COVID Variants – Time to Stop Jumping at Shadows

Former UK Prime Minister Theresa May spoke truth to power in the House of Commons last month. The Government, she said, was not leveling with the British people about three things:

• We were not going to eliminate or eradicate COVID-19. There would never be a time when there would never be a case of this infection somewhere in the UK.
• Variants would keep on coming. If we waited until there were no new variants, we would never open our doors or our borders again.
• Sadly, people would continue to die from COVID, much as they do from influenza or other human respiratory viruses – perhaps 10-20,000 every year.

The former prime minister was saying nothing that has not been said for months by the chief medical officer, the chief scientific adviser and many other leading scientists. Today, we are seeing the Government’s acknowledgement.

The present wave of mild infections is what endemic COVID looks like in a vaccinated population. Similar waves will continue to sweep through from time to time. We will get better vaccines and better therapies but we are already preventing most serious illness and death.

We no longer need any intervention that we would not have considered desirable in November 2019 to control other seasonal respiratory viruses. All that a further delay would achieve is to give a few more vaccine doses to people who are at intrinsically low risk anyway. If not on 19 July, then when? There will always be arguments for further delay.

How did 19 July come to be set as Liberation Day? This date was delayed from 21 June to allow for more time to evaluate the impact of the delta variant. Many of us thought this was unnecessary but went along with it because of the firm commitment to an end date, even if that came with small print. Now it is about to happen and some people are very angry. Why?

What is the real threat from the delta variant? It seems to be more transmissible – which means that more people can get infected. But this does not mean that people get seriously ill or die in the numbers we saw in January. The increase in hospital admissions does not match the increase in cases. We have to look behind the numbers and ask what they mean.

Clinicians and NHS leaders are saying publicly that the people now coming into hospital are rarely desperately ill: they need access to oxygen and dexamethasone for a few days and then they go home again. The most vulnerable groups are not in hospital because they have been fully vaccinated. The NHS is not panicking about overload, although concerned about a possible slowing in clearing the backlog of cases in some areas. If Liberation Day is delayed, this will not be because the NHS leadership has called for it.

Who wants delay? There are still people who are seeking to eliminate COVID. Some actively want to reconstruct society so that our everyday lives are completely organized around the avoidance of infection. They want us to walk in fear every time we set foot outside our homes and to be timid about all human contacts inside them. We may live longer but utterly impoverished lives, in every sense of the word. And we will still all die sometime. Others are genuinely well-meaning but not trained to think through the implications of their actions. If you only have a narrow scientific or medical education, it is easy to focus on the details and lose sight of the bigger picture. Your good intentions are absorbed by those with a more explicit political agenda.

We can see this with the issue of variants. The details of the virus are a fascinating topic for immunologists, virologists and geneticists. This is exciting science with all sorts of opportunities for interesting, important and well-funded research. But does any of it matter on the grand scale. If there is a potential worst case variant, how likely it is to occur? Are we being asked to jump at shadows?

Viruses are inherently unstable. Cellular organisms, which include humans, reproduce through DNA, which has a lot of error-checking built in. This is why a lot of human pregnancies end without a woman ever knowing she was pregnant. Something goes wrong in the development of the fertilized egg and it is expelled as a heavy period. It is estimated that at least a quarter of all pregnancies end this way.

Viruses reproduce through RNA, which has relatively few error-checking mechanisms. This varies a bit. COVID has more error-checking than influenza, for example, which makes it a little more stable. Nevertheless, this means there is a potential for variation every time a virus makes a copy of itself and reproduces. Variants are normal.

Now think how many times the COVID virus has reproduced since it crossed into humans. This is not the number of infected humans but the number of human cells that it has hi-jacked. The number is in unimaginable trillions. Think of the stars in the night sky or the grains of sand on your favorite beach. Out of all these events, just four variants of concern have emerged. They are closely clustered around the same small set of genes in a particular area of the spike that the virus uses to enter human cells.

This area forms part of the target for the current vaccines. They prime the human immune system to recognize the spike. If a variant changes the spike, the immune system may not recognize it as easily.

The immune system is quite complex but the basics are straightforward. When the immune system encounters an intruder, like a virus, the first response is to send antibodies to block it from reproducing. If antibodies were there all the time, though, your blood would be like tomato ketchup, too thick to flow and do its normal job. There are, then, specialist cells that remember viruses and make antibodies when they need to. A third kind of cell is also produced which is more of a hunter-killer and actively destroys the virus rather than just blocking it. The speed with which the system works is affected by age and general health.

What is happening now is that people who have been vaccinated are meeting the virus and responding quickly to contain it. Younger people have a faster and stronger response, even if they have not been vaccinated, which is why their risks are lower anyway. Even if the variant is only a partial match for the vaccine, your immune system is on the case.

If you are a lab scientist, variation is fascinating. You can imagine all sorts of possibilities for wider genetic changes. Worst case scenarios are especially exciting. For pandemic management, though, we need to be more realistic. What is the actual likelihood of a variant changing the spike so much that it beats the vaccines? The fact that we have not yet seen this happen does not mean that it could never happen. But it is a strong indication that any variant that changes the spike too much cannot survive because the modified spike cannot do its job of getting into a cell to infect it. Evolution, natural selection, weeds these extreme variants out.

When variant forms of COVID appear, we must, then, learn not to jump at shadows. No-one can ever say there will never be a risk – but everyday life is full of much more common risks that we tolerate because of the benefits that they deliver. We could resign ourselves to a risk-averse world, as the remaining, and increasingly shrill, enthusiasts for an elimination strategy would like or we could vote with our feet. We could assert our right to mingle, to embrace, to crowd together. If some are more risk-averse than others, let them be – but do not let them force postponement of Liberation Day.