Identification of antiviral protein IFN-γ as a potential biomarker for Long COVID

SARS-CoV-2 causes the production of the antiviral protein IFN-γ, which is associated with fatigue, muscle pain, and depression. A new study shows that IFN-γ production persists in Long COVID patients until symptoms improve, highlighting potential biomarkers and therapeutic targets.

A University of Cambridge-led study identifies the protein interferon gamma (IFN-γ) as a potential biomarker of long-term coronavirus fatigue, highlighting the immunological mechanisms underlying the disease. . This could pave the way for the development of much-needed treatments and give us a head start in case future coronavirus pandemics occur.

This research today scientific progress, Researchers followed a group of patients suffering from long-term coronavirus fatigue for more than two and a half years to understand why some people recover and others don't.

COVID-19 continues to affect millions of people around the world for an extended period of time, placing a huge strain on health services. According to the ONS, as of March 2023, an estimated 1.9 million people (2.9% of the population) in the UK alone had experienced self-reported long-term coronavirus. Fatigue remains the most common and debilitating symptom, and patients are still waiting for effective treatments.

This study shows that initial infection with SARS-CoV-2 triggers the production of the antiviral protein IFN-γ, which is a normal response of the immune system. For most people, symptoms of COVID-19 stop and production of this protein stops once the infection subsides, but researchers found that some patients with long coronavirus have high levels of IFN-γ. We have found that it lasts up to 31 months.

We have discovered potential mechanisms underlying the long coronavirus that may represent biomarkers, or telltale signs of symptoms. We hope this will pave the way for the development of treatments and help provide a definitive diagnosis for some patients.”

Dr. Benjamin Krishna, co-author from the Cambridge Institute for Therapeutic Immunology and Infectious Diseases (CITIID);

The research began in 2020 when Dr Nyary Sithole set up the Long Corona Clinic at Addenbrookes Hospital in Cambridge, where she collected blood samples from patients and embarked on immunology research. Mr. Shihor immediately enlisted the help of Dr. Benjamin Krishna and Dr. Mark Wills of the University of Cambridge Medical School.

“When the clinic started, many people didn't even believe Long Coronavirus was real,” Dr. Shihor said. “We are grateful to all the patients who volunteered for this study. Without their support and participation, this study clearly would not have been possible.”

The research team looked at 111 confirmed coronavirus patients admitted to Addenbrookes Hospital CUH, Royal Papworth Hospital, Cambridge and Peterborough NHS Foundation Trust 28, 90 and 180 days after the onset of symptoms. Between August 2020 and July 2021, they recruited 55 Long coronavirus patients attending Addenbrookes' Long Coronavirus Clinic. All had experienced severe symptoms at least five months after acute COVID-19 infection.

The researchers analyzed blood samples for signs of cytokines, small proteins important in the function of immune system cells and blood cells. Researchers found that the white blood cells of people infected with SARS-CoV-2 produced the pro-inflammatory molecule IFN-γ, which persisted in Long COVID patients.

Dr. Krishna says, “Interferon gamma can be used to treat viral infections such as hepatitis C, but it causes symptoms such as fatigue, fever, headache, muscle pain, and depression. It's familiar to virus patients. For us, it was also a decisive weapon.”

By conducting a 'cell depletion assay', the research team was able to identify the exact cell types involved in IFN-γ production.They pinpointed an immune cell known as CD8+ T cells However, they were found to require contact with another immune cell type, CD14+ monocytes.

Previous studies have used different approaches and cohorts to characterize IFN-γ, but this study's focus on fatigue revealed a stronger effect . Previous studies also noticed that IFN-γ levels were rising, but patients were not followed long enough to see when they dropped.

The Cambridge team followed a coronavirus cohort for up to 31 months after infection. During this follow-up period, more than 60% of patients experienced resolution of some, if not all, of their symptoms concomitant with a decline in IFN-γ.

Supporting long-term coronavirus patients with vaccinations

The research team measured IFN-γ release in Long COVID patients before and after vaccination and found that IFN-γ was significantly reduced after vaccination in patients whose symptoms resolved.

“If SARS-CoV-2 continues to persist in Long COVID patients and triggers an IFN-γ response, vaccination may help resolve this. However, we still need to find effective treatments.” said Dr. Krishna.

“The number of long-corona patients is gradually decreasing, and vaccination seems to play an important role in this. But new cases are still occurring, and the big question is what will happen when the next coronavirus pandemic arrives. We may face another prolonged wave of coronavirus. Understanding the causes of the long coronavirus now could give us a huge head start.”

microcoagulation

Several well-known previous studies have proposed that microcoagulation is the main cause of long coronavirus.

Although not excluding a role, these new findings suggest that microcoagulation is not the only or most significant cause.

Classification of long-lasting new coronaviruses

This study claims that the presence of IFN-γ could be used to classify Long COVID into subtypes, which could be used to personalize treatment.

“It is unlikely that the various symptoms of long coronavirus are all caused by the same cause. We need to differentiate between people and customize treatments. Some patients recover slowly, while others remain in a cycle of fatigue for years. I need to know the reason,” said Dr. Krishna.