[WORK IN PROGRESS]

See this important disclaimer about my utter lack of credentials: (TODO link)

At a Glance

  • The mere presence of a virus or a bacteria is not an indicator of disease
    • Ex: Everyone has C. Acnes on their skin, but only some people develop Acne Vulgaris (“acne”)
  • Along the same lines as the above, we must always distinction between a pathological state and a physiological one
  • Asymptomatic COVID-19 is an oxymoron because it’s not a disease and it’s barely infectious
  • COVID-19 is commonly diagnosed through PCR tests, but we have to apply the pathological vs physiological distinction here!
  • Furthermore, the PCR tests are very flawed. After resolution of SARS-CoV-2 infection you can be PCR+ for months after
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Introduction

This is a hybrid article that explores the distinction between a patho…physio…and applies this concept to SARS-CoV-2, the virus associated with the disease COVID-19, which most of us have heard way too much about across the last year+. (Blah blah blah)

The germ theory of disease was a huge leap forward in our understanding of illness. But most of us have a dangerously oversimplified understanding of what the germ theory of disease actually is. Implicitly, many of us believe that it tells us that all bacteria or viruses cause harm (false), or that the presence of a bacteria/virus is the only thing we need to look at (false). In actuality, not all bacteria/viruses are pathogenic; of those that are pathogenic, their pathogenicity might not actually be “triggered” until/unless the underlying host (the infected person) falls into a state of nutrient deficiency, immune disregulation, or a pro-inflammatory state.

Pathological vs Physiological

Before we dive into what exactly we mean when we describe a state as “pathological”, or when we describe a bacteria or virus as “pathogenic”, let’s talk about a word that most of us are familiar with: disease.

A disease is loosely defined as “a particular abnormal condition that negatively affects the structure or function of all or part of an organism”. So, in order for something to be called a disease, it has to actually represent some type of problem for the individual in question.

Now, the term pathology refers to, essentially, the study of disfunction, particularly the cause and effects of diseases. A pathological state is a disease state. And thus for example a pathogenic bacteria is a bacteria that is actively causing - or at the least tends to cause - disease.

On the other hand, we have the concept of a physiological state, which can be thought of as a “normal” (non-pathological) physical state.

There are some ideas in medicine that are so fundamental that they are essential to every field of medicine. These include ideas like the precautionary principle* (the idea that one should exercise caution and careful, rigorous review when deciding whether to take a given action under uncertain circumstances), the hippocratic oath (first: do no harm), and finally what I’ve taken to calling the pathological vs physiological distinction. In essence, the pathological vs physiological distinction is the recognition of the fact that when analyzing a medical situation, one must take care to distinguish between normal, non-dysfunctional physiological states, as opposed to dysfunctional, pathological states.

Why is this idea important? Well in short, it can be summed up in the old adage: “if it ain’t broke, don’t fix it”. By problematizing something that is not actually a problem, we risk causing (and indeed almost certainly will cause) unnecessary harm.

Let’s apply this manner of thinking to the disease known as COVID-19 as well as its associated virus, SARS-CoV-2, which causes (or more accurately, can cause) COVID-19. COVID-19 stands for “Coronavirus Infectious Disease 2019”: coronavirus is the family of viruses to which the betacoronavirus SARS-CoV-2 belongs, infectious means it can be spread to others, and we already defined disease above as essentially an abnormal state of dysfunction.

It is my belief that one of the most serious issues with the societal handling of the emergence of SARS-CoV-2 is the failure to distinguish between the physiological state of having a virus and the presence of a *truly pathological disease state*.

Having defined what COVID-19 actually stands for, as well as outlining the basic concepts of a disease, a physiological state, and a pathological state, we have the requisite pieces to examine the first contradiction of how COVID-19 is labelled. The following scenario will illustrate the problem. Before proceeding, note that with the benefit of time it is now known that truly asymptomatic spread of SARS-CoV-2 is exceedingly rare (albeit technically possible) [TODO: CITATION], whereas pre-symptomatic spread does occur [TODO: CITATION]. Proceeding:

An illustrative example

–

Patient: Hey doc, I’ve got a coronavirus infection that is causing me no symptoms whatsoever, and overwhelming evidence points to the fact that I couldn’t infect someone even if I tried. Diagnose me please!

Doctor: This is an open-and-shut case. You’ve got coronavirus infectious disease 2019.

Patient: …

–

If my little skit hasn’t made it clear, a truly asymptomatic individual does not have a disease. Furthermore, COVID-19 is properly defined as an infectious disease, yet truly asymptomatic spread is exceedingly rare (note for rhetorical effect we use slight hyperbole with the “I couldn’t infect someone even if I tried” language - but only slightly).

So if we’re being intellectually honest and logically consistent, we must accept that the term asymptomatic COVID-19 is an oxymoron. It’s been defined as something that can’t exist and never could. You can’t have a disease without symptoms, and you need to be able to readily infect someone to call something infectious.

This might seem like just a nit-pick or a silly gripe, but it’s actually indicative of a tremendous problem with how we have responded to the emergence of SARS-CoV-2. We have problematized normal physiological states to such an extent that people feel a crippling sense of guilt for becoming personally infected with the SARS-CoV-2 virus even in the utter absence of symptoms. A true “takedown” of the whole concept of collectivism and particularly medical collectivism - which has led to such wonderful innovations as eugenics, forced sterilization and mandatory vaccination in the US alone - is out of the scope of this article, but if we set aside the nebulous ethical issue of assigning guilt to viral transmission for a timebeing, hopefully we can agree that from a purely personal perspective, it doesn’t make sense to freak out over merely being infected with a virus in the absence of a detectable disease state.

We all have an uncountable quantity of bacteria and viruses within us at all times, and were someone to wave a magic wand and completely eradicate them from our bodies in an instant, we would probably end up dead within a couple days (but at a minimum we’d have a very, very bad time). Our bodies, much like the observable universe itself, exist in a beautiful state of metastable [TODO: see if metastable makes sense as a word here] dynamic equilibrium. We are not mere individuals in the biological sense, but rather we are ourselves communities, a sort of biochemical garden in which - to look at one small slice - colonies of acidophilus (acid-loving) bacteria exist in delicate harmony with our various immune cells and all the other various components of our body. [TODO: I like this sentence but the last half of it needs a bit of reworking]

Now let’s examine more specifically what a COVID-19 case is defined as. Definitions of what exactly constitutes a COVID-19 case vary, but in many countries - and the US is no exception here - the mere presence of a positive PCR test is considered sufficient to diagnose a case of COVID-19. For example, here’s some guidance from the US CDC. We’ll skip straight to the Laboratory Criteria section, and specifically what counts as Confirmatory Laboratory Evidence:

Detection of severe acute respiratory syndrome coronavirus 2 ribonucleic acid (SARS-CoV-2 RNA) in a clinical specimen using a molecular amplification detection test

[TODO: case definition stuff]

In an upcoming section we’ll look at, mechanistically, how the presence of SARS-CoV-2 RNA is actually detected, but for now let’s assume that we have a laboratory test that tells us with perfect accuracy whether someone is actively infected with the SARS-CoV-2 virus. In reality no such test exists, but it will help us illustrate the next point.

Just as in the first scenario we examined, the mere presence of SARS-CoV-2 is not indicative of a disease state. Thus a “proper” definition of COVID-19 should really be defined as the confirmed presence of SARS-CoV-2 together with clinical symptoms. If we don’t require the presence of clinical symptoms, then what we have is not a “COVID-19 test”, it’s a “SARS-2 test”. Remember: COVID-19 is [supposed to be] the disease, and SARS-2 is the virus! The problem is that the CDC - and numerous other medical organizations across the entire globe (although happily, not all of them) - have erroneously conflated the two. The virus is not the disease. Just as the mere presence of HIV is not indicative of AIDS, the presence of SARS-2 is necessary but not sufficient for COVID-19.

Again, the working definition being actively used in many organizations worldwide is patently absurd. It demonstrates a total lack of understanding of the pathological vs physiological distinction, by labelling a potentially innocuous and potentially harmful state - the presence of the SARS-2 virus - as a state of disease in its own right. That’s simply wrong, and it has tremendous implications for how we think about and thus respond to the existence of SARS-CoV-2 and its associated disease COVID-19.

If a country is pursuing a goal of containment (the US is not, although we like to incur all the negatives of trying to do so anyway), it makes sense to track the incidence of SARS-2 itself beyond merely tracking disease states: fine. Additionally, even in a country that isn’t practicing containment (and most countries aren’t), it’s cool to be able to track the spread of the virus itself. That’s fine. But it needs to be reported as a separate metric, not conflated (perhaps intentionally) with the disease state, which serves to drum up unnecessary fear and ultimately will lead to worsened health outcomes. Frightening people unnecessarily is bad, and it leads to them making irrational decisions that end up harming their health.

Polymerase Chain Reaction

Next we’ll take a look at the most common method for detecting SARS-CoV-2 infection. PCR, or polymerase chain reaction, is a method of exponentially amplifying specific subsections of DNA in a sample (via input of “primers”) in order to detect the presence of a sequence of DNA. In the context of COVID-19, it’s used to identify RNA associated with the SARS-CoV-2 virus.

(If you’re curious about what “polymerase chain reaction” actually means, any “science word” that ends in -ase denotes an enzyme (a chemical substance that acts as a catalyst to bring about a biochemical reaction). A polymer is a chain of very large molecules (macromolecules) composed of repeating subunits. Putting the two together, polymerase is an enzyme that brings about the formation of a particular polymer (especially DNA or RNA). The chain reaction comes from the fact that the genetic material (DNA or RNA) gets repeatedly doubled with each cycle of the polymerase chain reaction.)

[TODO: quote from mullis about the basic concept]

PCR, and more specifically qPCR (quantitative PCR), is a powerful technique with a bunch of different applications. But there’s a fundamental flaw with how we apply it in identifying COVID-19.

There’s two main problems with how we as a society are applying PCR:

(1) As we discussed earlier in the article, the mere presence of a virus or some other pathogen is not an indicator of disease in its own right.

[TODO: give example case definition https://www.icd10data.com/ICD10CM/Codes/U00-U85/U00-U49/U07-/U07.1 ]

(2) When applied improperly, qPCR can return false positives. There’s actually two main types of false positives: what I’d call (a) “long tail false positives”, as well as (b) “true false positives”.

Long tail pseudo-false-positives

(a) The former is by far the most common and is the most glaring indictment of our mass-testing response to COVID-19. As we discussed, PCR works by performing stages of exponential amplification of the target genetic material. Eventually the genetic material has been amplified so much that the test hits on not just a true infection but also on the remnants of a past infection.

Let’s take a step back. When your body detects an infection it’s going to break out a number of tools in its immunological toolkit. One of these methods is by having lymphocytes (TODO: verify it is lympocytes, I’m 90% confident) release a reactive oxygen burst upon a SARS-CoV-2 virion or an infected cell. This is the chemical equivalent of detonating a cellular hand grenade. As a result its target will be blown to pieces. This will leave remnant viral debris floating around to be gradually cleaned up; this debris includes chunks of SARS-CoV-2 viral RNA.

The “lymphocyte producing reactive oxygen burst” scenario is just one particularly fun to visualize example; but the important thing is to understand that past infections leave pieces of viral RNA hanging around for some time. As a result, depending on the parameters of the specific PCR test in question, someone can still test PCR+ months after clearing an infection.

To use a relevant example, many people are familiar with George Floyd, who died in the course of a police encounter. If you look at the Hennepin County Autopsy [TODO: link], they note that Floyd was PCR+ at his time of death. Yet a little digging shows that he had recovered [TODO: when’d he recover -> a couple months?] a couple months before he actually died. This PCR+ result did not represent an active infection; it was a “long tail false positive” caused by the free-floating viral debris that had not yet been fully cleared out of his system.

These long tail false positives are especially concerning when looking at how we classify COVID deaths. Definitions vary but in almost every area the rule is simple: “if you’re PCR+, and you die, you’re a COVID death”. It’s why a young man who died in a motorcycle accident was initially labelled a COVID death by the state [TODO: link story] until the county health official got enough media attention to get it changed. It’s also why scores of people who died of “natural causes” will be considered COVID deaths regardless of whether they successfully cleared their SARS-2 infection weeks before dying.

It’s also got obvious implications for how we treat people in a clinical sense, as well as the restrictions and quarantine measures that are forced upon an individual. A single long-tail false positive can prevent someone from working for weeks. Or it can lead to their pneumonia being mis-diagnosed as a result of SARS-CoV-2 as opposed to some other virus.

True false positives

(b) There’s also the possibility of a true PCR false positive; that is, someone who has never had SARS-CoV-2 infection receiving a positive result. This is much more rare, but can occur when the [TODO: improve accuracy] primers themselves get amplified.

Both the long-tail false positives and the true false positives are why we need to define COVID-19 cases the same way we do for any other disease. It’s possible to have HIV without having AIDS. Similarly, it’s possible to have SARS-CoV-2 without any associated disease; but the way we currently define it that’s actually not the case. Again, because a positive PCR result alone is all that’s required to label somebody a COVID-19 case, we end up with almost a completely meaningless case definition. Not only does this perpetuate the environment of fear and hysteria, but it also makes cases in their current form a completely absurd metric.

Double-counting cases

Finally, while this doesn’t fully fit with the theme of the article, it’s worth noting that there’s no de-duplication built into the system. You can take 5 PCR tests and if they’re all positive that’s considered 5 “new” cases, not 1. The absurdity of that should be self evident.

* There’s some debate as to whether the precautionary principle is actually the right approach or not. The complexities of the ethics there are out of the scope of the article, but it’s worth saying that it would have really come in handy if we’d followed it for the COVID-19 pandemic at a minimum. (Specifically: universal masking / lockdown / rushing out vaccines)

~~~~~~~~~~~~~~~~~

TODO

  • Mention the C. Acnes example in the actual article (right now it’s only in at a glance)

CODING CODE COVID-19 DEATH => https://www.icd10data.com/ICD10CM/Codes/U00-U85/U00-U49/U07-/U07.1

https://twitter.com/Kevin_McKernan/status/1320536482298384390 The Live-Dead qRT-PCR problem, the testing industrial complex and its impact on society

https://www.ukcolumn.org/article/deceptive-construction-why-we-must-question-covid-19-mortality-statistics - looks like it might be relevant