January 14th, 2022

A Viral Infection is a Race and Vaccines Help You Win the Race

I’m decidedly not a virologist, but I do pay attention, and it strikes me that a glaring omission continues to be made in explaining to us all about how viral infections and vaccines work.

A viral infection is a race — a race that starts when a virus gets into you and successfully enters a cell, which it takes over to turn it into a factory for making many, many more copies of itself. A typical, COVID-infected cell is thought to produce roughly 100,000 to one million virus particles (AKA virions, or just individual viruses)! Copies of an invading virus are thought to number between one billion and 100 billion in an infected person, and yet their total mass is about the same as a that of a speck of dust. They are incredibly tiny! So are the active ingredients in each of the vaccines. The 30 micrograms of a Pfizer adult dose is about 1/20th the size of a single grain of table sugar or one tenth the size of a grain of table salt! Also therefore roughly the size of the period at the end of this sentence. That's the size of the technological miracle that so many people have been taught (by liars and charlatans) to be overly skeptical of. Similarly, it’s thought that all of the COVID-19 viruses in all of the infected people on the planet have a mass of between a mere four ounces and around 20 lbs!

See: https://www.pnas.org/content/118/25/e2024815118

An infection is a race between the virus, which wants to multiply exponentially so that it can spread to other people, and our immune system, which wants to kill it off. It is always a race — not a binary thing, not an either/or, on/off, black/white, yes or no thing! Once it starts, the race is a matter of degree. Yes sometimes the race is won early by your immune system so you never even know you were infected, because the number of your cells that was affected is small. And yes sometimes the race is won by the virus so overwhelmingly that it kills you. But those are just the extremes of the spectrum of outcomes of the race.

Vaccines always work by helping your immune system run the race. It’s always you (your immune system) that kills the virus, not the vaccine. The vaccine greatly accelerates the race you run, by allowing your immune system to race ahead several days worth toward the finish line, rather like Wile E. Coyote with ACME Rocket-Powered Roller Skates, absent splatting into a sandstone cliff. All’s fair in love, war and racing a virus. The vaccine makes your race happen faster and better than it otherwise would have happened, by teaching your immune system something about the enemy before the enemy arrives, so that it doesn’t have to spend many days learning about the enemy. It takes time to mobilize for a war, especially one with an unfamiliar enemy. Vaccines allow you to get mobilized ahead of the outbreak of war, so you're already pretty much ready to fight effectively when the war starts.

When polio was still a great threat in the U.S. and around the world, before the huge advance of the polio vaccines developed by Jonas Salk in the 1950's, the number of “subclinical” to “clinical” cases of polio was fifty to one. That means that for every 51 actual infections, only one person “got sick”. It’s the same thing with every infectious virus, but with widely varying ratios of those two numbers. With HIV, for example, the ratio is hugely higher than 1 to 50, very close to 50 out of 50, unfortunately.

Coronaviruses are the same way. For each of them, some infected people will run the race and pull ahead of the virus so early on in the race that they never feel any symptoms, but this is far less likely with a "novel" virus like SARS-CoV-2, our current foe. Other people will fall behind so badly right off the bat that within roughly two to four weeks they’re dead. The race plays out in a million different ways, mainly as a matter of degree (how far ahead or behind the virus does your immune system get and when?) but also as a matter of quality (if you do fall behind, in which of many ways will the virus injure you?).

If instead you take an anti-viral drug like Pfizer's highly effective, new Paxlovid 2-drug cocktail, the drug again doesn't quite attack the virus directly. I gather that most of the anti-virals work by interfering with the virus’s ability to multiply, not by destroying or permanently deactivating viruses that already exist. So you need to get the drug into yourself before the virus’s great, logarithmic population explosion is very far along, so its numbers stay quite low. That way, as your immune system ramps up over a period of many days, the virus can't injure very many of your cells as your defenses are taking time to ramp up. So it’s still up to you to kill the viruses that exist within you, but the anti-viral drug, if it works as intended, will have made that task much, much easier by stopping the virus from injuring you very much, by keeping it in a state of suspended animation with a much lower population for several days while you're busy for a week or two mobilizing for the war. Unfortunately, batches of Paxlovid take 6 to 9 months to make and the process can't be sped up, so the drug will be in short supply for perhaps something like many weeks. Pfizer seems to have initiated about one batch per month, starting late in the first half of 2021, each larger than the prior one.

The third most important class of medicinal helpers, monoclonal antibody treatments, provide pre-made antibodies so that you don’t have to wait around for your immune system to build them. The antibodies are custom-tuned to the particular virus. This again can give your immune system a much better chance of winning the race in an early stage, by reducing the time required to field the army of customized antibodies necessary to get the upper hand in the race. Unfortunately most of the ones we had have become useless as a result of the evolution of the virus into the omicron variant. Also, these treatments are extremely expensive, at around $20,000 dollars a crack. The vaccines are cheap (and more effective). One other thing: a typical hospital stay for COVID runs a bill of around $600,000! If that's not a good reason to be careful with the dangers of a serious infection, nothing is.

Now imagine that a vaccine is constructed, molecule by molecule, to stimulate your body to make antibodies which precisely match some of the protein molecules on the tip of the crucial spikes of the virus, but the virus evolves via random mutation (the viruses do this constantly by not being very accurate about making copies of themselves as they multiply inside of an infected person). The protein molecules partially change, so the antibodies built in response to the proteins built according to the plans provided by the code of the mRNA vaccine now only partially match the new virus. So the vaccine’s message to our immune system still helps, but not as much. The antibodies we’ve previously learned to make just barely stick onto the new spikes of the invading virus. You’re still better off than if you'd not been vaccinated, because the virus’s replication is slowed more than than would have been the case if we’d never been taught about the previous version of the virus, and it may well be enough that the virus doesn’t whip you badly in the race, but the virus does pull ahead for a time to such a degree that you do feel some degree of symptoms, usually mild. These races can work out a million different ways, but the vaccines always help in some degree unless they are a total mismatch for the enemy. They don’t stop infections from occurring! They just help you win the race, and sometimes that seems to have stopped infections because they were too slight to notice.

The omicron variant is very different from the previous ones. Luckily the existing vaccines help just enough that after three doses the serious damage that omicron does is still on average cut down tremendously, in the range of 90 to 95% reduced for most people, but something like half of the 3X vaccinated people will still get symptoms, because our pre-mobilization against omicron isn’t as good as it would have been against delta. A vaccine made just for omicron will probably be able to keep the likelihood of symptomatic illness a lot lower. Moderna expects to begin delivering such a vaccine by sometime in March, 2022, though by then the worst of the omicron spike in cases will be mostly over. Pfizer is also working on an omicron-specific vaccine.  I've heard that neither will have to again go through the same multi-month safety and efficacy trials that their original mRNA anti-COVID vaccines did, just as our annual flu shots don’t have to repeat their safety and efficacy trials when each year’s flu vaccines are aimed at new strains of influenza virus. Thank goodness.

In the meantime, so that we don’t spread the virus around to vulnerable people who will get very sick, so that we don’t get tens of millions of people mildly sick too, so that we don't fill our beleaguered hospitals and the working lives of our beleaguered medical people with readily avoidable illness, so that we don't waste billions of dollars on avoidable health care costs, so that we have medical services available for all the usual illnesses, and so that we cut back on the opportunities of the virus to continue to mutate into ever more dangerous foes, STOP SPREADING IT AROUND. BE CAREFUL. DON'T BE A JERK and pretend you’re special somehow and you won’t catch it or give it to other people. Everyone can catch it and everyone can give it to other people! Set a good example by wearing a high-quality mask even if other people aren't! Omicron is thought to be the most transmissible human respiratory virus in history! It’s ultra-easy to catch it or spread it. Or as David Lance Goines once inscribed in a poster about VD, “Don’t give the gift that goes on giving”.                                                                                                                                                                                 

—Joseph Holmes                                                                                                                                                                                                                       

PS: “Vaccine Effectiveness” is a measure of the percentage reduction in “cases” or “disease” among vaccinated people, compared with unvaccinated people, in research carried out on the general population. It’s easy to see how saying that a given vaccine is, for example, “70% effective” is apt to be misinterpreted as meaning that 70% of the time it totally works and 30% of the time it totally doesn’t. But again, that’s totally wrong. Rather, it’s just a useful, albeit misleading, description of the apparent results.

When the FDA says that a vaccine is “70% effective”, what they actually mean is that among those infected people who would all, without the vaccine, have experienced symptomatic infection i.e. “illness” (an infection where the virus got the upper hand in some degree), 70% wouldn’t even get to that point and would instead appear to have been totally unaffected by the virus. The other 30% no doubt also did better but maybe not enough better to see an obvious difference. I haven’t seen any explicit data on that. But it has to be a spectrum (of outcomes), not simply a black and white pair of outcomes among people who got the vaccine.

The FDA has chosen not to approve vaccines that don’t cut symptomatic illness (“cases” or “disease”) by at least 50%. I can think of several reasons they might have for doing that. We are all fantastically lucky that many people doing research on a wide range of scientific puzzles over the last few decades managed to succeed in solving those many pieces of the puzzle that were absolutely required in order for the miraculous mRNA vaccines to become reality, just in time to protect billions of us in this current pandemic. It's extraordinary for any vaccine to be 90 to 95% effective, as they were against their original targets. To appreciate the details of this history, read this amazing story of dedicated and clever scientists trying to answer questions which each of them had concluded were important, often when others didn’t agree:

“Halting Progress and Happy Accidents: How mRNA Vaccines Were Made” in the New York Times, January 15, 2022


If you can't load the story because of the NYTimes paywall, perform a search on the title of the article and follow that link and perhaps you'll be able to read it.