Covid-19: Omicron’s “Weakness”: Luck or Evolutionary “Design”?

Hypothesis: There may be some truth in the old wives’ tale that diseases become milder over time, though perhaps only those caused by respiratory viruses. Unlike previous variants which primarily infected the lungs, the Omicron variant of SARS-CoV-2 mainly affects the upper respiratory tract. Omicron is thus less dangerous to human health and also more infectious, so reproduces more efficiently, outcompeting other strains and thereby “weakening” the virus. Perhaps a similar process has occurred in the past for other respiratory viruses.

There’s an old wive’s tale that diseases weaken over time. This is sometimes justified by statements such as “it doesn’t benefit a virus to kill its host”. This is absolute poppycock, of course – all the virus “cares about” is spreading to new hosts. Whether you die or recover is irrelevant. In fact, attendant spread can occur, when it benefits a disease vector to be more serious, because it can spread to those looking after you, in a healthcare setting, for example. Nevertheless, there does seem to be evidence that respiratory viruses, in particular, do become milder over time and become one of the many diseases we call “colds” – without killing off so many people that only those with natural resistance are susceptible. (Though it would be churlish not to admit that the existence of naive populations, for example in the pre-Columbus Americas, amounts to some counter-evidence). Now, with the Omicron strain, SARS-CoV-2 seems to have weakened. Could there be something in the old wive’s tale after all?

Or is Omicron just an incredible piece of luck?

Omicron causes less serious disease than earlier variants, so is rapidly displacing the previously dominant variant, Delta, around the globe. But the reason why Omicron is more transmissible is also why it is less serious. Multiple groups of researchers, including Ravi Gupta’s team in Cambridge, have determined, in Deenan Pillay’s words, that:

“In essence, it [Omicron] looks to be more able to infect the upper respiratory tract – cells in the throat. So it would multiply in cells there more readily than in cells deep in the lung.”

Deenan Pillay, quoted in the Guardian.

It is a bit of a surprise, at least to me, that a more infectious, less serious variant has arisen. The previous variants, Alpha and Delta, were progressively more serious and more infectious than the original Wuhan strain because (as I understand) they were able to infect the same lung cells more readily and reproduce more rapidly. Not only did this help them to infect people more quickly, it also led to more serious disease, perhaps at least in part because the immune system had less time to respond to an increasing viral load.

Reading the opinions of many epidemiologists (I’m not working in a vacuum here!), I held the view – until late November 2021 that is – that future variants would be descendents of Delta, and that the pandemic, or at least the epidemic in the UK, would end when population immunity to Delta was achieved by vaccination and infection. This immunity would be topped up, I thought, by annual boosters (or better vaccines) and seasonal infections. Covid-19 would fade into the background.

Omicron blew all this out of the water.

But, with hindsight, was this bound to happen? Omicron appears to exploit two conditions which not only give it a selective advantage over previous Covid strains, but also, logically, would seem to apply generically, i.e. to any similar virus.

First, it turns out that different strains of a virus can preferentially infect either lung cells or cells in the airways. Drbeen explains in this Youtube lecture (thanks to John McCone for the recommendation) that Omicron infects cells by a different mechanism than do previous variants, such as Delta, allowing the new strain to thrive in the upper airways. This causes less serious disease, although, unfortunately, Omicron can still infect lung cells by the original mechanism, sometimes fatally.

Because different strains of the same virus have similarities, immunity to one strain confers at least some immunity to the other. That’s why the existing vaccines – developed not even for Delta, remember, but for the original Wuhan strain – work against Omicron, albeit not quite as well as against the original Wuhan strain, Alpha and Delta. And Omicron infection reportedly generates immunity to Delta and other variants.

Second, viruses that infect the upper airways are, all else being equal, more transmissible. Presumably you simply exhale more viral particles from an upper airways infection than from deep down in the lungs.

Because it spreads more easily, Omicron is outcompeting Delta. There is evident selection for this weaker strain of the SARS-CoV-2 virus. Perhaps we could even see strains weaker than Omicron (or weaker variants of Omicron) that are less dangerous to the lungs, but create even more transmissible upper airways infections.

But the property of being able to preferentially cause infection in either the lungs or the upper airways may be shared by many respiratory viruses. Since upper airways infections are both less serious and more easily spread than lung infections, there would in general be selection pressure on such viruses to cause less serious disease.

Could it be that there’s some truth in the old wive’s tale, after all?

At this stage this is a speculative hypothesis, although there may be circumstantial evidence from past pandemics. Real-world experiments are not possible, of course. I’m not sure, for example, that we want to let loose the 2003 SARS-CoV virus, with its ~10% infection fatality rate, to see if it weakens in the same way as SARS-CoV-2 is apparently doing!

A further interesting question is, is it possible that humans (and most likely other species) are adapted through their own evolution to direct the evolution of respiratory viruses to cause less serious disease?! Maybe it’s an evolutionary adaptation for infections of the upper airways to be highly infectious, so that respiratory viruses are evolutionarily driven to be less dangerous. Perhaps there’s a reason there are so many viruses that cause the common cold (the latest estimate I read was 200). After all, it’s slightly odd, when you think about it, that so many similar diseases exist with approximately the same severity.