Mutant and virus are two words that rarely go well together. Reports from the UK that a variant of SARS-CoV-2 has emerged (called lineage B.1.1.7), and may be more readily transmissible, aren’t what we want to hear just before Christmas, or any time.
However, it isn’t necessarily a nightmare scenario. Coronaviruses have relatively low levels of mutation, particularly in comparison with influenza. But they do mutate so variants are expected. They may still be able to be controlled by vaccines in the pipeline.
Proving a selective advantage can be difficult
It can be difficult to establish whether spread of a variant is due to a selective advantage, or due to the fact that people infected with that variant are ignoring public health guidance and spreading it more quickly.
During the northern summer a variant that appeared to emerge in Spain and then quickly spread across Europe. Analysis of genomes and travel patterns indicated that the spread was not due to a selective advantage but because many people had holidayed in Spain and then returned home. Poor screening and containment meant that infections weren’t well controlled.
For over six months there has been a debate about whether a variant (called D614G) with a mutation in the spike protein (which is involved in helping the virus enter cells) was more transmissible. That still hasn’t been fully resolved.
However, looking at patterns of infections in people, using genome sequences, has either not shown evidence of a selective advantage, or it may have an advantage but the evidence isn’t compelling since “the signal is difficult to detect.”
A recent genome analysis identified six strains of SARS-CoV-2. Particular patterns of mutations distinguish the strains, rather than each strain having a unique mutation. One of these, called type VI, has become dominant, making up over 72% of the sequenced genomes. The authors suggest that type VI has a selective advantage, but that they do not know what the advantage may be.
The UK variant possibly arose from persistence in some patients and antigen selection
[Update: header edited to correct potential selection processes]
The new UK variant appears to be more infectious (but not more pathogenic), according to the UK’s Chief Medical Advisor. That evidence hasn’t been published yet, but its very rapid spread (able to be tracked because of good testing and sequencing in the UK) seems to be a key factor in this conclusion.
A preliminary genomic analysis suggests that lineage B.1.1.7 is unusual. It has 14 amino acid replacements, and three deletions, a large number compared to other variants. Eight of the changes are in the spike protein.
This level of mutation may be due, these authors suggest, to treatments involving convalescent plasma resulting in stronger selection pressure on the virus populations due to high concentrations (or greater diversity) of antibodies and to viral persistence in some patients.
The authors hypothesise
“… that the unusual genetic divergence of lineage B.1.1.7 may have resulted, at least in part, from virus evolution with a chronically-infected individual.”
They stress this remains to be proven. Further laboratory analyses are required.
A new South African variant too
Media reports of another new strain emerging in South Africa (called 501.V2) appeared over the weekend as well. This lineage is reported to have “between 10-20 mutations that were not previously seen in viruses from South Africa prior to September.”
South Africa’s Health Minister commented that “… clinicians have been providing anecdotal evidence of a shift in the clinical epidemiological picture, particularly noting that they are seeing a larger proportion of younger patients with no co-morbidities presenting with critical illness.”
The key words to focus on are “anecdotal evidence.”
Update 22 Dec: A pre-print paper on the new South African variant – called 501Y.V2 – describes eight mutations that define this variant, including three in the spike protein receptor-binding domain. It shares a mutation – N501Y – with the new UK strain (and other mu