SARS-COV-2: Where do we now stand?

I’ve argued a few times now, that mass vaccination against the Wuhan spike protein will end up terribly exacerbating the pandemic. I still think everything is pointing in this direction. Specifically, I’d like to expand a bit today on the situation faced in the United Kingdom, which together with Israel was among the first places to begin mass vaccination.

Excess mortality in the United Kingdom right now is limited, but this is to be expected. After all, after two years of widespread infection, the most vulnerable people have lost their lives. This dynamic is why it’s commonly observed that deadly flu seasons are followed by mild flu seasons. In addition to this, once all the survivors have had some degree of exposure to this virus, its mortality rate declines. Repeat exposure however, is very unlikely to drop the mortality rate more.

Additionally, hospitals have gotten much better at treating COVID patients over time. We now have monoclonal antibodies and protease inhibitors, people are generally no longer placed on ventilators and the overall ability to treat people has simply gotten much better. Because of improved treatment, we would expect the rate of hospitalization to decline less than the rate of death, even if the virus were to become less virulent over time thanks to widespread immunity. If early treatment was taken seriously, hospitalizations could go down more too.

When we look at the burden on hospitals placed by SARS-COV-2, it’s unfortunately not really getting any better. What we’re now seeing, is that emergency departments can hardly cope with the massive number of people needing medical care. Take a look at some of the numbers here, for waiting periods in England:

In Scotland, where around 97% of elderly have received booster shots against the virus, hospitals are also struggling to cope.

You can see here, that they’re struggling to treat patients within four hours:

As the virus grows more infectious over time, because it makes use of everyone’s infection enhancing antibodies that bind to the NTD domain, it seems to lose some of its seasonal character. As an example, Australia was seeing massive waves during their summer and the currently ongoing wave in the UK is rather late in the season too. Still, I would consider it likely that we will see a breathing pause during the summer, with relatively few people getting infected.

But that brings us to the nastier part. We’ve seen a growing trend of frequent reinfections with various Omicron variants. What seems to be happening, is that infection after vaccination generates less protection against reinfection than it does in people who are unvaccinated. You can find a good thread on the topic here.

The implication of this, is that through repeat vaccination we have interfered with the development of herd immunity. After three shots of Spike protein, or two shots and an infection before the Omicron era, the immune system has grown so confident in how it should deal with SARS-COV-2, that it struggles to adjust its toolkit to new variants.

And simultaneously we’re dealing with the reality, that vaccination against future variants is going to be very difficult. Allow me to illustrate what I mean. An antibody reacts to a chain of amino acids, generally between 4 and 12 amino acids in length. They tend to be very specific: Any single mutation that changes an amino acid makes an antibody useless. The genetic code can produce a total of 22 amino acids.

In other words, to escape an antibody that binds to a region of six amino acids in an antigen, the virus theoretically has 64.000.000 options available to it. This is an exaggeration of course. Some of these amino acids would make the protein nonfunctional, some antibodies may tolerate a single change and perhaps you have other antibodies available that would recognize the changed epitope. But the point I wish to make is that the virus has many different ways to escape from an antibody. And when it escapes from an antibody in many different ways, in the form of many different variants, it becomes difficult to generate an effective vaccine against all of these variants.

Take a look at an example, that illustrates my point. A lot of antibodies are affected, by a change to the 452 position in the Spike protein. However, we see that many different mutations, resulting in many different amino acids, happen to this position simultaneously. Right now you can find 452M in Belgium, 452R in France and 452Q in North America, along with the original 452L. And changing an amino acid before or after this position, could probably work to avoid the relevant antibodies too.

The reason the vaccine was once so effective, is because the virus was so strangely similar anywhere you looked. As soon as we learned of SARS-COV-2, it already had an affinity to the ACE2 receptor 10-20 stronger than SARS-COV-1. You can tell me how such a thing could gradually have evolved in nature, passing from person to person without us noticing, but to me it looks like evidence that it emerged from a lab. Regardless, after its emergence, we saw effectively no real genetic change throughout 2020. This made developing a vaccine relatively easy.

As soon as everyone had developed immunity however, the virus underwent immense pressure to evade our immune response. Because there are many different ways to accomplish this, with many different mutations, genetic diversity now increases dramatically around the world. And as the genetic diversity increases, any vaccine that is deployed will inevitably become less effective, more akin to the performance of a flu shot than to the big success we saw at the start of 2020.

Important to understand here in this process is epistasis. A mutation that evades an antibody will typically have some negative effect that prevented it from emerging earlier, it may destabilize the protein for example, or reduce affinity for the ACE2 receptor. Because of this, any single mutation often rapidly leads to more mutations, that help compensate for whatever negative effect was caused by the antibody evading mutation. Different mutations to evade the same antibody, may then in turn encourage different compensating mutations.

When it comes to the specific technical details, I can’t elaborate much, as structural biology is not my expertise. However, the general principle should be clear: From the perspective of the virus, there are many different roads that lead to Rome. And when the virus has many different ways to walk to Rome, the vaccine manufacturers are left with the difficult job of now guarding every single entrance, to keep this virus from sneaking into the city.

I don’t write a lot anymore about the mass vaccination campaign or the lockdowns, because there is not much new to be said. The general population has been disillusioned by these vaccines, you can see for yourself how many people in the US took a booster shot, or how many people choose to vaccinate their children. In addition, governments recognize that the general population will no longer put up with any more lockdowns, it would be political suicide. The few people who still think these vaccines are a good idea, can’t be persuaded to reconsider.

However, the evidence still points in the same general direction: Vaccination has caused outbreaks of Omicron, that have lead to unprecedented numbers of infections and massive amounts of RNA in sewage. Fortunately, improved treatment and previous exposures, have led to a situation where the virus has become far less deadly, despite still causing many hospitalizations.

It’s possible that I am too pessimistic, that SARS-COV-2 will not cause any more rounds of massive numbers of people dying in the streets as they did in India, or in hospitals as they recently did in Hong Kong. However, if we continue to face constant waves of people being hospitalized by this virus, that’s not really any major consolation. After all, these people tend to end up stuck with long term effects, including damage to their immune system.

Overall, my expectation is that Western nations that have given most of their population three or four rounds of Wuhan spike protein, will continue to see the steady wave of hospitalizations that the United Kingdom is seeing. These hospitalizations ultimately translate into excess deaths, even though people may die beyond the 28 day period that is used to define a COVID death.

The problem here again is that we have invoked an immune response in the whole population that worked well against the original variant, but inevitably puts our population at a steadily growing disadvantage against future variants, by homogenizing our immune response, both at an individual and a population level.

The effect I expect from this, is that although nations like Algeria will be mostly done with SARS-COV-2 (unless they decide to mass vaccinate all of a sudden) until some dramatically different variant show up, nations like the UK and Denmark now face a long steady wave of constant hospitalizations from this virus, hopefully with some relief during the summers.

Over time, evolutionary biologists will begin to speak out about what has happened and after a few years, the taboo will die, as it will become widely acknowledged that the mass vaccination campaign was a bad idea. At some level, almost everyone already realizes it was a bad idea. About 30% of adults in the US got the booster shots. However, it’s still taboo to say it out loud, it’s one of those forbidden truths you can’t state if you wish to enjoy a position of power in society.

The closest equivalent I can think of to what we have done, is to replicate the disastrous Dengvaxia experiment in the Philippines, that has left numerous children with an apparent lifelong increased susceptibility to suffering severe Dengue, on a global level. Side effects like myocarditis and blood clots are nasty, but at least they reveal themselves within days after receiving a shot.

The Dengvaxia experiment on the other hand is so frightening, because it is causing children to die years after they received this vaccine, simply because their immune systems can now no longer properly deal with other strains of Dengue that differ from the vaccine strains.

It seems perfectly plausible to me based off everything I have read, that people who received these booster shots will still be dying from increased susceptibility to this virus, five or ten years from now, simply because their ability to adjust their immune response to future variants has been negatively affected.

The worst case scenario would be one of mass death in developed highly vaccinated nations, as various positive feedback loops start to interact in a manner that begins to trigger a catastrophe in the coming months:

-Infection enhancing antibodies lead to more people getting infected.

-With more infections, more opportunities for mutation occur.

-The mutations accelerate each other, as evading one additional antibody becomes more useful when most antibodies have already ceased to work.

-With more  infections, the infection enhancing antibodies are constantly being naturally boosted.

-Every infection damages the immune system, by killing a portion of our T cell population tasked with protecting us against this virus, thus enhancing our susceptibility to more severe reinfection and chronic infections.

-With a growing number of such chronic infections, the ability to accumulate many different mutations grows too.

-As genetic diversity of the virus increases dramatically, we end up constantly exposed to variants that we’re still susceptible to.

The big wildcard, that I don’t know how to incorporate is as following: How does our ability to treat this virus change over time? Do we discover more effective antiviral drugs, or are we bumping into a ceiling when it comes to our ability to treat this virus?

You could of course ask “what about the 19th century coronavirus outbreak”? It did not turn into a catastrophe. However, it differed in a number of important aspects that we’re now dealing with, that separate the current virus from the previous coronavirus that jumped into our species and triggered a pandemic:

-We have now engaged in a mass vaccination campaign, that has homogenized our immune response.

-The human population has grown dramatically.

-The human population has grown much older and chronically ill than it was in the late 19th century. As a result, we should expect to see more chronic infections.

-New variants that emerge are now much better capable of spreading from one region of the globe to another region, because we’re now all connected thanks to the airline industry. If Omicron had emerged in 19th century rural Africa, would it have shown up in Europe within days, or would it have exhausted its local niche in some isolated African village before it managed to spread to another region?

This is why I tend to look at this pandemic, as a rolling stone at the top of a hill. Its natural inclination, was for it to roll towards the side of herd immunity: Eventually our natural protection against spreading it from one person to the next person, exceeds the speed at which it can come up with new variants to evade our immune response.

This works in many different ways. Your body develops trained innate immunity and you may develop T cell immunity and antibodies. During an infection itself, your general habit will be to stay at home in bed, where you’re unlikely to infect other people. In addition, the virus has to compete for hosts with all the other respiratory viruses out there.

On the other hand, as a species, we can take tremendous effort to push the stone, that is rolling towards herd immunity, in the opposite direction: We can push it towards constant reinfections, as its ability to give rise to new variants grows so much that it exceeds our own ability to force this virus out of the community of respiratory viruses that circulate in our species. We have many different tools to do this:

-Force competing respiratory viruses into near extinction

-Send sick patients into nursing homes, the equivalent of igniting tinder to burn wood

-Encourage widespread vitamin D deficiency, by discouraging people from going out into the sun

-Slow down the spread, thereby allowing it to acquire mutations before it has consumed all of its hosts, like overcrowded deer on an island without predators who eat all the vegetation before it can regrow.

-Practice mass vaccination, that would initially increase susceptibility to infection due to temporarily immune suppression, until eventually triggering an unusually narrow antibody response, that prohibits the development of sterilizing immunity, but turns your body into a training ground that gives rise to antibody escaping variants.

-Deploy drugs like Molnupiravir, that encourage the acquisition of new mutations.

And so my thesis remains, that we have performed a lot of effort to push this stone that was slowly rolling towards herd immunity back up the hill, only to push it down the opposite side of the hill: The direction that ends in constant reinfections, where its acquisition of additional genetic diversity exceeds the pace at which we acquire the capacity to keep different variants from reinfecting us.

Igor has also argued this, by looking at the various developing nations that did not practice mass vaccination and now seem to enjoy herd immunity. Of course we may eventually see new radically different variants that will then again infect susceptible people in those nations, but to suggest this disproves the theory would be incorrect: After all, those new variants would have been unlikely to emerge if we had not turned Western populations into the evolutionary stepping stone that gives birth to these new variants.

Of course, there are aspects in this whole equation that helped make herd immunity more difficult to achieve, that are intrinsic to the industrial lifestyle. With more people on immunosuppressant drugs, there are more people who become breeding grounds for new strains with large numbers of mutations. With a larger population, the virus has more time to develop new mutations before it runs out of susceptible hosts. And most importantly, in the era of globalism, any new variant doesn’t just die out locally. It has a good chance to show up in every continent. These were all factors that worked against us.

As much as I would like to agree that we’re now done with this virus, that society has returned to normal, I see no reason to believe this. We have created the exact situation where we face the constant prospect of more waves.

8 Comments

  1. I wonder just how likely the evolution of a highly lethal ADE variant is and if a rogue nation or organisation is not already trying to speed up the evolution of such a variant since all Western nations have few and almost identical vaccines.

    Lab leaks seem to be many times faster than natural selection and as we can see very easy to cover.

    • Yes. It looks plausible to me, but you’ll really need a background in structural biology to properly judge it.

      what’s clear to me is that my own expectation, that we would witness various BA.2 descendants with spike mutations show up everywhere, is proving correct. It’s hard for me to judge how close we are to complete neutralizing antibody evasion however.

  2. It looks as if the media and the politicians want us to think about other things at the moment, because it’s gone fairly quiet on the covid front – at least in the UK. This time last year the 7 day “moving average” was 1 covid confirmed death a day in Scotland. Now it’s more than 10 times that number and yet nobody seems to bother.
    As always, I appreciate you taking the time to write about this subject. I have the feeling we have not heard the last of it but this lull is refreshing.

  3. Question: what is going to happen to the BINDING ISOMERIC ANTIBODIES which have been produced by the immune system in response to the cmRNA coding with Pseudouridine? What is the defining factor which will constitute a sufficient condition for these isomeric abs to be activated, that is, to become neurotoxic prion-like T-bacilli proteins?

    The main difference between Omicron (Mers-Cov-2) and Delta (Sars-Cov-2) is the fact that, as of yet, the prion domain of Omicron has not been activated (the virulence of Delta was due exclusively to the activation of its prion domain, and now we know that IgG abs are related to the REGN10987/B38 abs (which have an IgG format), prions and Mers-Cov). This is the reason why the mask mandates and lockdowns were removed temporarily.

    So, what is going to happen next? Avian flu. That is, Omicron will activate its prion domain, and this pandemic will be described officially as an avian flu pathogenic agent (either H5N1 or H7N3). This is when huge lockdowns will be implemented, possibly even a new vaccination campaign.

    Ultimately the pathogenic agent (M. avium, aka Sars-Cov-2 / M. influenzae, aka Mers-Cov / M. africanum, aka ebola/marburg/galloping tuberculosis) will reach its final destination, just like it happened in the year 1918 (see the gjenvick.com website, the “Is The Influenza A Chinese Plague 1918 12” article)

  4. Rintrah, thank you for your very well thought out article. Your “worst case” scenario will quite likely play out indeed, with Chronic Covid taking over entire population with no chance for the vaxed to escape. The UK has 1 out of 17 people infected with Covid right now.

    I want you and me to be wrong about that “worst case” but I am afraid that it will come indeed. We (collectively) need to start looking for solutions ASAP.

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