Coronavirus mutations similar to those in the UK variant could arise in cases of chronic infection, where treatment over an extended period can provide the virus multiple opportunities to evolve, scientists say.
A team led by University of Cambridge researchers observed the virus mutating in the case of an immunocompromised patient treated with convalescent plasma.
They saw the emergence of a key mutation, also seen in the new variant, that led to the rapid spread of the virus before the country was forced into lockdown in January.
But there is no suggestion the variant originated from this patient.
However, the researchers say the effect they observed is unlikely to occur in patients with functioning immune systems.
Using a synthetic version of the virus spike protein created in the lab, researchers showed that specific changes to its genetic code – the mutation seen in the B117 UK variant – made the virus twice as infectious on cells as the more common strain.
As the coronavirus replicates itself, its genetic code can be mis-transcribed, leading to errors, known as mutations.
Mutations that might change the structure of the spike protein, which sits on the surface of the virus, are are of particular concern.
The DeltaH69/DeltaV70 amino acid deletion in part of the spike protein is one of the key changes in this variant.
Although this deletion has been detected multiple times, until now, scientists had not seen them emerge within an individual.
In a study published in Nature, UCL infectious diseases researcher Dr Steven Kemp and Cambridge professor Ravi Gupta documented how these mutations appeared in a Covid-19 patient admitted to Addenbrooke’s Hospital in Cambridge.
The patient was a man in his seventies who had previously been diagnosed with marginal B cell lymphoma and had recently received chemotherapy,
This meant his immune system was seriously compromised.
After admission, the received a number of treatments, including remdesivir and convalescent plasma – blood plasma containing antibodies taken from the blood of a patient who had successfully cleared the virus from their system.
Despite his condition initially stabilising, he later began to deteriorate. He was admitted to the intensive care unit and received further treatment, but later died.
During the patient’s stay, 23 viral samples were available for analysis, the majority from his nose and throat.
Researchers found that between days 66 and 82, after the first two administrations of convalescent sera, there was a dramatic shift in the virus population, with a variant bearing DeltaH69/DeltaV70 deletions, alongside a mutation in the spike protein known as D796H becoming dominant.
Professor Gupta, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease – who led the research, said: “What we were seeing was essentially a competition between different variants of the virus, and we think it was driven by the convalescent plasma therapy.
“The virus that eventually won out – which had the D796H mutation and DeltaH69/DeltaV70 deletions – initially gained the upper hand during convalescent plasma therapy before being overtaken by other strains, but re-emerged when the therapy was resumed.
“One of the mutations is in the new UK variant, though there is no suggestion that our patient was where they first arose.”
After analysis, the researchers found the DeltaH69/DeltaV70 deletion by itself made the virus twice as infectious as the previously dominant variant.
They believe the role of the deletion was to compensate for the loss of infectiousness due to the D796H mutation.
Prof Gupta said: “Given that both vaccines and therapeutics are aimed at the spike protein, which we saw mutate in our patient, our study raises the worrying possibility that the virus could mutate to outwit our vaccines.
He added: “This effect is unlikely to occur in patients with functioning immune systems, where viral diversity is likely to be lower due to better immune control.”
Co-author Dr Steve Kemp (UCL infection and immunity) said: “When several mutations occur together, it is likely that they are being transmitted on single viruses, and so can have public health implications if a particular variant becomes dominant in the population.”
