Myocarditis after the Pfizer Vaccine: Uncertainties

I wanted to do a quick post about incidents of myocarditis (inflammation of the heart muscle) in young men after the Pfizer vaccine.  This has been in the news for a bit, but I don't think the uncertainties involved in this issue have been properly explained.  Ultimately, I'd like to be able to fit this risk into my risk analysis framework, but we have to deal with the uncertainties first, and in this case they make for a very difficult risk to assess.

Background Rate

Whenever I hear a report of a possible complication associated with one of the vaccines, the first thing I do is research to find out, what is the background rate of that complication?  I then look at the rate at which this complication is being reported by vaccine takers, try to adjust based on how much I think this complication might be underreported, and then the difference between background rate and the adjusted rate for vaccine takers is the increase of risk or this complication that can be imputed to the vaccine.

With myocarditis, however, I found that there isn't a simple answer for determining what the background rate of myocarditis is, especially among young men which is the demographic of concern.

The most up-to-date summary on myocarditis incidence rates I know of is "Epidemiological Impact of Myocarditis", published just this past February.  It describes the current state of knowledge as follows:

Myocarditis was considered a rare disease until intensified research efforts in recent decades revealed its true epidemiological importance. While it remains a challenge to determine the true prevalence of myocarditis, studies are underway to obtain better approximations of the proportions of this disease. Nowadays, the prevalence of myocarditis has been reported from 10.2 to 105.6 per 100,000 worldwide, and its annual occurrence is estimated at about 1.8 million cases. This wide range of reported cases reflects the uncertainty surrounding the true prevalence and a potential underdiagnosis of this disease.

"Between 10 to 105 cases per 100,000" is a very wide range.  There are several reasons for this:

Variability of Severity and Symptoms

Myocarditis is a generic description of any sort of inflammation of the heart muscle.  It can have a number of different causes, and it can be more or less serious, depending on the cause and the degree.  The noticeable effects of myocarditis can range anywhere from "none" (as in, you have myocarditis but just don't notice anything) to "mild chest pains" (which I think is the most common manifestation) all the way up to "sudden death" (see Myocarditis in Clinical Practice).

It is this last part that has caused the medical world to try harder, in recent years, to get a handle on how often myocarditis is happening.  What they have noticed was that in autopsies of people who died suddenly and unexpectedly from heart failure, myocarditis was frequently present even though the patients had not exhibited any of the classical observed symptoms (see Myocarditis and Sudden Death).  If myocarditis is capable of being present with little or no symptoms and yet still causing or contributing to death, there must be many more people who have it at any given time and do not know it, nor suffer any obvious consequence from it.  There would be no reason for these people to come to the attention of the medical world, so the conclusion has been that we don't really know how often myocarditis happens, but we know that it is very under-diagnosed.

One possible measure of how much it is under-diagnosed comes from a study of post-Covid athletes, Prevalence of Clinical and Subclinical Myocarditis in Competitive Athletes With Recent SARS-CoV-2 Infection.  There, they evaluated patients just from symptoms first but later followed up with an MRI.  When they did the MRIs, they identified 7.4 times as many incidences of myocarditis than they did by just symptoms alone.  Now, this study was just for a very particular demographic in a very particular circumstance, so I'm not sure how well it generalizes to the population as a whole.  However, it does mean that a difference between actual rates of myocarditis and reported rates of myocarditis all the way up to, say, 10x are within the realm of possibility.

Variability of Understanding

Given that the medical world has fairly recently recognized myocarditis as being under-diagnosed, increased effort has been put into understanding its spread.  This has led to better tests and procedures developed to detect it in patients who come in with relevant symptoms.  Indirectly, this also leads to a variety of answers to the question of "how prevalent is myocarditis?", depending on how old the specific paper is.  Recently, I have seen this paper cited in support of an incidence rate of myocarditis in children at 1.13 per 100,000: The Incidence of Pediatric Cardiomyopathy in Two Regions of the United States (cited in this NPR article: Pfizer's COVID Vaccine In Teens And Myocarditis: What You Need To Know).  However--crucially--this study was published in 2003.  There are more recent studies that have reported some very different numbers, and I think that's important to recognize.

Variability by Age and Gender

One of the things we know for sure is that there is an age and a gender component to myocarditis: at least, reported myocarditis.  Importantly for the current discussion, the demographic that is most susceptible to myocarditis is young men.  This is something that has also been revealed more clearly in recent years.  The 2003 study I mentioned above did see a slightly higher incidence rate of myocarditis in teenage boys compared to other children, but only by a bit less than 2x as much.  A newer Finish study (2014), on the other hand, has identified a much higher difference--closer to 18x higher prevalence in teenage boys compared to other children (Occurrence and Features of Childhood Myocarditis: A Nationwide Study in Finland).  In what might be considered a companion study of adults, the Finns discovered that the peak incidence occurred in mean aged 16-20 years, declining steadily by age after that (The effects of gender and age on occurrence of clinically suspected myocarditis in adulthood).  Here's the key graph from the first study so that you can appreciate the dramatic difference that occurs for this age group specifically (unfortunately, I don't have access to the full data of the second study):

I don't believe it's completely understood why boys in particular have these higher rates of myocarditis, but I know testosterone levels are suspected.

When you have this level of variability in a specific sub-group, this can lead to higher variability in end-results of a lot of studies, because it then becomes a question: how many of a particularly susceptible sub-group did you include within this study compared to that study?  Especially when we don't know the exact mechanism which causes teenage boys to be more susceptible to myocarditis, this can make it difficult to get consistent results across studies.

Variability by Region and Viral Background

In the first study I mentioned, there was a reported rate as high as 105 cases per 100,000 people.  This specific rate was reported for a particular region: Albania.  Are Albanians particularly susceptible to myocarditis?  Well, maybe--but on the other hand, it may have had more to do with the types of diseases that had been recently prevalent in Albania at and before the time of that regional study.

The majority of cases of myocarditis in the developed world are thought to be caused by viral infections: a virus attacks the heart muscle in some way, and then the immune system triggers inflammation of the damaged tissue.  It's known that certain specific viruses are more prone to causing myocarditis than others, and some of the viruses that have this property are otherwise not very serious.  The incidence rates of myocarditis, then, can fluctuate greatly depending on what specific diseases were recently going around in the region under study.  This may well have been what happened to Albania here.

Here it is relevant to point out that Covid is one of those viruses that has been shown to cause myocarditis--at a rather high rate, as well (possibly even as high as 25%, depending on the study you look at).  Further, we know that Covid has spread much more rapidly among young adults than was earlier appreciated (see here: Difference in Severe Acute Respiratory Syndrome Coronavirus 2 Attack Rate Between Children and Adults May Reflect Bias), and we know that it spreads in this demographic very often undetected.  So we have at hand here in the United States a plausible, ready provider of large amounts of occult myocarditis in young adults.

Combined Variability

When you add up all these sources of variability, you get a lot of uncertainty, because each of the causes of uncertainty I've described so far are independent of each other.  For example, the 105 cases per 100,000 were only from reported cases.  Multiply that by 7.4 as a very plausible ratio between actual and reported, and you get a rate of 777 per 100,000.  And if you were looking for the incidence rates for just the young men in that area, well, you could easily multiply that number by 2 or 3 as well because of the increased prevalence in that group.  So we are looking at plausible ranges of background myocarditis at anywhere from 2 per 100,000 all the way up to *2300* per 100,000, depending on various things that we don't have a great way of knowing.

Rate of Myocarditis Among Vaccine Takers

Ok, so on that very unsatisfactory note, we now we have to move to the rate of myocarditis that we're actually seeing in young men taking the Pfizer vaccine.  The best numbers I've been able to get for the States so far has been from this news report: CDC confirms 226 cases of myocarditis after COVID-19 vaccination in people 30 and under

The CDC is still going through cases they've found on VAERS (as of the time of that news article, they were about half way done), but what they've found so far is:

79 cases of myocarditis/pericarditis reported in teens ages 16 or 17 years after a second dose of vaccine, while the expected number was two to 19 cases, according to Dr. Shimabukuro. There were 196 cases in young adults ages 18-24 years, while eight to 83 were expected.

I know that the first number (79) is out of about 7 million teens who have so far been vaccinated over the course of about 1 month.  If they were expecting 2-19 cases from 7 million people over one month, that means that they were expecting myocarditis at a rate of 0.3 - 3.4 per 100,000 per year.  That corresponds OK with the older 2003 report I mentioned above, but it does not correlate well with the Finnish data.  So I wonder if whoever is analyzing this for the CDC has good updated numbers on myocarditis prevalence, or whether they are using dated information.  Then again, it could be argued that the 2003 study, while not as recent as the Finnish study, at least was a study done in the States, and as we have seen, there can be dramatic regional differences in background rates.

Meanwhile, Israel has reported that "between one in 3000 and one in 6000 men ages 16 to 24" who have been vaccinated have developed myocarditis (news story here: Israel reports link between rare cases of heart inflammation and COVID-19 vaccination in young men).  That's between 17 and 34 per 100,000.  The scientist (Mevorach) is quoted as saying that his is between 5 and 25 times the expected rate, which implies that he thinks the expected background rate is 1.4 to 3.4 per 100,000.  That tells me, again, that he might be behind the times when it comes to background rates of myocarditis in young men, as those numbers don't agree with the Finnish study in the least.  He might well be using the same numbers the CDC is using?  That would seem less valid for Israeli data, though.  Anyhow, compared to the Finnish study, the rates reported are more like 1x-2x the expected background rate.  That's suggestive of a difference, but given the other possible variabilities here, hardly what I would call conclusive.

Europe has also reported some numbers, but as their vaccine program is heavily behind and still heavily targeting the elderly, their numbers are a lot less relevant.

Adjusting the Reported Rate

So, given the bare rates reported above, how would we need to adjust them to get closer to the true number of cases of myocarditis after vaccination?  Unfortunately, this is going to be very difficult to do.

Since VAERS is a self-reporting database, there are likely to be other cases that happen that are unreported.  However, no one really has a great handle on what this ratio between reported and unreported incidents is.

We have done research on VAERS in the past that makes it quite clear that the more serious the side-effects are, the more likely they are to be reported in VAERS.  About 76% reporting for the more serious side effects was the highest that particular report found (see here: The reporting sensitivity of the Vaccine Adverse Event Reporting System (VAERS) for anaphylaxis and for Guillain-Barré syndrome )

But that high rate of reporting was during the swine flu epidemic, and the researchers rightly pointed out that the high levels of media reporting on the pandemic may have increased reporting percentage in that case.  So what are we to expect in the age of Covid, in which media reporting and public concern about possible side effects of a vaccine under an unprecedented Emergency Use Authorization rollout?  Especially given the fact that the official guidelines for reporting Covid vaccine related side-effects are much more stringent and inclusive than they ever have been for any other vaccine (see the special "Covid-vaccine-only" official guidelines here: https://vaers.hhs.gov/faq.html )

I think it's very reasonable to expect that side-effect reporting for the Covid vaccines will be much higher than normal, and probably higher than they have ever been.  But in reality, no one has actually studied or measured this, and we can only go from intelligent guesses.  Personally, I think the rate is likely to be all the way up to 90% or higher--but I don't have much to back that number up aside from feeling.  Lower numbers are plausible--for the most trivial of side-effects and for other times, reporting rates as low as 1% have been seen.

So I could see plausible ranges of reporting ratios here all the way from 10% to 90%, given that the symptoms of mild myocarditis are frequently very mild and could be dismissed as no big deal.  So instead of 17 to 34 cases per 100,000, maybe we are actually seeing more like 170 to 340 cases per 100,000.

Bottom Line: What can we say about vaccines causing myocarditis?

Unfortunately, I think the honest answer to this question is, "not a lot".  Given the numbers that I am seeing, it is entirely plausible that the vaccines have no causal link to myocarditis at all.  It is also entirely plausible that the vaccines are causing myocarditis in young men, maybe even at a rate as high as about 1 in 3000.  The problem is that there is too wide a range of plausible answers for us to say for certain what is actually the case.

There can be other clues aside from mere numerical prevalence: for example, there is some coincidence of timing, where apparently there are clusters of cases around 4 days after the second dose.  However, I have seen things like this appear chimerically in data on an initial analysis, only to vanish after longer vigilant analysis, so I don't trust this datapoint yet.

I, personally, am very suspicious that this link between vaccination and myocarditis didn't become evident until after the vaccine was approved for 12-16 year olds--precisely the age group that the latest studies are showing to be much more prone to myocarditis than anyone else.  I think it's quite likely that this is a false signal based on an underappreciation of the true background rate of myocarditis in young men.  However, other more expert people than myself have held that there is *probably* something here, so I admit my opinion is not a consensus.  Also, I think that the contrary to my opinion is very possible as well.

So what should we do, in practice?  Well, the first thing not to do is avoid taking the vaccine.  At a very worst case, the vaccine would be causing myocarditis at a rate of something like 1 in 300--that's multiplying the Israeli number by 10x for all of the very mild, asymptomatic cases we assume might be happening without being caught.  If you also account for the same sort of thing on the Covid side, however, you get a rate of myocarditis at 1 in 4.  In other words, if you get Covid, you are at least about 100x as likely to get myocarditis than if you got the vaccine, and probably more like 200x-500x more likely.  You would have to be *really* certain you were not going to get Covid in order to make those odds work out in your favor.

Another reason to get the vaccine is that the cases of myocarditis we have seen from the vaccine have definitely been on the mild side, and again, that is less the case with what we've seen from the virus.  So the incidence numbers alone don't tell the whole story.

The one practical thing that I believe we can take away from this is a single recommendation: for teens and young men who get the vaccine, I would personally recommend avoiding strenuous exercise for the week following the second dose, just in case.  Strenuous exercise is the single most common circumstance that is seen in conjunction with myocarditis that leads to a serious attack.  In case there is any increased risk of myocarditis with the vaccines, abstaining from strenuous exercise for the likely critical period seems to me to be a prudent decision.

[Draft] Is it an Abuse of Power for the Government to Mandate Vaccination?

DRAFT

This post is a continuation of a discussion from Facebook.  The question we are debating here is:

Is it ever allowable for the government to mandate that a citizen submit to a medical procedure, such as vaccination?  Or, on the contrary, does an unwanted medical procedure--something done to the body of the individual--always violate the personal integrity of the recipient, such that even if it would be for the common good of the nation, a government must respect the wishes of any individual refusing vaccination as inviolate?

1. Summary of the Argument So Far

Here are some of my key take-away points from the initial discussion:

1.1. We are here asking whether there is an intrinsic and necessary bar from the government enacting a vaccine mandate--whether it is permissible for the government to make such a law under any circumstance, or whether instead the nature of personal responsibility or the inviolateness of conscience or some such thing makes it this wrong for the government to do this under any circumstance.

1.2. It is admitted that if such an inviolate freedom exists, it might only apply to the innocent, and that there could be some crimes that would result in the forfeiture of this right to medical self-determination.  This is not on-topic; we're talking about laws that apply to all or most citizens.

1.3. It is also established that there could be other, prudential, reasons for not wanting such mandates to be enacted.  Some such reasons discussed were wanting to avoid the temptation of the government to intrude unnecessarily into the private life of citizens, and wanting to limit government's power to forestall the slide into tyranny.  We are not discussing arguments of this sort now; this discussion is about the logically prior question of the intrinsic possible powers of government.  If it is wrong per se for any government to make laws of this sort, the prudence of such laws for our current world situation is irrelevant.

1.4. The distinction has already been made between laws that impact the common good and laws that are directed solely to the private good of individuals, and it has already been conceded that laws should not be passed that only affect the private good of individuals.  But it was also conceded that vaccination laws do affect the common good, so the claim which we are contesting is that the individual right to medical self determination pre-empts the responsibility of the government over things affecting the common good, in this case.

1.5. I'll point out here that most of the examples given so far as moral parallels haven't been very satisfactory.  Most of the things pointed out as "you wouldn't expect the government to be able to mandate X, would you?" have been things that only affect the private good, whereas the things pointed out as "we already admit that the government can mandate Y, right?" have been things that are done to people's properties and not to their bodies.  Vaccination might be a singular thing in that it is performed on individual's bodies, and yet also has a very clear impact on other people and on the common good.  Or maybe we just haven't thought of other good parallels.

1.6. One parallel that was raised but hasn't been answered yet is the example of a suicidal mother with an unborn baby, starving herself to death.  I think we would all agree the State would be right to force intravenous hydration in this case--but the point was mentioned and then the discussion moved on with anyone directly addressing it.

1.7. The attempt is being made to use the principle of the union of the soul and the body to claim that self-determination over the body is as inviolable as self-determination over the soul.  So far, this is the heart of the current disagreement, I think.

2. On "Personal Bodily Integrity"

The claim is that government mandated vaccines would violate an unalienable right of citizens in some way: maybe you could call it the "right to medical self-determination".  Another way this was put is that man's "moral stewardship" over his own body is absolute, at least insofar as decision making about it can't be compelled by the State.

So first off, I grant that there are certain aspects of the human person which are inviolate and about which the government should not legislate, even if they have a bearing upon the common good.  After thinking about these aspects of human life that I would agree are out-of-bounds, I think there are three very closely related concepts here at play here: dignity, responsibility, and integrity.  In none of these, however, do we see that absolute freedom from the State is accepted.

2.1. Dignity

I have two examples related to dignity:

2.1.1. The ability of man to choose his own individual life "path" and to choose his own way in life is a reflection of his being created in the image and likeness of God, and is hence a matter of high dignity.  This is reflected in the fact that it is considered a sacred and inviolate right of people to choose whether or not they wish to marry and to whom.  It would be a grievous overstepping of government authority to mandate marriages to its citizens.

Nevertheless, this doesn't mean that the choice of matrimony is entirely free from government regulation.  The government validly makes laws to prohibit near relations from marrying, for example, to prevent inbreeding.  The sovereign choice of whom to marry is thus still subject to laws, insofar as their choices have an impact on the common good.

2.1.2. There is no higher aspect of man's dignity than his relationship to God.  Therefore, conscience provisions prohibiting governments from dictating man's beliefs are the hallmark of a good and free society.

Nevertheless, freedom of conscience and freedom of religion are not unbounded, and are still subject to limiting laws for the sake of the common good.  In Thomistic thought, this fact is expressed in terms of whether or not the State has the right to punish heresy (it does).  This sounds quaint, but is not so far off from American jurisprudence as you might think; the rationale by which Thomas justifies the right of the State to do this is the damage to the peace and well-being of society that heresy can cause.  Likewise, freedom of religion in American thought does not give one license to preach any and every thing you want.  Openly preaching sedition or openly calling for the assassination of politicians, for example, is illegal no matter how much you justify the talk with your religious beliefs.  In both cases, the limiting factor on freedom of religion is the genuine common good.

Conclusion: If these two aspects of human life--self-determination in a family and freedom of religion--which are of the very highest human dignity, are not on that account free from all government regulations, then medical self-determination (which is clearly a lesser thing than those), is not therefore free from government regulation on account of dignity.

2.2 Responsibility

Aside from dignity, we also believe in that responsibility of rule follows the principle of subsidiarity: laws should be made by those responsible authorities who are closest to the subject matter of the law.  Therefore it seems that decisions about one's body should most properly be taken by the person himself, who is obviously closer than anyone else possible to the body in question.

You can enumerate the reasons behind subsidiarity as follows:

1. Those who are closest to the subject matter of a law know the most about the subject matter.  They are therefore the best able to make good decisions about how that thing should be ruled.
2. Those who are closest to the subject matter of a law are affected by the consequences of the law most directly.  Therefore, they have a stake in the correctness of the law, and are incentivized to avoid capricious rule.
3. Those who are closest to the subject matter of a law are often naturally fit to rule about said subject matter.  For example, parents are the proper rulers of their children, as ordained by nature.

But do these reasons apply to laws regulating the body in all cases?  We will see that they do not, and that when they do not apply, we do accept that the government can step in as the more appropriate lawmaker.

2.2.1 Knowledge

While individuals are usually the most well-informed about their own personal health, there are a number of things in which it is unreasonable to assume that the average person is best aware of, even regarding his own body.  For example, controlling bacteria growth in the food chain is a complicated process that involves very specialized knowledge and experience.  If you were to ask most people, "how do you ensure that you don't get botulism by eating the wrong foods?", they wouldn't have the first idea how to describe all the steps that need to be taken to do this.  It is therefore unwise for a State to leave the health of the publicly available food chain to personal, individual responsibility only, even though the ultimate end of all activities being regulated is what individuals put into their own bodies.  This is properly a State responsibility, not an individual one.

Likewise, individual citizens are often ignorant of even basic facts about immunology and epidemiology.  They usually don't have a very good idea of the relative risk to either themselves or to others by vaccinating vs. not vaccinating.  This is not a natural knowledge that just comes from being human and living a regular life; it is a specialized knowledge which previously didn't even exist in the world, and that only came about due to the long efforts of many scientists, and which is still increased regularly by a discipline carried out by specializing scientists who spend entire careers studying and improving this knowledge. 

Just as the public health of the food and water chains are the responsibility of the State rather than the individual, then, so to should be the public health of citizens as regarding vaccinations.

2.2.2. Scope of Effect

You might expect that because a law has to do with the body of an individual, that for that reason no other person could be as affected by the law as the individual to whom the law directly applies.  However, with vaccination this is not true.

Vaccinations work against infectious diseases, and these (by definition) spread.  Infectious diseases spread by growing; in other words, in order for a disease to spread throughout a community, each infected person must in turn infect more than one person (on average).  If the average person who catches the disease doesn't pass it on to more than one person, the disease will never grow and it will never be able to spread through a community.

Therefore, for any spreading infectious disease, the average individual who makes decisions that affect his susceptibility to disease is always in the minority of the people whom his actions will impact.  His decisions will impact himself, and more than one other person who is likely to become infected as a result of his actions, plus all the people they may infect, and so forth.

This same principle is operational in the military, where we grant that government has the authority to override the natural instincts of self-preservation over the health of the body inherent in every human, and order soldiers to do dangerous or unhealthy things, or difficult but healthy things that they would rather not do, except that they are so ordered.  This is because the actions and state of health of members of the military affect the lives of many more people than are in the army, because they are the guarding principle of the entire nation.  Therefore whatever individual health preference they might have is "outvoted" by the greater needs of the common good.

In the same way, the impact that  susceptibility to infection has on society is greater than the impact it has on the individual.  And therefore the proper responsible body is society and the State and not the individual.

2.2.3. Natural Fittingness

It may seem that nobody is more naturally fit to make decisions about a body than the person for whom that body is an integral part of their whole being.  

However, when God designed the human person, he did not give rule over all aspects of the body to the human person.  Some operations of the body are independent of our own rule, exempted from that rule by God Himself: involuntary actions.  Disease spread and vaccination involve entirely such involuntary human actions.  We can't choose whether or not to breath; we can't decide how many water droplets we will expel in each breath.  We can't tell our immune system to make this antibody or that antibody at will.

Furthermore, we cannot (in general) choose to change our social interactions so entirely as to preclude the possibility that we will become vectors of disease spread.  Governments may temporarily impose harsh restrictions on social interaction, but since man is by nature a social animal, these things can never last for very long.

Vaccination therefore is directed towards a part of human life that involves the confluence of a completely involuntary action of the human body (susceptibility to infection) with an essential and necessary part of human nature (close-quarters physical interaction).  While everyone participates in these things as individuals, they do not--as individuals--have the power to abrogate or essentially alter these things.  Therefore they do not, de facto, have natural fittingness as rulers over these things.

Conclusion: While most decisions regarding an individual's body do belong to the individual, by virtue of the rules of subsidiarity, none of those usual rules apply specifically to the question of vaccination.  In both knowledge, scope of effect, and natural fittingness, society or the State has a higher competency than the individual.  Therefore responsibility for decision-making regarding vaccination is appropriately given to the State and not to the individual.

2.3 Integrity

A final aspect of the human body that might make it off-bounds of government regulation is its integration with the soul into the whole human. 

2.3.1. While other laws might be validly written that affect the body accidentally, these only regulate how the body exist.  It seems, on the other hand, that a medical procedure effects what the body is.  By affecting the very nature of the body, such a law would touch on the identity of the human being itself.

Supposing, for example, in some small country there were a severe imbalance between men and women.  Could the State mandate (given technology that doesn't really work this way yet) that a certain percentage of the population accept a sex change operation so that the common good of procreation  could be better attained?  Pretty clearly, no, the State does not have the right to do this, even for the sake of the common good.

2.3.2. Another way to see that vaccination is more intrusive into the human integrity than other laws concerning the body is to see that while other laws require men to do something "with" their bodies (go to here, do this thing) or prohibit men to do something "with" their bodies (don't go here, don't do that), mandatory vaccination is almost the only type of law that requires people to do something "to" their body.

However, these arguments are faulty in several respects.

2.3.3. First, the association between any bodily change and identity / personhood is faulty.  While the soul is the form of the body, this does not imply that any bodily change therefore touches on the identity or soul of the person.  In fact, the relationship goes in the other direction: the essence of a man comes from the soul and not from the body.  Since the active principle is the soul and not the body, any modifications done to the body can only, at worst, hinder the actuation of the man's essence.  They cannot add to it.

Mutilations, such as sex change operation, can hamper the soul's ability to completely properly inform the body with its due purpose.  But nothing done to the body actually affects either the essence or the personhood of the subject of such a change.  Amputating a limb, for example, does not make the amputee any less of a person, nor decreases in any way that person's soul.

Mere bodily changes, therefore, do not affect what a person is, as a body/soul composite.  They can only affect how well the body/soul composite exists, if there is severe damage to the body.  Bodily changes that are not also mutilations, then, cannot affect the essence of the person at all.

2.3.4. Second, the above arguments misunderstand the nature of the bodily change brought about by vaccination.  Different types of bodily change affect different aspects of human life, and touch on different aspects of the human essence, because not only is the human being a composite of body and soul, but there soul itself is a composite of different levels and types of souls.  The human essence is composed of sub-essences which are unified into one.

Aristotle, and Aquinas after him, clearly distinguished between those actions that followed from deliberate choice and involuntary actions.  Only the first kind of actions were admitted to be properly human actions.  A man is a rational animal, and it is in his nature to deliberate and choose actions.  Those bodily functions that happen on their own without deliberate reason are called "actions of a man", or also, actions flowing from the vegetative soul of a man.  These involuntary operations are clearly of lesser importance in defining the nature of a man, as they are excluded entirely from the consideration of ethics, as being not relevant to the proper activity by which a man follows his true nature.

Even within the involuntary operations of a man, we can see a distinction between different components, depending on how closely they are related to the essential nature of man.  For example, the reproductive organs have a necessary link to procreation, and hence to the social and familial nature of man.  There are therefore more restrictions on the physical modifications that are allowed to these organs compared to other organs which don't have a function so closely related to the essence of man.  Or also the brain is the organ tied to the intellectual powers of the soul, and therefore must be treated with utmost respect and delicacy, given that reason is the very thing that is properly human.

The immunological functions of man are not in the same way tied to anything uniquely or specially human, but is a mere basic biological function of health which we share with all animals.  Modifications done to it, therefore, do not have anything like the import that modifications to other body parts might.

2.3.5.  Third, the above arguments are wrong to characterize the change caused by a vaccination as a change of what, even purely from the perspective of the immune system.  

In fact, the immune system is a nearly infinitely malleable system that is designed to learn how to recognize invasive particles, to remember which antibodies render those particles inert, and to recall and produce those antibodies when those invasive particles are again detected.

With a vaccine, an antigen is presented to the immune system, but is then processed by the immune system and eliminated from the body.  What is left over is not the vaccine, but the memory of the vaccine in the immune system.  While the immune system after a vaccination is in a different state than what it was before the vaccination, it has not suffered a change of nature.  Rather, it has simply operated in accordance with its nature and now has a bio-physiological memory of a previous experience.

When we learn something intellectually, we do acquire the forms of the new thing we learned as quasi-additions to our own essence.  But it is never said that learning something changes the nature of our mind, or that by learning something new we now are something different than we once were.  Rather, the mind is designed to learn an infinitude of possible forms, and after learning new ones, it has actuated its potency more perfectly than it previously did.

What happens to the immune system after a vaccination is exactly parallel, and is hence not a change of essence at all: it is an actuation of latent potency.

2.3.6. The argument that vaccination is a more intimate and invasive change because it is forcing us to actively do something "to" our bodies also fails.

Boethius, in the "Consolation of Philosophy", discusses the relative happiness of himself, suffering many privations to his body, to that of his captors, who were inflicting those privations on him.  Considered rationally, he concludes that his happiness is the greater.  For while many things were being done to his body against his will, none of those privations compared with the evil actions of his captors, who by their actions were distorting their very soul.  The evil they were inflicting on him was only surface level, whereas the evil they were inflicting upon themselves went to the very root of their being.

In other words, things done to your body can never compare in significance to things you do which have serious moral implications.

But can the government legitimately compel us to do things which have serious moral implications?  If it can, then the argument that compelling us to do something morally neutral to our bodies is too invasive fails.

And, in fact, it can.  For example, the government has the right to compel regular citizens who might have knowledge of a crime to come forward, to swear an oath to God that they will tell the truth, and then to tell the truth about their knowledge of that crime. Or if a citizen happens to have special knowledge that would be of aid in the pursuit of justice in a court, he could be compelled to come forward and offer expert testimony for the sake of justice.

These are actions that all admit that the government can compel us to take, and which have serious moral consequences.  By Boethius' principles, these compelled actions strike much more closely to the core of human nature than does the reception of a vaccine.

2.3.7.  As a further example, I will again point out that the very closest analogy to vaccination that exists outside of the medical world is the act of learning, as becoming immune through vaccination is essentially forcing your body to learn a physical shape in a physical way.

But the mind is in all respects a superior and higher aspect of man than the body.  If the government can mandate mental education for its citizens, which it does for the sake of the common good in order to have a more highly educated populace, then a fortiore, it must have the right to also mandate the physical education of the immune system, in this case for the sake of the physical common good of the population.

Conclusion: Vaccination involves no essential change to a person's body, imparts no change that has an import on functions of the body that are tied to essential characteristics of man-as-man, and is in every respect a less integral and fundamental part of human being and selfhood than other things which do admit of government control.  Therefore, it is appropriate for the State to mandate vaccination, and this in no way represents violence to the makeup of the individual's personal humanity.

3. Overall Conclusion

Mandated vaccination is clearly in the just scope of government authority.  There is no aspect of what vaccination does to a person, whatsoever, which is not matched or exceeded in significance by other things over which we all admit government does have legitimate authority.  Therefore, the argument that the State is violating inviolable rights or transgressing its proper boundaries by mandating vaccination is false.

Asymptomatic spread of Covid-19

There are many aspects of Covid-19 that remain poorly understood, and many plausible theories about Covid-19 that still require good proof.  The fact that Covid-19 is spread in large part by people with little to no symptoms, however, is not one of those things: this we know with reasonable certainty.  However, I find that some people still think that this is a questionable, or even a disproved theory.  I think this is usually simple ignorance, and that these people are getting their information from outlets that only report on studies when they think they can poke holes in them or when they think they challenge the standard narrative.  These outlets present a very one-sided, narrative driven view of the current state of knowledge on Covid-19.

Therefore I wanted to present a summary of the actual current state of knowledge, as I understand it.  This is going to be merely a summary, and I am only going to cite enough studies to illustrate the main lines of thought that support the theory that asymptomatic spread is a very important percentage of the total spread of the disease.

Asymptomatic vs. Presymptomatic

I should start by clearing up--again--a key terminology problem when talking about asymptomatic spread of Covid-19.  Namely, the difference between the terms "asymptomatic" and "presymptomatic".  The terms are not used consistently in the literature.  Some scientists reserve the word "asymptomatic" for only those people who catch a disease but never develop any symptoms of that disease, from start to finish.  Only the spread of the disease done by these specific people is then termed "asymptomatic spread".  If there is any spread of the disease done by people before they develop symptoms, but those people do develop symptoms eventually, that is called "presymptomatic spread."  However, not all scientists are so careful with the terms, and a lot of scientists talk about "asymptomatic spread", meaning any spread caused by people who don't know they are ill because they don't have any symptoms yet.  This would be the combination of any "true" asymptomatic spread (spread by people who never develop symptoms at any time) and the presymptomatic spread (spread by people who don't have symptoms at the time they are spreading).  And some scientists throw in here also spread caused by "pauci-symptomatic" people: people who have a few symptoms but think it's no big deal and that they can safely go about their normal business regardless.

In the case of Covid-19, when scientists talk about asymptomatic spread being a large component of infections, they are certainly talking in the second way, lumping together "true" asymptomatic with presymptomatic.  At this point, it is known that people who never develop symptoms can spread Covid, but I think it is generally accepted that this is less common and that the bulk of what is called "asymptomatic spread" is really "presymptomatic spread" or "pauci-symptomatic spread".

Regardless, the fact that truly asymptomatic spread is known it happen is one reason to continue using the term "asymptomatic spread" in the broader way, rather than calling it "presymptomatic spread".  "Presymptomatic" would be technically incorrect because this type of spread includes some "true" asymptomatic in it, while "asymptomatic spread" can be considered precisely correct since it is identifying spread which occurs in which there is not symptoms that could clue the spreader in to the fact that he is a danger to others at the time of the spread.

Anyway, this would all be pedantic term hairsplitting, if it weren't for the fact that I'm aware of multiple studies that have come out showing that "true" asymptomatic spread is quite rare, which were then picked up on by various people and waved around as examples that the concern over asymptomatic spread is overblown.  Aside from the fact that those studies are not conclusive and have good counter-studies that should be considered, the main problem is that those studies are only considering a small portion of what most scientists are talking about when they talk about "asymptomatic spread".

The bottom line: be careful about those terms and make sure you understand how it is being used in the context of a specific study.  I'm going to continue using the term "asymptomatic spread" in the *broader* sense for the rest of this piece, and I'll make sure to say "true asymptomatic spread" if I mean spread caused only by people who never develop symptoms.

The main lines of thinking that show asymptomatic transmission is a major problem

As I see it, there are three main types of studies that show that asymptomatic transmission of Covid-19 is a major problem.

1. Molecular biology studies that show the typical progression of viral load in patients infected with Covid-19.  By first principles, the time periods in which a patient is shedding the most virus from their upper respiratory tract should be the times when that patient is most infectious.  These studies have shown that viral load spikes strongly right around the time that symptoms first arise, so that total virus shed is usually split something like 50/50 (I think 40/60 is closer to the consensus on this) between the periods before and after symptoms start.  The clear implication of these studies is that most people infected with Covid-19 will be quite infectious for the period of a few days before any symptoms arise *and* into the period when just the hints of symptoms are arising--both times when people are quite likely to still be going around doing their normal routine.
2. Large scale epidemiological studies tracing the course of the epidemic over large populations have been able to establish some characteristics of the disease that must be true, or else the disease could not be spreading in the way in which it is observed to do on the large scale.  Here epidemic timeline studies are very important because you can track the timeline of how many people are hospitalized and when (on average) their symptoms started.  Reasoning backward to the number of people who must be getting infected to produce these amounts of hospitalizations, it becomes impossible to explain the numbers seen without a large reserve of "silent cases" spreading the disease without becoming visible in the official numbers at all.  These studies are backed up by other large-scale serological surveys which have proven that substantial portions of the population are being infected by Covid-19 without ever having been aware of symptoms.
3. In certain very controlled locations where there have been outbreaks, it has been possible to do very thorough contact tracing and determine (with more or less certainty depending on the study) who caught the disease from whom and when.  There have been quite a few of these case studies  at this point, and they have shown convincingly that asymptomatic spread is real and a very significant portion of the total spread of Covid-19.

Some examples of each of these study types

Following are some examples of each of these three kinds of studies.  I want to emphasize again that this is not a complete list; it is meant to be a representative sample only.

Studies on viral load:

Temporal dynamics in viral shedding and transmissibility of COVID-19

This was a key early study on viral shedding with Covid-19.  The important data is conveyed in figure 2, which I am reproducing here:

This shows that viral load, as measured in 92 patients starting from the first day they showed symptoms, only decreased over time.  In other words, the latest possible date of peak viral load was the day of first onset of symptoms.  They didn't have measurements before symptom onset, obviously, because they weren't measuring viral load in these people before they were identified as sick.

The inference from this is that viral load peaked no later than onset of symptoms, and probably somewhere to the left of where the charts begin, a day or two before onset of symptoms.  Combining this viral load data with contact tracing in the same region these patients were from, they concluded that 37% to 48% of transmission for this outbreak occurred pre-symptomatically.

Side Note: The narrow spike

There is something very important to understand about these charts; namely, that the Y-axis of these graphs (labeled "Ct value") is of a metric that is an exponential measurement.  "Ct value" refers to the number of times the sample has to be amplified before the virus genetic material could be detected.  That's why the numbers go down as they go up the Y-axis of the graph: the fewer times you have to amplify the signal, the more signal there is to begin with.

Because each increase in an amplification cycle is a multiplication of the genetic signal, for every one unit you go *down* as you move *up* the graph, you are essentially raising the signal to a power one more time, not just increasing it by one (really, increasing the exponent of an e^x factor, to be most precise).  So this is another way of saying that these charts are logarithmic, and that means they visually under-represent how much more viral load there is at the left-hand side of the graphs compared to to the right.

To illustrate this difference, I got hold of the data table for this paper, reproduced one of these graphs as a chart in excel, and then corrected the Y-axis values to indicate their true logarithmic nature.  This is what the viral load signal looks like if you make that correction:

From here you can see that almost all of the viral load is concentrated in the 3-4 days after the onset of symptoms, plus presumably a similarly narrow spike to the left of the chart before symptoms begin.  I believe that the profile of Covid-19's viral shedding explains a few key things that were previously puzzling to me before I saw this:

1. Covid-19 transmission has a propensity to happen in "super-spreader" events.  It's not spread evenly by everyone who gets it.  Rather, it appears that people who get it and are then unfortunate enough to be in a relatively crowded place during this period in which they are spreading the virus much more than otherwise are the primary spreaders of the disease.
2. Transmission among family members at home has been high, as one would expect, but not as high as I personally was expecting (I don't currently have the numbers at hand, but I was shocked at how low they were compared to my expectations).  Actually, what studies they have done in the West suggest that restaurants are a larger factor in disease spread than individual-to-individual spread in the family.  I think the "narrow spike" explains this.  When a person sheds virus liberally while they are sick for a week at at time, everyone in the home is practically guaranteed to get it.  However, if the sick person in the household sheds most of the virus in just a few days time, and they are out and about for half of that time period, then I can see that there is a chance that all of the other family members will luck out and miss catching the disease during its most contagious period.  This seems to be what is happening fairly often.
3. Some random sample population surveys have seemed to indicate that true asymptomatic people are extremely unlikely to spread Covid.  This was on the basis that when random people are sampled, and some who have had no symptoms are nevertheless found to test positive for the virus, the virus sampled from them was detected in a fragmented or low level state at which it was deemed very unlikely to be infectious.  But if there is only a short time span when you get Covid in which you are very infectious, and then a longer time period in which you are much less infectious but still clearing the virus from the system, this would make sense.  You would expect that most truly asymptomatic individuals you catch on the street would be currently non-infectious--but that wouldn't therefore allow you to judge that they had never been infectious.

Distribution of Transmission Potential During Nonsevere COVID-19 Illness

This was a study in Cleveland showing essentially the same distributions of viral load over time, though focused on nonsevere Covid.  From their conclusions: 

"This study shows that in otherwise healthy subjects with nonsevere illness from COVID-19, the SARS-CoV-2 viral load is very high within 2–3 days of onset of symptoms and falls rapidly by orders of magnitude within a few days . . . The extremely high viral loads within 2 or 3 days since onset of symptoms suggest that viral loads may be almost as high in the immediate presymptomatic period, suggesting substantial transmission potential in the presymptomatic period. "

Epidemiological studies:

Serial interval of novel coronavirus (COVID-19) infections

This was an important early study based on the Wuhan infection timeline.  You can look at a timeline of an epidemic and plot how fast new infections are occurring compared to the number of existing infections, and from that deduce (with good statistics) how long it takes (in the average case) between a person getting infected and that person passing along the infection to the next person.  This is called the "serial interval" of a disease.  In the case of Covid, when they did this they found a serial interval of about 4 days.  The incubation period (the time after someone is infected but before they start showing symptoms) is a full 3-7 days.  This implies that a lot of spread must be happening before symptoms show up.

Quote from the paper:

"The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset."

Asymptomatic Cases, the Hidden Challenge in Predicting COVID-19 Caseload Increases

This was a large random-sample study in Ontario showed that large amounts of asymptomatic infections (16-30% of all infected people, depending on age category).  Further, 47% of people who tested positive on a PCR at what was considered infectious levels were asymptomatic at the time.

Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study

This was a very large study in Spain that just verifies how there is a high rate of asymptomatic infections overall: 22-35% of all infections, in this case.

Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV-2)

Very thorough statistical analysis revealed that undocumented infections had to account for the bulk (~80%) of the spread in China.  Now, "undocumented" isn't the same as "asymptomatic", but at the least this proves that the greatest part of the spread of the disease happens from people who at least don't feel sick enough to come forward for medical care.

Contact tracing studies:

Now we can look at a series of case studies in which authorities had high control over patient movement and could decisively track actual point-to-point infections.  This has been the case in contained environments (nursing homes, prisons, etc.) and also in some nations with a much less exalted view of personal privacy rights regarding medical data than we have!

Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset

Taiwan locked things down very rapidly at the start of the pandemic, and used aggressive contact tracing to identify infections early and get people into isolation.  The conclusion from this study was that to get things under control, you need to assume that spread starts 4 days before symptom onset:

  "The findings of this study suggest that most transmission of COVID-19 occurred at the very early stage of the disease or even before the onset of symptoms"  

In addition, they mention in the "Limitations" section of the study that they might have actually "underestimated the importance of early transmission" in the study for various reasons.

Mass SARS-CoV-2 Testing in a Dormitory-Style Correctional Facility in Arkansas

Study in Arkansas correctional facility which reached the conclusion: 

"If testing remained limited to symptomatic individuals, fewer cases would have been detected or detection would have been delayed, allowing transmission to continue."

Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility

Study on an outbreak in a nursing home.  Conclusion: 

"More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility."

Rapid asymptomatic transmission of COVID-19 during the incubation period demonstrating strong infectivity in a cluster of youngsters aged 16-23 years outside Wuhan and characteristics of young patients with COVID-19: A prospective contact-tracing study

Case study of transmission within a cluster of 8 young people (16-23 years old).  Serial interval was just 1(!) day.  All ended up with just mild symptoms.  Demonstrates rapid transmission before any symptoms arise, and from people with only mild Covid (frequently unreported or not identified as Covid).

Presumed Asymptomatic Carrier Transmission of COVID-19

Case study of "true" asymptomatic spread in China.  One completely asymptomatic woman infected 5 family members.  So yes, this does happen as well.

The high prevalence of asymptomatic SARS-CoV-2 infection reveals the silent spread of COVID-19

Case study in Bahrain.  320 infectors and 1289 people infected.  In this study, they found that the asymptomatic infectors spread the disease at just as high a rate as the symptomatic infectors. 

"In conclusion, these data show that the high asymptomatic incidence of SARS-CoV-2 infection in Bahrain and subsequent positive contacts from an index case are more likely to be asymptomatic, showing the high “silent” risk of transmission and the need for comprehensive screening for each positive infection to help halt the ongoing pandemic."

Personal Anecdotes

Here, I want to add a final category, which is not a study but which is more easily accessible to most people.  At this point, there have been enough people who have actually had Covid that it is not difficult to do a little bit of "gum-shoe" detective work on your own.  Just ask the people who have had it whether they were aware of being around anyone sick before catching it, or if they are pretty sure they passed it along to someone else despite not showing any symptoms at the time of their known contact.

I have two siblings who have had it now, one of whom was quite careful of whom she was around before she became infected.  She's also pretty sure she infected someone else, despite not having any symptoms at the time they were in contact.

Likewise, my wife has two siblings who have been infected now, both of whom were being *extremely* cautious to avoid associating with anyone exhibiting any symptoms.  They say that anecdotes don't add up to data, but as I said, these anecdotes are multiplied millions-fold at this point and are fairly easy to access.

Conclusion

Again I stress, this is only a lazily compiled sample of the studies out there that all point in the same direction.  I spent very little time looking for studies beyond the ones with which I was already familiar, and I'm positive I could have easily doubled this list without effort.  The conclusion is clear: large amounts of asymptomatic spread of Covid-19 is now a firmly established fact and should be treated as such.

A secondary conclusion would be, there are better places to get information about Covid-19 than the blogs, social media, and news sites some people are relying upon.  It is a mystery to me why some of these outlets persist in fighting this specific point, given how much clear evidence is in its favor.

In the case of this article, (and previous posts), I have found that searching this online database of publications is very helpful:

Global literature on coronavirus disease

I would recommend spending some time searching through and reading relevant studies published in this database if you care to be informed about the best state of knowledge on Covid-19 currently.

A Look-Ahead at the State of Immunity Over the Next Few Months

How is vaccine production going to look by April?

Using current rates of vaccine delivery and expected increases that have been reported, my back-of-the-envelope math estimates that ~150 million U.S. residents will have received at least one shot of the Covid vaccine by the end of March.  Meanwhile, if surveys are to be believed, only about 2/3rds of American citizens actually *really* want the vaccine, and about 1/3 are either unsure or decidedly against it.  This means only about 145 million Americans are both eligible to get the vaccine *and* really want to get it.

Vaccine production will still be ramping up, however.  Pfizer, Moderna, and Johnson & Johnson will all still be increasing production and delivery at that time.  Early April is also the earliest time at which Novavax could also see FDA approval, which would increase the pool of available vaccines still more.  This means that at the beginning of April, pretty much all Americans that *want* the vaccine will already be vaccinated, *and* the supply will continue to go up.  So early April will mark the transition into the "vaccine glut" phase, at least for the U.S., where everyone who wants a vaccine is going to be able to get one with relative ease.  This is when the job of convincing more people to take the vaccine is going to be much more important.

What does this mean for immunity and reduction of spread of the virus?

We now know that even one shot of the mRNA vaccines starts conferring pretty good immunity after 3 weeks.  So in early April, we're going to have ~130 million people with good immunity from vaccines (subtracting off the people who were immunized at the tail end of March).  Further, the most vulnerable populations should have a much higher rate of immunity, and also a lot of people who are more prone to being serious spreaders should also have a much higher rate of immunity.  This should be devastating to the death rates for Covid, and really bad for its spreading capability as well.

In addition to immunity from the vaccines, we'll also have a fair amount of immunity from people having been infected and recovered.  Right now, there have been about 30 million known cases of Covid in the U.S., counting past and present.  The unknown asymptomatic cases are, as you would expect, unknown, but a decent estimate for the size of that population is double the size of the known cases.  Now, you can't just add those people into the total number of people with immunity from vaccines, because all lot of the people who get the vaccine may well have been unknown asymptomatic carriers from before as well.  However, it is the case that the asymptomatic unknowns are more likely to be young and healthy, and thus less likely to have already been vaccinated by the end of March.  So I think it's reasonable to add, say, 40 million people to the total number of people with some immunity to Covid by the beginning of April.

This means we'll have roughly 52% of the population with some immunity to Covid by the beginning of April, with that number rapidly increasing due to vaccines already given in late March and new vaccines given as well.  What is that going to do to Covid spread?

Estimates for Covid R0 vary, but I like the number 3 as a reasonable estimate.  This would be the reproductive rate *without* any social distancing measures--the "life as normal" reproductive rate.  In the naïve, "perfect mixing", epidemiology scenarios, you modify the R0 by the percent of population with immunity in order to get the current effective reproductive rate.  So, 50% immunity would drop an R0 of 3 down to an R of 1.5.  This still gives you spread and growth if you abandon all social distancing and masking measures, but it's not such a huge rate.  This is in the same ballpark as the seasonal flu.

Caveats

But there are some additional caveats we can put on these numbers.  First, I expect regulations enforcing masking will still be in effect in most places throughout all of March and into April.  These should continue to cut down on Covid transmissibility, and if you start with an R of 1.5, you only need an extra 33% reduction in transmissibility to keep the virus decreasing rather than increasing.  Second, Covid does not spread in the "perfect-mixing, simplified" style.  It seems to have a more asymmetrical style of spread than does the seasonal flu, relying more on super-spreader events than the flu does.  This *should* tend to mean that those people who are more likely to get and spread Covid will have already gotten the disease, recovered, and developed immunity earlier rather than later.  So those 40 million people we already added into the "some immunity" pool will more important to halting the spread of the disease than remaining people who have not yet had the disease.  The fact that we have been vaccinating with an eye to the more dangerous transmission scenarios (medical staff, prison inmates, etc.) should work in the same way.  How *exactly* this factor will influence Covid spread is difficult to quantify, but I think it is an important factor.  Third and finally, in early April winter will be mostly over.  At this point, it's pretty clear I think that there is a seasonal aspect to Covid and that it has reduced transmissibility outside of winter weather.  Again it is hard to quantify exactly what effect this will have, but again I suspect that it will be substantial.

Conclusion

With all of these considerations in place, I think we can foresee April being a very tough month to be Covid in the United States.  As I said, you only need an extra 33% protection against transmission to put a pandemic into subsidence if the R0 is 3-ish and you have 50% herd immunity, and I think the "extra factors" I mentioned will probably have at least that effect.  If I'm right, that means that it should be possible to remove all social restrictions in the U.S. in early April *and* still see infection numbers continue to decrease.  It's likely public authorities will proceed with more caution than this, and that's probably a good thing.  If it were up to me, when we get to this point, I'd remove all restrictions except requirements to wear masks in public indoor locations (being an easy restriction to live with that doesn't damage the economy) and aggressively continue a public vaccination campaign with the goal of getting to 80% vaccination rate (probably the best we can do considering the amount of vaccine hesitation).

The major factor that could throw a wrench in the spokes of this happy prediction is the spread of newer Covid variants.  What we really need to know to know how bad a factor this could be, is how much the newer variants escape the natural immunization from the original variant and the immunization derived from the vaccine.  That is the most critical new information I am looking for right now; I know there are trials and experiments looking for this information now and I am eagerly awaiting better information coming out of these.  For now, I'm retaining a cautious but hopeful optimism.

Long Term Side Effects of mRNA Vaccines Unlikely, Conclusion

Conclusion: A Different Category of Possibility

Having gone through all ways that I could think of mRNA vaccines could possibly cause long-term complications without those complications arising fairly soon after administration, I could not find any.  I couldn't even think of a mechanism by which such a long-term complication could happen.

This is not the same thing as a proof that such a thing couldn't happen.  "I thought about it very hard and I couldn't think of a way it could happen" isn't a proof--maybe you just don't know enough to think about the right things!  No one could claim to know enough about the human body and the immune system to be able to understand absolutely everything any therapeutic could do.

But that's why the title of this series of posts was "Long Term Side Effects of mRNA Vaccines Unlikely": unlikely, not impossible.  "Unlikely" is the limit of what we can prove at this point.

What I think this series does prove is that the risk of such a long-term complication lies in the realm of the true "unknown unknowns".  Especially considering how such a long-term complication has never before come up from a new vaccine, it would be a risk from out of left field--something truly new and unforeseeable.  

I think this is an important result that should have consequences on our own decision making.  One way of dealing with risks is appropriate if there are known possibilities of something bad happening, but if all you have is doubts that you know enough about some thing--even after all the experts have done everything they can to understand every possible risk about it--then it is not appropriate to consider this thing a risk in the same way.  The risk exists in a different category of possibility.

What I mean here might become more clear when you compare the risk of the new vaccines against some other things.

Comparative risk

Compared to Covid-19

Compared to the risks associated with getting the new vaccines, Covid-19 has many risks of long-term consequences.  There are flat-out "knowns": permanent lung damage and heart tissue scarring are the two most likely long-term consequence that we know about, but there are a whole host of other things that are known to happen to sufferers of severe Covid as well.  Then there are "known unknowns", such as the possibility of heart tissue damage even from mild cases, and the potential for nerve tissue damage (given that we see Covid has neurological side effects which may or may not involve permanent damage to nerve tissue based on what we know so far).

Then there are the "unknown unknowns".  And here, Covid has all of the same potential to cause issues that the vaccine does.  For the vaccine, by far the most likely class of problems from which some unknown long-term complication could come is auto-immune issues.  But everything that I identified as a potential for causing problems from the vaccine, the virus also does.  

Suppose there were some antibody that the immune system generates in response to the spike protein from the vaccine that ultimately causes some sort of long-term problem.  Well, not only does an actual infection from the virus also produce that spike protein, it 

1. produces the whole virus as well (giving the immune systems more features to react to and hence more chances to produce some hypothetical dangerous antibody), 
2. it produces them throughout the body in many more types of tissue as it spreads around (thus multiplying the number of possible interactions between the foreign invader and different types of human cells and exponentially increasing the chance of a human cell getting targeted by the immune system), and 
3. it produces them for far longer than the few days that the vaccine exists in the human body.  This length of time in which the immune system is in a heightened "battle mode" thus also increases the chance which I mentioned for some over-zealous member of the immune system to trigger an immunity against the wrong thing.

Some people have been nonchalant about the risks of catching Covid-19, but very hesitant to take the vaccine.  This makes no sense whatsoever.  Not only does catching Covid-19 carry with it all of the same risk of the unknown that the vaccine does, it has whole classes of risk--of things both known and unknown--which the vaccine does not.  I can understand the desire to avoid both things, but to consider the virus a relatively safe known compared to the unknown risk of the vaccine is pure ignorance or irrationality.

Compared to other vaccines

Most of what I have talked about in these series of posts applies similarly to a lot of other vaccines.  But not all, and it would be worth discussing those ways in which mRNA vaccines are likely to be safer than the more traditional types of vaccines.  This would be a good topic for a dedicated post, in fact.

The only specific thing I'm going to mention here is how the most common type of traditional vaccine works, which is by taking the actual virus and neutralizing it in some way, then injecting the deactivated virus into the body, thus eliciting the immune response.  Whatever way the virus is neutralized, it involves serious damage to the viral particles--by necessity, because "neutralize" is another way of saying "destroy the basic functioning capacity of the virus".

What this means is that a traditional vaccine involves the injection of randomly damaged microscopic material into your body: at the cellular level, billions of individually mangled viruses, possibly with weird broken structures and possibly with randomly scrambled RNA from radiation.  Normally this turns out OK, but there have been instances in the past where the damage to the virus itself has been suspected of causing the antibodies generated in response to them to be defective, and even possibly dangerous (read up on a failed RSV vaccine from the '60s for this, though the "damaged virus" theory is currently out of favor).

It has to be admitted that mRNA vaccines have a much cleaner, more predictable path towards generating immunity, at least in theory.  It has always been the theory that mRNA vaccines will be inherently safer than older vaccines due to the very targeted and controlled antigen that they generate and the very precise way in which this antigen is produced.

Up until recently, this idea has been just theory, but I think it is worth understanding that mRNA vaccines have some key theoretical safety advantages to older forms.

Final Conclusion

No one can claim perfect knowledge of the future, but when it comes to the long-term safety of the new vaccines, it is at least a very safe bet that they will turn out to be completely fine.  I did not hesitate to get the vaccine myself, and neither should anyone else.

Long Term Side Effects of mRNA Vaccines Unlikely, Part 3

Now we are moving on to consider possible long-term side effects from the genetic payload itself, the mRNA inside the lipid nanoparticle.

Purity of the genetic payload

The first question to ask about the safety of the genetic payload is, how sure can we be sure that the payload is what is intended and not defective or mixed with dangerous impurities?  Some concerns people have had in the past about vaccines include mercury impurities or worries about protein remnants from chicken eggs in which some vaccines are grown.  So it's worth looking at the manufacturing process for mRNA.  (A lot of the information from this section I got from these two videos: here, and here.  They are long watches but pretty informative.)

The manufacturing process

All living beings create messenger RNA from DNA as part of the regular life of the cell.  In the nucleus of the cell, you have DNA, free floating genetic "building block" material (the four basic molecules from which all RNA is built, the "nucleotides"), and an enzyme (called "RNA polymerase") that reads (transcribes) the DNA and builds mRNA from the nucleotides based on what it reads.

The manufacturing process mimics that setup.  First, you create a custom strand of DNA (your "template") that contains the genetic instructions for the protein you want.  Then you put that in a tub along with a soup of nucleotides and add a bunch of those enzymes (RNA polymerase) and some salts.  The enzymes will do their thing, read your DNA and convert all the nucleotides around them into the RNA you want.

The product of this is a tub full of some template DNA, some enzymes, some leftover nucleotides, and a bunch of RNA, some of it complete and some of it failed or partial.  The major challenge is then to strain and/or chemically separate the complete RNA from all the other stuff in the tub.  You then quality-control the result to ensure you have achieved sufficient purity of the final product.  Most of the manufacturing progress in this area has to do with clever ways of getting higher yields from the straining / purification part of the process.

Commoditization

A very important character of this process is that it relies entirely on commercial, off-the-shelf equipment and ingredients.  Creating small custom pieces of DNA is routinely done nowadays via various processes and any big genetics lab can do it.  You can buy both nucleotides and RNA polymerase online if you want to: here's a site where you can buy nucleotides and  here's a site where you can buy RNA polymerase.  Equipment for doing RNA transcription, including the filtering, are commercially available.  Hardware and software for doing the purity checks are industry standard.

This has very important safety implications, because it means that the manufacturing process for mRNA is not new, even though the specific mRNA for the vaccines is new.  Ways to guarantee sufficient purities of the end product have already been worked out by the industry.  Safety problems that can come about because of surprises in a new manufacturing process are therefore eliminated. 

This was a major time saver for the mRNA vaccine approval process as well.  Moderna, for example, when asked by the FDA about their manufacturing process, was able to say "it's mRNA in lipid nanoparticles: the same equipment and process as they did for Patirisan, which you already fully reviewed and approved".  This got them a quick "thumbs up" from the FDA on the manufacturing front and saved a lot of time.

Chemical vs. biological

Another important part of this manufacturing process is that it is entirely chemical.  It relies on no living organisms, nor on any cells from living organisms.  This means that you can theoretically crank out product much faster than vaccines that rely on growth cycles of living cells in "bioreactors".  It also eliminates a whole class of potential health problems with proteins from host organisms getting into the vaccine.

In conclusion, we can give the manufacturing process a "pass" in terms of innate safety.  It is tried-and-true in a way in which the specifics of the genetic payload itself is not, and it is not any more likely to have weird or new contaminants in it than any previous genetic therapeutic has been.  Furthermore, its chemical nature precludes a whole class of potential contamination to which older vaccines might have been susceptible.  

So now let's move on to considering the mRNA itself, and what possible long-term safety consequences it might have.  Theoretically, we can consider the mRNA in three stages: before it enters the cell, after it enters the cell, and the protein that is generated from it by the cell.

mRNA in the intercellular region

While the mRNA is packages in a lipid nanosphere to keep it from interacting with the body before it gets into a cell, what if some of the mRNA is unintentionally released into the intercellular region?  You can assume that at least a certain amount of this will happen, because nothing is perfect and some nanoparticles *will* break down before being absorbed by cells as designed.

I originally had a much larger argument planned for this section with multiple ways of showing that random mRNA fragments in the body aren't a problem, bringing in things like how the body handles natural cell replication failures and cellular disintegration being a normal occurrence.  Those arguments are all quite valid, but I think a simpler, common-sense argument is good enough: we can know that mRNA fragments aren't a problem in the intercellular region because we've been trying to get mRNA to do useful things for us for decades and we've found that they're so fragile that we *need* to use lipid nanospheres to get them to do anything.  The challenge of getting mRNA to survive the intercellular region has been described in this article: 

The complexity of the problem is enormous. Naked RNA or DNA molecules are rapidly degraded in biological fluids, do not accumulate in target tissues following systemic administration, and cannot penetrate into target cells even if they get to the target tissue. Further, the immune system is exquisitely designed to recognize and destroy vectors containing genetic information

Even using lipid nanoparticles, the mRNA vaccines have to be treated very carefully or the mRNA can be degraded just by the temperature.  It might not actually need the deep freezing that the vaccine as a whole needs (I think that's more due to the lipid nanoparticles than the mRNA), but nonetheless, it's not super-sturdy stuff.

There is only danger to the mRNA strands from the intercellular region, not the other way round, and this is true even on a minutes-to-hours time scale, let alone in the long-term.

mRNA in the cell

Some people have been very nervous about the vaccines because they hear it contains mRNA, which the think will modify the DNA in their cells, which they associate I think with comic-book-style mutations?  I'm not going to talk about this concern much, since other people are debunking it ably.  Just the fact that mRNA vaccines are injecting genetic material into your cells is not a rational cause for fear, any more than the fact that the common cold does the same sort of thing is a rational cause for fear.  I talk about this sort of irrational fear a bit in an earlier post, so I'm not going to say anything more about it now.

The spike protein

So, now for the end-product of the mRNA once it is produced by the cells: the spike protein.  Could it cause some long-term issues?  Let's run it through the same mechanisms we laid out in the previous post:

• Material accumulation: no.  We know from PCR tests of Covid-19 infected individuals (which are extremely sensitive and can detect even fragments of individual viral particles) that the body eventually eliminates all the spike particles from the system.  And this is for people who have system-wide infections, some of them lasting months, with the virus replicating all throughout the body and pumping out spike-covered viruses the whole time.  Once the infection is beaten, it only takes a matter of days or at most weeks before all of the particles are cleared.  A two-time shot in the arm will also be completely cleared.
• Persistence by self-replicating colonies: impossible.
• Damage to non-regenerative tissue: no.  All the same arguments that applied to lipid nanoparticles apply to the protein as well.
• Cumulative effect: no.  Same arguments apply.
• Interaction with adaptive or "learning" body mechanisms: no.  Again, the same arguments apply.

That again leaves the immunological response, which *is* a valid manner in which the spike protein could cause a long-term effect.  So now we are going to deal with that question.

Immunological response

Lipid nanoparticles

I said I would return to the immunological response to lipid nanoparticles in the previous post.  Here I will point out that the immunological response to foreign objects in the body relies on detection that those objects are foreign, and depends solely on the surface of the object in question.  The body is not able to probe into an object for foreign DNA, it must touch the surface of the thing.

For lipid nanoparticles, the surface of the particle is the PEG coating.  This is why the nanoparticles are coated in PEG in the first place, because it reduces immunogenic response.  Because of this, the surface of mRNA vaccines should look identical to all of the older liposome injections which were also coated in PEG, from the standpoint of the body's immune response.

This is not to say that there won't be a reaction--there will be some reaction.  However, what the immune system will be reacting to is exactly the same thing it reacts to in much older medicines: a tiny round particle coated in PEG.  We should therefore expect that the long-term possible side effects of the immune response to the lipid nanoparticles to be no different than the long-term side effects of the immune response to those older liposomes--which is to say, nothing.

The spike protein

The spike protein, on the other hand, is a new protein and we do not have long-term data on the immune reaction to it.  One concern that has been raised is, suppose the spike protein is similar in some ways to good, human proteins elsewhere in the body.  When the immune system develops a memory of how to neutralize the spike protein, couldn't it sometimes accidentally generate an antibody that attacks these human proteins as well?  In other words, couldn't the vaccine cause some sort of auto-immune condition to develop?

The answer to this is, possibly.  Auto-immune disorders of various kinds are certainly possible rare side-effects of all vaccines.  Now, I do not personally know (and I'm not sure if scientists do either) whether the mechanism which triggers an auto-immune disorder is what I have just described: bad antibody generation because of *similarity* between the antigen and some human protein.  It's possible that what happens is more of a simple mistake: the immune system gets excited by the presence of an invader, and then during the course of the immune system arousal some over-excited antigen presenting cell grabs a human protein of some sort and presents it to a T-cell.  But whatever the mechanism, we do know that this sort of thing does happen some times.

The long term?

However, knowing that this sort of thing could possibly happen isn't enough.  We know that this doesn't happen at any meaningful frequency in the short-term because of the safety data and adverse side effect tracking.  So for there to be a long-term risk of this, it has to be possible for an auto-immune disorder to arise after a vaccine is given, but not in the first year.

This does not match with how the immune system works.  In order for the immune system to build a long-term memory of some antigen which will trigger the multiplication and release of specific antibodies, it needs those antigen particles to be physically present.  Special cells grab bits of the offending material and present them to other cells, and this is the origin point of the immune "learning" process.  It doesn't proceed if there is no more offending material to present.  If the body's immune system is going to learn some incorrect antibody recipe to an antigen, it has to be while that antigen is present.  And we already said that the spike protein is completely eliminated from the body within days or weeks of the vaccine injection, so there is a short time-span in which this could happen.

Moreover, the nature of the human immune system response is to ramp up antibody production over the course of a few days to a week, keep up the antibodies while it sees that there is still an infection and for a while after that, and then spin down antibody production again to some background level.  We have studies on the timing of this surge and spin down with the new vaccines; here's an important study on this for Moderna.  You can see the antibodies spike shortly after the booster shot of the vaccine (about 5 weeks after the first shot) and begin steadily declining after that.

Since this is the case, the time of maximum danger from antibodies produced by a vaccine is 4-6 weeks after the injection.  If any auto-immune problems are going to be caused by vaccine-generated antibodies, they are for sure going to show up no later than that period.

Vaccine safety timeline

Because issues of auto-immune disorders or other problems stemming from the immunological response are common concerns for all vaccines, this question of timing of possible problems has been considered for a long time.  The history of all failed vaccines has been examined, and on that basis it is accepted among vaccine experts that if there are going to be any long-term side effects from a vaccine, they will manifest within six weeks of administration.  There are no known exceptions to that timeline yet in the entire history of vaccines.  Based on that, the FDA required two full months of safety data from the new vaccines before considering them for emergency use authorization, and this *wasn't* considered an accelerated timeline for approval.  The real reason the approval is considered "emergency use" rather than a full approval is not because of lack of long-term safety data--in fact, the reason is that for full approval, the FDA normally asks for a vaccine to show efficacy for a longer period of time than what we know so far for the Covid vaccines (great interview that talks about this among other things here).  They are more concerned with the effects of the vaccine possibly waning over time than they are about it possibly gaining more negative effects.

Conclusion

The process by which mRNA is mass produced is not new, but rather a known and well controlled procedure which we can trust.  The mRNA itself is a safe material which should not be expected to do anything unless it gets into the cytoplasm of the cell.  The spike proteins generated will cause an immune reaction, and the effects of this immune reaction will fully manifest by at least six weeks after injection.  We therefore have very good knowledge of what this reaction entails.  Rare long-term side effects are possible, but at this point we know that whatever auto-immune reactions do happen to some people are going to be extremely rare, at about the same frequency as they happen with ordinary vaccines that have been with us for decades at the most.