A study into the long-term health impacts of coronavirus has found it leaves tell-tale traces in your blood. In a study led by experts from the University of Leicester, researchers and clinicians from across the UK analysed the impact of covid-19 had on patients’ physical health, mental health and their recovery.
The study’s latest findings show that long-covid leads to ongoing inflammation, which can be detected in blood. Clinical Professor in Respiratory Medicine at the University of Leicester, Chris Brightling, said: “This study is a real step-forward in our understanding of long-covid.
"Finding different patterns of inflammation in people with long-covid that are suffering with different constellations of symptoms tells us we are getting closer to discovering the drivers of long-covid that will respond to targeted therapy."
University of Leicester Professor of Respiratory Research, Louise Wain, added: “This study was only possible thanks to the participants who took part and provided valuable biological samples that enable us to uncover the molecular changes in the blood and look at how they might relate to recovery from covid-19.”
In an analysis of more than 650 people who had been hospitalised with severe covid-19, patients with prolonged symptoms showed evidence of immune system activation. The exact pattern of this activation varied depending on the sort of symptoms that they predominantly had – for example, mainly fatigue or cognitive impairment.
The research suggests that existing drugs that modulate the body’s immune system could be helpful in treating long-covid and should be investigated in future clinical trials.
Professor Peter Openshaw, from Imperial’s National Heart and Lung Institute, added: “With one in ten SARS-CoV-2 infections leading to long-covid and an estimated 65 million people around the world suffering from ongoing symptoms, we urgently need more research to understand this condition. At the moment, it’s very hard to diagnose and treat.
“This study, which includes detailed clinical data on symptoms and a raft of inflammatory blood plasma markers, is an important step forward and provides crucial insights into what causes long-covid.”
Runaway inflammation
In the latest study, researchers included a total of 426 people who were experiencing symptoms consistent with long-covid - having been admitted to hospital with covid-19 infection at least six months prior to the study. They were compared with 233 people who were also hospitalised for covid-19, but who had fully recovered.
The researchers took samples of blood plasma. They also measured a total of 368 proteins known to be involved in inflammation and immune system modulation.
They found that, relative to patients who had fully recovered, those with long-covid showed a pattern of immune system activation. This activation indicated inflammation of myeloid cells and activation of a family of immune system proteins called the complement system.
Myeloid cells are formed in the bone marrow and produce various types of white blood cells that circulate in the blood and migrate into organs and tissues where they respond to damage and infection. The complement system consists of a cascade of linked proteins that are activated in response to infection or tissue damage.
Overactivation is known to be associated with many autoimmune and inflammatory conditions. Dr Felicity Liew, from Imperial’s National Heart and Lung Institute, commented: “Our findings indicate that complement activation and myeloid inflammation could be a common feature of long-covid after hospitalisation, regardless of symptom type.
“It is unusual to find evidence of ongoing complement activation several months after acute infection has resolved, suggesting that long-covid symptoms are a result of active inflammation. However, we can’t be sure that this is applicable to all types of long-covid, especially if symptoms occur after non-hospitalised infection.”
Subtypes of long-covid
The researchers were also able to obtain information about the range of symptoms patients were experiencing. They were also able to find which ones were most common.
They found that certain groups of symptoms appeared to be associated with specific proteins. For example, people with gastrointestinal symptoms had increased levels of a marker called SCG3, which has previously been linked to impaired communication between the gut and the brain.
Overall, there were five overlapping subtypes of long-covid with different immune signatures. Despite some commonalities, these included
- fatigue,
- cognitive impairment,
- anxiety and depression,
- cardiorespiratory
- and gastrointestinal.
The researchers stress, however, that these groups are not mutually exclusive. People can fall between groups depending on their symptoms.
But, the researchers do suggest this study could be useful in designing clinical trials, especially for treatments that target immune responses and inflammation.
Professor Openshaw concludes: “This work provides strong evidence that long-covid is caused by post-viral inflammation but shows layers of complexity. We hope that our work opens the way to the development of specific tests and treatments for the various types of long-covid and believe that a ‘one size fits all’ approach to treatment may not work.
“Covid-19 will continue to have far reaching effects long after the initial infection has passed, impacting many lives. Understanding what’s happening in the body, and how the immune system responds, is key to helping those affected.”
