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Source: B.1.1.7 UK Variant  Dec 24, 2020  3 years, 3 months, 3 weeks, 1 day, 20 hours, 31 minutes ago

University Of Cambridge Study Shows Neutralizing Antibodies Are Driving Mutations Of Spike Mediated SARS-CoV-2 Evasion Including In B.1.1.7 Variant

University Of Cambridge Study Shows Neutralizing Antibodies Are Driving Mutations Of Spike Mediated SARS-CoV-2 Evasion Including In B.1.1.7 Variant
Source: B.1.1.7 UK Variant  Dec 24, 2020  3 years, 3 months, 3 weeks, 1 day, 20 hours, 31 minutes ago
Some of the mutations on the B.1.1.7 U.K. variant are actually the result of neutralizing antibodies induced spike protein mutations and warrants concerns according to a new study led by scientist from University of Cambridge that is published on a preprint server and is currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2020.12.05.20241927v2


 
SARS-CoV-2 Spike protein is critical for virus infection via engagement of ACE2, and amino acid variation in Spike is increasingly appreciated. Given both vaccines and therapeutics are designed around Wuhan-1 Spike, this raises the theoretical possibility of virus escape, particularly in immunocompromised individuals where prolonged viral replication occurs.
 
The study team reported the fatal SARS-CoV-2 escape from neutralizing antibodies in an immune suppressed individual treated with convalescent plasma, generating whole genome ultradeep sequences by both short and long read technologies over 23 time points spanning 101 days.
 
Little evolutionary change was observed in the viral population over the first 65 days despite two courses of remdesivir.
 
However, following convalescent plasma the team observed dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and ΔH69/ΔV70 in the S1 NTD of the Spike protein. As serum neutralisation waned, viruses with the escape genotype diminished in frequency, before returning during a final, unsuccessful course of convalescent plasma. 
 
In vitro, the Spike escape variant conferred decreased sensitivity to multiple units of convalescent plasma/sera from different recovered patients, whilst maintaining infectivity similar to wild type.
 
The study findings data reveal strong positive selection on SARS-CoV-2 during convalescent plasma therapy and identify the combination of Spike mutations D796H and ΔH69/ΔV70 as a broad antibody resistance mechanism against commonly occurring antibody responses to SARS-CoV-2.
 
Corresponding and lead author Dr Ravindra Gupta, a virologist at the University of Cambridge, initially heard about a cancer patient who had come into a local hospital the month before with COVID-19 and was still shedding virus. The patient was being treated for a lymphoma that had relapsed and had been given rituximab, a drug that depletes antibody-producing B cells. That made it hard for him to shake the infection with SARS-CoV-2.
 
Dr Gupta, a leading authority on HIV drug resistance became interested in the case and helped treat the patient, who died in August, 101 days after his COVID-19 diagnosis, despite being given the antiviral drug remdesivir and two rounds of plasma from recovered patients, which contained antibodies against the virus.
 
Interestingly when Dr Gupta studied genome sequences from the coronavirus that infected the patient, he discovered that SARS-CoV-2 had acquired several mutations that might have allowed it to elude the antibodies.
 
His study findings has become a crucial puzzle piece for researchers trying to understand the importance of B.1.1.7, the new SARS-CoV-2 variant first found in the United Kingdom. https://www.thailandmedical.news/news/emerging-sars-cov-2-variants-in-uk-like-the-b-1-1-7-strain-and-the-501-v2-strain-in-south-africa-and-elsewhere-will-change-course-of-covid-19-badly
 
https://www.thailandmedical.news/news/u-s-cdc-indicates-that-vaccines-might-not-protect-against-new-uk-variant-b-1-1-7-new-details-show-new-variant-could-be-the-expected-super-strain
 
The B.1.1.7 UK variant strain, which appears to spread faster than others, contains one of the mutations that Gupta found, and researchers believe B.1.1.7, too, may have originated in an immunocompromised patient who had a long-running infection.
 
Infectious disease scientist Dr Jeremy Farrar, director of the Wellcome Trust  said, “It’s a perfectly logical and rational hypothesis.”
 
Researchers are still trying to figure out the effects of the mutations in B.1.1.7, whose emergence led the U.K. government to tighten coronavirus control measures and other countries in Europe to impose U.K. travel bans.
 
However the new variant, along with research by Dr Gupta and others, has also drawn attention to the potential role in COVID-19 of people with weakened immune systems. If they provide the virus with an opportunity to evolve lineages that spread faster, are more pathogenic, or elude vaccines, these chronic infections are not just dangerous for the patients, but might have the potential to alter the course of the pandemic.
 
To date that is still very unclear whether that is the case, but Dr Farrar believes it’s important to ensure doctors take extra precautions when caring for such people:
 
He said,“Until we know for sure, I think, treating those patients under pretty controlled conditions, as we would somebody who has drug resistant tuberculosis, actually makes sense.”
 
Scientists concern mostly focuses on cancer patients being treated for chemotherapy and similar situations.
 
Bur Dr Farrar added,  “We don’t yet know about people who are immunocompromised because of HIV, for instance.”
 
The new UK variant B.1.1.7 attracted researchers’ attention because it was linked to an outbreak in England’s Kent county that was growing faster than usual. Sequences showed that virus had accumulated a slew of 23 mutations that together caused 17 amino acid changes in the virus’ proteins, eight of them in the crucial spike protein. Among them are at least three particularly concerning ones.
 
Alarmingly one is 69-70del, a deletion that Gupta also found in his Cambridge, U.K., patient whose virus seemed to evade the immune system. It leads to the loss of two amino acids in