Vaccinology, Immunology, and COVID-19

Louis Pasteur worked at a time when very little was understood about microbes and even less was understood about the human responses that kept them at bay. He is best known for advancing germ theory, which distinguished itself from the prevailing concept of “miasma” or putrefaction suffusing the ether. “Gentlemen, it is the microbes who will have the last word.” he famously declared. His was a world where the power of observation trumped understanding. Part of what solidified his legacy as a brilliant scientist was that he recognized forces at work in the human body which counterbalanced his microscopic world of germs. His prescient recognition of what would ultimately come to be known as the immune system and his contributions beyond this, specifically in the field of vaccinology, have incredible relevance today.

The COVID-19 pandemic has taught us much about both the state of science and its application. On one hand, we have been able to seamlessly marshal incredible intellectual capital from teams of international scientists to deliver timely, lifesaving vaccines. On the other, we have seen that science can be weaponized and subordinated to politics. Following “the science” can be vastly different from using science intelligently to inform public policy. The ability of our public health institutions to communicate effectively in the world of Instagram, TikTok, and Twitter has been found wanting. Despite this, we continue to make advancements at a blistering pace. Like in the age of Pasteur, the sciences are once again thriving.

Vaccine technology has sped ahead, serving the critical function to break the link between infection and poor outcomes. While we were using the basic tenets of vaccinology and leveraging them with a new and powerful construct of mRNA, we were continuing to learn. It turns out that the large spike protein present on the virus is an incredible target. By inducing the body to protect itself against aspects of this rich site, we can create what are known as “neutralizing antibodies” that prevent infection. But there is more to the story. There are other components to the adaptive immune response, which include B cells and T cells in both activated and dormant forms. Vaccines stimulate these supportive cells as well, forming what is known as the anamnestic or memory response.

Pandemics have been around for millennia, possibly since the time of the first agricultural revolution 10,000 years ago. Over this vast expanse of time, they have found all sorts of ways to immiserate the populations they infect. Our experience today is vastly different say from the bubonic plague in the Middle Ages, cholera in the Renaissance, or even H1N1 little more than a decade ago. In order for this pandemic to finally end we will have to satisfy not only the significant reduction of infection and mortality, but also the social constructs that nest it. Our society is vastly changed from even a decade ago. For better or worse, we were able to implement a variety of movement restrictions or lockdowns which in effect delayed our having to confront this virus. The result is that we suffer from developmental delay, a collective Peter Pan syndrome, never learning to embrace what we must in order to evolve, mature, and begin to move on. We did this in an attempt to conserve resources and prevent excessive deaths. Fortunately, reducing infection and mortality to bring about the “medical end” of the pandemic will be much easier. In fact, sewn within the substance of the Delta variant are the very seeds of its demise. It has proved to be incredibly infectious. While this may be advantageous for its evolutionary biology, it virtually guarantees that its days are numbered.

With a more complete picture of vaccinology and immunology now at hand, we can see that a highly infectious variant introduced at this stage produces two important effects. The first is that populations acquire natural immunity through infection, and the second is that they are driven to seek out more vaccinations. The corpus in support of natural immunity and our understanding of it are continuing to grow. It is now routinely observed that natural immunity is protective against reinfection and severe outcomes. It is also robust and durable, producing not only neutralizing antibodies but also antibodies to parts of the virus apart from spike. Just like vaccination, it engages B and T cells to perform supportive functions. Natural immunity is also distinct from vaccination. It may produce higher levels of antibodies in the mucosal tissues of the nose and mouth, but it’s not as consistent as vaccination and likely produces fewer blood-borne neutralizing antibodies. What is perhaps even more interesting is that an immunologic synergy exists between both natural infection and immunization. This potent chimera—termed “hybrid immunity”—may end up being the most powerful protection of all against SARS-CoV-2. These important findings are not obvious. We understood natural immunity to be highly protective against measles or chickenpox, but it took the passage of time to reveal exactly how it would perform against this novel strain of coronavirus.

Some of the insights gleaned during the past two years may ultimately serve only to tell us more about who we are and where we are headed. Understanding the unique social and political forces at play may help explain why there has been such a disconnect between rapid scientific advancement and medical communication. Or, it may help us better empathize with someone who sees the pandemic through a different medical, political, or emotional lens. The advancements in vaccinology are actionable and will lead to a future where they are routinely deployed against other infectious diseases and even cancer.

But now it is time to turn to our insights in immunology, specifically natural immunity, that may be seized upon and applied to the real world in a way that is fair, open, and builds trust. It should be assumed that support for natural immunity does not imply that citizens should seek out natural infection or avoid vaccination. On the contrary, the push for vaccination must remain intense and the message clear—it is much better to meet this virus having been vaccinated. We must apply this understanding to better inform our public policy. The international community including the UK, Israel, and the EU is already preparing for more capacious regulations on this front. The same should be done in the US. Spectrum Health, a 14-hospital system based in Grand Rapids, Michigan recently announced that they would permit vaccine exemptions based on demonstrable natural immunity. Those with documented natural immunity will demand legal challenges to federal and state vaccine mandates arguing that immunity is immunity and it doesn’t matter how you get there. Ultimately, being supportive of a legitimate claim like this will build trust in our system and help to bring those who feel disenfranchised back into the fold.

In 1796, three decades before Pasteur was even born, Edward Jenner delivered the first cowpox inoculation providing a glimmer of hope against a virus that had been the scourge of humankind for centuries. He believed that its efficacy related to the “grease” in the disease and that it stemmed from “horse hooves”—a stark example of implementing a beneficial medical advancement without having the faintest clue how or why it worked. It was a testament to our ability to apply what we learned through empiricism even if we understood little about nuanced science. Today, we understand much more about both, but tend to forget that simple measures may have an enduring impact. Given how far we’ve come in these pandemic-spurred scientific disciplines—and how easily that lends itself to seduction by ever-more complex solutions—let us not forget that although we, like Pasteur, stand on the shoulders of giants, we must remain patient and continue to use the powers of observation to reveal truths about ourselves and the sciences we study.


This is a companion discussion topic for the original entry at https://quillette.com/2021/10/06/vaccinology-immunology-and-covid-19/

But is it really? If you listen to this very recent presentation by McCullough (very information rich, in contrast to this flowery, but on the whole unenlightening, prose) you hear,

Kostoff calculated in this paper, that because not everybody gets the respiratory infection, and because the infection is treatable and manageable, in fact, one is more likely to die after the vaccine than just take their choice with forgoing the vaccine and potentially getting COVID-19” (@15 min 40 sec)

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In the UK, it is. 25 all-cause deaths per 100K among unvaxxed, vs 15 all-cause deaths per 100K among fully vaxxed. Can’t get more clear than that.

In the US, in a cohort of 13 health jurisdictions, from mid June to mid July, controlled for age, you were 13X more likely to die without vax, than with full vaccination.

So…ummm…yeah, really.

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McCulloch is a representative of a free market ideology that routinely questions science that does not suit it. The ‘Truth for Health Foundation’ that he is ‘Chief Medical Officer’ for has the same agenda as the ‘foundations’ that are into climate change denial and who previously successfully obfuscated the health effects of tobacco.

What he represents is science in the service of ideology and sectional interests. He appears to have no practical current research participation, specialized knowledge or employment in the field of epidemiology. McCulloch is a cardiologist whose knowledge of epidemiology would likely go back to his undergraduate days. He is no authority on the subject in comparison with people of professorial standing and post doctoral qualification in the field.

However, to your average Jo in the street, he sounds very plausible, especially when he ‘empowers’ these ignoramus’s to mistakenly believe that they know vastly more than they actually do.

This kind of baloney has proven to be a very effective public relations strategy that has seriously corrupted the interface between scientific research and popular opinion.

The answer to the likes of McCullough is to just look at the hospitalization, ICU, ventilator and death results of people not vaccinating compared to with those who are. This is becoming particularly pronounced as more people get vaccinated.

Hospitalization, serious illness requiring large and protracted medical interventions, death or Long Covid are almost the sole privilege of the unvaccinated.

If you are vaccinated your chances of getting the disease are lowered. If you do get it, the results are possibly still unpleasant but moderate, like regular flu and rarely lead to hospitalization, let alone death.

It is overwhelmingly the unvaccinated who are clogging up their under siege hospital system.

It is a popular meme amongst free market lobby groups that being ‘a minority’ signifies ‘courage’ and a Galileo type ‘insight’ denied by the deluded majority who are in the thrall of ‘groupthinik’ and conspiracy ‘hoaxes’.

The reality is almost infallibly that this line is self serving bullshit and that the real reason the real experts who do have the qualifications to make pronouncements on public health during a pandemi,.don’t take any notice of ‘the brave minority’, is that they (the free market minority) are ideological wankers and obfuscators whose libertarian beliefs overwhelm their scientific judgement, in the service of corporates that stand to lose from the overwhelming scientific view.

The melancholy results of large scale corporately funded climate change denial and obfuscation has been to delay necessary policy for the common good. But those sods have cried wolf a just a bit too often to keep being believed by once naïve and easily manipulated suckers…

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Come on S.Cheung! This is your bread and butter. As you well realise, McCullough is making an absolute risk statement while your statement is on relative risk.

Unsubstantiated Baloney and Bluff Adelaidean. You have said nothing.

McCullough describes his epidemiology qualifications in the presentation if you had even bothered to listen to it. Character assassination will not work in his case - his comments are backed by data e.g. from the CDC. He absolutely takes up the issue of whether this is a “disease of the unvaccinated”.

Of course I said nothing - I just referred you to McCullough’s presentation, but I doubt you can be bothered listening to it.

Regardless of his claims to qualification in the area, his qualifications are overwhelmingly outside the field and he is widely regarded as an ideological fruitcake with seriously misleading views and not terribly honest about his affiliations.

Baylor health sues COVID-19 vaccine skeptic and demands Dallas doctor stop using its name

I mean the poor bastard is into hydroxychloroquine for Chrissake…

It looks very like his old alma mata is not only not happy to be associated with him in any way, but it is instituting a policy of compulsory vaccination that fundamentally contradicts his ‘controversial’ views.

‘Several doctors with the Texas chapter of nonprofit Doctors for America said in a letter published in December in The Dallas Morning News that McCullough gave “baseless, misleading commentary” promoting the use of hydroxychloroquine as “an early outpatient treatment for patients with COVID-19.” Studies have shown that use of the drug has been linked to “higher rates of harm,” the doctors wrote.’

Part of the reason why I am not going to waste my time reading what he has to say is that I and very likely your good self Adelaidean, are in no position to be able to independently and fully assess whether what he is saying is baloney or not, because neither of us (well certainly myself) are qualified to properly enter debate at a professional level.

All I can do is what I have done above, which is to assemble the simple facts of the matter that have been laid out for us by the statisticians who have given us the figures for vaccinated/unvaccinated outcomes, which seem to me to be both undeniable and decisive in this matter

But I do happen to understand the genre that McCullough is working with, in and through, which is why I listen to the real experts, who have years in the field after both graduate and post graduate study at the highest levels and reached the top of their profession in epidemiology, which is why they are in charge of our epidemiological response through our public health system and the likes of Peter McCullough aren’t

End of story mate.

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He might be making lots of statements. But I’m not going to listen to a wingnut on an AAPS podcast for any length of time. If you have a transcript, or the paper he is quoting, I’ll rip that apart later.

The Baylor suit against McCullough is a ridiculous attack based on something that he had no control over. He never “misrepresented himself”. It was FOX News that chose to declare he was associated with Baylor (which he had, in fact, been in a very prominent position).

Your assertions of his lack of qualifications are baseless. But then McCullough’s statements are based on published data whereas yours are just continuing the smear propaganda of anything and anyone that challenges the Vaccination Macht Frei meme.

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And I absolutely respect your choice not to listen.

I do not have any expertise in epidemiology, but I have a smell for bullshit and baloney, which is what I think you are peddling Adelaidean. No Pasaran.

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LOL. I found that Kostoff paper. What a joke!

First:

D’oh.

And the paper itself? Equally hilarious!

It’s not so much a scientific paper, and more just a rant, where they announce numbers without showing the math, and don’t have a “results” section cuz…well…you didn’t expect them to systematically examine facts, did you?

Hey, but wingnuts gotta do what wingnuts gotta do.

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I’m glad you made the effort S.Cheung, but the “Retraction Watch” blog is just a smear piece in this case because there has been no retraction. So not yet a joke …

And it is obvious in the statistics that the vaccines are more dangerous to children than COVID-19 itself - which is why so many scientists in the UK and the USA have questioned the wisdom of it. You don’t need Kostoff’s paper to tell you that.

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without a mind for data? Must make life a challenge.

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An interesting article and a good piece of history, but I would beg to differ with its central conclusion, as would Nature and McKinsey & Company:

That being said, I still maintain that for most below a certain age vaccination is the best personal choice. I started to write a long essay on this subject, but I abandoned it because it has all been said. Instead, I will try I different message. First trust you fellow citizen- if you give them the unvarnished truth (such as vaccination really does cause death, but in tiny numbers), ask them to vaccinate voluntarily and don’t try to threaten them with mandates or passports- then they might surprise- it is generally the case that where these principles were in place vaccine uptake has been highest.

Second, don’t incorrectly assume that vaccine misinformation played a greater role in people making poor decisions than the numerous and unforgiveable blunders of Public Health information. You are confusing cause and effect. The blunders came before the misinformation for the most part- whether we are talking about Faucci, Trump and Pelosi lying, the numerous reversals of the WHO, or the general global mixed messaging on masks and other measures. Conspiracy theories such as the 5G mast and ethnic medical paranoia (which is at least historically justified) might had continued to arise and circulate, but they wouldn’t have had the climate to grow without these blatant examples of Public Health failures.

Third, don’t let politics contaminate the pool for the purposes of narrow political interest. The BLM movement may have had just cause in many respects (though not as it turns out in relation to police shootings), but the responsible thing to do would have been to tell our kids to stay home, for the simple reason that this immediately caused half the country to abandon all trust at a moment when America should have been at its most stalwart and united.

Fourth, only circulate models for internal purposes. The behavioural economics of sowing fear to create compliance might be tempting, but in the end, as worst case predictions fail to materialise it will only sow doubt and frustration. In an interesting side note, many of the scientists involved in the 2018 IPCC special report lambasted the media for misusing their work (although most wouldn’t know it), because they were fully cognisant that the 12 years to change course narrative has the potential to backfire spectacularly when catastrophe fails to materialise. The actual deadline for irreversible damage in the report was 2053.

Fifth, we should all mentally prepare ourselves for what is to come. If like me, you’ve felt alternate shades of desperation, frustration and sheer despair at the various cynical gestures, collective crazy (on both sides) and the perhaps irreparable societal mistrust that has been sown, then it is better to adopt an air of fatalism and mentally steel oneself. With vaccination and a degree of continued personal caution, there is no reason why we can’t return to our ordinary lives pre-pandemic.

Here is the UK, where antibody levels in the adult population were at 94% in the August, daily case numbers remain at about two-third of their pre-vaccination peak, but hospitalisations and deaths are tiny by comparison. Eventually, COVID-19 will become like the seasonal flu in terms of impact and almost as frequent as the common cold. It might be like the bad uncle who returns every Christmas, but remember you’ll be able to see the back of him, every year.

As usual, my essays are to be found on my Substack, which is free to view and comment:

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The rate of death amongst children from COVID-19 are 2 in a million. The risks of myocarditis in children between 12 and 17 is between 1 in 6,000 and 1 in 10,000. The CDC’s arguments that the benefits of vaccinating children to protect the broader population, at the net (though admittedly small) increased risk to children’s health is an obsolete argument. All the empirical data now shows that regardless of what we do, with delta, the virus is here to stay and will become endemic.

Anyone with a knowledge of maths and game theory will know, it it now probably optimal to get vaccinated first and then get the virus- this will provide the greatest level of immunity in the event that a new variant emerges which is both more deadly and more virulent. The evolutionary biology is against it, but it has been known to happen.

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Adelaidean, in this matter, I do not need ‘a mind for data’, because there is a discipline called epidemiology manned by professional epidemiologists who do have all the genuine data, who overwhelmingly say that distancing, masks, lockdowns where necessary and vaccination is the way forward.

And if you so interested in the data, then you would have worked out by now that Covid is overwhelming the disease of the unvaccinated.

And the reason I am hard balling you is that you and your constituency have been a very problematic part of the Covid equation and it is reflected in the data. Louisiana is a US state with 2 million fewer people than Australia. They have lost to date 14,068. Australia has lost 1,357. And that is entirely because the attitude you are peddling to us here is widespread there, so vaccination rates are low and the disease is having a field day with them.

Trump’s America just keeps kicking own goals on this front, which is why overall, the US has lost more people to Covid than it lost to Spanish flu a hundred years ago. And the main difference between then and now is ideological idiocy for which there is no vaccine other than an education system that works, because brilliant technology and good medical advice just isn’t enough on its own when dealing with ideological idiocy.

We in Australia have a small corpus of Covid dickheads that have been making trouble in Melbourne, but fortunately for us, most people here trust their health officials for the very simple reason that they know what they are doing and are on top of their game

I would get a lot of satisfaction seeing unvaccinated fools making themselves very ill, but the downside is that they victimize the medical system that has to prop them up in hospital beds for up to two to three weeks.

I mean Adelaidean, if we did what you want and just let the disease rip, it might be worth it just to get rid of some fools, but they would do terrible damage to our health system on their way out, so it just wouldn’t be worth any possible pleasure in cheering on the corteges heading for the overwhelmed cemeteries which is what is happening in crowded and chronically poor places where they cannot afford to lock down and buy vaccine.

And finally Adelaidean, idiocy is not the monopoly of one side of politics. The Wokes are exactly the same when it comes to sex and race, which is another set of idiocies for wilting late modern societies to cope with, as their social infrastructure starts disaggregating into a sticky and chaotic mess as the post WW2 democratic consensus disintegrates and the lack of sustainability of the whole system makes itself felt…and everyone starts to feel a cold wind of uncertainty at their back…and the urge to dig in becomes overwhelming.

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