Protein linked to severe Covid-19

Patients with severe Covid-19 have been found to show increased levels of a key protein in their blood, in a development that could help identify those most at risk.

Levels of the protein were nearly 10 times higher in those who died from Covid-19 than in healthy individuals, the study has found.

Increased protein levels could help to identify patients at risk in early stages of disease and provide a target for new treatments, researchers say.

Large study

Researchers, led by Imperial College London and the Universities of Edinburgh and Liverpool, analysed blood from more than 500 Covid-19 patients across the UK.

The study included blood from people who developed different severities of Covid-19, as well as previously stored samples from patients who developed fatal swine flu in the 2009-10 outbreak and blood from healthy volunteers.

A protein, called GM-CSF, was found at higher levels in those who later progressed to severe Covid-19, typically within four days of symptoms emerging, compared to healthy participants or those who had experienced flu, the study showed.

The work builds on more than a decade of collaborative research involving the ISARIC global research consortium, the ISARIC4C network of UK institutions and more than 200 hospitals collecting data from Covid-19 patients.

Causes of inflammation

Several indicators of inflammation increased within the early stages of Covid-19 in those who went on to become critically ill, scientists found.

Increased levels of clusters of inflammatory proteins common to respiratory diseases were found, including a protein called IL-6, which was found to be elevated in both mild and severe Covid-19 as well as flu.

Substances found at levels higher than normal in Covid-19 patients included those linked to general inflammation, inflammation of the lining of blood vessels, and increased blood clotting. This suggests they may be driving the underlying processes seen in severe disease.

The researchers caution that GM-CSF is not the only important driver of severe disease, its presence alone in blood does not increase risk for patients, and further research would be needed to determine its use as a prognostic tool.

Several therapies which target GM-CSF are currently in clinical trials, though these are not currently approved for use in the treatment of Covid-19.

The research is published in Science Immunology and was funded by the National Institute for Health Research and the Medical Research Centre, part of UKRI.

We identified one inflammatory marker in particular, a cytokine called GM-CSF, which appears to specifically mark out severe Covid-19 and may play a role in driving severe disease. In future studies, we need to determine whether elevated levels of this protein in the blood at an early stage allow us to identify patients at increased risk of becoming very ill and may benefit most from receiving targeted treatments aimed at GM-CSF.

Dr Ryan Thwaites

This is another step forward in understanding this new disease. By studying patients with severe Covid-19 at large scale across the UK, we're building a clearer picture of lung disease in Covid-19. The lungs are being damaged by the patient's own immune system, rather than directly being damaged by the virus, and we can see specific signals in the immune system that might be responsible. Of course, clinical trials are needed before any change to the way patients are treated.

Dr Kenneth Baillie

ISARIC’s planning for an outbreak just like this has enabled timely discoveries that are informing case management and driving therapeutic developments.

Professor Calum Semple

** The Roslin Institute receives strategic investment funding from the Biotechnology and Biological Sciences Research Council and it is part of the University of Edinburgh’s Royal (Dick) School of Veterinary Studies. **

Related links

Scientific publication

Roslin Covid-19 research