MESSAGE
| DATE | 2021-02-02 |
| FROM | Ruben Safir
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| SUBJECT | Subject: [Hangout - NYLXS] Vaccine mutation Details from the UK COVID-19
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I am listening to the BBC this morning and it is expected that the
COVID-19 virus will be with us for the rest of our lives.
Looking for a supportive article I found with deep listing of all the
known worldwide mutations on the BBC website
https://www.bbc.com/future/article/20210127-covid-19-variants-how-mutations-are-changing-the-pandemic
It is rather thorough and worth pouring over.
One of the more interesitng snippets is thus:
Subsequent research has suggested that D614G made the virus more
infectious than the original version that emerged from Wuhan and appears
to have been more common in younger people. But this also came at a cost
– the mutation may have also left the virus more vulnerable to
antibodies, meaning it was less able to cause reinfections in people who
had already had the disease. This also meant it could be combated using
convalescent plasma from patients who had already recovered.
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What we know about the South African Covid-19 variant
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(Image credit: Mohammed Abed/Getty Images)

By Richard Gray
27th January 2021
Understanding what is driving new variants of the coronavirus to appear
and what the changes mean will be crucial in our vaccine arms race
against Covid-19.
E
Early in its existence, Covid-19 gained an ability that would prove
decisive in its relationship with human beings. The virus picked up a
seemingly small change in its genetic code. It was likely an unfortunate
accident – a fragment of genetic information from another virus got
muddled up with that of the coronavirus while they were both infecting a
bat.
Included within this tiny piece of genome, however, were the
instructions that altered a key part of the virus – its spike protein.
This important protein studs the outside of the coronavirus and is the
part that attaches to the outside of cells, helping the rest of the
virus to sneak inside where it can replicate.
This change to Covid-19's spike protein meant it could hijack an enzyme
found in the human body called furin. This enzyme acts like a pair of
molecular scissors, normally cutting open hormones and growth factors to
activate them. But when furin snips part of the Covid-19 spike protein,
which is normally folded in a series of loops on the outside of the
virus, it opens like a hinge.
"This exposes a new sequence in the spike protein," says Yohei Yamauchi,
a reader in viral cell biology at the University of Bristol, UK, who has
been studying how this change may have led Covid-19 to become more
infective in humans. "It is one of the changes that make this virus
really different from previous coronaviruses that caused Sars and Mers."
This new mutation meant Covid-19 could suddenly latch onto an important
molecule found scattered around the outside of human respiratory cells
called Neuropilin 1. This molecule helps to transport material inside
cells and deeper into tissues – the mutation was like handing Covid-19
the keys to a new door into our cells and meant the virus could
replicate in greater numbers in the human airways.
Although this mutation was just one in Covid-19's short existence, it
proved to be important. Some researchers believe it may be one of the
key mutations that allowed the coronavirus to jump species and begin
causing a rapidly spreading disease in humans. But almost as soon as it
did this, it began picking up other mutations.

Scientists have been able to track how the virus is evolving in swab
samples taken in Covid-19 testing centres (Credit: Prakash Mathema/Getty
Images)
With almost every person it infects, the virus changes very subtly –
picking up a letter in its genetic code here, another being deleted
there or swapped for something different. These occur usually because of
tiny errors as the virus takes over the cell's molecular machinery to
copy itself. Most have little effect other than helping scientists to
trace how the virus is spreading around the world. But occasionally a
mutation occurs that alters how quickly the virus spreads, how
infectious it might be or even the severity of the disease it causes.
This is leading to new variants of the virus emerging. The most recent
of these – the South African and Brazilian variants – are already
showing signs that the virus might be adapting to evade immunity in some
people. Although many of the tests are still preliminary on these new
Covid-19 variants, it is giving some clues about what might happen in
the future. (Read more about how Covid-19 might mutate in the future.)
Understanding what might be driving some of these changes to the virus
and what they do to its behaviour could prove essential as the pandemic
continues and as more people are vaccinated against the disease. Here
are some of the most important changes that Covid-19 has undergone so far.
The super shedder
The mutation that allowed furin to cut the spike protein was already
present in the Covid-19 virus as it began to infect people in Wuhan in
early December. A few short months later, the first cases began to be
detected in Europe and a major change in the virus occurred that would
prove significant for the course of the pandemic.
Although there is now evidence to suggest Covid-19 had arrived in Europe
as early as December 2019, the virus was initially spotted spreading in
northern Italy in February 2020.
Samples taken from there on 20 February revealed the virus had undergone
a mutation on the spike protein that dramatically increased the number
of viral particles that were shed by infected cells, particularly in the
upper respiratory tract of patients.
The mutation may have also left the virus more vulnerable to antibodies,
meaning it was less able to cause reinfections in people
Recent analysis, however, suggests this variant may also have originated
in China and had been circulating in a number of provinces there in late
January 2020. It was even found to have made its way to Bavaria,
Germany, on 28 January 2020 via someone travelling from Shanghai,
suggesting it was introduced to Europe on a number of occasions from China.
The mutation the virus picked up is known as D614G, and this change
seems to have enabled the virus to spread more quickly between people,
probably because infected people coughed and breathed more of the virus out.
D614G gives the Covid-19 spike protein a more "open" structure, which
improves its ability to bind to another receptor found on the surface of
human cells called ACE2. Covid-19's ability to bind to ACE2 was already
known to be one of the reasons it had been able to start infecting
humans in the first place, but this new mutation gave it an increased
ability to target human cells.
You might also be interested in:
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Subsequent research has suggested that D614G made the virus more
infectious than the original version that emerged from Wuhan and appears
to have been more common in younger people. But this also came at a cost
– the mutation may have also left the virus more vulnerable to
antibodies, meaning it was less able to cause reinfections in people who
had already had the disease. This also meant it could be combated using
convalescent plasma from patients who had already recovered.
Despite this, the D614G variant quickly became the dominant form of the
virus around the world.

The new British variant of Covid-19 has several mutations on the spike
protein that allows the virus to bind to human cells (Credit: Science
Photo Library/Getty Images)
The holiday virus
Then, as lockdowns eased in Europe over the summer and international
travel began to rise again, another significant new variant of Covid-19
emerged in Spain. First detected in June 2020, it spread throughout
Europe and by September it accounted for 50-70% of cases in Switzerland,
Ireland and the UK.
Named 20A.EU1, or more commonly the "Spanish variant", this version of
Covid-19 picked up a mutation on its spike protein that was designated
A222V. But the mutation does not occur in an area that binds to the cell
surface, so is unlikely to have produced increased infectivity. Instead,
researchers believe its rapid spread and high prevalence is more
incidental – due to the spurt of travel that occurred over the summer as
people squeezed in a holiday while restrictions were eased.
The antibody evader
While A222V mutations don't appear to have led to a dramatic change in
the virus's behaviour, another mutation that emerged in Scotland during
March 2020 set some alarm bells ringing. This mutation – known as N439K
– was discovered in around 500 samples taken from patients in Scotland
but by June appears to have died out in the country, possibly due to the
reduced spread thanks to strict lockdown restrictions.
The mutation to the Covid-19 spike protein not only appears to have
increased its ability to bind to ACE2 on human cells but variants
carrying this mutation have also shown some resistance to antibodies
taken from patients who have recovered from the virus. It has raised
concerns about the virus's ability to cause reinfections. But experts
say that it does not appear to cause any increase in severity of the
disease in patients. A recent report by the Covid-19 Genomics UK
Consortium (Cog UK) adds "there is no evidence that this mutation will
allow the virus to impair the immunity triggered by vaccines".
The H69/V70 deletion mutation increases the infectivity by twofold
In the autumn, however, new occurrences of this mutation in Covid-19
appeared – apparently independent of those seen in Scotland – elsewhere
in Europe and also in the US where they continue to spread. It is also
now occurring alongside another mutation – the deletion of two
apparently key amino acids on the spike protein, H69 and V70.
The repeat offender
In fact, the H69/V70 deletion has been popping up all over the world.
Scientists first began seeing it in samples in Thailand in January 2020
and then in Germany the following month, although both appear to have
occurred independently.
The H69/V70 deletion has been found to produce a change in the shape of
the Covid-19 spike protein so that a loop of molecules that normally
protrude from it are pulled in tighter. Although it is not totally clear
what benefit this might give the virus, it has been suggested it may be
an adaptation by the virus as it tries to evade the immune system,
although no change in the severity of the disease or impact on vaccines
has been spotted.
Ravinda Gupta, a clinical microbiologist at the University of Cambridge
who was among the first to identify the B117 variant, says the H69/V70
deletion mutation "increases the infectivity by twofold".

Millions of mink have been culled in Denmark after a variant of Covid-19
was found to be passing from the animals to humans (Credit: Mads Claus
Rasmussen/Getty Images)
An analysis of virus sequencing data from around the world suggests
H69/V70 deletions have occurred multiple times in Covid-19. For much of
last year it spread quietly, then a cluster of patients infected with
the virus carrying a H69/V70 deletion appeared in Denmark. This mutation
was appearing in a version of the virus that was being passed from mink
on farms to humans. While analysis showed the virus had mutated slightly
to become more infectious to the animals, some early data suggested it
was also less sensitive to antibodies contained in the blood serum of
patients who had recovered from Covid-19.
In August, however, the H69/V70 deletion started to become far more
common and was appearing in virus samples alongside the N439K mutation.
The British variant
This same H69/V70 deletion is one of the main features in the rapidly
spreading B117 "British" variant of Covid-19. Alongside this change,
B117 has accumulated 16 other mutations on its spike protein. "Many of
the mutations that are seen in this new variant are ones that we haven't
really seen before," says Gupta.
Among those is a mutation neighbouring the furin cleavage site on the
spike protein that proved so important in Covid-19's ability to become a
pandemic strain in the first place. This mutation, known as P681H, has
been found in other variants around the world before, including in a
lineage of the virus that emerged in Nigeria in December, called B11207.
The difference with the British variant is that it carries another
important mutation known as N501Y, which occurs in a key region the
virus uses to bind to cells. It is thought to help the virus bind more
tightly to the ACE2 receptor on the outside of cells.
Some public health officials are now predicting that B117 will become
the dominant form of Covid-19 in many countries
Although the exact impact of the other individual mutations that have
occurred in the British variant are still to be fully explored, when
combined, they have led the virus to become more transmissible between
people. This is perhaps because those infected with the virus produce
more infectious particles than with previous variants. It mean more of
the virus is expelled in tiny droplets by infected individuals when they
cough, talk and breathe.
Scientists have estimated that B117 replicates itself twice as fast as
the strain that emerged from Wuhan. Some public health officials are now
predicting that B117 will become the dominant form of Covid-19 in many
countries, including the US.
Exactly how the British variant occurred is still not clear, although it
is not thought to have accumulated so many mutations gradually. Their
sudden appearance together is a clue for some researchers.
"The working hypothesis is that this happened in a chronically infected
individual," says Gupta. There have been at least two cases of H69/V70
deletions occurring alongside other mutations in patients who have been
chronically ill with Covid-19 – one in an elderly woman in Moscow,
Russia, and the man in Cambridge, UK.
Both had received treatment for cancer which is thought to have reduced
the ability of their immune systems to fight off Covid-19. Because the
patients were infected for so long, the virus had time to replicate to
high levels in their bodies and accumulate mutations. When the patients
were given antibody therapy, those versions of the virus that were
better able to escape or outpace the treatment survived.

News of the B117 variant spreading rapidly in England led many countries
to close their borders temporarily, leading to long tailbacks (Credit:
William Edwards/Getty Images)
"We don't know where this might have happened yet with B117, but in
long-term infections the virus has a chance of fighting off a bit of
genetic pressure from a treatment," adds Gupta.
Recent mortality data released in Britain seems to suggest that the B117
variant is up to 30% deadlier than the earlier versions of the virus,
but this is yet to be confirmed in peer-reviewed scientific studies.
Even so, Gupta doesn't believe B117 will pose a problem for the current
vaccines being rolled out around the world. One recent study showed that
antibodies produced by participants in the Pfizer vaccine trial do seem
to act against this variant while results from the clinical trial of the
Novavax vaccine suggest it is almost as effective against the B117 as it
was against the original strain.
"But this is a warning sign that we need to not be complacent," says Gupta.
The South African Variant
Shortly after news of the B117 variant broke, scientists in South Africa
revealed that they too had identified another mutated Covid-19 virus
spreading within their own country.
"Following the first wave of SARS-CoV-2, we observed rapid resurgence of
infections in two regions of South Africa – the Eastern and Western Cape
Provinces," says Carolyn Williamson, head of the division of virology at
the University of Cape Town. She and her colleagues intensified their
sequencing of viruses from Nelson Mandela Bay and Garden Route district
in these two areas and found that a new variant had emerged in
mid-October and rapidly come to dominate in these two regions by the end
of November. By December the variant – called 501Y.V2 or B1351 – had
spread to a number of other areas of South Africa and was also detected
in neighbouring Zambia. It has since been found in at least 20 other
countries in travellers and has shown signs of spreading locally in some
too.
A recent study has shown that the South African variant is able to
escape antibodies in the blood plasma of patients who caught Covid-19
during the first wave of the pandemic. While this could be seen as a
worrying sign that current Covid-19 vaccines may be less effective
against this variant, it is important to remember that antibodies only
form one part of the immune system's response to the virus. Other types
of immunity, such as that provided by T cells, could still be effective,
although this has still to be tested.
A virus that is more transmissible and less pathogenic is more likely to
survive – Carolyn Williamson
Williamson and her colleagues found that this version of the Covid-19
virus carries eight distinctive mutations in the spike protein,
including three that are thought to have contributed to its higher
transmissibility.
"We do not know how this variant emerged," says Williamson. But she
speculates that it may have also occurred in someone with a long-lasting
infection. "Usually SARS-CoV-2 is an acute infection and rapidly
cleared... in some individuals there may be ongoing replication allowing
for viral evolution to occur."
Among the mutations Williamson and her team detected was the N501Y
mutation also seen in the British B117 variant. Another of the mutations
– K417N – has been suggested to combine with N501Y to increase the
strength with which the virus can bind to the ACE2 receptor on human
cells, but other computer modelling work has suggested K417N may
counteract the increased binding seen in N501Y.
There is currently no indication it causes more serious disease, but it
seems to spread more rapidly than previous forms of the virus. "A virus
that is more transmissible and less pathogenic is more likely to
survive," says Williamson. This is because if a virus kills its host too
quickly, it will not have time to replicate as much and spread to other
people.

The new variant spreading around Brazil has shown signs that it can
reinfect people who have already had the virus (Credit: Mauro
Pimentel/Getty Images)
Studies have suggested, however, that the K417N mutation may reduce the
virus's sensitivity to human antibodies. A third mutation called E484K –
which is not present in the British variant – also seems to reduce the
virus's vulnerability to antibodies. One study suggests that changes to
the E484 site in the spike protein can produce a 10-fold reduction in
the ability of some antibodies to neutralise it.
Results from a small trial of the Novavax vaccine against Covid-19
suggests that it is less effective against the South African variant
than it is against the original and British variants of the virus.
Antibodies produced by the Pfizer vaccine have also been found to be
slightly less effective against the South African variant. But whether
the South African variant will also be less vulnerable to other types of
immunity such as those provided by T cells is not yet clear. (Read more
about the importance of T cell immunity.)
The Brazilian variant
The E484K mutation is proving to be important in another concerning
variant that is now spreading around the world. The P1 variant contains
20 unique mutations, including the E484K change found in the South
African variant. It seems to have first emerged in the city of Manaus,
Amazonas state, in north Brazil, which has been particularly severely
hit by the pandemic. The variant was also detected in four travellers
who had flown from northern Brazil to Japan on 2 January this year.
This version of the virus also carries the N501Y mutation alongside the
E484K change and one called K417T. Although the exact consequences of
these mutations are still being investigated by scientists, the strain
has been designated as a "Variant of Concern" by global health officials.
The emergence of the Brazilian P1 variant raises concerns that the virus
may be developing an increased propensity for re-infecting individuals,
according to the US's Centre for Disease Control and Prevention.
We already have good information from laboratory studies about which
amino acid changes are likely to be the most worrisome
Another Brazilian variant, designated P2, has been found in two people
who caught Covid-19 a couple of months apart. This variant, however,
carries the E484K mutation, but lacks the other two that are concerning
scientists about P1.
While the E484K mutations have raised concerns that the virus might be
evolving in ways that allow it to evade parts of the immune system,
scientists from the Cog-UK consortium have said there is no evidence yet
to suggest that it is affecting the effectiveness of the vaccines.
But as Covid-19 continues to mutate, many virologists are looking at
ways to help them get ahead of the virus. Michael Worobey, a viral
evolutionary biologist at the University of Arizona, and his team are
developing an "early warning" test that might help detect new
potentially worrying variants of Covid-19 as they start spreading. (Read
more about how Covid-19 might mutate in the future.)
"We already have good information from laboratory studies about which
amino acid changes are likely to be the most worrisome," he says. "So,
we can use this to hopefully catch them early." That should help public
health officials and vaccine manufacturers be more prepared when the
virus undergoes its next major change.
* This article was updated on 29 January 2021 to include Novavax vaccine
trial results and again on 2 February to add details of a study on the
Pfizer vaccine's effectiveness against the South African variant.
--
--
So many immigrant groups have swept through our town
that Brooklyn, like Atlantis, reaches mythological
proportions in the mind of the world - RI Safir 1998
http://www.mrbrklyn.com
DRM is THEFT - We are the STAKEHOLDERS - RI Safir 2002
http://www.nylxs.com - Leadership Development in Free Software
http://www.brooklyn-living.com
Being so tracked is for FARM ANIMALS and extermination camps,
but incompatible with living as a free human being. -RI Safir 2013
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