News Medical – 24th February 2024
Some interesting and potentially important new research from the University of Cambridge which is also relevant to ME/CFS.
This research has found that Covid 19 produces an immune system chemical called interferon gamma – which can then remain elevated and persist in people with Long Covid. We already know that when interferon gamma is used as a treatment for hepatitis C infection it can produce fatigue, muscle pains and headaches.
So persistently elevated levels following an infection could well be playing a role in causing debilitating fatigue in Long Covid, and possibly in ME/CFS as well.
Raised levels of similar immune system chemicals (known as cytokines) have also been reported in ME/CFS causing what is known as low level immune system activation.
These findings also raise the possibility of using drugs which dampen down the immune system and cytokine production to treat Long Covid and ME/CFS….
SARS-CoV-2 triggers the production of the antiviral protein IFN-γ, which is associated with fatigue, muscle ache and depression. New research shows that in Long COVID patients, IFN-y production persists until symptoms improve, highlighting a potential biomarker and a target for therapies.
Dr Charles Shepherd, Hon Medical Adviser MEA
Article Extracts
SARS-CoV-2 triggers the production of the antiviral protein IFN-γ, which is associated with fatigue, muscle ache and depression. New research shows that in Long COVID patients, IFN-y production persists until symptoms improve, highlighting a potential biomarker and a target for therapies.
The study shows that initial infection with SARS-CoV-2 triggers production of the antiviral protein IFN-γ, which is a normal reaction from the immune system. For most people, when their infection clears, COVID-19 symptoms cease 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.
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.”
Dr Benjamin Krishna, Co-author, Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID).
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 set about studying their immunology. Sithole soon enlisted the support of Dr Benjamin Krishna and Dr Mark Wills from the University of Cambridge’s Dept. of Medicine.
The team studied 111 COVID-confirmed patients admitted to Addenbrooke’s Hospital CUH, Royal Papworth Hospital and Cambridge and Peterborough NHS Foundation Trusts at 28 days, 90 days and 180 days following symptom onset. Between August 2020 and July 2021, they recruited 55 Long COVID patients – all experiencing severe symptoms at least 5 months after acute COVID-19 – attending the Long COVID clinic at Addenbrooke’s.
The researchers analysed 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 pro inflammatory 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 pinpointed immune cells known as CD8+ T cells but found that they required contact with another immune cell type: CD14+ monocytes.
The Cambridge team followed its Long COVID cohort for up to 31 months post-infection. During this follow up period, over 60% of patients experienced resolution of some, if not all, of their symptoms which coincided with a drop in IFN- γ.
Vaccination helping Long COVID patients
The team measured IFN-γ release in Long COVID patients before and after vaccination and found a significant decrease in IFN-γ post vaccination in patients whose symptoms resolved.
Dr Krishna said.
“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,”
“The number of people with Long COVID is gradually falling, and vaccination seems to be playing a significant role in that. But new cases are still cropping up, and then there is the big question of what happens when the next coronavirus pandemic comes along. We could face another wave of Long COVID. Understanding what causes Long COVID now could give us a crucial head start.”