Unvaccinated as ‘variant factories’?

Dr Gerry Quinn

By Dr Gerry Quinn
Post-doctoral Researcher in Microbiology and Immunology

Media continues to promote unscientific ‘othering’ of the unvaccinated


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 the 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 (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 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:

Top Covid expert hits out at unvaccinated people as ‘variant factories’

VAX PAIN Unvaccinated people are ‘Covid variant factories’ as fears loom mutations could prolong pandemic, scientists warn

Top Covid expert hits out at unvaccinated people as ‘variant factories’

The effects of virus variants on COVID-19 vaccines

Postvaccination COVID-19 among Healthcare Workers, Israel

Doshi, P (2020) Covid-19: Do many people have pre-existing immunity?

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

Neilsen et al (2020) SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

Wang et al (2021) Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants

10 Martin (2014) Adaptation in the innate immune system and heterologous innate immunity

11 Van der Made et al (2020) Presence of Genetic Variants Among Young Men With Severe COVID-19

12 King (2020). An uncommon cold. New Scientist (1971) 246, 32–35

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

14 SARS-CoV-2 variants of concern and variants under investigation in England

15 Kustin et al (2021) Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals

16 Ioannou et al (2021) Transmission of SARS-CoV-2 variant B.1.1.7 among vaccinated health care workers

17 mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variant

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