[D66] [JD: 163] Unvaccinated as ‘variant factories’?

[R.O.]

(Game, set and match for the unvaccinated)

hartgroup.org
<https://www.hartgroup.org/unvaccinated-as-variant-factories/>


  Unvaccinated as ‘variant factories’?

By Dr Gerry Quinn
Post-doctoral Researcher in Microbiology and Immunology
11-14 minutes
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/Media continues to promote unscientific ‘othering’ of the unvaccinated/

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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.^1,2

Dr Schaffner said if infections continue to spread among the
unvaccinated, it can hamper thepandemic
<https://www.independent.co.uk/topic/pandemic> response. “/When it does,
it mutates and it could throw off a variant mutation that is even more
serious down the road/,” said Dr Schaffner according to CNN.^3

Similarly the World Health Organisation
<https://www.independent.co.uk/topic/world-health-organisation> (WHO)
recently stated that “The more we allow the virus to spread, the more
opportunity the virus has to change.”^4

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 ‘/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/.’^5  

*Are the unvaccinated fully exposed to the risk of virus infection?*

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.

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.

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.^6 More recently it was suggested that this could be as
high as 81%.^7 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.^8 So the number of naturally immune individuals
will have risen through exposure to the virus over time, even in the
absence of symptomatic disease. 

*Which gives the better protection, natural immunity or vaccination?*

This topic has been explored in depth in an earlier briefing paper
<https://www.hartgroup.org/natural-vs-vaccine-immunity/> 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. 

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. 

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.^9 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.^10  

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.^11  

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.

*Do virus mutations specifically occur in the unvaccinated?*

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.^12  

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.^13  

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.^14

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.^15 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.^16  

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. 

*Coincidences between mass vaccination rollout and new variants emerging*

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. 

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. 

“/This data shows that these mutations accumulating in the spike protein
are antibody escape mutations/,” says Hatziioannou. “/As soon as you add
a specific antibody, you see specific mutations./” 

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.^17

*Conclusion*

All viruses mutate and trying to blame humans for this phenomenon is as
stupid as it is divisive.

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.

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. 

*Endnotes:
*
1 Top Covid expert hits out at unvaccinated people as ‘variant
factories’
<https://www.independent.co.uk/news/world/americas/covid-vaccine-variant-factories-william-schaffner-b1878187.html>

2 VAX PAIN Unvaccinated people are ‘Covid variant factories’ as fears
loom mutations could prolong pandemic, scientists warn
<https://www.thesun.co.uk/news/15486850/unvaccinated-covid-variant-factories-prolong-pandemic/>

3 Top Covid expert hits out at unvaccinated people as ‘variant
factories’
<https://www.independent.co.uk/news/world/americas/covid-vaccine-variant-factories-william-schaffner-b1878187.html>

4 The effects of virus variants on COVID-19 vaccines
<https://www.who.int/news-room/feature-stories/detail/the-effects-of-virus-variants-on-covid-19-vaccines>

5 Postvaccination COVID-19 among Healthcare Workers, Israel
<https://wwwnc.cdc.gov/eid/article/27/4/21-0016_article>

6 Doshi, P (2020) Covid-19: Do many people have pre-existing immunity?
<https://www.bmj.com/content/370/bmj.m3563>

7 https://www.nature.com/articles/s41590-020-00808-x.pdf
<https://www.nature.com/articles/s41590-020-00808-x.pdf>

8 Neilsen et al (2020) SARS-CoV-2 elicits robust adaptive immune
responses regardless of disease severity
<https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(21)00203-6/fulltext>

9 Wang et al (2021) Ultrapotent antibodies against diverse and highly
transmissible SARS-CoV-2 variants
<https://science.sciencemag.org/content/early/2021/06/30/science.abh1766.full>

10 Martin (2014) Adaptation in the innate immune system and heterologous
innate immunity
<https://link.springer.com/article/10.1007/s00018-014-1676-2>

11 Van der Made et al (2020) Presence of Genetic Variants Among Young
Men With Severe COVID-19
<https://jamanetwork.com/journals/jama/fullarticle/2768926>

12 King (2020). An uncommon cold. New Scientist (1971) 246, 32–35
<https://www.sciencedirect.com/science/article/abs/pii/S0262407920308629?via%3Dihub>

13 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 <https://doi.org/10.1016/S0140-6736(21)00455-4>

14 SARS-CoV-2 variants of concern and variants under investigation in
England
<https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/993879/Variants_of_Concern_VOC_Technical_Briefing_15.pdf>

15 Kustin et al (2021) Evidence for increased breakthrough rates of
SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals
<https://www.nature.com/articles/s41591-021-01413-7>

16 Ioannou et al (2021) Transmission of SARS-CoV-2 variant B.1.1.7 among
vaccinated health care workers
<https://www.tandfonline.com/doi/full/10.1080/23744235.2021.1945139>

17 mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating
variant <https://www.biorxiv.org/content/10.1101/2021.01.15.426911v1>


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