Does a virus that spreads more rapidly have less chance to evolve?

Question

Now that the COVID-19 pandemic has been going on for a while, there are reports of many new variants, which have presumably arisen in the past year through mutation and spread through natural selection.

I'll assume that the outcomes of COVID-19 infection are either death or a successful immuse , others would have developed antibodies. Suppose for the purposes of discussion that those are the two end consequences (or correct my answer in your thinking.)

If eighteen months ago, everyone in the planet had been infected with COVID-19 in one very bad day, then many people would die, and the others would end up with antibodies. That might stop the spread of the disease, which would stop its evolution. (Feel free to address Typhoid Mary-like scenarios in the answer; or of course any misconceptions in this paragraph.)

Is there a perspective from which—or set of circumstances under which—drawing out a pandemic can actually worsen the effect of a disease by giving it more chance to evolve?

(I've put the question in terms of COVID-19, but I think it's really a generally question, no less applicable to COVID-20 and above. :-) Please feel free to answer in general terms. I am not looking for a discussion about what public health measures may or not be appropriate to the current pandemic.)

Answer 1

Any evolutionary process has two components to it:

• generation of genetic diversity in a population, and
• shifts in the distribution of genetic variants under selective pressure.

For a virus like SARS-CoV-2, every infection results in a vast amount of replication, some of which will be variants generated through imperfect replication. Thus, the more rapidly a virus is spreading, the more opportunity it has to generate genetic diversity. Conversely, if there's not many infections going on, then there won't be much evolution because there won't be much diversity generation.

With regards to selection, the more actions that we take against the virus (e.g., mask wearing, social distancing, vaccination), the more selective pressure that it is under, since these actions differentiate between strains that are more or less effective in evading them. If the pressure goes too high, however, this breaks down. With highly effective countermeasures (e.g., rapid vaccine distribution while not letting our guard down), then there won't be much evolution because most variants won't have an opportunity to infect any new host: each new generation of infections will be driven more by countermeasure failures unrelated to viral efficacy, and thus there will actually be little effective selection.

The highest opportunity for evolutionary change, then, is with poorly coordinated countermeasures. This produces an intermediate rate of spreading, with both much viral replication and many opportunities for selective pressure on infections. It's really much the same as the problem with stopping a course of antibiotics prematurely, only on a societal rather than individual scale.

Bottom line: countermeasures are still a good idea, even when potential evolution of variants is included. People and governments that don't take the problem seriously, however, are threats to all the rest of us.

Answer 2

RNA viruses, like SARS-CoV-2, influenza, HIV, etc all have high mutation rates caused by an error-prone RNA replicating protein (known as an RNA dependent RNA polymerase or RdRP) that they use to reproduce their RNA genetic component. The error rates are high enough in these viruses that you can say that the virus exists not as a single species, but as something known as a quasi-species, which you can visualize as a cloud of individual virions, each with genetic variants from the "original" genome, some of which will be more "fit" than others in terms of evolution. These more fit ones are the variants that you see being talked about in the news. Note that the error rate of the RdRP is in terms of base changes per 1000 bases per 1 replication cycle, and the number is usually around 3-4.

The fitness of a virus is not necessarily related to any one variant, often a number of seemingly unrelated mutations in several proteins are required to make it fitter in any of the following characteristics:

• Evading immune response
• transmission
• Invasion of the host/infectivity
• viral titre (how many viral particles are produced)
• replication rate
• host-range (what species it can infect)
• Tissues it can infect

Often, being better at one of these features means that it does poorly in others. A fine example of this is the H5N1 influenza that raged across the world a few years ago - it was great at killing people and even better at killing birds (it is an avian virus), but it was terrible at actually infecting people, it just couldn't sustain transmission in humans and even those exposed on a regular basis (i.e. working with chickens in endemic virus areas) didn't often get infected, even if they seroconverted.

SARS-CoV-2 has hit a pretty sweet-spot, it can transmit really well, it is highly infectious, has a fairly broad host-range, and has a long lag-time (~2 weeks) before people know they are infected, and some never do show symptoms. On the other hand, in some people it isn't at all great at evading the immune system, it actually seems to potentiate it, causing something known as a cytokine storm, where the immune system goes into hyperdrive and causes serious inflammation. This is what actually kills people - the swelling of their airways in response to the infection limits oxygen transport and slowly suffocates them.

Now, you talked about antibodies: Antibodies are not the be-all and end-all like they are often considered. An antibody response to an infection does not necessarily mean that you can not get an infection from it again, it simply means that the infection is minimized to some extent. The extent of the protection is highly dependent on the individual (i.e. your response will be different to mine), and on the organism with which you are infected. If you had say Smallpox and survived, you (and I too, if infected) would likely have a life-long immunity to smallpox. However, have an infection with a different pox virus, such as Orf virus, and you might only be protected for 6 months.

You, yourself (assuming you are >10 years old) and everyone around you is likely to have antibodies against at least 1 of the influenza viruses, but this won't stop you from getting sick from them again, it might however limit your infection so that you don't feel so bad for as long (and can then spread it more effectively...). So you have antibodies, but they don't eliminate the flu, and as a consequence we have a vaccine against influenza. Now the vaccine also doesn't cause complete protection, but that's beside the point. The reason you need to get an influenza vaccine each year is because the viruses have mutated over that year so that they are no longer the same as the previous year's flu viruses, so your body doesn't fully protect against the new viruses.

In the case of the SARS-CoV-2 vaccines being distributed currently world-wide. If you have been following the data, even in a fairly superficial manner, you will have seen something like "the Pfizer vaccine has a 95% protection rate" this means that it protects against 95% of illness from SARS-CoV-2 (i.e. symptomatic infection and actual infection in 95% of people). However, you might have also heard about people being concerned that there is less protection against the "South African" variant. This is an example of evolution causing an escape mutant. Evolutionary pressure has been applied to the virus, and it has produced a means to get around that pressure, to some extent. This will be an on-going process in terms of SARS-CoV-2; we will need new vaccines regularly to cope with the new variants as they arise.

TLDR: the virus will evolve anyway, the evolution happens in as little as a single cycle of virus replication.