The first trial with a drug to treat long-lasting Covid-19 sequelae

The first trial with a drug that targets fatigue and muscle weakness in people with persistent Covid-19 sequelae, or "Long Covid", is underway in the UK.

This is also the first trial in patients with prolonged Covid-19 sequelae (also known as 'Long Covid') who did not need to be hospitalized when infected, according to the Guardian.

May pave the way for many other important tests

The drug, called AXA1125, targets cellular energy machinery known as mitochondria, which is thought to cause dysfunction in a group of 'Long Covid' patients experiencing severe fatigue.

If successful, it could pave the way for similar trials in patients with other forms of post-viral fatigue, including myositis/chronic fatigue syndrome (ME/CFS).

Long Covid is becoming a matter of increasing global concern. (Graphic: South China Morning Post).

Mitochondria help regulate various cellular processes and play an important role in converting chemical energy from the human diet into adenosine triphosphate (ATP) - the energy that cells depend on to fuel their growth. promote essential reactions.

The source of ATP depletes quickly, so cells must constantly regenerate. That can be done through a process known as glycolysis, which produces lactic acid as a by-product. But ATP is produced more efficiently through oxidative phosphorylation, which involves mitochondria.

Evidence suggests that SARS-CoV-2 can hijack cellular mitochondria, promoting viral replication but disrupting ATP production.

'It's essentially a fuel switch. The virus gets into the mitochondria and tries to move it in the direction of glycolysis to make more virus particles, but it damages the cell ," said Bill Hinshaw, president and chief executive officer of Axcella, the company that developed the virus. develop new drugs, said.

Can be of great help to people experiencing "Long Covid"

An estimated 56% of Covid-19 patients with long-term sequelae experience fatigue, and many also have difficulty exercising.

Dr Betty Raman at the University of Oxford, who is studying the impact of Covid-19 on organ health, said: 'Initially, we thought these symptoms were related to organ inflammation. But after six months of follow-up, we found that even though their hearts and lungs had recovered, these patients were still unable to exercise."

Further investigation revealed that such patients were accumulating lactic acid in their muscles at a faster rate than healthy subjects - a potential marker of mitochondrial dysfunction. 'In a normal, healthy person, mitochondria will be very active in replenishing ATP to maintain energy , ' Dr Raman said.

"Long Covid" affects the quality of life of people with Covid-19 even after they have recovered from the disease. (Photo: New York Times).

AXA1125 is designed to normalize mitochondrial metabolism in diseases that may cause mitochondrial imbalance. So far, the drug has been tested in people with non-alcoholic fatty liver disease, with some promising results.

Raman is launching a study of 40 patients experiencing severe fatigue after recovering from Covid-19 to see if it is possible to improve their exercise tolerance and reduce fatigue. metabolism of mitochondria in their muscle tissue or not.

Half of the study participants will receive AXA1125 for 28 days, and the other half a placebo. Results are expected in mid-2022.

'I don't think this drug alone is the solution for all because 'Long Covid' is a complex disease, but if it works it will bring significant benefits to the patient, ' Mr Raman said.

Professor Amitava Banerjee, of University College London, who is leading a separate trial of the diagnosis and treatment of prolonged Covid-19 sequelae, said: 'It's really good to test different drugs and different mechanisms. different regime. Fatigue mitochondrial dysfunction is an issue that has been analyzed and studied for some time, but we do not know how common it is in this patient population or how it correlates with severity of their symptoms".

He is awaiting approval to begin testing "alternative" drugs such as antihistamines and aspirin in 'Long Covid' patients who are not hospitalized. Meanwhile, a trial to identify treatments that enhance recovery after Covid-19 patients is discharged from the hospital has been conducted.

According to Dr Charles Shepherd, medical advisor at the nonprofit ME Association, if AXA1125 helps reduce fatigue in 'Long Covid' cases , it could also have an important impact on people with ME/CFS .

'We now have substantial research evidence indicating that there is mitochondrial dysfunction in patients with ME/CFS and its impact on muscle energy metabolism appears to be a significant contributing factor in activities that cause fatigue'.

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