Today’s news from Denmark is worrying. Coronavirus appears to have mutated in farmed mink and re-entered the human population. Thousands of mink are now being culled. Denmark has the largest mink-farming industry in the word. Over 200 people are reported to have been infected with a mink-associated strain of the virus. Among this new crop of infections, one mink-related variant has appeared that hasn’t been seen before. (So reports Matthew Baylis, Oxenhale Chair of veterinary epidemiology at the University of Liverpool, in the Guardian 10 November.)
Viruses replicate during the infection process. Replication is not a perfect process - it makes errors, which show, in our experience, as the way we need to get fresh ‘flu jabs every year, because the viruses we are trying to avoid are never quite the same from year to year. Coronaviruses also mutate in a similar manner to ‘flu, but at a slower rate - probably its only redeeming feature. This could have consequences for our efforts to control the pandemic. The majority of mutations are not damaging to humans, but occasionally a mutated virus will enable greater growth or transmissibility, or will succeed in escaping the human immune system response, which means that there is more of the resultant illness, Covid19, about. This doesn’t always mean that the illness will be more deadly. SARS-CoV-2 (our virus of the moment), has been a nasty little beast for the reason that it can spread without the spreader carrying symptoms, which has made it far more difficult to control. How do you persuade people to take it seriously when they feel perfectly well? The previous SARS virus (Cov-1) was more deadly, but easier to control because it spread only after symptoms developed.
There was a mutation of ‘our’ virus in February of this year, tagged D614G, a mutation which allowed it to transmit more easily from person to person, and led to the first UK lockdown in late March, when it became apparent that the virus was spreading at a worrying rate. Other mutations have been observed since (they look at blood samples from infected people in labs, in case you’re wondering how they know) but none so far that are likely to worsen any of those key elements above of the virus: its ability to replicate, to transmit, to make the disease more severe, or to make it easier to evade the human immune system.
These are the 4 key mutations that we will need to worry about seriously in the future, should they occur. Such mutations are however possible at any time. "The longer the pandemic continues, the more likely it will be that we will see another important mutation arise." (Dr Jeremy Rossman, virologist, University of Kent.)
A second critical issue being kept under observation is that when we start using antiviral therapies and vaccines, these could also have effects leading to mutation. We have to think of this mutation process as being akin to a simple evolutionary mechanism. The virus does what is in its interest. Whatever it achieves in any of the above key ways, aids its survival, and survival (by replication) is the name of its game. The way this works is that the use of, say, a successful antiviral treatment, puts selective pressure on the virus to mutate in the direction of rendering such treatments ineffective. This is the same mechanism that has begun to make anti-biotics less effective than they were. Some vaccines, such as the Oxford vaccine, generate immune responses to the viral spike protein as the main way they work. Mutation might make it harder for the anti-bodies that the vaccine encourages to recognise the virus, and so it could become less effective.
We will see cases where the vaccine is not effective. Anyone who has had the ‘flu vaccine, and still had ‘flu, will understand this. But on the plus side, there are over 300 therapies now in use, such as remdesivir, which we did not have before, to treat people with severe Covid19. And over 200 vaccines are now in development. Worrying mutations may allow us to vary the treatments available, or combine therapies, in order to keep the virus at bay.
But the longer the virus is in circulation, the greater the chance of a new mutation appearing. Which leads me to consider how we can hope to keep people willing to take it seriously, in terms of continued efforts to keep conscious about their behaviour. Consciousness, as many of us have discovered through the pandemic, is not a free gift - it has to be worked for. We have to keep thinking about what we do and where we go and who we meet. And how. Which brings me back to Danish mink.
There is a group of diseases that pass from animals to humans - estimates suggest that as much as 60% of infections can be spread between humans and animals. They include diseases such as measles, once caught from cattle, thousands of years ago but now exclusively human, and Ebola, which periodically passes from bats to humans. There are also food-borne diseases caused by bacteria such as salmonella and campylobacter, that we only get from the consumption of animal products and almost never pass from person to person. Having had a dose of campylobacter a decade ago, probably caught from fish, I can testify how ugly and debilitating it is.
COVID-19, the disease that comes from coronavirus, in the Danish case, spread from animals to humans in the Netherlands, before transmitting from humans back to domesticated animals such as cats. We know the virus multiplies in felines although there is no evidence so far of it spreading from cats to people. We also know that it has transmitted from humans to farmed mink, where it’s suggested it came initially from infected farm workers. A more serious situation has emerged in Denmark, where the virus appears to have mutated in farmed mink and then re-entered the human population. However, this mutation might have led to changes in the sequence of amino acids that make up the virus’s “spike protein.” This is the more worrying type of mutation – it is the type which potentially gives the virus one of the 4 key openings I listed above, the one which allows the virus to evade human immune systems. It could (and I emphasize could) make it more difficult to maintain immunity in people who have already had the virus – which means difficulty in hanging on to the antibodies which their immune system has developed during the process of protecting them. This means they are more open to repeat infection. For similar reasons, some of the vaccines under development could become less effective. The Oxford vaccine however has developed an interesting process which promises to be capable of swift adaptation to meet a new situation.
Various animals have been suggested as intermediaries in this passage back and forth of infections between animals and humans. Some, like ferrets, are often kept in cages alongside mink in the kinds of conditions which breed respiratory infections in humans. The Asian palm civet (a cat-like animal) is another possible source, maybe picking up the virus from bats and transmitting it to humans. Pangolins have been implicated in Sars-Cov-2, as the intermediary between bats and humans.
It seems that the time has come when we have to consider seriously whether such conditions as animal wet and dry markets can be allowed to continue. There is not much of a case for mink farming anyway. Pangolins are an endangered species because of harvesting for their scales. These markets bring with them ill treatment of animals, and serious danger to humans. It is time we thought again about the whole project of bringing animals and humans together in these conditions.