One of the things that I’ve discussed in the context of the COVID-19 epidemic is that it is primarily a disease of our immunosuppressed. That tells you a lot about how we need to view the disease in terms of how it actually works, and how we need to frame our discussion going forward. I’ve been Tweeting about this all week — that viral DOSE matters. Why? Two populations are getting hit pretty hard. One, of course, is the immunosuppressed. But the second is our health care providers. And believe it or not, the physics of what is happening to both groups is remarkably similar.

What matters in the context of viruses like COVID-19 is the viral replication rate, as well as the immune response rate — how fast viruses manage to make themselves (modeled, once again, by the ever-popular exponential curve) and how fast the immune system scales up the various antibodies and white blood cells that form the main line of defense. The fact that multi-celled organisms exist is a sign that we’re better at this in the long run than single-celled organisms, like bacteria, or those super-small strands of encapsulated DNA that make up viruses.

But that’s cold comfort to someone suffering from COVID-19, in a major way.

So let’s break this up into the three cases, and take the broader view of what’s happening.

Case 1 – viral replication rate >> immune response rate

In this case, the body doesn’t stand a chance. You get infected, you’re the perfect petri dish, the virus overwhelms your immune system, and you die. Viruses like Ebola, with potential death rates of 90%, operate under these principles.

Why aren’t there more of these? Well, viruses that do this kill off their host. And unless they can survive living in a buzzard’s gastrointestinal tract, you rot on the ground and that virus is not successful. Humans encounter these types of viruses, they flare up, and then an outbreak ends relatively quickly, because the transmitter is, well, dead.

Case 2 — viral replication rate << immune response rate

In this case the virus doesn’t stand a chance. The poor, hapless virus floats into your system, tries to grab on, and then the immune system reacts/overreacts and pulverizes the virus. Dosage — how much of the virus you get into your system — matters. If you don’t get any kind of dose, you won’t see any kind of symptoms at all, as your mean immune response will likely take care of this in no time at all. This is the kind of thing we see with a common cold, typically a rhinovirus. A few symptoms, followed by a cessation in a day or two. And if the cold isn’t particularly virulent, or you don’t get a big dose, you likely will never know that the virus entered your body.

This kind of virus isn’t a whole lot more successful than the first, as it gets wiped out relatively quickly. It has to have someplace to go hang out until conditions (temps./humidity) are ripe for it to come out again.

Case 3 — viral replication rate ~= immune response rate

This is where things get interesting, and COVID-19 seems to fall into this category. Are there signs (without an intensive study) that this points to? Absolutely. A 5-14 day incubation period, before symptoms are shown, are a sign that the virus is slow to warm up to virile levels. The fact the disease itself runs some equivalent 14 day period is more evidence that there is a triggering that occurs. The fact (as we know it) that the virus kills 1% of its patients (terrible, but not so terrible) or the fact that you can even beat back the virus if you’ve got pneumonia is more evidence.

What this means also is that immunosuppressed people have more of a sliding window of rate with respect to their immune systems, that diminish the immune systems’ rate constant (the exponential factor) and make the infection worse if your immune system is indeed impaired. Not good.

What it also shows it that viral dose matters — how big a hunk of the virus you get into your system from exposure in the first place. That’s why masks matter. And experts are starting to chime in — see this opinion piece in the New York Times by Rabinowitz and Bartman from Princeton, who coincidentally happen to be in chemistry and genomics — not infectious diseases. I’m sure they’re using similar logic. A larger dose means that the virus, in this sliding window world, gets a bigger head start, and so can get to the point in more cases where it can overwhelm health care providers’ immune systems. So if they had some smaller weak point, even if they were younger, they could get knocked out of the fight. Or even die.

Understanding this mental model, though, is still in our favor. Instead of being afraid of sub-microscopic invaders, we can now start using more macroscopic notions, and cross-disciplinary ideas. Radiation and how people handle dosing says “shield the user” and it doesn’t always mean wearing lead-lined clothes. Placing appropriate barriers between people also helps, especially because we know that the virus is droplet-spread. Different jigs in high traffic situations will make a statistical difference. Here’s a great piece on a simple acrylic box that doctors in Taiwan are using during intubation. You can imagine how messy that is, if someone has pneumonia in both lungs.

The other thing that can really help is understanding the need to cycle various health care providers out of front-line exposure roles. There is a whole new playbook that we can use. And we should use it — especially in convincing health care professionals who have not yet been hit at epidemic levels. We need to understand that these populations are people under stress, and likely to be reaching for familiar solutions — “More PPE” which really means “more of what I’m familiar with.” But if those gowns aren’t available, or are even rationed, we need to introduce a deeper understanding, with hopefully some collaborative problem-solving. And as dissemination of novel techniques starts bearing fruit, more will clamor for these different approaches. And we need to be ready to help.