Risk Analysis of the Moderna and Pfizer Vaccines, part 2

Some background medical facts

I'd like to get to evaluating the risk that if one gets the vaccine, one will spread the disease anyway even though not getting it.  But this requires some understanding of the background science that not everyone will necessarily have.  So I'm going to make a couple of key distinctions in this installment.

Distinction between the virus and the disease

Medical science distinguishes between a disease and the virus which causes the disease.  The virus is the actual micro-organism that replicates in individuals: in the case of Covid, this has been named "SARS CoV 2" ("Severe Accute Respiratory Syndrom Coronavirus 2).  The *disease* is defined as the set of symptoms that infection with this microbe can produce, in this case named "Covid-19" ("Coronavirus disease that emerged in 2019").  Going forward, though, I'm going to call both the disease and the virus simply "Covid" as a convenience, unless necessary for disambiguation.

This distinction between virus and disease is important because the same pathogen can cause a variety of different symptoms depending on various factors.  The same virus can attack different parts of the body, it can replicate to various degrees of success, and the individual body which is infected can react to this infection in different ways.  Let's examine these types of variation in a bit more detail.

Variation by different body parts

Covid replicates by attaching to cells which have something called an "ACE2 receptor", entering them and hijacking the natural cellular reproductive mechanisms.  The mechanism by which Covid replicates means that it can attack any portion of the body containing cells which have these receptors, which (it turns out) is quite a large variety.  They are found in cells of the lungs, heart, blood vessels, kidneys, liver and gastrointestinal tract, and are also plentiful in neurons.  Blood platelets also have ACE2 receptors, meaning that Covid can cause system-wide blood clotting and can therefore damage any part of the body that is susceptible to capillary clotting.  Testicular cells express ACE2 and so the testes have been noted as a potential attack vector for Covid.  The uterus and placenta contain cells that express ACE2.

This wide array of potential cell targets for Covid at least partially explains the wide array of symptoms that have been associated with the disease, including (but not limited to) the following:

• Associated with cells of the nervous system:
• Anosmia (loss of the sense of smell / taste)
• Heart palpitations
• Brain fog
• Associated with epithelial cells in the lung:
• Pneumonia
• "ground glass opacities" in the lungs
• Associated with platelets:
• Blood clotting
• Associated with cells of the cardiac muscles:
• Damage to heart tissue
• Stroke
• Associated with cells of the intestinal lining:
• Nausea
• Diarrhea
• Associated with the liver
• Raised levels of liver enzyme
• At least temporary liver damage
• Associated with testicular cells
• Testicular damage
• Possible infertility
• Associated with cells of the uterus and placenta
• "Severe maternal disease" (not sure what that means)
• "Adverse pregnancy outcome"
• Infection of baby in the womb

Variation by replication amount

The severity of the disease may vary by how successful it is in replicating throughout the body.  There are various reasons why the disease may have different success rates in replicating in a particular individual.  One of the most interesting of these reasons is known as the "inoculum"--the size of the initial "dose" of virus that you get when infected.

There is research that strongly suggests that the amount of virus you are exposed to when you are first infected has an effect on how sick you ultimately become.  This is why, for example, they recommend that individuals who live with a family and are sick wear a face mask.  It might be very likely that they will infect their cohabiting family members, but by trapping a lot of the exhaled virus behind a mask, the amount of virus their family members will initially inhale will be smaller, and they are therefore likely to come down with a correspondingly milder form of the disease (one link here).

One of the theories behind this is that a smaller initial dose means that the virus takes longer to replicate up to very large numbers.  The longer that the virus takes to get up to full potential, the longer the body has to mount its own defenses and deploy them throughout the body.  By getting a jump on the virus, the body's immune system has a better chance of keeping it contained and under control before it gets out of hand.

There is some support for this theory by studies which show a large difference in the amount of virus shed between mildly ill patients and severely ill patients: a factor of 60 times larger according to some studies.  It should be noted, however, that the question of the relationship between amount of virus shedding and severity of the disease is not always clear cut and there are seemingly contradictory studies on this.

Variation by reaction of the body to the virus

The body can react differently to an infection.  There are a few important things to note here.

First, most of the most common symptoms of Covid, as with the cold and the flu, are actually caused by the body's reaction to the virus more so than the virus itself.  Extra mucus production is due to the ramp-up of white blood cells to combat infection.  This leads to congestion and headache.  Fever and chills are caused by the body raising the temperature in order to make a less hospitable environment for viral reproduction, leading in turn to muscle aches and fatigue.

All of these things aid in the body's fight against the virus, but are not strictly necessary to it.  It is possible for the body to produce antibodies and clear the virus from the body without doing these things.  This at least partially explains the phenomenon of asymptomatic infected individuals--people who become infected and even contagious, but do not seem to come down with the disease (i.e,, the symptoms).  This is a known phenomenon in a number of diseases sometimes called "subclinical infections".  

What I would like to point out here about subclinical infections is that there is a crucial point of ambiguity if we are talking about people who are infected but have little to no symptoms: it is possible either that these people have a very mild infection (as from the point above) or it is possible that they have a fairly respectably sized infection but are not exhibiting the classical symptoms that are caused by particular aspects of the body's immune response.  Or it could also be some combination of those two factors.

At the other end of the spectrum from subclinical infection is what happens when the body's immune response overreacts to the presence of the virus.  It is possible for the immune system to respond far to aggressively to a reaction, causing it to attack healthy cells as well.  In the extreme, this is called a "cytokine storm" and can be deadly.  It is thought that the Spanish Flu was particularly good at inciting a cytokine storm, and that was why it was able to kill so many otherwise healthy young adults.

The distinction between "asymptomatic" and "pre-symptomatic"

A key component to analyze the risk of spreading Covid is the phenomenon of asymptomatic spread.  At this point everyone knows that this is a major characteristic of Covid.  However, a lot of people are still not clear on what exactly this means.

A key point of ambiguity is, what is meant by "asymptomatic"?  Unfortunately, the term is used differently in different scientific studies, and the confusion over the term spreads out from there.  Sometimes, the term "asymptomatic" is used strictly for those people (mentioned above) who get infected but never show any symptoms over the whole course of the disease.  These people are obviously important from an epidemiological standpoint, because they have the capacity to be long-term unconscious spreaders of the disease.

Sometimes, on the other hand, some people will use the term "asymptomatic" also for the time period when a person is already infected but not showing any symptoms yet.  Every infected person goes through this phase, because there is always an incubation period for the disease of some length.  If a person is using the term in this way, then "asymptomatic transmission" can be used to describe someone who passes on the disease before they develop symptoms.

However, if someone is using the term "asymptomatic" more strictly, then the period of time before a person starts showing symptoms is called "pre-symptomatic" rather than "asymptomatic".  In this case, a true "asymptomatic transmission" would only happen from a person who never shows symptoms throughout the whole course of his disease, not when someone passes on the disease before then exhibiting symptoms.

As I said, the term "asymptomatic" is ambiguous and gets used in both ways.  You have to be careful to distinguish in which way it is being used when you read a particular study, and sometimes even when you read particular passages out of a single study.