Can common infections trigger lifelong health conditions? It’s possible, new studies suggest

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In most people, norovirus causes a few painful days spent in the bathroom and then is quickly forgotten. The Epstein-Barr virus can pass without any indication. And many people are shaking off COVID-19.

But a growing body of research suggests that in some unfortunates the immune system overreacts to these seemingly minor insults, leaving years or even a lifetime of symptoms.

“The wrong genetics with the wrong infection at the wrong time,” explained Dr. Judith James, rheumatologist and vice president of clinical affairs at the Oklahoma Medical Research Foundation. “I think we have mounting evidence that it means people should have it on their radar.”

It has long been suspected that seemingly simple infections can leave a lasting imprint.

New research has found a probable connection between a norovirus attack, more commonly known as the stomach bug, and Crohn’s disease, a long-lasting inflammatory bowel condition.

Other recent studies have attributed an Epstein-Barr infection to subsequent multiple sclerosis.

And 10% to 30% of people who contract COVID-19 have symptoms that persist for months or years.

Usually, a trigger occurs when an insect or drug looks at the immune system as its own cells or tissues, said Dr. Raymond Chung, a liver specialist at Massachusetts General Hospital and Harvard Medical School. This mimicry stimulates a response, and thus the response perpetuates the problem.

Understanding how that cycle begins and then gets strengthened could lead to treatments, Chung said.

“If we could really catalog those passages, then I think we would be in a better position to think about breaking the waterfall,” he said. Carefully reducing the response will be key, she said, because broadly blocking the immune response “could lead to unwanted consequences.”

While people can’t avoid everyday pathogens, it’s important to identify the connections between them and the long-term consequences, Chung said.

“Knowledge is power,” he said. “It is really up to us to understand our predispositions to these kinds of exaggerated and aberrant responses, but it will take time.”

Short-term illness, long-term misery

For decades, researchers have believed that infections and insults could lead to long-term problems.

Chickenpox is known to reappear later in life as shingles, an extremely painful nerve disorder. The 1918 flu led some people to develop Parkinson’s disease. A human papillomavirus infection can lead to cancer years later. And it has long been thought that chronic fatigue syndrome must result from some kind of infection.

But solid scientific evidence has only accumulated in recent years, said Mark Davis, who directs the Stanford Institute for Immunity, Transplantation and Infection.

Mapping the human and mouse genomes helped researchers understand the role of immune system genes on a deeper level, he said.

Research on norovirus used a mouse with the same genetic mutation often linked to intestinal disease. When it became infected with norovirus, the mouse’s immune system produced T cells that damaged the gut, as expected. But it also prevented the T cells from releasing a protective factor that would otherwise restore the gut. Hence, the mouse was less able to recover from the infection.

While it’s difficult to prove that the same thing happens in people, the study provides a plausible explanation for this infection-disease connection, said the paper’s senior author, Ken Cadwell, who studies how viruses interact with the immune system, at the New York University Grossman. School of Medicine.

By itself, the gastric bug is usually “irrelevant,” said Dr. John Wherry, who heads the Institute of Immunology at the University of Pennsylvania’s Perelman School of Medicine. A number of people have a genetic mutation which in itself is equally irrelevant. But when someone with a seemingly irrelevant mutation receives a seemingly irrelevant infection, it can disrupt the balance of the insects living in their gut, leading to intestinal disease.

It was difficult to prove this sequence of events, because the virus disappeared when the symptoms appeared. The researchers knew that the balance of gut microbes was out of control, but until this new study, the instigator was not shown to be a simple infection, he said.

“It’s a triplet combination,” Wherry said. “This is like a real ecosystem.”

Why are some people more vulnerable?

Genetics is a key factor in this cascade of diseases.

But figuring out which genes cause vulnerability to which infections is no easy task.

“There are many diseases and each one will have a different set of molecules at play,” Davis said.

Overall, about 1 in 12 people will develop an autoimmune condition in their lifetime, James said.

Young adult women are known to be particularly vulnerable to autoimmune diseases, although no one knows exactly why.

“Women often have slightly stronger immune responses, and this is most noticeable during the childbearing age,” she said. Hormones may play a role, but they don’t fully explain the difference. “We don’t have all the answers.”

Anyone with autoimmune disease in their family has a higher risk of developing autoimmune disease on their own, James said. Identical twins, however, may or may not get an autoimmune disease if their twin does, or they may develop it decades later. Autoimmune diseases can also be “sporadic”, arising without any obvious family ties.

Siblings of children with type 1 diabetes are known to be more at risk for the disease themselves. So efforts are underway to understand their common genetics and track changes in the siblings’ immune systems “before the disease even develops,” James said.

Since these conditions rarely begin at birth, there is likely to be some sort of tipping point that occurs later in life, such as an infection, James said: “Maybe you need a lot of genetics and a little infection or a lot of infections. and part of the genetics “.

Rather than identifying most people as being at high risk, it may be easier to quickly see when someone’s immune system is overreacting to an insult such as an infection, he said.

“Could we just re-activate things a bit” or the progression of prevention, he wonders.

Although these long-term symptoms may be an individual thing “between a particular insect, a particular person, and perhaps a particular moment in time,” there are common mechanisms in these conditions, Davis said. Hopefully, this means that scientists will eventually learn how to harness these mechanisms to develop treatments.

“It is becoming clearer how these diseases started,” Davis said. “What isn’t clear is why they persist in certain people. Why doesn’t the system get back into balance again?”

Understanding it and treating the disease, “this is the next chapter in all of this,” he said.

Can you protect yourself?

Davis is desperate to develop a test that identifies a troubled immune system, the way a cholesterol test indicates heart problems.

“As an immunologist, I feel embarrassed” there isn’t one, he said.

Davis scoffs at commercial “immune promoters,” saying that at best they just separate people from their money and could be harmful at worst.

Living in a bubble isn’t the answer, Chung said. In recent years, research has shown, for example, that over-protecting children by avoiding allergens in early childhood can actually increase the risk of allergies later in life.

What is really needed is for researchers to understand what makes someone more vulnerable to the long-term consequences of infections, Chung said: “Part of that is genetics. But part of that might also be understanding what the your immune profile at any given point in time. So we can ask ourselves, is it problematic? Is it a risk signature? “

A healthy lifestyle – getting enough sleep, avoiding cigarettes and too much alcohol, and eating a healthy diet – are all important for protecting the immune system, James and others said.

Growing evidence suggests that the microbiome, the insects that live on and in everyone’s body, can affect the immune system. But it’s still too early to know what can be done to boost immune health through the microbiome, James said.

While there’s little people can do to understand their risk, researchers say there’s no point in panicking.

“I’m not one who gets hysterical about these things,” Wherry said. “Infections and microbes are part of our world, part of our life, part of the life span.”

Instead, it makes sense to make simple behavioral changes, like washing your hands frequently, wearing a mask at a crowded airport, and staying at home rather than dealing with illness, he said.

“If you know that all of your friend’s family members have been sick in the last week and are inviting you to dinner,” he said, “maybe do a rain check for the next week.”

The study compares the antibody responses in the blood serum of patients recovered from COVID-19

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