The new variant: a note on the evidence

Boris Johnson introduced a third lockdown last night after an assessment by Britain’s four chief medical officers that the NHS wouldn’t be able to cope within three weeks on present trends. ‘Cases are rising almost everywhere, in much of the country driven by the new, more transmissible, variant,’ the medical officers said in a statement. With Covid caseloads clearly rising in hospitals nationwide, the grounds for action are pretty clear. But how sure can we be that the new variant is to blame? 

One question seems to be asked again and again: if the new Covid variant is much more transmissible, why isn’t it rising everywhere? Why just in London and the South East? Why lock down the rest of the country if there’s no sign of hospitals being inundated or things out of control in the rest of England? There are two answers to that: one technical, one more straightforward.

Let’s start with the easy one: yes, the virus is on the rise nationwide. The below graph shows Covid in the most important age groups, the over-60s:

But those trying to understand the data — and what it does and doesn’t tell us about the new variant — may be interested in the below technical explanation.

Let’s go back to the Saturday press conference announcing Tier 4 on 19 December. Sir Patrick Vallance presented the below graph about the new variant to illustrate its growth. It cites ‘ONS data’ to the effect that the new strain accounted for 62 per cent of the cases in London — after having been as low as 28 per cent on 18 November. The areas shown are London, the South East and the East of England.

The ONS has not been tracking the new variant per se. It tracks positive Covid cases with only two of the three marker genes: ‘ORF1ab and N genes’. Normal PCR testing looks for these two and also another one: S protein. But for weeks, the ONS has been tracking Covid cases which tested negative for the spike protein. The technical term for this is S-gene target failure (SGTF) — but for simplicity, let’s call it S-negative.

This lack of S-gene signal is not because the virus lacks spike protein. It is because the new virus has mutations which means that the PCR test does not pick it up the spike protein gene. But not all S-negative variants are the new, highly transmissible strain. The problem here is that PHE regarded the S-negative tests as reliable markers of Covid from the middle of November. But other versions of the virus are also S-negative. As the ONS puts it:

“This means the S-gene is no longer detected in the current test, and cases that would have previously been positive on all three genes are now positive only on the ORF1ab and the N-gene (not the S-gene).

At the beginning of November, fewer than two thirds of the S-negative results accounted for the new, more transmissible strain. As it has become more numerically dominant, however, the proportion of tests accurately reporting this variant of concern has increased to around 98 per cent.

PHE worked out early on that the new variant always tested S-gene negative. So its advice was that, from 18 November, the S-negative Covid tests should be considered as indicative of the new strain.

In December PHE advised the ONS of a methodology change: from 18 November the S-gene negative Covid cases would be categorised as a new variant. That’s what led to the above chart. But if you track down the ONS study (here) you end up with S-negative Covid cases abundant everywhere; making up half of all Covid cases in Northern Ireland — where there was no surge. So does that mean the new virus was everywhere?

Not all S-negative tests are the new variant

This is where we may be looking at a case of mistaken identity. The ONS says the S-gene negative tests are ‘compatible with’ the new variant but there are (and have been) other explanations for it. As the ONS states: ‘There are also other reasons why a swab may be positive for only these two genes, including lower viral load in the sample, which is why we have always seen a small percentage of this type of positive result.’

It could be that Britain is not the first country with the new variant, but simply the first to discover it. We have a genuinely world-beating ability to check every single letter of code in anything with genetic material, including viruses. We send one in every ten new diagnoses to be examined in this manner — and it is a far more accurate way of properly characterising viruses than the simple PCR test. And yes, this kind of monitoring is also far more costly in time and resources — which is why analysis of every isolate is not carried out.

But crucially, data from these genome studies show that the new variant genuinely is increasing in every region of England: the grounds for concern, which have led to the new lockdown, are absolutely not based on a misreading of ONS data. There are tangible biological differences which make the new strain more likely to be more infectious. We know that one of the mutations carried by the new strain renders the spike protein more adhesive to its target on our cells — a process which is essential for the establishment of an infection. We know that this mutation, on its own, also makes the virus more infectious in mice. And we must not overlook the growing body of evidence demonstrating that people infected with the strain produce greater quantities of virus particles and presumably, therefore, infect more people. That is why the government felt there was no other option than to enforce another lockdown to minimise our contact with one another.