only to further understanding of the causes of long covid, but also to develop effective treatments.”

Currently, there are no tests to diagnose long covid, but these findings suggest that biological markers for the complement system measured in blood samples could facilitate the formal diagnosis of Long Covid.

Effective treatments for long covid are also lacking, with current treatment approaches limited to symptom relief and rehabilitation. The researchers hope that their findings will underpin testing of targeted therapies to inhibit the complement system and restore health.

Dr Zelek, Cardiff University School of Medicine, said “Currently, we don’t have a single effective treatment or medication for long covid other than limited treatments that provide some symptomatic relief. Our research suggests that targeting overactivation of the complement system may provide an effective treatment for some individuals with long covid.

“This research is exciting because medicines that target the biomarkers we identified and decrease activity of the complement system are already used in clinical medicine to treat other diseases. So, by working with drug manufacturers to repurpose these medicines we may be able to provide effective treatments for long covid.”

The researchers hope that pilot drug trials to test the repurposed medications in long covid patients selected based on the blood markers they have identified can be initiated in the near future.

The research, Complement dysregulation is a prevalent and therapeutically amenable feature of long COVID, was led by Professor Paul Morgan, Professor David Price, Dr Helen Davies and Dr Wioleta Zelek, and published in Med, a flagship medical journal published by Cell Press.