Such insight is certain to give serenity now to many people — while rattling others. It also will upgrade our understanding of just how SARS-CoV-2 has evaded both disease-induced and vaccine-induced immunity with such startling swiftness.
So, what gives? Whatever happened to real immunity, the type where you don’t just get a milder infection, you don’t get disease at all? When you get a measles shot, for example, you never get measles. Period. And why haven’t the same remarkable scientists who have given us rapid diagnostic tests, life-saving vaccines and effective therapies been able to sort out just exactly what we are talking about when we talk about immunity?
Right now, at least in the context of Covid-19, many think of the immune system as having two main components: antibodies, which can prevent an infection sinking into the tissue, and T-cells, a type of white blood cell that are tasked with grinding down an already established infection. The system is much more complex but focusing on these two pillars is helpful to understand the challenges ahead.
Thus far in the pandemic, our antibody repertoire has not been up to the task — witness wave after wave of disease, even among those with previous disease and/or vaccination. What has worked well has been our immune system’s prevention of serious disease, a central job of the engulfing T-cells.
With Covid-19, scientists first focused on measuring antibody levels, a relatively simple and familiar approach. Antibodies are floating in the bloodstream so that a simple tube of blood can be used to determine levels. The problem is that the body makes more than one antibody per pathogen; it is not a yes or no situation. Rather, an antibody might be produced against a section of the coronavirus spike protein or a corner of the viral envelope or its core proteins or somewhere else altogether.
Our ability to measure the other main part of the immune response — the T-cell side — requires a much slower and more sophisticated lab set-up owing to the way the T-cell works. On first meeting a specific infection, the T-cell is unfamiliar (“naïve”) and slow to attack; but on subsequent meetings, it has “memory” so that it can quickly and efficiently go about its destructive business.
In the lab, researchers stimulate the T-cell by presenting it with “bait” — a scrap of the infectious particle or a lab-built, synthetic string of mini-proteins (called peptides). If the T-cell recognizes the bait, it fiercely prepares to attack it. If the bait is not recognized, the T-cell shrugs and moves on.
Up to now, measuring this stimulation (also referred to as “activation”) of the T-cell has been difficult. Blood samples must be rapidly processed and specific cells separated out. This sort of testing took experts days to perform — one patient at a time. Broad-scale testing — the type that public health experts need to inform decisions — was impossible.
The latest advance hinges on a simple adjustment regarding what to measure. Rather than observe the behavior of the T-cells, scientists can measure the various chemical products the T-cell spits out after being stimulated. The more chemical (a group of “cytokines” or “chemokines”) produced, the more equipped the T-cell is to seek and destroy the specific infection.
These new tests, if as good as advertised (always a big “if”), will indeed help us pick our way through the months ahead as we prepare for another surge and think about the optimal way to deploy both the current array of vaccines and — hopefully — the coming generation of more Omicron-focused products. In a best-case scenario, these novel tests could be adapted to determine if someone is “safe” to be around whatever the latest variant or subvariant might be.
Such availability though likely is not around the next corner. Though the work presented thus far may help public health officials determine how best to deploy resources, they will not yet provide the answer for a worried individual to the basic question: am I protected? Our tests right now, even with the latest addition, simply are not accurate enough. The question is particularly pressing for those with abnormal immune systems.
Furthermore, this big, essential step forward comes with a crucial caveat. Thus far during the pandemic, each bit of progress has been accompanied by a sigh of relief that “we are almost out of the pandemic” that results in corner-cutting and the urge to proclaim victory. Rather, this is only yet another tool to help us understand just when — or if — such a victory can confidently be claimed.
