Oh, Omicron! Oh, Omicron! How Hysteric Should You Make Me?

Renewed variant discussion brings more paranoia. Is it warranted, or should we be skeptical?

I planned on not making this post since so many on social media have been commenting on the recently discovered variant (Omicron). I’ve been researching for a post about Vitamin D and was going to include a bit of information there. However, that is taking longer than I thought so I am making this separate post.

As many are aware by now, a new SARS-COV2 variant was discovered in South Africa, named Omicron.

Now, I won’t get into the concerns about jumping Greek letters, but with talks of new variants comes with renewed concerns, but more strikingly more paranoia and hysteria.

As I intend to do with this Substack, it does us no good to work ourselves up without the proper information. Otherwise, why act hysterically over things we know nothing about? So here, I’ll try to discern some of the information that I have seen so far, while also making critiques about the media reporting on this topic. It’s important to know whether these concerns are founded, or if they are hyped up by media hysteria.

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What do we know about Omicron?

With all of this discussion taking over many news outlets, you would expect that we know plenty about this variant, right? Well, like always, the answer here is a pretty obvious “it depends”.

We do know that this virus has mutations in the spike protein, but we don’t know exactly the concern with these mutations yet. There’s a big discrepancy between molecular data and evidence from assays. Sequencing techniques provide information about what mutations may be present, but they don’t indicate what effects these mutations have. This usually requires in vitro analysis of the binding efficacy of the new spike protein. It’s the same thing that occurs with antibody effectiveness against mutations. Therefore as it stands, a lot of this information, as it relates to new mutations, is more speculative than informative, and it’s important to remain skeptical about the presentation of all of these new mutations.

If you look up any reporting on the mutations found with the Omicron variant, you’ll notice most outlets don’t even discuss what these mutations are. Most outlets have reported that there’s an unusually high number of mutations with Omicron or that this variant may escape immunity. All vague assertions with no actual substantive evidence, far from something to become paranoid over.

But that doesn’t mean that there isn’t some information out there.

Here’s a list of the mutations taken from UK’s Surveillance of Variants of Concern:

There have been discussions about an unusually high number of mutations in the spike protein. Now, I don’t know what would constitute “unusually high”, but it’s strange that this keeps circulating around media outlets.

As is becoming more obvious, many media outlets seem to report on each other’s reporting, and so certain words and phrases pop up in many media outlets. It’s a concerning finding, as it means that most media outlets many not be knowledgeable about the actual topics that they are covering.

This is more of an aside, but it’s something to note when going through various media sources; redundancy to this degree is not good, and it calls into question the veracity of these reports when these people may repeat what each other is saying without understanding the actual context.

But let’s look into the mutations with a bit of specificity.

If we look specifically at the spike protein, you can notice that typical mutations are there, such as an N501Y mutation. As I previously discussed in my post on mutations, the type of mutations that appear tend to be predictable. As a general rule, the more mutations that occur in a region the less likely those regions play a critical role to the virus. It doesn’t work all the time, but it’s based on the idea that vital spike protein regions are under extreme selective pressure.

It’s the most double-edged sword scenario if there is to be one. Mutations in the receptor binding domain can either increase the virus’ infectivity, or it may completely demolish a virus’ ability to bind to a receptor. It’s the reason why the receptor binding domain of SARS-COV2 tends to remain conserved, and if it doesn’t the mutation tends to be predictable, as in the case of the N501Y mutation which has popped up in several variants. It’s one of the reasons why many variants tend to contain similar mutations as this specific mutation tends to be highly beneficial whereas other mutations are likely to be deleterious to the virus and causes that strain to die out.

One thing that stands out here is the 69-70 amino acid deletion. This is a deletion seen in the Alpha/UK variant. It was the easiest way to determine if someone was infected with this variant; PCR testing would have the S protein show up negative while the N protein and the ORF1 would appear positive. It occurred pretty frequently when I was doing COVID testing and it’s a pretty obvious discrepancy, and it’s something we noticed over a year ago when discussions of variants began to emerge.

Concerning, then, that reports that cover this variant don’t seem to discuss this similarity to the Alpha variant.

Here’s an excerpt from the New York Times on this deletion:

Dr. de Oliveira and his colleagues determined a quick way to gauge how quickly Omicron was spreading in South Africa. Although sequencing the entire genome of a virus is slow, the scientists figured out how to identify Omicron with a standard nasal swab test known as P.C.R.

The tests are fast because they look for just two of the coronavirus’s 29 genes — the spike gene and another gene called nucleocapsid. Thanks to its new mutations, Omicron does not test positive for the spike gene. So researchers could simply look for samples that tested positive for nucleocapsid, but negative for spike.

Now, as someone who has conducted COVID testing I may be more knowledgeable about testing information. However, this information has been well-known with Alpha, and well-known for over a year. The presentation here make it seem has if this is a new revelation, that they have just discovered a new way to easily detect this deletion. It’s a nitpicky argument to make, but it indicates that many people who are reporting on the current information on COVID are not building off of previous knowledge.

As it seems to happen over and over again, what is happening now is what has always been, and prior information does not seem to be used to build upon but to become memory holed as if it never occurred. It’s a shame, because the unique deletion may indicate that Omicron may have been derived from the Alpha variant or that the virus happened to obtain this mutation separate from the Alpha variant (convergent evolution).

The difference between the two would argue the evolutionary lineage of the spike protein. For a journalist to not be aware of the previous prevalence of this deletion with Alpha indicates a blind spot in the media’s knowledge, and it’s a blind spot that propagates insufficient information to readers.

A last thing I will note with this protein, one that may point to the mutations to be concerned about, are the apparent mutations within the furin-cleavage site. The furin-cleavage site is a highly contentious region. It’s one of the residues that has called into question the natural origins of this virus, as this residue is not found in bat coronaviruses, and that the genetic sequence here seems to contain codons that tend to be found in humans.

In laymen’s terms, the furin-cleavage site is a polybasic region (a region comprised of many basic amino acid residues, predominately lysine and arginine residues) of the S1/S2 spike protein that is recognized by the protease furin. When SARS-COV2 binds to the ACEII receptor, furin on the surface of a host cell’s membrane recognizes this cleavage site and cleaves the spike protein. This enables the virus to enter into the host cell. Thus, the furin cleavage site plays a pivotal role in the virus’ ability to infect host cells.

Here, mutations may point to a few things to look out for. The furin cleavage site is vital to the infectious nature of this virus, and thus a mutation that persists here, using the logic outlined above, most likely serves to benefit the virus. It’s the reason why Delta became more virulent, as Delta contained mutations within the furin-cleavage site. In what manner this residue change affects transmissibility may be more difficult to discern. It may be that the new amino acid makeup of the cleavage-site makes it more recognizable to furin, and thus may increase the rate that the virus can enter host cells. It’s another speculation, and we will need to wait for more information to understand what exactly is attributing to a possible increase in infectiousness.

Once again, it’s an area that may be of concern, but without any information I find it hard to argue for the massive paranoia we are seeing right now. One thing that remains important is to keep the idea of infectious/transmissibility and lethality separate from one another. Just because a virus become more infectious does not mean that the virus is more lethal. In fact, they tend to operate inversely of one another.

But here lies another serious flaw with the reporting of this virus. Many outlets have reported about this “500%” increase in infectious between Omicron and Delta. Now where did this information come from? It came from this tweet:

Eric Feigl-Ding @DrEricDing

⚠️My god—the new #B11259 variant being possibly ~500% more competitively infectious is the most staggering stat yet. Also, #NuVariant has more than >2x the number of bad spike mutations than Delta. Here’s an updated 🧵👇 Model by @JPWeiland matches up with graph by @jburnmurdoch

Dr. Feigl-Ding is an interesting character. He’s probably one of the most prominent epidemiologist as it relates to COVID, and a quick look at his tweet thread sends up many red flags, and not in the way that he intends. Such a Twitter thread is anathema to the histrionics that have invaded much of the COVID discourse; it doesn’t spell an informative thread of information, and instead reads more like the workings of a hypochondriac. Every little post here is read as something to make people scared, rather than informed.

Now, there’s nothing wrong with being concerned, but being concerned and skeptical has always been my preferred way to operate. Dr. Feigl-Ding has made his way around detractors of the COVID narrative, usually for the same reasons as I have outlined. Many of his critics point to his tweets as nothing more than fear mongering, and in a time where people are experiencing highly biased and divisive narratives this type of projection does no good in keeping the public rational.

What’s more alarming, is that the graph he posted is being used to push the “500%” narrative. A shame that this graph has been reported on by media outlets, as I find it wholly lacking of any context. In fact, looking up the tweet by the modeler points to a tweet indicating that the model was made using limited data.

JWeiland @JPWeiland

The 500% model is based on latest sequencing data out of South Africa over time-  It is important to note that there is limited data at the moment, and it is very possible that more data will reveal a slower takeover.  With all my heart I hope that is the case.

Over time I’ve found my patience within the realm of COVID to continuously be tested, because many of the people who are supposed to relay this information in a manner that is both informative and sensible tends to always be lacking.

And remember that this isn’t the first time this has occurred with COVID. Many people criticized the UK’s Health Advisor Neil Ferguson when the pandemic first emerged. His case fatality reports (CFR ~ 1-5%) in the Imperial College of London spelled certain doom for most of the world, and the results were used to push for many of the lockdowns and mandates seen worldwide. The problem? The data was heavily flawed. The case fatality rate reported was on orders of magnitude far greater than the actual numbers, possibly by a factor of 10. What did the actual numbers point to? A bad flu season.

Now, this point is highly contentious. I would argue that COVID is more severe than a bad flu season, but nowhere near the numbers used to push for the global lockdowns that we have seen. And this wasn’t the first time Ferguson has pushed for such fear mongering.

As many in the UK are aware, Ferguson played a role in pushing mass hysteria when it comes to the emergence of mad cow disease. In fact, he’s been wrong on many of his predictions.

An excerpt taken from National Review points to his prediction failures:

Ferguson was behind the disputed research that sparked the mass culling of eleven million sheep and cattle during the 2001 outbreak of foot-and-mouth disease. Charlotte Reid, a farmer’s neighbor, recalls: “I remember that appalling time. Sheep were left starving in fields near us. Then came the open air slaughter. The poor animals were panic stricken. It was one of the worst things I’ve witnessed. And all based on a model — if’s but’s and maybe’s.”

In 2002, Ferguson predicted that, by 2080, up to 150,000 people could die from exposure to BSE (mad cow disease) in beef. In the U.K., there were only 177 deaths from BSE.

In 2005, Ferguson predicted that up to 150 million people could be killed from bird flu. In the end, only 282 people died worldwide from the disease between 2003 and 2009.

In 2009, a government estimate, based on Ferguson’s advice, said a “reasonable worst-case scenario” was that the swine flu would lead to 65,000 British deaths. In the end, swine flu killed 457 people in the U.K.

And it’s not just Ferguson that have pushed fear mongering. Our very own Dr. Fauci here in the US has been indicted (metaphorically) for pushing propaganda during the AIDS epidemic. One such instance included a newborn who was found to be HIV positive.

At the time, Dr. Fauci pushed the narrative that HIV could spread indoors, and that family members should become fearful of one another. As more evidence appeared, the real cause of infection was likely due to the mother, herself HIV positive, breast-feeding her newborn. The AIDS epidemic served as such a controversial role in medicine, one that Dr. Fauci has played a role in spreading misinformation that have stigmatized many communities.

Many of those pushing for public health measures have not done so with a clean background. Most have done so under idea to push fear and narratives moreso than to create an informed, rational-minded populace.

It’s the reason why I draw so much derision to Dr. Feigl-Ding and his threads. I don’t feel informed, I don’t feel more knowledgeable reading his tweets. I feel as if I’m intended to be scared, and by being scared I will become more impressionable to fall back into mandates and lockdowns. Why else would this occur around the winter season (something that many people have drawn criticism for even mentioning, even though it’s become the norm in many realms of discusison), before the holidays, after many people have protested against vaccine mandates. Strange now, that it’s perfectly acceptable to push for border closures and to bring back masking when the former was seen as xenophobic and the latter is not backed by recent evidence.

(Editor’s note: The study I cited did not indicate that masking is ineffective overall. It instead argues that there is a distinction, such that KN95 masks are most likely to be beneficial whereas surgical and cloth masks do not. My inclusion of this paper is more to indicate the lack of this distinction by many in the media. If KN95 masks are clearly more effective, where is the encouragement to tell people to wear better masks? It’s again an incoherent policy that lacks any nuance and actual concern with rational thought.)

The emergence of new variants should rightfully be met with concern, but it should always remain that the concern should match the evidence. As we see it now, we do not have the evidence to support such widespread hysteria, and even more contradictory is that evidence so far suggests that Omicron is far more mild than Delta:

Again, there is a BIG difference between being concerned and engaging in panicking behavior. It does no good to be concerned over things that we do not know of. It seems that this position has pervaded much of the modern discord, where fear and panic overtakes the idea of remaining skeptical about the uncertainty.

My working phrase is that in the absence of information, people turn to panic, and when enough people panic we may witness a mass psychosis. As we enter deeper into the Winter season in this Northern Hemisphere, remember to not fall to the temptation of panic and histrionics. Remember to remain evidence driven and not narrative driven.

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New Variant, New Vaccines, Possible Original Antigenic Sin Emerging?

A few months back discussion began to circulate around the concept of Original Antigenic Sin. It was used mostly to argue about information coming from UK’s Surveillance Report that suggested fully vaccinated people did not produce high Nucleocapsid antibody titer levels post-infection.

At the time, I argued that many of the reports people brought up in regards to the UK data were misattributed to OAS. As I indicated in my posts (Part I here and Part II here), the evidence did not seem to substantiate the claim. I found it hard to argue that the presentation of anti-spike antigens would lead to the lack of anti-N antibodies seen, and that the interpretation from the graphs were also incorrect.

What I did mention, if OAS were in play as it pertains to COVID, was that vaccinations against variants would be where we are most likely to see the presence of OAS. A big driver here would be the term “antigenic distance”. Like two cousins figuring out how distantly related they are before it’s considered incest, antigenic distance argues that the closer two antigens are in structure, the more likely previous exposure to one would cause a “back-boosting” of antibodies against the previously exposed antigen, rather than to the newly presented one. The two antigens, therefore, would be far too “related” to one another that our immune systems may not be able to discern the two antigens and produce separate immune responses.

Remember that OAS is a working model, and at the time there is no exact evidence of this occurring. But we do have evidence of antibodies formed from prior seasonal coronavirus infections binding to SARS-COV2. Also, out of all the possible scenarios, this seems like the most likely one to occur.

This is extremely important, and the reason I bring this up is that recently pharmaceutical companies such as Pfizer have argued that they may have a vaccine that targets the Omicron variant ready within a few months of finding out if the variant escapes immune systems.

These reports are extremely concerning, as it points to this grand naivety that we can continue to keep vaccinating as more variants arise. If such a thing were to occur, I see this leading to nothing more than perpetual vaccination for many years down the line. What’s worse, if OAS does occur we may find out that people may be provided a false sense of protection. Their lack of antibodies that directly target the Omicron variant would leave them essentially naïve to the new variant. It’s this lack of understanding that raises red flags. It seems far more easily said than done, and it misses any nuance with respect to the complexity of the immune system.

Even more strange, how could the vaccine be produced in such a short time frame? Shouldn’t a new vaccine undergo the same EUA process as before, or is it that these new vaccines could be built upon the evidence of the prior vaccines? Otherwise the time frame may take too long, and new variants may arise by then. But it also suggests that the vaccines already in circulation should have been remade to target Delta, especially since the “100 day” production argument being put forth would suggest that Delta-specific vaccines should be produced in short time.

At this point I find all of this stuff surrounding vaccines to be nonsensical, and so this does nothing but to add to the already large pile of incoherent science and policies.

Withstanding this, we should be concerned that, if OAS were to ever rear it’s head, it would be in a scenario exactly like this one.

Editor’s note: I was misusing the term “virulence” in place of “infectiousness/transmissiblity”. That was a mistake on my part and I have replaced the terms where necessary. I should not have overlooked that detail as it changes the intentions of my writing in the places that I have used it. I apologize for that mistake.

Also, for a little fun, I found this South Park scene very timely in its release. Please refrain from becoming like these characters, and think rationally before panicking.

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