Mini-Throughput: Mutant Math and New Strains of Covid

The rise of new more infectious strains of COVID-19 are the biggest story in science right now. The good news is that the vaccines appear to work against the new strains. While the South African variant is more concerning, it still provokes a sufficient immune response. And the pharma companies have indicated that tweaking the vaccine for the new strains should be fairly straight-forward. The bad news is that these new strains are spreading rapidly and our efforts to confine them to certain countries is almost certainly a case of too-little too-late.

So, does this mean our efforts were for naught? Does this mean we would have been better off pursuing a herd immunity strategy instead of lockdowns?

Let’s talk about mutation for a second.

The way to understand mutation is to think of it as a game of telephone. A virus’s properties are encoded by the strain of DNA or RNA inside it — a string of compounds that is the virus’s blueprint. We abbreviate these sequences with the letters A, C, G and T. So, DNA is basically a long message that reads ACGTAAACTGTATCGGATC only zillions of letters long. When the virus is replicated, that genetic messages is copied into the next virus. For our telephone analogy, that is one person whispering what they heard into the ear of another. And just like every time one person whispers their message into another’s ear, there’s a chance the message may be garbled, there is always a chance that replicating a virus will garble the message. One or more of those letters may change. Instead of hearing ACGTAAACTGTATCGGATC, the next virus hears ACGTATACTGTATCGGATC. That change of A to T is what we call a mutation.

The best way to keep mutations from happening is to keep the number of links in the chain small by keeping people from being infected in the first place. The more infections, the more times the virus is copied and the more likely it is that a letter will be changed.¹ Think of that game of telephone again. If I whisper, “Now is the time for all good men to come to the aid of their country” into my wife’s ear, she’s likely to repeat it correctly. If she then whispers it into my daughter’s ear, she’s likely to repeat it correctly. But each link in the game of telephone increases the likelihood of a “mutation” in that message. If we put a thousand people into that game of telephone, what comes out at the end might be something like “purple monkey dishwasher”. It will bear no resemblance to what went in.² This is why herd immunity was always a bad idea. Because the more people are who are infected, the more likely you are to get a mutation.

Most of the changes in the viral message don’t matter. They don’t affect the behavior of the virus very much. They are useful for tracking the virus by looking at the spread of different “families”, but won’t affect the ultimate outcome. But the viral world is evolution on steroids. Viruses replicate so fast and in such massive numbers that bad mutations will die out almost immediately while advantageous ones spread quickly.

COVID-19, for example, has an R of about 1.1, given our current precautions, meaning each infected person will infect about 1.1 people before either dying or clearing the virus. But the new COVID strains are much more infectious. Let’s call that an R of 1.6. That doesn’t sound like a huge difference. But remember, viruses spread exponentially.³ Let’s say that the infection cycle — the time from when you catch the disease to when you infect someone else — is five days. After a month, 100 COVID victims with the original strain will have spread the disease to 130 people. The ones with the mutant strain will have spread it to 400. After two months, those numbers will be 200 and 7000. This also means that even a rare mutation will rapidly become the dominant infection. Let’s say that we start out with only 1% of the victims having the new more-infectious strain. Within three months, 90% of the victims will have that strain.

Side note: one of the things that could be made clearer to the general public is what “more infectious” means. What it means is that your odds of catching the disease, given any scenario, are increased. Any time you interact with a person who has COVID-19, there is a chance of catching the disease. The odds are high if you are indoors, unmasked and interacting for a couple of hours. But they are not 100%. Because even being exposed to the virus doesn’t guarantee that it will latch onto your cells and successfully replicate. Sometimes you get lucky. The odds of infection are low if you are outdoors, at a distance and masked. But they are not 0% because, in theory, even a single tiny virus could get exceptionally lucky. What the new strain means is that your risk in both scenarios is increased because the virus is now rolling loaded dice. Let’s just make up some numbers here. Maybe your odds in the first case were 60% and now they’re 90%. And maybe in the second case, it was 1% and now it’s 2%.

What this means is that preventative measures are not less important, they’re more important. If you were 30 times safer before in back-of-the-envelope calculation, you’re 45 times safer now. In fact, some experts are recommending that everyone use either an N-95 mask or double mask, since that will reduce the number of viral particles a sick person emits (i.e., lowering the number of dice rolls the virus gets). I fear, however, that this will just cause people to give up. We need to emphasize that while double-masks and N-95’s are great, even one mask is still massively better than no mask.

Now, one of the arguments of the herd immunity crowd has been that mutation is a good thing. Viruses, they argue, tend to mutate into less lethal variants because there is an evolutionary advantage to being less lethal: they can infect more people. This argument is extremely weak. And in the case of COVID-19 specifically, it’s nonsense:

• History is replete with viruses that never mutated into less lethal versions. It’s replete with ones that mutated into more lethal versions. Smallpox was absolutely devastating throughout its millennia-long reign of terror, sometimes killing as many as 30% of its victims. Most years the flu is fairly dangerous, but occasionally it comes back with a particularly vicious strain. If you expand to bacteria — which are even more prone to gene-splicing — the Plague kept coming back for centuries, including a version in the Black Death that was known to wipe out entire villages. During the 16th century, Mexico was essentially depopulated of its 20 million natives by Cocoliztli, a disease which we have still not positively identified. Whatever it was, it mutated into a much more lethal version, with later waves having fatality rates of 90% or more.
• This is because viruses do not really care whether you live or die. All they care about is that you can spread the disease. As long as the virus doesn’t kill you before you spread it, it’s fine. In the early days, HIV was nearly 100% lethal. But because it took years to kill, it spread just fine. In fact, here we are, 30 years later, and the disease is still the leading cause of death in young women globally. Ebola and other hemorrhagic fevers have very high lethality rates but can also spread very rapidly (Cocolitztli might have been one).
• With COVID specifically, the entire danger, as I noted in my first post on the subject, is that it has a long asymptomatic phase during which it is still infectious. COVID-19 could be massively lethal but still spread like wildfire as long as it didn’t kill immediately. See its predecessors in smallpox and the flu.

In short, the possibility and now the reality of new strains was never an argument for the herd immunity approach. They were and are one of the most powerful arguments against it.

As I’ve said in previous blog posts, if this is a war, the new strains are the virus’s new weapon. This weapon may have neutralized some of ours: the monoclonal antibody therapies appear to be far less effective, for example. But others, like the vaccine, are still very effective. And still others, like masking and social distancing, are now less effective but still very good.

The best way to neutralize the virus’s new weapon is to deprive it of the ability to innovate by infecting new bodies. We have brain power; it has mutation. Let’s strengthen our weapon while weakening COVID’s.

1. There is some evidence that these new mutations are arising in hospitals. The longer someone is alive with active virus, the more likely they are to produce a mutation. But there’s not much we can do about that other than letting people die.
2. If you want to make telephone more fun, line people up so that they are whispering into each other’s left ear. Our right ear processes speech much better than our left ones.
3. One of the classic problems to illustrate exponential spread is this: imagine a lake is infected with an algae bloom that doubles every day. After 45 days, it has covered half the lake. How long will it take to cover the other half? The answer is one day.