Potential pathway to diagnose and treat Long COVID identified

By Sharin Hussain via SWNS

Long COVID may be linked to high levels of an inflammatory protein, according to a new study.

Cambridge University researchers have identified the protein called interferon gamma (IFN-γ) as a potential biomarker for Long COVID fatigue.

They say it could pave the way for the development of therapies and provide a head start in the event of a future coronavirus pandemic.

Study co-author Dr. Benjamin Krishna said: “We have found a potential mechanism underlying Long COVID which could represent a biomarker, that is, a tell-tale signature of the condition.

“We hope that this could help to pave the way to develop therapies and give some patients a firm diagnosis.”

SARS-CoV-2, linked to coronaviruses, triggers the production of the antiviral protein, IFN-γ, which is associated with fatigue, muscle ache and depression.

The new research shows that, in Long COVID patients, IFN-y production persists until symptoms improve, highlighting a potential biomarker and a target for treatments.

The study, published in the journal, Science Advances, followed a group of patients with Long COVID fatigue for over two years to understand why some recovered and others did not.

According to the Office for National Statistics (ONS), an estimated 1.9 million people in the UK, about 2.9 percent of the population, were experiencing self-reported Long COVID as of March 2023.

Long COVID continues to affect millions of people globally, putting a strain on health services.

The most common system is fatigue and patients are still waiting for an effective treatment.

For most people, when their infection clears, COVID-19 symptoms clear and production of this protein stops, but the researchers found that high levels of IFN-γ persisted in some Long COVID patients for up to 31 months post-infection.

The research began in 2020 when Dr. Nyarie Sithole set up a Long COVID clinic in Cambridge’s Addenbrooke’s Hospital, where he started collecting blood samples from patients and studying their immunology.

Dr. Sithole said: “When the clinic started, a lot of people didn't even believe Long COVID was real.

“We are indebted to all the patients who volunteered for this study, without whose support and participation we would obviously not have accomplished this study”.

The team studied 111 COVID-confirmed patients admitted to Addenbrooke’s Hospital, Royal Papworth Hospital and Cambridge and Peterborough NHS Foundation Trusts at 28 days, 90 days and 180 days following symptoms.

Between August 2020 and July 2021, they recruited 55 Long COVID patients, all experiencing severe symptoms at least five months after acute COVID-19.

The researchers analyzed blood samples for signs of cytokines, small proteins crucial to the functioning of immune system cells and blood cells.

They found that the white blood cells of individuals infected with SARS-CoV-2 produced IFN-γ, a proinflammatory molecule, and that this persisted in Long COVID patients.

Dr. Krishna said: “Interferon-gamma can be used to treat viral infections such as hepatitis C but it causes symptoms including fatigue, fever, headache, aching muscles and depression.

“These symptoms are all too familiar to Long COVID patients. For us, that was another smoking gun.”

By conducting ‘cell depletion assays’, the team managed to identify the precise cell types responsible for producing IFN-γ. They could pinpoint immune cells, CD8+ T, but they required contact with another immune cell type, CD14+ monocytes.

The 31-month follow-up period found that over 60% of patients experienced resolution of some, if not all, of their symptoms which coincided with a drop in IFN- γ.

Dr. Krishna added: “If SARS-CoV-2 continues to persist in people with Long COVID, triggering an IFN-γ response, then vaccination may be helping to clear this. But we still need to find effective therapies.”

He also said that the number of people with Long COVID is gradually falling, and the vaccination has significantly helped but what happens when the next coronavirus pandemic comes along so understanding what causes Long COVID now could give us a crucial head start.

The new findings also suggest that microclotting cannot be the only or the most significant cause.

The study argues that the presence of IFN-γ could be used to classify Long COVID into subtypes which could be used to personalize treatments.

Dr. Krishna added: “It’s unlikely that all the different Long COVID symptoms are caused by the same thing. We need to differentiate between people and tailor treatments.

“Some patients are slowly recovering and there are those who are stuck in a cycle of fatigue for years on end. We need to know why.”