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<div class="header reader-header reader-show-element">(Game, set
and match for the unvaccinated)</div>
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<div class="header reader-header reader-show-element"><a
class="domain reader-domain"
href="https://www.hartgroup.org/unvaccinated-as-variant-factories/">hartgroup.org</a>
<h1 class="reader-title">Unvaccinated as ‘variant factories’?</h1>
<div class="credits reader-credits">By Dr Gerry Quinn <br>
</div>
<div class="credits reader-credits">Post-doctoral Researcher in
Microbiology and Immunology</div>
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<div class="reader-estimated-time" dir="ltr">11-14 minutes</div>
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<figure><img
src="https://www.hartgroup.org/wp-content/uploads/2021/07/Virus-1024x800.jpg"
alt="" width="287" height="224"></figure>
<p><em>Media continues to promote unscientific
‘othering’ of the unvaccinated</em></p>
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<hr>
<p>Several media outlets in the UK have simultaneously
released a story alleging that unvaccinated people are
risking their own health and will become potential
factories of coronavirus variants.<sup>1,2</sup></p>
<p>Dr Schaffner said if infections continue to spread
among the unvaccinated, it can hamper the<a
href="https://www.independent.co.uk/topic/pandemic">
pandemic</a> response. “<em>When it does, it mutates
and it could throw off a variant mutation that is even
more serious down the road</em>,” said Dr Schaffner
according to CNN.<sup>3</sup></p>
<p>Similarly the <a
href="https://www.independent.co.uk/topic/world-health-organisation">World
Health Organisation</a> (WHO) recently stated that
“The more we allow the virus to spread, the more
opportunity the virus has to change.”<sup>4</sup></p>
<p>Given the lack of proper follow-up data of vaccinated
individuals, the real life picture of the epidemiology
of vaccinated versus unvaccinated is incredibly muddy.
This in and of itself is something of a scandal given
that the vaccines use an entirely novel technology, the
efficacy of which has yet to be determined. Indeed in
one study in Israel, it is noted that ‘<em>clinicians
should have a high level of suspicion of reported
symptoms and avoid dismissing complaints as
vaccine-related until true infection is ruled out and
vaccinees are tested</em>.’<sup>5</sup> </p>
<p><strong>Are the unvaccinated fully exposed to the risk
of virus infection?</strong></p>
<p>There is an assumption in many of these articles that
the immunity of populations and individuals are the
same. However, most people by now will be aware that the
risk of serious illness with the SARS-CoV-2 virus is
more likely in the elderly, those with weak immune
responses and those in certain at-risk categories such
as those receiving cancer therapy or cardiac patients.</p>
<p>The vast majority of the vulnerable population have now
been immunised. The proportionate risk to the rest of
the UK population has always been significantly lower;
in some instances as much as 1000-fold.</p>
<p>There is also an underlying assumption in these
articles that there is no immunity without vaccines.
This is simply not the case. In September 2020, it was
shown that up to 50% of the UK population displayed
various forms of T-cell immunity to the new virus from
exposure to previous endemic viruses.<sup>6</sup> More
recently it was suggested that this could be as high as
81%.<sup>7</sup> In addition, a recent study found that
rapid and efficient memory-type immune responses occur
reliably in virtually all unvaccinated individuals who
are exposed to SARS-CoV-2, whether they were symptomatic
or not.<sup>8</sup> So the number of naturally immune
individuals will have risen through exposure to the
virus over time, even in the absence of symptomatic
disease. </p>
<p><strong>Which gives the better protection, natural
immunity or vaccination?</strong></p>
<p>This topic has been explored in depth in an <a
href="https://www.hartgroup.org/natural-vs-vaccine-immunity/">earlier
briefing paper</a> and the simple answer is that
natural immunity is superior to the highly specific
antibody immunity acquired from vaccination. We must
also factor in the additional risks (e.g. adverse events
such as myocarditis, clotting etc.) that occur from
vaccination itself when asking the question of which is
‘better’. This risk-benefit analysis will be vastly
different between age cohorts due to the different
profile of the disease in the young and old. </p>
<p>Once a person has recovered from SARS-CoV-2 they will
have developed natural immunity. This immunity covers a
wide spectrum of defensive mechanisms. Most people are
aware of antibodies and their important role in the
neutralization of viruses. In the case of natural
immunity, these antibodies are generated to all parts of
the virus and not just the spike protein. This gives
people the ability to fend off many variations of
SARS-CoV-2. This, along with the additional tools
(e.g.innate, T-cell and mucosal immunity) provides a
comprehensive arsenal of future protection from
SARS-CoV-2 infection and structurally related viruses. </p>
<p>A recent study of people who developed natural immunity
during the first wave of SARS-CoV-2 showed that their
plasma contains four antibodies that are extremely
potent against 23 variants of SARS including variants of
concern.<sup>9</sup> To add to this protection, it is
even thought that the innate immune system which is the
first line of defence against disease can be trained to
have a decreased activation threshold to new pathogens
that are structurally similar to those that have been
encountered previously.<sup>10</sup> </p>
<p>Unfortunately many of the novel COVID vaccines are
designed to evade most of the innate immune system so
they will not prime this process. The importance of the
innate immune system can be seen in people who have
deficiencies in the production of interferon, an
important signalling compound in the innate immune
system. People with this deficiency have higher rates of
severe illness and death.<sup>11</sup> </p>
<p>Natural immunity is superior to vaccination-induced
immunity because it includes the innate immune defences
as well as specific immunity which is directed at
multiple parts of the virus and not just the spike
protein targeted by vaccine-induced immunity.</p>
<p><strong>Do virus mutations specifically occur in the
unvaccinated?</strong></p>
<p>Mutations occur quite frequently in RNA viruses. These
typically arise when the virus is under selective
pressure, for example by antibodies that limit but do
not eliminate viral replication. The positive news is
that the older strains of cold virus which are now
relatively harmless were once thought to be a lot more
dangerous, but have now mutated through a series of
variants into something less harmful.<sup>12</sup> </p>
<p>In early April 2021, there was a great worry among some
scientists that sub-optimal vaccination strategies would
create a selection pressure on the virus facilitating
the emergence of variants.<sup>13</sup> </p>
<p>However we can now see that the case fatality rate of
the latest Delta variant has dropped to 0.1%. Previously
it had been calculated to be 1.9 % for the Alpha (Kent)
variant. The infection fatality rate will be lower still
as not all cases are diagnosed.<sup>14</sup></p>
<p>The question as to whether variants emerge more in the
vaccinated or unvaccinated have been the subject of many
research studies, most connected to the efficiency of
the vaccination strategy. In one study in Israel, in
April 2021, the Beta (SA) variant was found in eight
times as many of the vaccinated as the unvaccinated.<sup>15</sup>
However, in a more recent study from Greece, researchers
found that there was no significant difference in the
number of infections of the Beta (SA) variant between
vaccinated and unvaccinated in health care workers.<sup>16</sup> </p>
<p>New variants would still have emerged without the
introduction of vaccinations as they did prior to the
vaccine rollout. The virus mutation rate is constant and
vaccination has not altered this rate. What is less
clear is whether vaccination has increased the rate at
which certain variants come to predominate. Because
vaccination targets a specific immune response to the
spike protein, it is theoretically possible that
variants that can evade this particular immune response
will be selected for in the vaccinated population. The
unvaccinated have a very broad immune response to all
parts of the virus through different parts of the immune
system which might not create the same selection
pressure. This hypothesis rather suggests the opposite
of what is being propagated in the media. It is a topic
that needs careful scientific enquiry instead of the
headline grabbing ‘othering’ of those who do not wish to
be vaccinated at this time. </p>
<p><strong>Coincidences between mass vaccination rollout
and new variants emerging</strong></p>
<p>The first three significant new variants emerged from
Brazil, South Africa and the UK which were all sites of
vaccine trials. There have since been further variants
which have appeared after vaccination roll out in
several other countries. Some experts have speculated on
the coincidence of such events and this phenomenon is
currently being studied. In one study recently posted as
a preprint and not yet formally reviewed, Theodora
Hatziioannou, a virologist at Rockefeller University in
New York, and her colleagues created a
‘pseudo-coronavirus’ carrying a non-variant version of
the spike protein. This was grown in the presence of
individual antibodies extracted from the blood of people
who had received one of the two FDA-authorized COVID-19
vaccines, one from Pfizer/BioNTech and one from Moderna.
Some antibodies spurred the pseudo-SARS-CoV-2 to acquire
various mutations. </p>
<p>They tried the experiment again with no antibodies
present and none of the three mutations — the ones in
the triple-variant threat — evolved the same evasive
manoeuvres. </p>
<p>“<em>This data shows that these mutations accumulating
in the spike protein are antibody escape mutations</em>,”
says Hatziioannou. “<em>As soon as you add a specific
antibody, you see specific mutations.</em>” </p>
<p>Hatziioannou and others think there are also clues to
be found in the genomes of viruses that took up
long-term residence in the bodies of immunocompromised
COVID-19 patients. The prevailing theory was that escape
mutations could have emerged in people with chronic
infections, who might be receiving monoclonal antibody
treatments or convalescent plasma, and therefore
supercharging the selective pressures the virus has to
contend with.<sup>17</sup></p>
<p><strong>Conclusion</strong></p>
<p>All viruses mutate and trying to blame humans for this
phenomenon is as stupid as it is divisive.</p>
<p>The current hospitalisation rate and mortality rate
from the Delta variants is considerably lower than for
previous variants and therefore the scare stories around
it have been utterly misplaced.</p>
<p>Whether mass vaccination leads to selection pressure
that results in variants that can evade vaccine induced
immunity will become evident over time as we examine the
international data and timings of vaccine roll-outs. It
is certainly a topic that needs careful scrutiny as
there is the as yet unproven (but not discounted)
theoretical possibility that vaccination may be making
the situation of ‘mutant variants’ worse. </p>
<p><strong>Endnotes:<br>
</strong><br>
1 <a
href="https://www.independent.co.uk/news/world/americas/covid-vaccine-variant-factories-william-schaffner-b1878187.html"
target="_blank" rel="noreferrer noopener">Top Covid
expert hits out at unvaccinated people as ‘variant
factories’</a></p>
<p>2 <a
href="https://www.thesun.co.uk/news/15486850/unvaccinated-covid-variant-factories-prolong-pandemic/"
target="_blank" rel="noreferrer noopener">VAX PAIN
Unvaccinated people are ‘Covid variant factories’ as
fears loom mutations could prolong pandemic,
scientists warn</a></p>
<p>3 <a
href="https://www.independent.co.uk/news/world/americas/covid-vaccine-variant-factories-william-schaffner-b1878187.html"
target="_blank" rel="noreferrer noopener">Top Covid
expert hits out at unvaccinated people as ‘variant
factories’</a></p>
<p>4 <a
href="https://www.who.int/news-room/feature-stories/detail/the-effects-of-virus-variants-on-covid-19-vaccines"
target="_blank" rel="noreferrer noopener">The effects
of virus variants on COVID-19 vaccines</a></p>
<p>5 <a
href="https://wwwnc.cdc.gov/eid/article/27/4/21-0016_article"
target="_blank" rel="noreferrer noopener">Postvaccination
COVID-19 among Healthcare Workers, Israel</a></p>
<p>6 <a href="https://www.bmj.com/content/370/bmj.m3563"
target="_blank" rel="noreferrer noopener">Doshi, P
(2020) Covid-19: Do many people have pre-existing
immunity?</a></p>
<p>7 <a
href="https://www.nature.com/articles/s41590-020-00808-x.pdf"
target="_blank" rel="noreferrer noopener">https://www.nature.com/articles/s41590-020-00808-x.pdf</a></p>
<p>8 <a
href="https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00203-6/fulltext"
target="_blank" rel="noreferrer noopener">Neilsen et
al (2020) SARS-CoV-2 elicits robust adaptive immune
responses regardless of disease severity</a></p>
<p>9 <a
href="https://science.sciencemag.org/content/early/2021/06/30/science.abh1766.full"
target="_blank" rel="noreferrer noopener">Wang et al
(2021) Ultrapotent antibodies against diverse and
highly transmissible SARS-CoV-2 variants</a></p>
<p>10 <a
href="https://link.springer.com/article/10.1007/s00018-014-1676-2"
target="_blank" rel="noreferrer noopener">Martin
(2014) Adaptation in the innate immune system and
heterologous innate immunity</a></p>
<p>11 <a
href="https://jamanetwork.com/journals/jama/fullarticle/2768926"
target="_blank" rel="noreferrer noopener">Van der Made
et al (2020) Presence of Genetic Variants Among Young
Men With Severe COVID-19</a></p>
<p>12 <a
href="https://www.sciencedirect.com/science/article/abs/pii/S0262407920308629?via%3Dihub"
target="_blank" rel="noreferrer noopener">King (2020).
An uncommon cold. New Scientist (1971) 246, 32–35</a></p>
<p>13 <a
href="https://doi.org/10.1016/S0140-6736(21)00455-4"
target="_blank" rel="noreferrer noopener">Robertson,
J.F.R., Sewell, H.F., Stewart, M., 2021. Delayed
second dose of the BNT162b2 vaccine: innovation or
misguided conjecture? Lancet 397, 879–880</a></p>
<p>14 <a
href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/993879/Variants_of_Concern_VOC_Technical_Briefing_15.pdf"
target="_blank" rel="noreferrer noopener">SARS-CoV-2
variants of concern and variants under investigation
in England</a></p>
<p>15 <a
href="https://www.nature.com/articles/s41591-021-01413-7"
target="_blank" rel="noreferrer noopener">Kustin et al
(2021) Evidence for increased breakthrough rates of
SARS-CoV-2 variants of concern in
BNT162b2-mRNA-vaccinated individuals</a></p>
<p>16 <a
href="https://www.tandfonline.com/doi/full/10.1080/23744235.2021.1945139"
target="_blank" rel="noreferrer noopener">Ioannou et
al (2021) Transmission of SARS-CoV-2 variant B.1.1.7
among vaccinated health care workers</a></p>
<p>17 <a
href="https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1"
target="_blank" rel="noreferrer noopener">mRNA
vaccine-elicited antibodies to SARS-CoV-2 and
circulating variant</a></p>
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