Author: John Hanno

BBC News

‘Long Covid triggered our MCAS, but doctors didn’t believe us’

Liz Jackson – BBC News – November 26, 2023

People with long Covid feel “forgotten, unheard, disbelieved, isolated”, barrister Anthony Metzer KC told the Covid-19 Inquiry last month on behalf of advocacy groups for people with the condition.

A growing number of people who have secondary illnesses thought to be triggered by long Covid – including an immune disorder called mast cell activation syndrome (MCAS) – say this feeling is especially acute.

I spoke to two young Londoners who, like me, have been diagnosed with long Covid and now MCAS and are starting to feel better, but faced poor treatment by doctors.

In George Cooper’s case, he says one was “so unreceptive to the point where they were actually angry”, and for Elle Gorman, they questioned whether she was “not eating on purpose”.

Warning: This article contains details some may find distressing, including illness and mention of suicide.

The National Institute for Health and Care Excellence defines long Covid, or post-Covid syndrome, as symptoms during or after infection that continue for more than 12 weeks and are not explained by an alternative diagnosis.

The BMJ says MCAS “is characterised by recurrent sudden-onset episodes of severe systemic symptoms associated with the release of mast cell mediators“, which can include histamine.

George, 27, from Putney in south-west London, was recovering from glandular fever when he became “really ill” in March 2020 with suspected Covid.

Although there was no testing at all during this time, antibody tests in June of 2020 showed he had been exposed to the virus and, after experiencing months of lingering symptoms, he was diagnosed with long Covid.

‘I lost almost half my body weight’

The keen runner and rugby player said he began getting food allergies, swollen lymph nodes, palpitations and was fainting, and had “massive stomach pain to the point where I was like, what is this, am I dying?”.

More than two years later George was seen by an NHS long Covid clinic and was told he might have MCAS.

But when he took the news to his GP “he effectively said ‘you’ve got ME (myalgic encephalomyelitis) and you’ll have it for life’,” George explained.

A different doctor advised him to pay for a private appointment, where a consultant also suspected MCAS and prescribed antihistamines and ordered biopsies – but George was unknowingly reacting to bulking ingredients in the medicine and was still getting sicker.

He said he developed non-viral hepatitis and saw another GP who looked at his diagnosis of suspected MCAS and was “so unreceptive to the point where they were actually angry”.

“I’d gone from being 87kg (13st 10lbs) and playing rugby to 47kg (7st 6lbs) and I was near to not being around, I think, because I was eating food that was making me sick, and I was in so much pain,” he continued.

George reached out for help again when he started having thoughts about taking his own life.

“I was so low. I think it had taken everything from me, and I didn’t trust anything around me or anyone, including myself,” George said.

A different doctor suggested he should go to an eating disorders clinic and George said he agreed because he felt most doctors thought he was “just mentally ill” and his MCAS was “in his head”.

At the clinic, George struggled. If he didn’t eat he was told to drink liquid nutrition drinks which made him vomit, but five days into his stay the results of his biopsy from months earlier came through.

He had MCAS.

He said the news “just made me whole”, adding: “I nearly wasn’t here.”

“When I was discharged the psychologist said she thought I never had an eating disorder in the first place and I shouldn’t have been there,” he said.

George is now on MCAS medication with different ingredients and is recovering, but said it had been “difficult not to get angry”.

“I’m more wary around doctors now,” he said. “I don’t think I’ll ever actually fully process things from that time, and PTSD has been discussed.

“It’s OK to say ‘I don’t understand’. But to say ‘you’re wrong, that’s not happening’, is a totally different kettle of fish.”

Why isn’t the health system helping?

There are no NICE guidelines for MCAS, which would allow NHS staff to recognise and treat it – even though the NHS recognises other forms of mast cell disease such as mastocytosis.

While the NHS doesn’t yet recognise MCAS, medical bodies in other countries have begun to, among them the American Academy of Allergy, Asthma and Immunology, and global research into its links to long Covid is growing.

Joy Mason from UK charity Mast Cell Action said MCAS had “loose diagnostic criteria” and no national guidelines, making it “very complex to discuss in a short appointment”.

Researchers are looking into links between long Covid and other illnesses, and are examining whether treatment with medicines like antihistamines could be effective.

Prof Danny Altmann from Imperial College London is running one of Europe’s largest immunological studies into long Covid, and he and co-authors published a review of the immunology of long Covid, which noted some investigations “highlighted features of the long Covid immune response that are reminiscent of mast-cell activation”.

Despite this, the immunologist said there were no “rock-solid studies” on MCAS yet, though he pointed out “the bar [is] quite high” for research to get off the ground.

“They might have shifted their immune profile to be more allergic and one of the things that speaks to that is the only properly powered big randomised controlled drug trial – the Stimulate ICP trial at University College. One of the four arms is using two different histamines as a trial to see in a properly controlled environment whether that works,” he said.

Prof Altmann stressed that relying on private prescribers was only a temporary solution and researchers, drug companies and health authorities needed to “bang heads together and say ‘these are the steps that would be needed to get large-scale long Covid clinical trials in a way that satisfies the authorities, these are the drugs… these are the cohort sizes’.”

• Long Covid: What’s changed, and what we know now
• Long Covid: Three years and no magic bullet
• Scans reveal new clues to long Covid symptoms

I approached NHS England to ask whether it recognised MCAS, or had plans to request a NICE review of the condition, but after incorrectly signposting me to NHS information about mastocytosis, the press office declined to answer any questions about MCAS.

An NHS spokesperson said: “Long Covid remains a relatively new condition and research is under way to continue to build our understanding of how best to diagnose and treat people affected by the condition.”

The spokesperson advised those concerned about ongoing symptoms after Covid-19 to “see their GP team, who can rule out any other possible underlying causes for symptoms”.

“If appropriate, they will also be able to refer to one of over 100 specialist long Covid clinics for further support and treatment from a wide range of health professionals that can address both the physical and psychological aspects of living with long Covid.”

If people suspect they have symptoms that correlate with possible MCAS, they should speak to their doctor.

The New York Times

How Viral Infections Cause Long-Term Health Problems

Apoorva Mandavilli – November 22, 2023

Every day, Davida Wynn sets herself one task: Take a bath. Or wash the dishes. Or make an elaborate meal. By the end of the chore, she is exhausted and has to sit or lie down, sometimes falling asleep wherever she happens to be.

“Anything beyond that is truly excruciating,” Wynn, 42, said.

Her heart races even during small tasks, and she often gets dizzy. At least once a month, she falls at her home outside Atlanta. Once, she badly bruised her face, and another time, she banged up her knee.

Wynn was infected with the coronavirus in May 2020, when she was a nurse in a hospital COVID unit, and became so ill, she was put into a medically induced coma for six weeks. Ever since, her bloodwork has indicated that she is experiencing extreme inflammation, a hallmark of autoimmune disease.

Infection with the coronavirus is known to leave behind a long legacy of health problems, many of which are characterized as long COVID. But mounting evidence suggests that independent of that syndrome, the coronavirus also befuddles the immune system into targeting the body, causing autoimmune disorders in some people.

This outcome is more likely in those who, like Wynn, were severely ill with COVID, multiple studies suggest.

COVID is not unique in this aspect. Scientists have long known that infection can set the body down the path of autoimmune disease. The classic example is Epstein-Barr virus.

About 1 in 10 people who have mononucleosis, which is caused by the virus, go on to develop myalgic encephalomyelitis/chronic fatigue syndrome. A landmark study last year even linked the virus to multiple sclerosis.

Many other pathogens can also seed autoimmunity — but only in an unlucky few people.

“We are all infected with a multitude of viruses, and in the majority of cases, we don’t get any autoimmunity,” said Dr. Alberto Ascherio, a public health researcher at the Harvard T.H. Chan School of Public Health who led the multiple sclerosis study.

Infections with bacteria such as chlamydia and salmonella can inflame the joints, skin and eyes — a condition called reactive arthritis. Enteroviruses can mislead the body into attacking its own pancreatic cells, leading to Type 1 diabetes.

Like Epstein-Barr virus, dengue and HIV are thought to cause autoimmunity in some people. Still, COVID seems to foment a long-term reaction that is distinct, said Dr. Timothy Henrich, a virus expert at the University of California, San Francisco.

“There’s something specific about SARS-CoV-2 that seems to set it apart, in terms of the severity and duration,” he said, referring to the coronavirus.

Early in the pandemic, scientists found that antibodies that target the body instead of the pathogen — so-called autoantibodies — are important in COVID. Those who had autoantibodies to interferon, a key component of the body’s first-response system to pathogens, before they encountered the coronavirus were more likely to fare poorly or to die of COVID.

About 10% of patients with severe COVID, most of them men older than age 55, had these antibodies, compared with just 0.3% in the general population.

Since then, dozens of studies have found autoantibodies in people who have had COVID. Up to half of people who have had the illness carry antibodies that can alter the immune system, damage blood vessels, impair blood pressure regulation and lead to diabetes, rheumatoid arthritis and blood clots.

One study found autoantibodies in children with multisystem inflammatory syndrome, a rare condition associated with COVID.

The autoantibodies seem to be independent of long COVID. A few studies have linked a subset of autoantibodies to long COVID and found that their presence is one of four major risk factors for the syndrome.

But other teams have reported that the autoantibodies and long COVID don’t always accompany each other. Based on an analysis of thousands of proteins, “this autoantibody signature seems to be a COVID-related phenomenon, post-COVID and not long COVID-related,” Henrich said.

But some researchers caution that the mere presence of autoantibodies does not herald autoimmune disease.

“In every viral infection, you get autoantibodies, and this has been known for decades,” said Dr. Shiv Pillai, an immunologist at Harvard Medical School.

Many years from now, scientists may record a higher incidence of autoimmune diseases in those who had severe COVID, he said, but that is not a foregone conclusion: “There may be many, many other factors that have to be fulfilled for someone to get the disease.”

Why only some people develop autoimmune conditions is unclear, but the answer is likely to involve dozens of genes and an environmental catalyst.

Lupus is preceded by high levels of autoantibodies more than 10 years before disease onset, but many relatives of patients with lupus who have a similar genetic background never develop the disease.

“The most likely explanation is that you have all these risk factors, you have all these things ready to go, and there’s a final trigger,” said Dr. Iñaki Sanz, an immunologist at Emory University.

To conclusively link a virus to an autoimmune condition, rigorous studies would need to follow a large number of people over many years. The best example of such a study is the one that tied the Epstein-Barr virus to multiple sclerosis.

EBV, a member of the herpesvirus family, infects nearly everyone at some point. Once in the body, it persists forever; the virus can be reactivated by conditions including stress and hormonal changes. (Reactivation of EBV is another of the four risk factors for long COVID.)

To probe its association with multiple sclerosis, Ascherio and his colleagues conducted what they call an “experiment of nature” — a long-term study of more than 10 million active-duty soldiers in the U.S. military.

Between 1993 and 2013, the researchers collected 62 million serum samples from this racially diverse group. Those who were infected with EBV had a 32-fold increase in the risk of multiple sclerosis, compared with those who did not have the virus, the scientists found. They did not observe similar relationships with other viruses.

Fewer than 1 million Americans have multiple sclerosis, suggesting that other factors must also be involved. Still, researchers are now enthusiastic about the idea of a vaccine against EBV to prevent multiple sclerosis. (No vaccines against EBV are currently available, although some are in clinical trials.)

Studies from other teams support the association between EBV and multiple sclerosis. Danish researchers followed more than 25,000 people with mononucleosis over decades and found that it doubled their odds of developing multiple sclerosis.

And a study published last year offered a possible explanation: EBV mimics a human protein, potentially misdirecting antibodies made against the virus.

About 1 in 4 people with multiple sclerosis has these antibodies, “providing the basis for how EBV could evoke an autoimmune reaction that would cause multiple sclerosis,” said Dr. William Robinson, an expert in autoimmune diseases at Stanford University who led the study.

This sort of molecular mimicry is one path to autoimmunity. But in other cases, the body might never fully clear a pathogen after infection, and the persistence of the virus — whether live virus or just remnants — might keep the body in a state of immune high alert, eventually leading to autoimmunity.

Both possibilities suggest treatments. In some small number of people, antiviral drugs and vaccination can ease the symptoms of long COVID, hinting that live virus may be the source. Henrich is conducting a study looking at monoclonal antibodies at high doses that would soak up errant viral fragments lingering in the body.

“If the viral proteins are causing an auto-reactive process, then by getting rid of those viral proteins, it might actually improve overall health,” Henrich said.

For Wynn, there is no relief in sight. She has tried a plethora of medications, including treatments for rheumatoid arthritis, but so far has not responded to them.

“It’s been a long and tedious process,” Wynn said. “And I will tell you, from a mental perspective, it has been absolutely draining.”