SARS-CoV-2 mutations similar to those in the UK B1.1.7 variant may occur in cases of breast infection, where extended treatment over a period of time can give the virus several chances to develop, say scientists. .
Writing in Nature, a team led by Cambridge researchers is reporting how they could monitor the SARS-CoV-2 mutation in the case of a vaccinated patient treated with convalescent plasma. In particular, they saw the emergence of a significant mutation that was also seen in the new version that led the UK to be forced back into a tight lock, although there is no suggestion that this change came from this patient. .
Using a synthetic version of the laboratory-generated Spike protein virus, the team showed that specific changes to its genetic code – the mutation seen in version B1.1.7 – made the virus twice. as infectious on cells as the most common snoring.
SARS-CoV-2, the virus that causes COVID-19, is a betacoronavirus. Its RNA – its genetic code – is made up of a series of nucleotides (chemical structures represented by the letters A, C, G and U). As the virus repeats itself, this code can be misinterpreted, leading to errors, known as mutations. Coronaviruses have a relatively small rate of change at approximately 23 nucleotide replacements per year.
A particular concern is mutations that can alter the structure of the ‘spike protein’, which sits on the surface of the virus, giving it the crown-like shape. The virus uses this protein to bind to the ACE2 receptor on the host cell surface, allowing it to enter the cells where it clears their apparatus to allow it to reproduce and spread throughout the body. Most of the vaccines currently in use or being tested focus on spike proteins and there are concerns that mutations may affect the effectiveness of these vaccines.
UK researchers within the Cambridge-led Consortium of Genomics UK (COG-UK) have identified a specific variant of the virus that involves significant changes that appear to be causing it. more infectious: elimination of amino acid ΔH69 / ΔV70 in part of the spike protein is one of the main changes in this difference.
Although the ΔH69 / ΔV70 deletion has been detected several times, to date, scientists have not been seen appearing inside an individual. However, in a study published today in Nature, Cambridge researchers document how these mutations appeared in COVID-19 patients admitted to Addenbrooke Hospital, part of the Foundation Trust NHS Cambridge University Hospitals.
He was the man involved in his seventies who had previously been diagnosed with peripheral B cell lymphoma and had recently undergone chemotherapy, putting his immune system at serious risk. Following admission, the patient was given a number of treatments, including antiviral drugs remdesivir and convalescent plasma – that is, plasma containing antibodies extracted from the blood of a patient who had been vaccinated. clean the virus from their system. Despite his initial situation becoming stable, he began to decline. 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, mostly from his nose and throat. These were followed as part of COG-UK. It was in these sequences that the researchers observed the genome of the virus.
Between days 66 and 82, after the first two administrations of convalescent sera, the team observed a large shift in the number of viruses, with a variant of ΔH69 / ΔV70 removal, coupled with a mutation in the spike protein to the virus. called D796H, gaining the upper hand. Although this variant appeared to be dying away, it reappeared when the third course of remdesivir and convalescent plasma treatment was administered.
Professor Ravi Gupta from the Cambridge Institute for Therapeutic & Infectious Disease, who led the research, said: “What we saw was competition between different variants of the virus, which we believe was guided by the convalescent plasma treatment.
“The eventual winning virus – which had a D796H mutation and ΔH69 / ΔV70 detoxification – first got the upper hand during convalescent plasma treatment before being ingested by other strains, but it appeared again when the treatment was resumed. It is one of the mutations in the new UK version, although there is no suggestion that we first came in the patient. “
Under strictly controlled conditions, the researchers created and fabricated a synthetic version of the virus by deleting ΔH69 / ΔV70 and mutating D796H both individually and in combination. The combined mutations made the virus less sensitive to convalescent plasma neutralization, although the decrease in susceptibility to the antibodies in the plasma appears to have been caused by D796H mutation alone. After D796H mutation alone, infection was lost in the absence of plasma, similar to mutations acquired by viruses to escape immune pressure.
The researchers found that the deletion of ΔH69 / àsV70 by itself made the virus twice as susceptible to the variant as it had previously been. The researchers believe that the role of eradication is to compensate for the loss of infection due to D796H mutation. This paradigm is a classic for viruses, where escape mutations are followed by or alongside compensatory mutations.
“Because both vaccines and chemotherapy target the protein spike, which we saw mutate in our patient, our study raises the worrying possibility that the virus could spread around our vaccines. , “said Professor Gupta.
“This effect is unlikely to occur in patients with active immune systems, where viral diversity tends to be lower due to better immune control. But it clarifies the care that we need to take it when treating patients with immunosuppression, where prolonged viral reproduction can occur, giving the virus a greater chance of getting around. “