Long COVID Symptoms Linked To High Levels Of Inflammatory Protein

A new study has identified a protein that, when it persists, appears to be linked to the symptoms of long COVID. As a result, it could represent an easier way to diagnose the condition and potentially even a new avenue for treatment.

Researchers first recruited 55 patients with long COVID, all of whom were experiencing severe symptoms at least 5 months after having had COVID-19. The patients provided blood samples, which were then analyzed for their levels of cytokines, a group of small proteins involved in the proper functioning of immune and blood cells.

The analysis revealed that the initial infection with SARS-CoV-2, the virus that causes COVID-19, triggered the production of a cytokine called interferon gamma (IFN-γ). This is a normal response from the immune system; IFN-γ triggers inflammation, which can be a sign that the immune system is fighting an infection. Under normal circumstances, IFN-γ production should stop once the infection has cleared.

In patients with long COVID, however, high levels of IFN-γ continued to be produced – for some, even up to 31 months after their initial infection. Since IFN-γ is pro-inflammatory, its persistence may be behind some of the most common symptoms of long COVID, as study co-author Dr Benjamin Krishna explained in a statement.

“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.”

Another key finding that reinforced their conclusion was that, for the over 60 percent of patients who experienced either partial, or complete resolution of their symptoms, their IFN-γ levels also dropped. Whilst this is an interesting sign, the authors caution that it’s still not clear what caused the symptoms to disappear. 

They also state that it’s not clear whether IFN-γ is a mediator of the symptoms seen in long COVID, or if it is a biomarker of them – a biological indicator of a condition. Either way, the results suggest it warrants further investigation.

Long COVID is estimated to affect at least 65 million people across the globe and continuing research could identify the best way to help this group. The authors argue that there are potentially many different causes of long COVID; identifying these through research and finding a way to use them to spot the condition could help to personalize diagnosis and treatment.

“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,” said Krishna.

“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.”

The study is published in Science Advances.

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