Key inflammatory markers identified in COVID-19
A new study involving the University of Liverpool has identified new biomarkers of inflammation that both indicate the severity of COVID-19 and distinguish it from severe influenza.
Led by the united kingdom's International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) and supported by the UK Coronavirus Immunology Consortium (UK-CIC), the study is that the largest of its kind so far
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Published in Science Immunology, the study identifies clusters of disease markers (including two called GM-CSF and IL-6) that scale with COVID-19 severity. IL-6 is already proven to be a target for therapies that reduce disease severity in severe COVID-19, but GM-CSF has potential as a replacement marker of severity that distinguishes COVID-19 from influenza, giving insights into the causes of severe disease and potentially offering a replacement focus for therapy.
It is important to know why some patients with COVID-19 experience severe disease, while others recover with less medical support. A 'cytokine storm," where uncontrolled levels of cytokines (proteins released by immune cells) cause excessive inflammation, has been identified as a driver of COVID-19 severity. Anti-inflammatory drugs like corticosteroids (e.g., dexamethasone) or people who interrupt cytokine function (e.g. tocilizumab) substantially reduce mortality in COVID-19 patients. However, studying the underlying inflammatory response in additional detail can help researchers to spot new therapies and target healthcare resources to the foremost at-risk individuals.
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Teams of researchers from across the united kingdom, including Imperial College London, University of Edinburgh, and therefore the University of Liverpool, combined their efforts to demonstrate that only select features of the cytokine response to COVID-19 distinguish the foremost severe sorts of the disease. Using the ISARIC4C platform, the researchers recruited 471 hospitalized COVID-19 patients (who were stratified by disease severity) alongside 39 outpatients with mild disease. They analyzed 33 disease markers within the plasma of those patients.
They found that a lot of inflammatory cytokines were elevated in severe COVID-19 which levels are generally indicative of disease severity. The investigators identified patterns within the info that are characteristic of the foremost severe cases of COVID-19; two cytokines, especially, IL-6 (interleukin 6) and GM-CSF (granulocyte-macrophage colony-stimulating factor) playing central roles. in comparison with archived samples from severe influenza patients, GM-CSF stood out as a selected marker for severe COVID-19. This cytokine also can be detected in early COVID infection, indicating it's going to play a pathologic role in early disease development in some patients.
While older patients showed a greater all-around inflammatory response, age wasn't a selected determinant of GM-CSF levels during this study. this means that a disease-specific mechanism that exacerbates age-dependent inflammatory responses is probably going to work in COVID-19. There was also no difference found between responses of men and ladies as has previously been reported in other smaller studies.
The findings from this study could impact patient care and treatment in two ways. First, the study has rationally identified GM-CSF as a key component of the inflammatory response and as a possible therapeutic target. Further research is additionally needed to ascertain if GM-CSF might be used as a marker in early disease to spot those in danger of happening to develop more severe symptoms.
Dr. Ryan Thwaites, author and Research Associate at Imperial College London, said: "Understanding the underlying mechanism of the immune reaction in patients who are very ill with COVID-19 is crucial to allowing us to spot potential therapeutic targets. The immune reaction is incredibly complex but by assessing levels of multiple markers and the way they relate to every other, we've been ready to increase our knowledge of the immune profile of severely ill COVID-19 patients."
Professor Calum Semple, ISARIC4C lead and Professor of kid Health and Outbreak Medicine at the University of Liverpool, said: "ISARIC's planning for an epidemic a bit like this has enabled timely discoveries that are informing case management and driving therapeutic developments. Also, deserving recognition is that the NIHR clinical staff in the least our NHS hospitals and therefore the university staff that support the outbreak laboratories in Glasgow and Liverpool who together collated the info and samples that enabled these discoveries."
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