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Viral Load: The Missing Surveillance Window

Why Do We Need A “False Breakthrough” Type, Anyway?

In the first post of this series, I introduced a typology of breakthrough infections that helped me organize the rest of this discussion. If you review that typology now (go ahead, I’ll wait) there is something about it that ought to strike you as a bit weird. Why on Earth should there even exist a Type 3a, “False Breakthrough Infection” category? How could it have come about that we are arguing about whether or not an infection is, in fact, an infection?

There is actually something unusual about the clinical status of a COVID-19 diagnosis: rather than being assessed on the basis of a constellation of symptoms, as is the case for most diseases, a case is declared a case on the base of a laboratory test, almost always a “Reverse Transcriptase Polymerase Chain Reaction” (RT-PCR) assay. And an RT-PCR test is a very sensitive test, capable of detecting very low levels of virus particle concentration (AKA “viral load”). It’s actually very impressive that a laboratory technology such as PCR, which would ordinarily require PhD-trained scientists to understand and operate, was rolled out so quickly and widely, and is now operated by hundreds of thousands of hourly-salary technicians, millions of times per day, with extremely low error rates. This is one of the scientific responses to the pandemic that went very right.

With every benefit there is a cost, however. In this case, the ability to detect extremely low levels of viral load collides with the characteristic response of a correctly-functioning, vaccine-primed, SARS-CoV-2-aware human immune system. As we have already discussed, when a human organism in possession of such an immune system is attacked by the virus, the virus does not explode on contact or bounce off some kind of impenetrable armor. Instead, the virus gains entry and begins to infect cells and reproduce itself. Early on in the process, however, the immune system becomes aware of the infection and duly moves to shut it down. What level of peak viral load can be attained before the response gains the upper hand is a matter of competing rates—rate of viral growth versus rate of various immune system infection-clearing processes. With the original SARS-CoV-2 strain, and some of the early prominent variants, it was very clearly the case that a lot of “breakthrough” infections that people were panicking over, and which were ostensibly lowering estimates of vaccine protective effectiveness against infection, were actually cases of perfectly normal vaccine-primed immune systems doing their jobs without a fuss, and of RT-PCR test ringing up “Positive” based on the very low viral loads characteristic of a failed infection. Hence, Type 3a, “False Breakthrough”.

But wait. Something’s not right. Why is this super-sensitive assay being fooled?

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