Breathe easy: how respiratory viruses evolve to become milder

The Queen has suffered ‘mild, cold-like symptoms’ from her Covid-19 infection, according to Buckingham Palace. The wording reminds us that, except in the very vulnerable, the common cold is always and everywhere a mild disease. There are 200 kinds of virus that cause colds and they hardly ever debilitate healthy people, let alone kill them. Yet we were recently told by the New and Emerging Respiratory Virus Threats Advisory Group (Nervtag) that ‘it is a common misconception that “viruses mutate to cause less severe disease”’. If that is the case, how did all common colds become mild — and why would Covid not do the same?

As somebody with a background in evolutionary biology, I knew that Nervtag’s claim (which bizarrely cited myxomatosis, a flea-borne disease of rabbits, to support its argument) was misleading. Surely they were aware that, mostly due to the work of Professor Paul Ewald, the dominant belief in evolutionary theory about disease virulence is that it depends on the mode of transmission? Though sometimes lethal at first, respiratory diseases do evolve to become milder, while sexually transmitted, waterborne or insect-borne diseases (such as myxomatosis) don’t.

And ‘evolve’ is the right word, not ‘mutate’. The way medical scientists talk about evolution is sometimes alarmingly naive, as if random mutation is what drives it. No, no, a thousand times no: it’s selection. For example, I took a train this week, putting me at risk of catching Covid from a fellow passenger. But if two other people had been planning to travel on the same train, one with mild omicron and the other with severe delta, the latter would have been more likely to change their mind and stay home because of feeling unwell. That’s selection. The fiercest enemy of a virus is another virus. Omicron ousted delta at least partly because people with mild symptoms were more likely to go to work or parties (or not notice they were ill) than people with severe ones.

There has been an almost obsessive reluctance among public health experts to admit that omicron is intrinsically mild. ‘There is no reason to believe [omicron] is intrinsically less virulent,’ wrote Professor Sunetra Gupta on The Spectator’s website last week, adding: ‘The idea that all viruses evolve in this direction is entirely incorrect.’ Yet the evidence shows it is not just the protective effect of vaccines that have made omicron milder, but the virus’s behaviour too. As one study in Nature concludes: ‘Lower viral pathogenicity and higher population immunity do not have to exclude one another. Most likely both play a part.’

Now it is true that a long time ago evolutionary biologists used to argue, sloppily, that natural selection was about the ‘good of the species’ rather than the individual, so all viruses eventually became mild. The biologist René Dubos said in 1965 that ‘given enough time, a state of peaceful coexistence eventually becomes established between any host and parasite’. But that sort of happy--clappy thinking went out decades ago. Competition drives nastiness in some disease and mildness in others, depending on how they are transmitted.

There are four coronaviruses that cause common colds and all are mild. About half of all colds are caused by rhinoviruses, of which there are around 100 types. None is lethal. That cannot be a coincidence. If mutation can make a disease more dangerous, why have rhinoviruses never turned into killers? As Niall Shanks and Rebecca Pyles put it in a 2007 paper titled ‘Evolution and medicine: the long reach of “Dr Darwin”’: ‘The rhinovirus works its evolutionary mischief by keeping its host mobile — and hence typically in contact with other susceptible persons.’ It achieves this by, for example, staying in the nasal mucosa, and not invading the bloodstream.

By contrast, in the case of an insect-borne disease such as yellow fever, plague or malaria, killing the victim is fine as long as they get bitten first so the disease can spread. Dr Shanks and Dr Pyles wrote: ‘Since malaria is propagated by biting mosquitoes, the parasite pays no penalty for an immobilised host — especially one too weak to swat the insect vector.’ But killing the vector would be a mistake and sure enough, such diseases kill people but not insects. Nor do sexually transmitted diseases such as HIV and syphilis become mild, though they kill very slowly and after a long period of latency: they need to wait until you change partners.

An anomaly is the 1918 flu, which was mild until August 1918, then turned nasty. Professor Ewald thinks this exception proves the rule. In the peculiar conditions of the trenches, severe cases spread faster than mild ones because they were evacuated to field hospitals and home, infecting others along the way, while mild cases stayed put. In other words, nurses and stretcher-bearers behaved like mosquitoes. Hence Professor Ewald is relaxed about the prospect of 1918’s history repeating itself: ‘By failing to investigate the selective processes that favour increased or decreased virulence of virus strains, experts still run the risk of spending too much time and too many resources in attempts to block a 1918-type pandemic.’

Yet here surely there is a worrying lesson about the past two years. In the weird world of lockdown, severe strains of Covid were favoured by selection. If you tested positive but felt fine you were told to stay at home. If you fell badly sick you went to hospital, where you gave your illness to healthcare workers and other patients. So mutants that were more infectious, such as alpha and delta, paid no penalty for being just as virulent, maybe more so. The natural evolution of Covid into just another mild cold was therefore possibly delayed by at least a year.

Of course, the idea that only respiratory viruses evolve to become milder is just a theory and needs to be challenged. The continuing virulence of direct-contact diseases such as measles and smallpox needs explaining, for example. But it is unforgivable for official advisers at Nervtag to be ignorant of the theory. Send for some Darwinians, Boris!