Get vaccinated! It could help you, like, not die…

(Everything you ever wanted to know about vax but were afraid to ask)

Ok, I’ve just about had it with all the ignorance and misinformation surrounding Covid vaccines. For some reason even smart and knowledgeable people have a blind spot when it comes to them. Maybe vaccines just got a bad rep from the days of antivaxx activists creating “vaccines cause autism” memes a decade ago, and it is subconsciously coming out now at a time of great fear, uncertainly and doubt that Covid has unleashed on our planet.

Let me be clear — our kids these days get dozens of shots and those vaccines are VERY safe. But new vaccines, like any new medical treatment, definitely need to have their safety and efficacy proven before being allowed to be used in millions of people. And yes, ideally, it would be nice to have a few years to monitor them before that. But in case you haven’t noticed, we are in the middle of the worst pandemic the world has seen in a century, and unless we stop Covid, it just might take the crown for the worst pandemic ever.

Vaccines are our only hope of stopping it and thanks to science and technology, humanity is in a great position to do so — we can create novel vaccines in silico in a matter of hours, start testing them in vitro in days, in animals in a couple of months, and then test their short- and mid-term safety and efficacy in humans in another few months.

This provides us with a great advantage over the SARS2 virus, as, on average, it acquires only about 25 new mutations per year (in a 30k genome), which means that the chances are very high that we can stamp it out before it has enough time (and seronegative people!) to develop enough mutations to avoid the antibody repertoire that our vaccines create in every vaccinated person.

What is the point of a vaccine? To help your body not let the virus get into your cells and start replicating. And even if some of it still manages to get into cells, to speed up the process of your immune system killing those cells. Yes, those infected poor little cells of yours are goners, c’est la vie.

All right, so how can we help the body prevent the virus from entering cells? With neutralizing antibodies. Normally those are only generated after your immune system acquaints itself with a pathogen, and they take many days to get produced in large enough numbers. That’s what vaccines are meant to shortcut: they present the immune system with the very part of the virus that it uses to get into cells — the spike protein — so that our bodies generate neutralizing antibodies in advance. This way, if and when the virus does find its way into our body, those neutralizing antibodies will bind to its spike and not let it get into any meaningful number of cells. Which means that not only we won’t feel sick but also that we won’t produce and ‘shed’ (i.e. spread) copies of the virus that could infect others and potentially kill grandma even if you, oh brave man, are willing to take your chances playing the Covid roulette.

So do you see how vaccines are not only good for you, but good for everyone, as they very effectively can help stop the spread of a new virus? Come on, you don’t need a PhD to understand this.

Ok, seriously, your chances of dying from Covid itself are much higher than your chances of dying from a vaccine. There have been no vaccine-related deaths reported in clinical trials, and even after 250 MILLION doses have been administered in the US, only ~4500 deaths were reported in VAERS as potentially having any sort of a connection:

Even if all of those deaths were indeed caused by a vaccine, that is still a meager 1 in 55556 chance of dying (or ~0.002%). And even that is a huge overestimation, as CDC reports just a few of those deaths to be causally related to vaccinations.

Note that 1.5M Americans die from heart attacks, stroke or cancer every year. Which amounts to about 4K people per day. So having 4.5K deaths in a cohort of ~150M people getting 250M vaccine shots in a period of 5 months is actually significantly lower than expected background mortality.

So what are your chances of catching Covid and then dying from it? Obviously, they greatly depend on your age, as well as where you live, and a few other factors. But let’s just focus on US numbers and do some quick estimations — enough to give us the right orders of magnitude.

We have these nice CDC data from the time when there were just 15M cases in the US (after about 6 months of the pandemic). Now it’s 33M, in case you missed it.

We also have these recent data for deaths:

So using the above three sources, I have put together a quick spreadsheet to estimate the risks of catching Covid, dying from it once caught, and the cumulative annualized risk of catching Covid and dying from it as of early 2021 (when total Covid cases were ~28M). Here it is:

Nothing terribly surprising there: the older you are, the much higher your chances of dying from Covid. But even if you are aged 30–39, your risk of dying is not negligible: 0.14% is nothing to sneeze at, pardon the pun. And if you are aged 50–64, that risk is tenfold greater: 1.5%! Given that all adults had about the same 10% probability of catching Covid in the past year, the overall risk of doing so and dying from it is definitely worrying: 0.15% for the 50–64 group or a whopping 1% for the 75–84 group.

Or at least those were the numbers in the past year, and they would probably remain so if nobody was vaccinating. Fortunately, thanks to all people who got a jab, rates of new infections are rapidly dropping in the US. However, the chance to catch Covid and die is still quite sizable. Probably not 0.15% or 1% anymore for 50–64 or 75–84 groups, but even if it is 10x lower now thanks to vaccinations, it is still 0.015% or 0.1% for the unvaccinated.

Which means that even in worst case vaccine death scenario and best case reduced Covid transmission rates scenario, today your risk of getting Covid and dying is still 10–50x times higher (0.015% or 0.1%) than the risk of dying from a vaccine (<0.002%).

As I said, it would have been great to wait a few years to study the long-term effects of Covid vaccines, but we just don’t have the luxury. Allowing Covid to ravage the planet and potentially develop novel variants while we wait for any potential vaccine long-term effects to manifest themselves is just dumb. This will leave millions more dead (ok, I concede, no unknown long-term issues there) and hundreds of millions Covid survivors susceptible to potential Covid long-term issues. And given a choice between potential long-term issues from Covid or the vaccine, I think the vaccine is a much safer choice.

Especially because the vaccine is essentially a much smaller subset of the virus, which, unlike the virus, does not replicate and gets fully eliminated from your body in a matter of days. Only its memories remain, in the form of antibodies and, well, memory B-cells and T-cells — and, again, all those are a subset of what usually remains after a Covid infection. So if you are willing to brave Covid for the sake of getting that “natural” immunity, you really shouldn’t worry about braving a vaccine.

What is even more encouraging is the fact that the clinical effects of a vaccine shot are obviously waaay less severe than the effects of catching a live virus. This has been documented in numerous studies, so the fact that the short- and mid-term safety of vaccines is much higher than that of Covid, makes a pretty compelling case that long-term safety of vaccines is similarly much better.

Wait, let me get this straight. You prefer to risk dying from Covid for protection against getting it a second time rather than get a vaccine and not risk dying from Covid? That makes zero sense.

And just because the epitope repertoire from a “natural” Covid infection is broader than that of a spike-specific vaccine, doesn’t automatically make it better for protection from subsequent infection. In fact, it might even make it worse. Read on.

What exactly is an epitope repertoire? It’s the collection of various short fragments of viral proteins that the immune system is trained to recognize and attack after a natural infection or a vaccine. When our immune cells encounter the natural virion, they will slice up its various proteins into these short fragments and will eventually raise armies of B-cells and T-cells, meant to produce antibodies against those fragments or kill infected cells displaying those fragments.

However, as I already mentioned, not all antibodies are created equal. To protect from future infections, the most useful antibodies are neutralizing antibodies — ones that will prevent the virus from entering our cells. Unfortunately, our immune system does not know which antibodies will be neutralizing, and which ones won’t, as it will blindly pump out antibodies against the epitopes it encounters. But we, humans, armed with our brains, know that only antibodies that stick to the spike protein can be neutralizing, as the spike protein is the only thing the virus has sticking out of it, and all other proteins are hidden inside. So for the purposes of a vaccine, we can just present the immune system with the spike and not divert its resources on producing useless antibodies, like against the N (nucleocapsid) protein, for example. Especially since higher N antibody titers were observed to be associated with worse disease progression:

In case you don’t even know what ADE is, it stands for Antibody-dependent enhancement, which is basically when your antibodies turn from friend to foe and instead of preventing the virus from entering your cells, actually help it get in. ADE has been observed in Dengue and HIV and potentially in first SARS, so scientists were rightfully concerned that it might be an issue with SARS2 as well.

Thankfully, no ADE has been observed with SARS2 in any of the human vaccine trials. And ADE is not exclusively a vaccine thing, in fact, “natural” immunity might actually have a higher chance of ADE for future reinfections, as it’s got a broader antibody repertoire than the vaccine-generated one, so more chances for some particular viral epitope to turn out to be enhancing.

Yeah, ok, that is just crazy talk. But yes, that is what Geert Vanden Bossche said:

Not only would people lose vaccine-mediated protection but also their precious, variant-nonspecific (!), innate immunity will be gone (this is because vaccinal antibodies outcompete natural antibodies for binding to Covid-19, even when their affinity for the viral variant is relatively low).

I was going to write my own rebuttal of Geert’s claims but when I googled him, I came across the following detailed deconstructions of his conjectures: one by Edward Nirenberg, and another one by Snopes. Here is an excellent response to Geert’s quoted claim by Nirenberg:

This is absolute, unvarnished nonsense. Bossche is referencing the production of natural IgM, which is generated by B1-B cells as a stopgap measure against infections until more potent responses can be initiated; these antibodies are polyreactive, nonspecific, and critically: constitutively produced. They are always present for as long as B1-B cells generating them live. IgM is pentameric and thus even though it has lower affinity than antibodies that have had the opportunity to evolve superior binding affinity, it can compensate with the fact that it has 10 binding sites instead of 2. However, IgG antibodies bear many of the same effector functions (actually, they tend to be better at many of them, as Table 10.27 shows) and they can diffuse into extravascular sites unlike IgM. Principally, antibodies against SARS-CoV-2 could be of value if they are neutralizing. Bossche presents no evidence to support that natural IgM is neutralizing (rather than just binding) SARS-CoV-2.

Bottom line: Geert is wrong. Don’t listen to Geert.

Umm, no, this could be a reason to fear SARS2, and want to get vaccinated to not get SARS2, but in no way can this be a reason to fear vaccines.

The question about SARS2 integrating into our cells is still an open one. Yes, there’s been this study that showed that in vitro (in a Petri dish) they can induce LINE-1 reverse transcriptase (which is a part of endogenous human retroelements which make up almost half of our genome) to integrate parts of SARS2 genes into human DNA. Is that a big deal? No, because those SARS2 snippets will probably not be used by our cells to make new proteins and even if they were, those proteins won’t be able to assemble full virons, and moreover those proteins, even if indeed expressed, would likely quickly trigger an immune response and death of said cell.

After their in vitro success, the authors then tried to detect whether there were similar insertions in Covid patient tissues and potentially detected some genome sequencing reads that could have been legit, or could have been due to contamination:

Chimeric reads generally accounted for 0.004–0.14% of the total SARS-CoV-2 reads in the samples. A majority of the chimeric junctions mapped to the sequence of the SARS-CoV-2 NC gene (SI Appendix, Fig. S6 C and D). This is consistent with the finding that NC RNA is the most abundant SARS-CoV-2 subgenomic RNA (56), making it the most likely target for reverse transcription and integration. However, recent data showed that up to 1% of RNA-seq reads from SARS-CoV-2–infected cells can be artifactually chimeric as a result of RT switching between RNA templates, which can occur during the cDNA synthesis step in the preparation of a RNA-seq library (57). Thus, because there is a mixture of host mRNAs and positive-strand viral mRNAs in infected cells, the identification of genuine chimeric viral–cellular RNA transcripts is compromised by the generation of artifactual chimeras in the assays.

In any case, those reads contained only the N (nucleocapsid) gene, which is just a structural protein used to pack viral RNA in the virion. No big deal. Oh, and if you think this can somehow lead to false positive PCR patient swabs, don’t: most PCR patient tests use the spike gene to establish a positive Covid diagnosis, so no, this potential integration of SARS2 N gene into DNA inside cells can in no way cause false positives in swabs from your nose.

Finally, again, if you are worried about SARS2 integrating into you genome, this is all the more reason to get vaccinated. mRNA vaccines don’t even contain the N gene (just the spike) and won’t integrate into your genome.

No! On the contrary, vaccines prevent new variants from appearing. Most of the current novel variants appeared before mass vaccinations have started. So the virus clearly can create novel strains in the absence of vaccine-provided immunity. Moreover, all of the known strains are still neutralized by vaccine-mediated or natural immunity, albeit not as effectively as the original strain. Still, vaccines can protect against them.

Thinking that vaccines can make this pandemic worse is not just alarmist, it also shows a misunderstanding of the dynamic process that a pandemic is. Vaccines actually greatly reduce opportunities for the virus to develop new variants because they take away 2 main ingredients for that: new people to infect and the time to do so.

Recall that the virus infects vaccinated people at 10–20x lower rates. Basically the more vaccinated people there are, the fewer new people the virus has a chance to infect, thereby greatly reducing its effective reproductive number and ultimately extinguishing it from existence, as without reproduction it will, well, go extinct. This effect of vaccinations is orders of magnitude stronger than any potential additional selection pressure that vaccines could put on a virus.

(Disclaimer: climate change is real!)

Well, children under 18 aren’t even authorized to be vaccinated in many countries yet, and are definitely the last who should be. Their Covid risk profile is highly favorable and indeed the biggest value from vaccinating some subset of the under 18 age group — probably the 12–18 subgroup — comes from further increasing herd immunity.

The biggest epidemiological issue with children is that many of them are potential silent superspreaders: asymptomatic carriers who interact with a lot of other people from diverse age groups:

That said, if a high enough percentage of adults is vaccinated, we might be able to stamp out Covid even without vaccinating children under 12. Basically it depends on us getting the viral effective reproductive number low enough. In any case, debates about the merits of vaccinating children should have no bearing on the merits of vaccinating adults.

Moreover, the only reason not to vaccinate children is an over abundance of caution — essentially, the fear of unknown unknowns. As I said in the beginning, kids get dozens of vaccines, and they tolerate them very well. Their immune systems are in excellent shape, which can be seen from how they deal with Covid — most don’t even notice it. So tolerating a vaccine which is a subset of the virus causing Covid should be even less of a problem. Same logic applies to any potential long-term effects, as Covid’s unknown unknowns are probably likely worse than those of a vaccine.

Nope. Not by a long shot. Even if you believe the outcome of the severely statistically underpowered clinical trials which show IVM reducing Covid mortality, that mortality risk still remains extremely high: 1.4–3.9% depending on the trial:

Those numbers are crazy high when looked from a population level perspective, as with such a highly transmissible virus as SARS2, they imply millions more dead if we relied on IVM as an alternative to vaccinations.

Now, don’t get me wrong, if you want to use IVM as treatment, go right ahead. Or even if you think it could be an additional prophylactic measure to vaccines. But if you think IVM can protect you from Covid better than a vaccine — that is just nonsense.

Some young and healthy people think that a 0.1% risk of dying from Covid is negligible, so they shouldn’t even bother getting a vaccine. The problem with that line of reasoning is threefold. First, the anticipated loss in the case of that 0.1% scenario is infinite: you die. A rational person would do anything possible to lower the probability of that happening. Second, if there are many people who think like that, even having 0.1% of them die is unfortunate — they would be dying needlessly. Finally, even if 99.9% of them survive Covid, they could infect many more people whose risks of dying or developing long-term issues from Covid are much higher, and therefore the implied costs of such selfish thinking to society are many times greater than just the loss of life of the selfish 0.1%.

Also, even if you survive Covid, your subsequent risk of death is increased by 50%. And risk of developing various cardiovascular, neurological or other complications is also increased by 50% if you weren’t hospitalized or by several times if you were:

Another study in a younger cohort had similar findings:

Trust me, Covid is no picnic even when it’s mild.

Right, those pesky brain-eating LNPs. Well, first of all, if you are really so afraid of the LNP/mRNA technology, you could just get an old-fashioned vaccine. But really, even with LNPs I don’t really see any cause for concern. First of all, they have been shown to remain well-localized at the site of an intramuscular injection:

From the above you can see that most of the injected mRNAs stay in the injected muscle and their next most popular destination is the nearest lymph node where the immune system magic happens.

Second, even though some LNPs do go on a rollercoaster ride around the body, the proportion of those that do so is very small. For example, only 1/10000 of injected mRNAs make it to the brain of mice. By the way, that was a HUGE dose those mice were injected with — 300 mcg/kg, which is way higher than the doses used in Covid mRNA vaccines: 30 or 100 mcg in Pfizer and Moderna shots, respectively, for a whole 50–100 kg human, i.e. a 150–1000x lower dose per kg than poor mice got. Which I am sure translates to an even lower percentage of LNPs going for a ride in our bodies but for the sake of an upper bound, let’s try to estimate how many brain cells we can expect to lose to zombie LNPs.

First, let’s see how many mRNA molecules are in a single vaccine shot. The vaccines encode the full viral spike which is a ~1300 amino acid protein, so an mRNA for it is ~3900 nucleotides (each aa is coded by 3 nts). The average molecular weight of a nucleotide in a long RNA chain is about 300 Da. With that, we can do the following calculation:

~1300 aa spike * 3 nt/aa * 300 Da/nt = 1.5 MDa = 1.5e6 g/mol

6e23 molecules in 1 mole, so in grams 1 copy of our mRNA weighs
(1.5e6 g/mol) / (6e23 copies/mol) = 2.5e–18 grams

Thus, 100 mcg of S mRNA (Moderna) should contain
1e–4 g / 2.5e–18 g/copy = 4e13 (40 trillion) copies, while

30 mcg (Pfizer) contains about 12 trillion mRNAs.

How many mRNAs fit inside a single LNP? This one actually turned out to be a tough question to answer, but I found this paper that used a human EPO mRNA for their LNP characterization studies and have this wonderful figure:

EPO is about 2.5 times smaller than the viral spike, so we can divide the above number by 2.5 for our mRNA vaccines. Most vaccine LNPs are reported to be about 100 nm in size, so let’s say we get 30 mRNAs per 1 Covid vaccine LNP.

This means that in a single vaccine dose we get ~0.4–1.2 trillion LNPs (between Pfizer and Moderna). Let’s just continue with 1 trillion LNPs for ease of estimation. How many LNPs do we need to get in a cell to cause significant damage? Well, a typical mammalian cell contains 360,000 mRNA molecules. Let’s say getting ~10% of that could probably overwhelm a cell and cause cell death. ~30,000 vaccine mRNAs means 1000 LNPs per cell, which means that 1T LNPs could probably kill 1B cells. Now, before you freak out, know that there are 40T cells in a human body, so 1B is just 0.0025%. Also, many LNPs probably will get intercepted by tissue-resident immune cells before they have a chance to enter muscle cells in your shoulder.

And what about brain cells? If we use the mouse data observation that 1/10000 of injected LNPs get to the brain, this would put an upper bound of ~100M LNPs that could potentially get there after an injection, and thus potentially kill 100K brain cells. Again, if that sounds like a lot, recall that we have ~100B neurons, so 100K is just 1 part per million of our total. I think I probably lost more brain cells playing beer pong.

Finally, this was just an educated guess of what the vaccine might do, but the ultimate proof in the pudding comes from clinical trials and observations of what actually happens. And no rotting brains or concerning neurological symptoms have been observed in any of the vaccine trials, in sharp contrast to Covid infections where a large percent of people develop loss of smell/taste, brain fog, anxiety and other neurological symptoms, which often persist long after the infection has been cleared.

So again, when it comes to messing up your brain, vaccines do not even come close to Covid.

While vaccines can reduce your chances of getting Covid by 10–20 times, they don’t offer perfect protection. Also, you don’t get full protection right away — you actually need two shots for the full Monty, and while a single shot does provide protection, it doesn’t kick in until 2 weeks after the jab. This is why you should still play it safe and not go partying a day after the jab thinking you’re now immune to Covid.

The good news is that even a single jab provides some level of long-lasting protection, even against new variants. Here are the neutralizing antibody titers 1 year after the jab (from this preprint):

In fact, it seems that a single vaccine dose provides a similar level of neutralizing antibodies as a natural infection:

Also, as you can see from the same graph above, getting a vaccine after a prior infection greatly increases the level of neutralizing antibodies.

More good news is that even if people do get Covid after vaccinating, it seems that their average viral load is much lower (4x lower according to this preprint), and the severity of their clinical manifestations might be decreased:

Around 20% of those who were admitted to hospital for treatment had been vaccinated, but their cases weren’t serious, the Ministry of Health said Monday. Almost none of the critical and severe cases requiring intensive care had been vaccinated, and no one who has been vaccinated has died of Covid-19.

Radegonde said Thursday that only two people in the country are in intensive care.

“The conclusion is that the vaccines are protecting the people. Those who have been vaccinated are not developing any complications,” Radegonde said. “We remain confident that the vaccines — both of them — have helped the country. Things would have been worse.”

I like mRNA vaccines — not only do I think that mRNA LNP technology is more ‘pure’ than viral delivery vectors, the mRNA vaccines seem to have the highest safety and efficacy profiles.

For a much more detailed analysis, here is a recent Nature paper on the topic. I’ll just post this pretty straightforward graphical summary:

Basically, according to that paper, Moderna (mRNA-1273), Novavax (NVX-CoV2373), and Pfizer (BNT162b2) take the podium, while Sputnik (rAd26-S+rAd5-S) gets an honorable mention.

This one is a bit tricky, at least at first glance. Obviously, if you just had Covid, you should have plenty of protection against reinfection. The issue is that neutralizing antibodies don’t stick around for too long — in a matter of months their levels greatly decline. So if you catch the virus after that, it will enter your cells, and it will then be up to your T cell immunity to take the brunt of the load of eradicating the virus from your body for the second time.

Not a huge deal, but risks still exist in the case of reinfection, although reinfections do seem rare and milder than the original infections. But you could still infect others from your reinfection, continuing the virus’ march across our planet and giving it new opportunities to mutate. So getting a vaccine a few months after the original infection makes the most sense to me.

In fact, this is what I myself have done. I had Covid back in June 2020, and got a Pfizer shot in May 2021.

Oh and there’s some new data about new vairants that very nicely illustrates why you might still want to get a jab even if you had a prior infection: because a prior infection by itself (or a single vaccine dose) has very low neutralizing titers against some new variants but a jab after a prior infection has a much higher neutralizing titer:

I would also expect to see similar neutralizing titers after the second vaccine dose in the absence of prior infection.

Even though I am a strong vaccine proponent, I am absolutely against any mandatory vaccinations. That just goes against my core principles. I am also not a fan of coercing people into vaccinating. I think it should be done completely voluntarily after all the pros and cons have been examined. At the same time, I think that any reasonable person, after examining all available data, and weighing all those pros and cons, will choose to vaccinate. Because not only does that lower most adults’ chances of dying from Covid by at least 10–20x, if not 100x, but also because vaccines are the key to eradicating Covid altogether.

So. What are you waiting for?

Funding sources and Conflict of interest statement

This article was sponsored by grant FU0042069420 from the Vaccine Manufacturers Guild, grant FU200133701337 from the EcoHealth Pangolin Malayance, and grant DOS655360B from the Gates 5G Depopulation Foundation.

The author declares no conflict of interest.

Life mission: defeat aging. Here I write mostly in English, my Russian articles are on Habr. I am also on Facebook, LinkedIn, YouTube, etc.