Just when we thought there was cause for hope in the Covid-19 vaccines, we’ve hit a wall. Christmas is off and we might all be locked down for months longer. In reality, the vaccines, even once 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 in such a short timeframe was never feasible.
However, an increasing drift towards some sort of normality by the spring appeared possible. The UK government’s decision to introduce tier four lockdown restrictions across London and much of the south east, and the travel bans imposed on UK citizens by other countries have created chaos. What prompted such action?
The answer is a new variant of Sars-CoV-2, thought to have enhanced infectivity. Retrospective analysis traced the first identitified case of the variant, named “VUI – 202012/01” (the first Variant Under Investigation in December 2020), to Kent on 20 September. By mid November, around a quarter of all cases in London were caused by the new variant and by mid December nearly two thirds were. Modelling of the relative rate of appearance of the new variant has indicated it might be 70 per cent more transmissible than earlier versions of the virus, although this has yet to be demonstrated directly. One alarming suggestion, from researchers at Imperial College London, hints that children might be more vulnerable to infection with the new variant. If this proves correct, the ramifications are serious both for increased transmission and for potential school closures.
Older versions of the virus were clearly being displaced by this new one, implying enhanced transmission. But evidence that it might also cause worse disease, and a higher mortality rate, has not yet emerged. In fact, viruses often evolve to become less virulent but more contagious because that increases their overall ability to transmit. However, a virus that replicates more quickly will reach higher numbers faster and some individuals, who would normally mount an adequate immune response, might now struggle if their immune response lags behind.
Data on disease severity should be available already. The national consortium of laboratories sequencing viral isolates picked up in the testing programme can pinpoint its distribution. If the clinical picture also points to increasing hospitalisations and deaths where the new variant is most prevalent, we can infer the worst. Minimising spread seems sensible. But the virus has been circulating for at least three months already, so there is little chance of halting its transmission now.
Will the vaccine deal with the crisis? Perhaps, and the current vaccines will work against this new variant. But we need to be cautious. The mutation in the new strain that is attracting most attention is within 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 then entering and hijacking the cell’s machinery to replicate and create many new copies of itself. The Sars-CoV-2 coronavirus has been mutating constantly since its first appearance. Such mutation is normal. It is the basis of the evolution of all life forms. Changes occur at random as errors creep in while the genome is copied. Many mutations are detrimental and thus lost quickly. Others are neutral, neither enhancing nor diminishing viral fitness. On rare occasions, however, a change can improve viral fitness. When these happen, as with the novel variant, the virus transmits more readily.
The viral genome encodes the proteins that create the virus itself and mutations lead to changes in that structure. The proteins themselves are made up of strings of little chemicals called amino acids. One of the amino acid changes in the new virus sits in precisely the part of the protein that binds to ACE2, allowing it to bind tighter. Other mutations are appearing in the S protein too. It is the original S protein, the one found in the ancestral virus from Wuhan, that comprises all of the vaccines currently licensed, and most others in development.
There is no great cause for fear as antibodies and T-cell responses, the two branches of protective immunity, hit multiple sites along the S protein, so the new variant is still recognised by immune effectors in vaccinated people. However, as the vaccine is used more widely, the virus will be under increasing pressure as it enters hosts equipped with destructive antibodies. Only viruses with mutations that enable them to evade such antibodies will survive. As these survivors propagate, new mutations will appear, each new S protein resembling the original version less.
These vaccine-evasive variants are indeed possible, although the likelihood of their emergence is not yet clear. That the S protein must retain the ability to bind ACE2 constrains the number of mutations possible. Moreover, the remarkable scientific advances achieved during the pandemic mean that, in principle, we can alter the S proteins added to the vaccine almost as quickly as they emerge.
The flu virus has a far greater capacity to mutate than Covid-19 and it is for this reason that we produce new versions of the flu vaccine each year. It is relatively straightforward to amend the sequence of the vaccines we have now created, although some degree of safety and efficacy testing will be needed on each occasion.
In short, the new variant, with its increased contagiousness, is cause for alarm. If it turns out to be more virulent too, so much the worse. If it is the first step towards a series of viruses drifting away from the structure of those used in generating vaccines, this is worse still.
We must keep testing to detect the viruses and sequencing to trace the mutation problem. But we also need to redouble our efforts in other areas too. Drugs that target parts of the virus beyond the S protein, for example, are needed more urgently than ever. A clear and robust test-and-trace system, supported by enforced isolation, is as critical as ever, too.
The UK has been at the forefront of scientific efforts to combat coronavirus. But ultimately, whether countries have dealt successfully with Covid-19 has been dependent on political intervention – where Britain has fared rather less well.