Researchers from Southampton have identified a blood profile that could help identify COVID-19 patients at greatest risk of worsening and direct them to studies of specific treatments that could alter their immune system responses.
“Prevention of a cytokine storm”
Cytokines are cell signaling molecules, many of which are associated with inflammation, that are released into the bloodstream after infection and that help direct protective immune responses.
In patients with severe COVID-19, the immune system can overreact, which leads to massively increased cytokine levels in the blood – a “cytokine storm”. Instead of helping the body fight the virus, this overreaction is extremely harmful to the cells and tissues of the body itself and can be fatal.
Identifying those who are more prone to this reaction and tackling hyperinflammation could be a key avenue to reducing the severity of COVID-19 and death.
“Identification of the most vulnerable patients”
The study, published in Respiratory researchanalyzed blood samples from 100 COVID-19 positive patients enrolled in the NHS Foundation Trust (UHS) at Southampton University Hospital between March 20 and April 29, 2020 in the first phase of the pandemic.
They found that high levels of the cytokines IL-6, IL-8, TNF, IL-1β, and IL-33 in patients’ blood upon admission were associated with a higher likelihood of needing intensive care, artificial ventilation, and death. IL-1β and IL-33 showed the greatest effect.
This study was part of the CoV-19POC study – one of Dr. Clark-led study examining the clinical impact of point-of-care molecular testing in patients at UHS with suspected COVID-19, including tests that dramatically reduced the time to diagnose COVID-19.
Combining this cytokine test with a clinical assessment of the patient’s condition could help doctors identify and treat those who are at greatest risk of getting worse.
Dr. Anna Freeman and Dr. Hannah Burke, Fellows Clinical Research Fellows and joint first authors, commented, “This project was a great opportunity for collaboration within the medical school, leveraging resources from both the respiratory and infectious diseases teams.
“As early stage researchers, this study provided us with a valuable opportunity to learn how we can make academic impacts on the evolving COVID-19 pandemic.”
“Investigation of new treatments”
So far, two treatments have been found for those hospitalized with COVID-19, with the steroid dexamethasone shown to reduce deaths in patients requiring oxygen by up to a third. The mechanism by which dexamethasone is protective is not known, but as a non-specific anti-inflammatory agent, it suggests the potential benefit of controlling the inflammatory immune response.
The Southampton team hopes that by accurately identifying the cytokines that cause hyperinflammation in every COVID-19 patient, doctors can target them (e.g., with an IL-33 blocker current in UK studies), which is the greatest Bringing benefits to individual patients – an approach known as “precision medicine”.
Professor Tom Wilkinson said, “These results from the ongoing COVID research program in Southampton have identified key inflammatory signals that will help guide the development of treatment strategies for this new disease.
“It is becoming more and more obvious that COVID is very heterogeneous. Only by using these techniques to stratify the condition can we target the most important disease mechanisms with the best treatment for that person. ”
Dr. Tristan Clark said, “Our results suggest that on-site testing for COVID-19 and cytokines is possible and will, in the future, identify infected patients and the most appropriate treatment for them in near real time.”
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