Patients with severe Covid-19 show increased levels of a key protein in their blood, which researchers believe may help identify those most at risk.

In an analysis of more than 500 coronavirus patients across the UK, scientists identified several inflammatory markers in blood that increased within the early stages of Covid-19 in those who went on to become critically ill.

One marker in particular, a cytokine called GM-CSF, was found at higher levels in those who later progressed to severe disease, compared to healthy controls or those with flu.

It was found to be almost 10 times higher in those who died from Covid-19.

Increased GM-CSF could help to identify those at risk of developing severe Covid-19 and provide a target for new treatments which could modify their course of disease, according to the team led by Imperial College London, University of Edinburgh and University of Liverpool.

Dr Ryan Thwaites, from the National Heart and Lung Institute at Imperial, said: “People may be familiar with the term ‘cytokine storm’, in which patients hospitalised with Covid-19 have increased levels of inflammatory proteins in their body linked with severe outcomes and death.

“Our new study shows that there are many inflammatory markers raised in Covid-19, but that these are more in the range of a ‘response’ than a ‘storm’.

“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 allows us to identify patients at increased risk of becoming very ill and may benefit most from receiving targeted treatments aimed at GM-CSF.”

Researchers analysed blood samples taken from 471 patients admitted to hospital with the disease across England, recruited through the ISARIC4C study.

They also analysed blood from 39 outpatients with mild Covid as well as stored samples taken from 20 patients with fatal H1N1 influenza, isolated during the 2009/10 swine flu outbreak.

The team further looked at samples from 36 healthy volunteers without respiratory disease as a control.

Analysing the samples for 33 known inflammatory markers showed increased levels of clusters of inflammatory proteins common to respiratory diseases.

This included a cytokine called IL-6, which was found to be elevated in both mild and severe Covid-19 as well as influenza.

According to the study published in Science Immunology, several markers were elevated in Covid-19 groups, including those known to be 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.

GM-CSF levels increased in relation to severity of the disease and were elevated early on in patients that would progress to severe disease – typically within four days of symptoms emerging, researchers found.

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

Peter Openshaw, professor of experimental medicine at Imperial College London and senior author on the paper, said: “These insights into the molecular drivers of disease are crucial in improving our understanding and clinical management of Covid-19.

“Through world-leading collaborative clinical investigations such as ISARIC4C, we hope to inform the worldwide community of clinicians and investigators about where to look and what to target.

“This work is the culmination of more than a decade of research from UK collaborators, starting during the outbreak of H1N1 influenza in 2009 and carrying through to the current Covid-19 pandemic.

“It proves beyond all else the power and effect of collaborative working.”

The study by the the UK’s International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), supported by the UK Coronavirus Immunology Consortium (UK-CIC), was funded by the NIHR and UKRI MRC.