The Pandemic’s Moving Line: A Quantitative Reckoning

All pandemics end. There is maybe only cold comfort in that while still enduring one, but there is some comfort in it just the same. 

History is rife with plagues and pandemics, many orders of magnitude worse than this one. Eventually, they all did end. This one will, too.

Between now and then, what exactly is going on? Are things going well as we look for light at the end of this long tunnel, or is it yet another on-coming train?

A bit of both, perhaps.

The first thing to note is how fraught with peril predictions about the pandemic course all are, my own certainly included. This is for many reasons, but principal among them the pandemic’s moving line. The pandemic in all of its particulars – virology, genetics, transmission, human behavior, policy responses, and the concomitant infodemic – is a constantly moving target. 

Complicating matters further, predictions themselves potentially add to the Brownian motion of these many component parts. Honest declarations of improving epidemiology may invite carelessness that reverses a favorable trend. Projections of a worsening situation due to the advent of a new viral strain may, conversely, provoke extra precautions that obviate the threat and prove the prediction wrong.

Pandemic predictions are fraught with peril, unless we recall the adage: the best way to predict the future is to create it. Now, as ever, we are much involved in creating the course of the pandemic. We all have choices to make.

Those choices, alas, preclude a panacea. The only best pandemic choice is not to be in one, and that option was foreclosed to us long ago. Once in a health crisis, all choices involve some risk, and all reasonable choices involve potential benefit. Collectively, and individually, our task is to shop for the most favorable risk/benefit ratio.

If you are concerned about the recent pause in AstraZeneca COVID vaccine distribution due to a potential link with rare blood clots, or the current (as I write this) pause in the Johnson & Johnson vaccine for much the same reason (yes, these vaccines are compositionally similar, both making use of an adenovirus vector) - you are right to be. 

Any potential risk of vaccination is cause for concern because vaccines are, generally, administered to healthy people to keep them that way. The bar for “concern” is set much lower, and the bar for “safety” much higher, when an intervention is aimed at preventing a calamity, rather than responding to one. To illustrate the contrast, the risks of receiving an intra-aortic balloon pump for cardiogenic shock are massively greater than any potential vaccine risk, but virtually no one declines the procedure on that basis, because the alternative is almost always certain death in short order.

All medical and public health decisions are about shopping for the best risk/benefit ratio among the viable options. The greater the dangers of non-action, the higher the procedure-related risk tolerance ought to be, and generally is. The lesser the dangers of non-action, the more reliably safe and decisively beneficial an intervention needs to be.

Much of the basis for vaccine reticence in general, and specifically as a response to COVID, is because vaccination is preventive. From my point of view, as a Preventive Medicine specialist, that is an attribute of singular merit, in a space we so often neglect. But it certainly does challenge the human brain to embrace the risks of doing something while currently doing fine. In clinical decisions affecting individuals, and in policy decisions affecting populations, we tend to find crisis response an easier call than crisis prevention. So it is that innumerable heart attacks and strokes, along with the occasional pandemic, we are quite capable of preventing are instead given license to plague us.

Concern about vaccine risk is understandable. Surprise about vaccine risk is, however, naïve. Of course there is some non-zero risk involved. Consider that eating involves some risk of lodging an obstruction in your trachea that, absent a prompt Heimlich maneuver, will kill you. In the United States, Statista tells us the odds of dying from choking on food are about 1 in 2500. That is roughly 400 times greater than the possible COVID vaccine risks observed to date. Does that tempt you to renounce eating?

The author's daughter, crossing the NYC Marathon finish line in 2019

Many other illustrations suggest themselves, from driving, to showering, to lightning strikes. We make decisions involving some risk many times, every day, either blithely inattentive to the risk, or because our brains have quietly sized up the risk/benefit ratio and settled on a choice.

All medical options involve some risk; risk avoidance is not realistic. We can all only shop to minimize risk, maximize probable benefit. The context to gauge vaccine risks is the alternative set of risks associated with contracting SARS-CoV-2, and being harmed by it. If every blood clot noted to date is, indeed, a direct result of vaccination and not due in whole or in part to other factors, the observed risk is something like 1 in a million. The risks of dying of COVID in the U.S. are at this point about 2 per 10,000 for the population at large, or 200 times higher than any apparent vaccine risk. The risk of being hit by lightning in any given year, by the way, is about 1 in 500,000 – or twice the apparent vaccine risk to date.

The pandemic numbers are in flux, of course, so these illustrations matter more because of general principles than quantitative particulars. All choices- doing something, or opting out- involve risk. All choices may also involve select benefits. Invite your brain to weigh these fairly on balanced scales.

Some, rare adversities of vaccines are to be expected at the scale of millions when even just eating engenders a much higher risk, to say nothing of taking a shower or crossing a busy street. For much the same reason - scale- the advent of new strains complicating the course of the pandemic are to be expected, too.

The numbers of us infected by SARS-CoV-2 around the globe are far greater than the numbers documented, suggesting a billion or more infected humans. Each of us infected is apt to harbor, for a time, hundreds of millions to billions of viral particles. If we just settle on simple numbers- a billion viral particles in each of a billion people- the resulting number is one you don’t hear mentioned often: a quintillion. It is, roughly, a billion times the total number of humans who have ever lived. It is a number so enormous, our brains really can’t grasp it.

That colossal population of virions is compounded by a generation length measured in days, not decades. Every few days, one batch of a quintillion or so viruses is replaced by a new generation of the same.

The mutations that drive the development of ominous new strains of SARS-CoV-2 are entirely random; the virus cannot think, and is in no way “working” or “scheming” to overcome our native immunity, or high-tech immunizations. But there is a simple law of replication at work: the replicators that happen to replicate best will replicate best. So self-evident as to be insipid, this law is incontrovertible. Whatever versions of a virus replicate themselves most effectively will come to prevail in a population. 

What favors successful viral replication? High rates of transmission above all. The virus may or may not benefit from causing more severe disease, but will always benefit if it can get from one of us to many of us more reliably. The mutations offering this potential advantage, however, may occur in the context of other mutations that are advantageous, disadvantageous, or neutral- to the virus, and to us. A strain that replicates better, eluding the defense of immune system and/or vaccine, and happens to be more virulent, too, is our nemesis.

Cognition and the quality of decision-making are on the human side in this arms race; but quantity very much favors the virus. Imagine that a meaningful mutation happens only in one out of a billion viral particles, a very low rate. Imagine further that only one in a million meaningful mutations confers an advantage on the virus, also a very low rate. Those numbers- a million times a billion- add to a quadrillion. In a population of a quintillion viral particles, there would be a thousand such mutations, rare though they are.

In simplistic terms, (V x T x M) = S, where V is the number of viral particles in circulation at a given time; T is time; M is the mutation rate; and S is the number of differing strains in circulation. (To any mathematicians among you: yes, I know this is a function, not an equivalence, but this is the simplest way to display the concept for all to understand.)

The longer the pandemic goes on, and the more of us infected, the more new strains. The more new strains, the greater the potential for more of us to get infected, and…well, I trust you get the idea. It is decisively in our interest to curtail viral transmission and end the pandemic as expeditiously as possible.

All pandemics end, and this one will, too. Predicting the end of a pandemic is a dubious enterprise, however, because the relevant parameters are in constant flux, the line - always moving. The one best way to predict our pandemic future is to create it. That means sizing up risks and benefits of actions, and inactions, fairly and in context, and making sensible choices for each of us, and all of us, accordingly.