People with weak immune systems 'may trigger coronavirus variants'
People with weak immune systems may be breeding grounds for dangerous Covid variants, scientists warn
- Virus may get extra opportunity to mutate and adapt to body in long infections
- Man in Boston, Massachusetts, battled Covid-19 for 154 days before he died
- Lab workers found the virus had changed in dozens of places during his illness
- Variants could be emerging from long-infected people across the world
The coronavirus variants causing panic around the world may be starting in people with weak immune systems who spend weeks or months battling the virus, scientists have warned.
Doctors in the US have revealed that a Covid strain living in an immunosuppressed patient for 150 days changed so much that they could find 50 differences in its genetic code.
These changes, which happen randomly as the virus reproduces in order to spread, are what can drive changes in its shape which can affect the way the virus functions.
Fifty per cent of the alterations in the US patient occurred on the virus’s spike protein, which it uses to bind to human cells, despite the spike accounting for just two per cent of the virus’ genetic code.
The patient, a 45-year-old man from Boston, was also on a cocktail of antiviral and antibody therapies which may have put ‘evolutionary pressure’ on the virus to evolve to evade the immune response, according to Professor Ian Jones, a virologist at the University of Reading.
The study provides clues about how the three variants causing international alarm in the UK, Brazil and South Africa, may have originated. All three also have key changes on their spike proteins which make them either more transmissible, deadly or immune-resistant.
Coronavirus constantly mutates as it spreads between people and reproduces inside hosts but the majority of the changes make no difference to the way the virus looks or behaves.
Most people who catch the disease are able to recover within a fortnight, and remain infectious for an even shorter time, which gives the virus a tiny window to evolve and jump to other people.
But in people who struggle to shake off infection for months, such as cancer and transplant patients, coronavirus is given ample opportunity to genetically shape-shift and spread back into the population, Professor Jones told MailOnline.
People who are sick with Covid-19 for an exceptionally long time may be breeding grounds for new variants of the coronavirus to emerge, scientists say, because their continuous infection gives it opportunities to evolve (Stock image of staff at a hospital in London, England)
The patient in Boston was treated at Brigham and Women’s Hospital after being admitted in spring last year, the Los Angeles Times reports.
He was diagnosed with a rare disorder called antiphospholipid syndrome in his twenties, which caused his immune system to attack his own organs and create deadly blood clots.
He had been prescribed immunosuppressive drugs which kept his immune system in check and prevented fatal overreactions – but the medicine meant his body was less able to fight off the coronavirus.
During his 154-day Covid battle he was admitted to hospital six times, including stints in ICU, before passing away from the disease last summer.
He was eventually put on three courses of the antiviral medication remdesivir, and one dose of Regeneron’s experimental cocktail of monoclonal antibodies, blood cells which help the body fight off the pathogen.
US scientists reported three homegrown ‘super-covid’ variants in as many days in January and experts say the world should brace for many more emerging in countries all over the world.
And the more people get coronavirus, the more of these highly infectious variants will emerge, scientists believe.
Experts theorise that ‘super-covid’ variants are only going to become more common as case numbers surge across the globe, because the more cases there are, the greater the number of people with rare, chronic infections will be – and these cases offer a unique opportunity for new, stronger COVID-19 variants to evolve.
‘My (highly speculative!) hypothesis is that the emergence of these variant viruses arises in cases of chronic infection during which the immune system places great pressure on the virus to escape immunity and the virus does so by getting really good at getting into cells,’ wrote Fred Hutchinson Cancer Center scientist Dr Trever Bradford wrote in a Thursday Twitter thread.
Weaker immune systems allow the virus to stay in the body for a longer time, during which the immune system keeps fighting it. Duking it out with the immune system teaches the virus how to stick around better.
Dr Bedford isn’t the only one who thinks so.
‘The uptick in mutations [we are seeing] is expected because there is more circulation of the virus, and more chances for a mutation to occur,’ Dr Ali Mokdad, an epidemiologist with the University of Washington’s Institute for Health Metrics and Evaluation told DailyMail.com.
And when people are infected for a long time, ‘it is giving the virus an opportunity to mutate within the same host,’ Dr Mokdad explained.
He says scientists suspect that that is how the UK variant, B117, arose: ‘A person who was infected for 12 days was the one who started this whole thing,’ though that theory is yet to be confirmed.
The more infectious B117 variant has become dominant in the UK. Similar variants have cropped up in South Africa, Brazil and the US. Now, the US has two other variants. So far, they all appear to likely be more infectious, but not more deadly. Scientists think vaccines will work against them, but that is the key question still looming over them.
‘That’s why this debate of cutting the dose [of vaccines] or only giving the first dose is very, very dangerous’ Dr Mokdad says.
‘You want [a vaccine] to knock down the virus very, very low. We don’t want to get this virus used to something in small doses so the virus can develop immunity, we want to make sure that when the virus comes into contact with these immune antibodies, it loses every time, and fast.’
Swabs taken from his nose and throat revealed that, compared with a sample taken during his first hospitalisation, the virus had changed in 20 places.
The genetic code, a sequence of 30,000 molecules, had changed in 11 places and nine parts of it had disappeared completely.
And following tests after he had been admitted to hospital multiple times kept finding dozens more of these changes every time his illness worsened.
Doctors weren’t sure whether he kept getting sicker because his weak immune system couldn’t destroy the virus or because it kept mutating so much that the white blood cells and antibodies couldn’t recognise it as the same virus.
One doctor at the hospital that treated the man, Dr Jonathan Li, said this series of changes in the virus was basically a condensed, sped-up version of what happens as the virus spreads between people around the world.
And Boston immunologist Dr Bruce Walker told the LA Times that infection in a patient with a weak immune system that can’t clear the infection on its own is ‘the worst possible scenario for developing mutations’.
Doctors are also more likely to be put those patients with chronic Covid on a long course of drugs or therapies, which puts ‘evolutionary pressure’ on the virus, he added.
Professor Jones told MailOnline: ‘Couple those two together, then you could give the virus much longer to select for changes that then evade therapies or immune responses.’
He added: ‘Covid is normally an acute infection and most people clear it in about two weeks.
‘Mutations are a ticking time clock, and in normal patients the virus has five days worth of throwing out mutants to see if they give an advantage.
‘But in immuno-compromised patients that might be more than a month, which gives the virus much longer to accumulate mutations.
‘It doesn’t necessarily means these mutations will make virus any worse, but it increases the risk of one of them being able to [change the way it behaves].
‘The added-on factor is that because immunosuppressed people may not be able to mount a natural immune response, it’s possible they will then be treated with therapies.
‘They are treated with antivirals like remdesivir, which seeks to inhibit virus replication directly, and the second one is therapeutic antibodies, which is given as an injection, giving immune compromised people the immunity they cannot gen themselves.
‘Couple these two together then you could select for viruses that then evade either of those therapies — evading an antibody response or therapeutic response.
‘The virus will then select mutations that would be an advantage in those environments.’
Once the virus accumulates a mutation that gives it an evolutionary edge over other strains inside an immunocompromised person, it still needs to spread back into the population to become widespread.
This means the host has to be ‘well enough to cough or sneeze’, according to Professor Jones, which makes makes the emergence of such variants even more unlikely.
The virologist said this highlights the need for stringent personal protective equipment (PPE) in hospitals, where most chronically-ill Covid patients end up during their battle with the disease, to halt the spread of dangersous variants in their tracks.
He added: ‘If these patients are in hospitals and covered in PPE they are not going to transmit anything’.
The man who had COVID-19 for 154 DAYS: Patient with immune condition, 45, had four bouts of the virus before dying
Scattered reports have emerged of people being reinfected with coronavirus after testing negative – but one man may have had three ‘recurrences’ of COVID-19 over the course a gruelling, ultimately fatal, 154-day battle with the infection.
In a case report, Brigham and Women’s Hospital physicians describe the struggle of a 45-year-old man who had a severe autoimmune disorder and seemed to be turning the corner against the virus on multiple occasions.
Despite aggressive treatment, the virus stayed with the unidentified man for 154 days.
And it mutated at an alarming and unusual speed inside his body, which was not as well equipped to fight infection as an average person’s would be.
A 45-year-old man with an autoimmune condition had COVID-19 for 154 days, despite seeming to be on the verge of clearing it three times and testing negative once. Ultimately, complications of the infection killed him, and scientists found the virus had mutated (file)
Health officials have made very clear that people with compromised immune systems should stay home as much as possible and be particularly careful not to catch coronavirus.
But the case study shows just how dangerous COVID-19 can be to immunocompromised people – and how they might become dangerous reservoirs for the virus to mutate within before spreading to others.
The man suffered from a condition called antiphospholipid syndrome (APS), an autoimmune disorder that in which the body produces off-target antibodies that attack important blood proteins that prevent unnecessary clotting, instead of pathogens.
It is unclear exactly how common the condition is, but researchers suspect that it could be the driver of up to one percent of all blood clots, and as many as 20 percent of strokes in people under 50.
These people have to take blood thinners if they have any history of clots, or be on low-dose aspirin.
The man described in the case report, published Wednesday in the New England Journal of Medicine (NEJM) also suffered from a complication of the autoimmune disorder known as diffuse alveolar hemorrhage, in which blood vessels bleed into the lungs.
In an effort to keep these life-threatening conditions, the man was on blood thinners, steroids and drugs that suppress the immune system, putting him at high risk for coronavirus, for multiple reasons.
The vast majority of mutations to the virus that infected the patient were to the spike protein (lavender), which is worrisome because the spike is the target of most vaccine candidates and treatments
He came to a hospital with a fever and promptly tested positive for coronavirus.
Doctors began treating the man with a five-day course of the antiviral remdesivir and bumped up the dosage of his steroids out of concern that he might be bleeding into the air sacs of his lungs, due to his pre-existing condition.
By day five, he was discharged, and did not need supplemental oxygen.
But his improved state didn’t last long. Over the course of the next 62 days, he was supposed to be quarantined at home, but instead had to be readmitted to the hospital three times for abdominal pain, trouble breathing and fatigue.
Each time, his blood-oxygen levels were below normal and his doctors remained on edge that he would suffer pulmonary bleeds, and his steroid dose was bumped up to try to prevent them.
However, his viral load of SARS-CoV-2, which causes COVID-19, fell lower over the course of that 62-day period – an encouraging sign he would clear the infection.
But 105 days after his first diagnosis, the man wa admitted again, with the same issues, and a higher viral load, ‘which caused concern for a second COVID-19 recurrence,’ write the study authors.
He was given another course of remdesivir and finally tested negative for coronavirus afterward, but he wasn’t out of the woods and remained on treatment.
A little over a month later, the man was positive again, which ’caused concern for a third recurrence of COVID-19.’
This time, he was given Regeneron’s experimental antibody cocktail.
But for this man, it was not the ‘cure’ that President Trump claimed it had been for him.
A week after getting the antibody drug, the man had to be put on a ventilator. His viral load was nearly as high as the previous test had suggested, and he had developed a fungal infection in his lungs.
Despite treatment with more remdesivir and antifungal, the died, 154 days after his initial positive test.
When the Brigham and Women’s scientists sequenced the genome of the virus that infected the man, they found an alarming evolution.
Not only had it seemed to linger in his body for more than 150 days, coronavirus had mutated more quickly than scientists have observed it do in most samples.
And most of the changes were to the portion of the genome that codes for the spike protein, the protruding elements on the virus’s surface that allows it to infect human cells.
The spike protein is also what vaccines and treatments – including Regeneron’s antibody cocktail, and Pfizer’s promising vaccine candidate – target.
‘Although most immunocompromised persons effectively clear SARS-CoV-2 infection, this case highlights the potential for persistent infection and accelerated viral evolution associated with an immunocompromised state,’ the study authors wrote.
It’s unclear whether the mutations to the spike protein the strain of virus the researchers found in the man would make it more or less infectious, more deadly or even more treatment-resistant.
But, the case is a worrying reminder that people – especially those with weakened immune systems – can be reservoirs, where the virus can become a stronger form of itself, and from which it could jump to others and potentially evade treatments and vaccines.
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