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Is this why some people get sicker than others with Covid-19?

 

Why are some people affected more severely by infections, including Covid? It’s a question that’s perplexed scientists but now they think they know part of the answer at least: autoantibodies.

Not only might they help explain our vulnerability to infection, but also to conditions such as rheumatoid arthritis and diabetes, ageing and even long Covid.

‘Proteins that attack us from within’ sounds more like a description for a new sci-fi film than a very real threat to humankind. But autoantibodies — also known as ‘rogue’ antibodies — are just that.

They are immune cells that turn against us, instead of defending our bodies against infection, they attack our healthy tissues and vital organs.

This process is responsible for a long list of autoimmune diseases such as rheumatoid arthritis. 

In each case the immune system misfires, mistaking a part of the body as foreign, and releases autoantibodies to go ‘on the attack’ — in the case of rheumatoid arthritis, it results in joint inflammation.

Why are some people affected more severely by infections, including Covid? It’s a question that’s perplexed scientists but now they think they know part of the answer at least: autoantibodies. A stock image is used above [File photo] Why are some people affected more severely by infections, including Covid? It’s a question that’s perplexed scientists but now they think they know part of the answer at least: autoantibodies. A stock image is used above [File photo]

Why are some people affected more severely by infections, including Covid? It’s a question that’s perplexed scientists but now they think they know part of the answer at least: autoantibodies. A stock image is used above [File photo]

People with healthy immune systems also produce auto-antibodies. Up until about 20 years ago, it was thought they simply eliminate them but scientists have since discovered that autoantibodies hang around in low numbers in some people.

But as we age, their number increases (it’s thought they have some role in the ageing process).

Today, immunologists are particularly interested in the role that autoantibodies might play in Covid-19 and long Covid.

Working as part of an international project, Dr Jean-Laurent Casanova, an expert in human genetics and infectious diseases, and his team at Rockefeller University in the U.S. have been investigating the factors that increase the risk of getting severe Covid-19.

They found that patients hospitalised with it have a much higher level of autoantibodies than unaffected patients, and estimate that autoantibodies could account for around a fifth of all Covid-19 deaths.

They found that autoantibodies exacerbated infection by blocking the activity of molecules that help fight viral infections.

They also believe that low levels of autoantibodies could help explain why some people suffer no — or mild — symptoms of Covid.

Other recent studies have identified a range of autoantibodies in the blood of patients with severe Covid-19 that cause harm in different ways, for example, by attacking proteins that help control blood clotting.

This process is responsible for a long list of autoimmune diseases such as rheumatoid arthritis. In each case the immune system misfires, mistaking a part of the body as foreign, and releases autoantibodies to go ‘on the attack’ — in the case of rheumatoid arthritis, it results in joint inflammation This process is responsible for a long list of autoimmune diseases such as rheumatoid arthritis. In each case the immune system misfires, mistaking a part of the body as foreign, and releases autoantibodies to go ‘on the attack’ — in the case of rheumatoid arthritis, it results in joint inflammation

This process is responsible for a long list of autoimmune diseases such as rheumatoid arthritis. In each case the immune system misfires, mistaking a part of the body as foreign, and releases autoantibodies to go ‘on the attack’ — in the case of rheumatoid arthritis, it results in joint inflammation

And since autoantibodies can be detected in blood tests, screening could help identify people with high levels who, therefore, may need preventive treatment — or spot the infected people who need early aggressive treatment.

Professor Adrian Liston, a senior group leader at the Babraham Institute in the UK, leads a programme of work seeking to understand the changes occurring in the immune systems of patients with Covid-19.

He says while it is too early to say whether autoantibodies play a role in acute disease or long Covid, their presence requires attention.

‘It is certainly a very plausible pathway because we have evidence that autoantibodies can stick around for years or decades, unlike the virus, so it provides a good explanation for why long Covid symptoms persist after the virus is gone,’ he says.

But another possible explanation is that the virus ‘could initiate an inflammatory circuit, where inflammation breeds inflammation, which breeds more inflammation, even after the virus has gone — and we just don’t have enough research to say for sure’.

But it’s hoped that such research will pave the way for innovations in diagnostics and treatments. Professor Liston predicts there will be a diagnostic tool for long Covid based on autoantibodies within the next six months and possibly a treatment based on autoantibodies for long Covid after that.

While Covid has no doubt triggered more interest in autoantibodies, they were already the subject of intense research prior to the pandemic, partly because of concerns about the worrying rise in autoimmune diseases.

There are four million people in the UK known to be living with at least one autoimmune condition but, according to Dr Louisa James, a senior lecturer in immunology at Queen Mary University of London, the prevalence is set to rise, partly because there are ‘probably more syndromes and conditions out there where our immune system is playing a role that was previously unrecognised’.

For example, a recent study found that fibromyalgia, which causes widespread pain, may be an autoimmune condition caused by antibodies that affect sensitivity to pain, she says.

Paul Morgan, a professor of immunology at Cardiff University, is excited about what the future of autoantibody research could yield and says applying knowledge from the study of autoimmune disease could help bring new treatments for Covid-19 and long Covid.

If autoantibodies are indeed responsible for many of the symptoms of long Covid, ‘then you could use the sorts of approaches developed for autoimmune diseases — drugs that reduce the levels of harmful antibodies — to treat long Covid.

‘That’s why it’s important, it might give us a way of actually treating the disease — by targeting autoantibodies.’

 

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