6 January 2021

The truth about the new Covid-19 variants

How coronavirus mutations could imperil the vaccine rollout.

We have lost control. Just when we thought there was cause for hope in the Covid-19 vaccines, we hit a wall. On 5 January, a full national lockdown was reimposed. The vaccines, even once they had been proved to be safe and efficacious, had little chance of impacting the virus this winter. Production, distribution and application to all of those in need of it in such a short time was not feasible.

Although a return to normality by the spring this year appeared possible, an inexorable rise in infections throughout the autumn indicated a worrying new trend. By mid-December the reason was clear.

A new variant of Sars-CoV-2, with enhanced infectivity, had appeared in the UK. The variant, named “VUI – 202012/01” (the first Variant Under Investigation in December 2020) or lineage B117, was first isolated in Kent on 20 September. By mid-December nearly two thirds of all cases in London were caused by this new variant. It is now spreading across the country and around the world.

The relative rate of appearance of the new variant suggests it is between 50 and 70 per cent more transmissible than earlier versions of the virus. The new variant means that children might be better able to transmit the virus. Another strain from South Africa (501.v2) with enhanced transmissibility has also been detected in the UK.

[see also: How the mutant strain took hold]

There is no evidence to suggest that these new variants cause worse disease, or higher mortality – viruses often evolve to become less virulent but more contagious because of their increased ability to transmit. But increased transmission is destructive nonetheless: more infections more quickly, more ill people, more deaths. The NHS is running out of bed space in intensive care units. Even the Nightingale hospitals, hastily assembled in the spring and summer of 2020 in anticipation of surging cases, will not prevent the health services reaching a point where doctors may need to choose who receives life-saving treatment and who does not.

In mid-December, there were about 20,000 to 30,000 reported cases each day, which is now translating into around 500 deaths every 24 hours. Today, the number of cases is about 55,000 to 60,000 a day, which means that more than 1,000 people will be dying every day by late January. This is as bad as the worst period of April last year.

Will the vaccines help? Perhaps. But there is need for caution. The mutations – changes in genome sequence – are within the gene that produces the spike (S) protein. It is the S protein that enables the virus to bind to receptors (primarily the ACE2 receptor) on our cells before entering and hijacking the cell’s machinery to replicate and create new copies of itself.

Mutation is normal. It is the basis of the evolution of all life forms. Many mutations are detrimental to the virus and so disappear quickly. Others are neutral and neither enhance nor diminish viral fitness. But on rare occasions, a mutation can improve viral fitness. When this happens, as with the new variants of coronavirus now detected in the UK, the virus becomes more transmissible.

The viral genome encodes the proteins that create the virus – mutations change that structure. The proteins are composed of strings of chemicals called amino acids. In the new variants, one of the amino acids latches on to the part of the protein, binds more tightly to the ACE2 receptor and initiates infection. Scientists are still trying to determine the reasons for increased transmission.

The two branches of protective immunity – antibodies and T-cell responses – hit multiple sites along the S protein. So people vaccinated with the original S protein are still protected from the new variants. But the South African variant has undergone significant changes from the original Wuhan coronavirus, losing more of the sites against which current vaccine immunity is raised. This is why scientists and medical experts are now so concerned. There is also the fear that S-protein-based vaccine use will force the virus to mutate again, evade existing immunological effectors and propagate further.

These so-called vaccine-escape variants are possible. New vaccine technologies developed for Covid-19 enable us to alter the vaccine S protein sequences almost as quickly as mutants emerge. The flu virus mutates more readily than coronavirus, which is why we produce new versions of the flu vaccine every year. Amending the vaccines may be relatively straightforward, but testing them and repeating the logistical challenge of population-scale injection will be difficult. Other vaccine designs, such as the Chinese CoronaVac or the Scottish-manufactured Valneva vaccine, which use whole killed-virus particles, produce a greater variety of immunological responses, and offer an attractive alternative route to mass vaccination. The launch of both vaccines is expected in 2021. Those infected with the virus itself will also have more robust immunity because of the additional viral antigens to which they were exposed.

The decision at the beginning of January to delay the time between administering the two doses of the vaccine has received a mixed response. It seems a single shot is “good enough” in protecting people. Maximising the number of people with some protection as quickly as possible with limited vaccine stocks makes some sense. But a vaccine that is “good enough” against the virus for which it was designed might be less effective against new variants. These could survive, propagate and mutate further. This is all conjecture, but with lives at stake, this recent logistical decision over vaccine administration was needed fast.

The new coronavirus variants are cause for alarm. Their enhanced contagiousness has confounded efforts to contain Covid-19. If they are the first in a series of viruses mutating away from the structure of those used in the first-generation vaccines then our hoped-for conquest of Covid-19 remains more distant than we thought.