Moving Goalposts: COVID19 Variants & Herd Immunity from Vaccines

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TLDRInTheFront: Currently-known variants of SARS-COV-2 move the goalposts on public health responses and raise the bar for reaching herd immunity through vaccination. Evolution, too, is a complicated “frenemy” in this fight and understanding the forces involved help us make sense of how to better manage the pandemic going forward.

FullContextInTheBack: It is about a year into the COVID-19 pandemic now, and the struggle to maintain control over it seems more desperate than ever. There are a lot of sick people around with COVID-19 – more than at any point in the last 13 months – and the pandemic is claiming more lives in an accelerating pattern every day, at least for now*. On top of that the news of variants of the virus that are more contagious, that are resistant to certain immunotherapies, or that cause erroneous test results, has shocked people around the world. Lets talk about those. (To help understand the terms: mutation, isolate, strain, and variant see this post on “Playing Darts.”)

 

The Rogues’ Gallery: The list of known variants

The list of variants grow every day, but a few of the most important (and a summary of their most important traits) are ^{[1,5,18,20,21]}:

• D614G mutation ^[25,21] – This mutation leading to a number of variants was first identified in Europe over the spring/summer of 2020. It appears to be at least somewhat more contagious than the at the time wild-type**. This variant also appears correlated with the increasing prevalence of anosmia. Now, it is so prevalent as to be considered the new wild-type.

• Cluster 5 / ΔFVI-Spike ^[6,7,8,21]– This variant appeared in Denmark, connected with mink farms there. It appeared to decrease the effectiveness of neutralizing antibodies and probably reduced (though likely did not eliminate) the efficacy of vaccines to wild-type virus. The variant has been declared extinct after a swift, thorough lockdown and public health intervention that included culling nearly the entire population of mink in Denmark.

• B.1.1.7 / VOC-202012/01*** ^[2,3,4,21]– This variant was identified in fall/winter of 2020 in the southeast of England, the hypothesis being that it developed inside a patient with “long haul” COVID-19. That is due to microevolutionary forces, to be discussed later. It appears to be substantially more contagious (due to the N501Y mutation) than wild-type, and is correlated with higher rates of erroneous results on one common COVID-19 testing platform.

• B.1.1.207 ^[23,21]– This variant first appeared in Nigeria in August of 2020. The implications that the mutations in this variant have on virulence, transmissibility, and immunogenicity are not fully understood, but it has not grown to rapid prominence or been associated with a substantial increase in mortality so the effects appear to likely be modest.

• 501.V2 (aka B.1.351) ^[9,10,11,21]– This variant was first detected in South Africa on 18 Dec 2020. It appears to be correlated with higher virulence (meaning more severe illness), with the effect being most pronounced in younger people without comorbidities. In addition, it seems to be correlated with a “second wave” of COVID-19 in South Africa, suggesting that it is more transmissible than wild type. Definitive evidence of these claims is still being sought after. There’s also evidence that one of the mutations characteristic of this variant allow it to escape neutralizing antibodies. (This will be covered more in-depth in a followup-article.)

• B.1.1.248 ^{[12,13,14,15,21]}– This variant was first detected in Tokyo on 5 Jan 2021 in travelers from Brazil. This variant appears to be correlated with an increase in transmissibility of the virus. It also has the same mutation that 501.V2 has which allows it to potentially escape neutralizing antibodies, and research into the effect of this is still ongoing.

• CAL.20C ^[16,17,21]– This variant was first detected in California in July of 2020. It has increased in prevalence from 0.1% at that time, to more than 36.4% in recent days, suggesting that there could be some effect on transmissibility. Additionally, the L452R mutation that is characteristic of this variant is known to decrease the effectiveness of some monoclonal antibodies, suggesting that it might have a broader effect on immunogenicity. Studies are ongoing.

 

… and that is only a subset. Genomic surveillance of COVID-19 has been ongoing throughout the world as the pandemic has burned through the global population, and there are literally tens of thousands of mutations that have been tracked. However, I have chosen this “rogues gallery” because these are known to or are thought to have a significant effect on the main three areas of epidemiological concern: transmissibility (how easily the virus spreads), virulence (how sick the virus makes people) and immunogenicity (whether a person immune to some other variant of the same virus is also immune to this virus, and to what extent).

 

But Why?: The Evolutionary Forces At Play

Evolution is happening all around us, all the time. We might think of the living world as a static – or at least slow-moving – but, especially at the smallest levels, it is staggeringly dynamic. Humanity uses this to its advantage some of the time, such as when developing new crop varieties or domesticating animals, but a lot of the time those forces work against us (think antibiotic resistance, or viruses evolving to infect humans instead of bats). However, the goal of evolution is not to help or to harm any one species. It is simply this:

 

Every population of living things exists to maintain or expand its population, as best it can. Whatever strategy they can pursue in furtherance of that goal, using the tools (genes) at their disposal, will be used thus. ^[24]

 

This is strictly about biology, not psychology. Ways of life for humans are much more complicated and (largely) irrelevant to the discussion of what is happening with COVID-19 itself. So, given that caveat, the thing we need to be asking ourselves about all of these mutations is “Does this help the virus reproduce?”

 

Does making people individually sicker help the virus to reproduce? No, not really. Very sick people naturally isolate themselves and/or seek medical attention, and that limits a virus’s ability to pass to new hosts. Thus, it is uncommon for viruses to evolve such that they become more deadly to their primary hosts. When they do, it is usually as a by-product of some other mutation that allows it to do something more evolutionarily useful.

 

Does spreading more easily help the virus to reproduce? Yes, absolutely! So, over time, viruses do tend to evolve to greater contagiousness. That is especially true for quickly spreading viruses responsible for pandemics, such as COVID-19, because past a certain point the viruses are competing against each other and so the one that spreads the fastest tends to get to the most susceptible hosts the quickest. This is also the most common mutation because it generally involves “perfecting” an existing function, and that is generally far simpler than gaining new abilities altogether.

 

Does gaining the ability to infect new host populations – or ones previously not susceptible to infection – help the virus spread? Yes, sometimes! Over time, new strains of a virus do tend to develop. That tends to happen more often to viruses where a widespread immunity exists to the wild-type, though, precisely because it is more “rewarding” in an evolutionary sense. That is, if there is a big pool of hosts that a virus stands to gain access to if it mutates through/past/around their existing immunity, then natural selection will much more strongly favor that mutation, and it will grow rapidly in prominence. If there is very little existing immunity to the virus, then those same conditions do not exist and it is less likely to happen. The other factor working against these kinds of mutations is complexity – it is often very, very difficult to work around the immune system, precisely because immune responses are targeted by the body to be as robust and effective as possible. It can happen, obviously, but it is difficult. The same can be said of “jumping species” to an entirely new set of hosts, such as what happened at the very beginning of the COVID-19 pandemic.

 

Finally, one must consider the math of evolution (though I promise I won’t make you do that math).

 

Mutations, even in RNA viruses, are various species of rare. The transcription errors at the heart of those mutations occur at a rate of about 2 per month in SARS-COV-2, which is about half that of Influenza and a quarter that of HIV ^[22]. However, the more viruses there are out in the world replicating, the more rolls of the proverbial dice there are going to be. That means that a major, uncontrolled viral pandemic that is burning its way through the global population of 8 billion people, replicating millions of times per person it infects, is going to mutate more often than a virus that only infects a handful of people before dying out. That holds true for intentional strategies like “induced herd immunity” strategy, as well as for lax public health measures in general. If it happens slowly, then the “reward” for breaching the existing immunity of the growing population of non-susceptible persons slowly increases, and if they are frequently “challenged” by the virus from coming into contact with it, then those dice keep being rolled (one more reason for vaccinated persons to keep wearing masks and maintaining social distance while the pandemic is still raging).

 

The Moving Goalposts of Herd Immunity

The math behind herd immunity is fundamentally fairly simple, if you know the R0 of a disease (the average # of people an average person will infect, if taking no precautions whatsoever and assuming total susceptibility in the population) – it is a fractional value of that R0 number. If R0 is 2, then 1/2 of your population needs to be immune to bring R below 1. If R0 is 5, then 4/5 of your population needs to be immune to bring R below 1. If R0 is 10, then 9/10 of your population needs to be immune to bring the R below 1 ^[19,27,28]. But, within that simplicity, hide some complicating factors. To start with, they are –

 

• Are all the immune persons and all the susceptible persons gathering together in their own groups? Then you will need to render some of those susceptible persons immune, or completely surround them with immune persons (while keeping them totally free of infection), in order to extend that blanket protection to them.

• How effective is your vaccine (or other strategy) at granting immunity? You need to divide your immunity number by that amount, meaning that if your vaccine is 2/3 (67%) effective and you need to render 2/3 of your population immune to bring the R below 1 then you need 2/3 divided by 2/3 = 100% of your population to be vaccinated.^[28]

• How is the R0 of the virus changing as the virus changes? If you start with a virus that has an R0 of 3, and then a mutation causes the R0 to change to 4, and then to 5, then your herd immunity number will climb from 67% to 75% to 80%. As a virus grows more contagious, herd immunity gets harder and harder to reach.

There are many more public health factors that need to be considered in how you respond to a virus, of course, but these are the most relevant for reaching and planning for herd immunity. When considering the variants thus far observed, the third factor is the most immediately relevant, because as they grow more transmissible that is expressed mathematically as a larger R0 value. As that increases, our slow march to herd immunity gets longer and longer.

 

The up-side of this, though, is that we know those variants exist. If (unlike the D614G mutation and like the Cluster 5 variant) we can successfully stamp the variants out, then we will not have to deal with them. In some cases that seems unlikely or it seems that it is too late (B.1.1.7 has been detected around the globe already, and CAL.20C is being detected in 30%+ of all samples in California right now, and B.1.1.248 has been circulating in Brazil for months), but in others it is still possible. If we act swiftly and surely, if we take precautions that probably seem more draconian than strictly necessary (for instance. Denmark culling nearly their entire domestic mink population)… then it is possible.

 

But what can *I* do?

It is natural to wonder, when this article dove into public health measures, science, vaccine deployment and government responses what an individual can do. The answer may be unsatisfying, but it’s true nonetheless:

 

Follow all public health guidance from local, state and national organizations, defaulting to the most stringent when you can or where they conflict. Wear a mask whenever outside of your home or interacting with persons who are not isolating with you. Get the vaccine when you can, and keep following that public health guidance after getting it, including for wearing of masks. When in doubt exercise reasonable caution, bearing in mind that the more prevalent the virus is in your community the more careful you have to be to avoid it. Remember that exceptions equal infections – people who regularly do unsafe things “just this once” will have their luck run out eventually. And, because fatigue is real, focus on making good habits rather than simply making good choices – choices take mental effort, whereas habits are mostly automatic.

 

We are a year into this, and it is likely elements will be with us for several months more if not a year or even more. Be prepared for this to be the midpoint, rather than the last chapter, in the pandemic. The less seriously we collectively take this the longer it will stretch on, so I cannot stress enough how important it is to form these healthy habits and keep to them whenever possible. I know that the population of people reading this are likely to already be doing much of the above, and are already taking this as seriously as they can, but it bore repeating all the same.

 

Stay safe out there, and may we stamp out this pandemic soon so that we can all slowly return to our normal social lives.

Sources:

1) https://en.wikipedia.org/wiki/Variants_of_SARS-CoV-2 (Wiki for List of variants of SARS-COV-2)

 

2) https://en.wikipedia.org/wiki/Variant_of_Concern_202012/01 (Wiki for B.1.1.7 / VOC-202012/01)

 

3) https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/947048/Technical_Briefing_VOC_SH_NJL2_SH2.pdf (Public Health England examination of B.1.1.7)

 

4) https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html (US Cases of B.1.1.7)

 

5) https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html (CDC Page summarizing information on emerging variants of COVID-19)

 

6) https://en.wikipedia.org/wiki/Cluster_5 (Wiki for Cluster 5)

 

7) https://www.ecdc.europa.eu/sites/default/files/documents/RRA-SARS-CoV-2-in-mink-12-nov-2020.pdf (European CDC examination of Cluster 5)

 

8) https://files.ssi.dk/Mink-cluster-5-short-report_AFO2 (Statens Serum Inst. [Dutch CDC] working paper on Cluster 5)

 

9) https://en.wikipedia.org/wiki/501.V2_variant (Wiki for 501.V2)

 

10) https://www.washingtonpost.com/world/africa/south-africa-coronavirus-second-wave/2020/12/18/d4a51aec-3ff7-11eb-b58b-1623f6267960_story.html (501.V2 connected to second wave of virus in South Africa)

 

11) https://www.reuters.com/article/us-health-coronavirus-britain-south-afri/uk-scientists-worry-vaccines-may-not-protect-against-safrican-coronavirus-variant-idUSKBN2990T3 (Scientists worry that as mutations accumulate, one will breach vaccine efficacy)

 

12) https://en.wikipedia.org/wiki/Lineage_B.1.1.248 (Wiki for B.1.1.248)

 

13) https://www.euroweeklynews.com/2021/01/13/brazil-confirms-the-circulation-of-a-new-amazon-rain-forest-variant-of-the-coronavirus/ (Brazil confirms new “Amazon Rainforest” variant of COVID-19 in circulation [B.1.1.248])

 

14) https://japantoday.com/category/national/corrected-update-3-japan-finds-new-coronavirus-variant-in-travellers-from-brazil (Japan finds B.1.1.248 in travelers from Brazil)

 

15) https://www.medrxiv.org/content/10.1101/2020.12.23.20248598v1 (Preprint analyzing genome of B.1.1.248)

 

16) https://www.medrxiv.org/content/10.1101/2021.01.18.21249786v1.full.pdf (Preprint paper analyzing CAL.20C)

 

17) https://www.cedars-sinai.org/newsroom/local-covid-19-strain-found-in-over-one-third-of-los-angeles-patients/ (CAL.20C found in over one-third of Los Angeles patients)

 

18) https://www.bbc.com/news/health-55659820 (How concerned should people be about the UK, South Africa and Brazil variants?)

 

19) https://www.who.int/news-room/q-a-detail/herd-immunity-lockdowns-and-covid-19 (WHO Q&A on Herd Immunity and Public Health Interventions)

 

20) https://www.bbc.com/future/article/20210119-covid-19-variants-how-the-virus-will-mutate-in-the-future (What the COVID Variants mean in the fight against the virus)

 

21) https://www.cell.com/cell/pdf/S0092-8674%2820%2930877-1.pdf (Characterizing the effect of the observed mutations to wild-type COVID-19)

 

22) https://www.nature.com/articles/d41586-020-02544-6 (The Coronavirus is mutating – does it matter?)

 

23) https://virological.org/t/detection-of-sars-cov-2-p681h-spike-protein-variant-in-nigeria/567 (Characterizing B.1.1.207)

 

24) https://blogs.scientificamerican.com/a-blog-around-the-clock/bio101-from-genes-to-species-a-primer-on-evolution/ (Basic Primer on Evolutionary Theory)

 

25) https://www.nature.com/articles/s41586-020-2895-3 (D614G Alters SARS-COV-2 Fitness)

 

26) https://www.nature.com/articles/d41586-020-02948-4 (Herd Immunity, and the False Promise of Induced Herd Immunity)

 

27) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151357/ (Early calculations of herd immunity level required to stop COVID-19)

 

28) https://www.thelancet.com/article/S0140-6736(20)32318-7/fulltext (Challenges to achieving herd immunity through mass vaccination)

 

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Endnotes
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• note: I don’t want to speak too soon, but it appears likely that we are at least leveling off if not decreasing in number of cases reported per day. That effect is still so recent that deaths have not been affected, yet, assuming they will be and that the decline is itself genuine.

 

** note: “wild-type” is scientific lingo for “the ‘normal/default’ form of the organism we are talking about”

 

*** note: This used to be VUI-202012/01. The “VUI” stands for “Variant Under Investigation” and “VOC” stands for “Variant of Concern” – since the investigation is substantially concluded, the name changed.