#16,079
While the UK is currently being dominated, and battered, by the Delta variant there are always concerns over what might come next. Two weeks ago, we looked at the UK's initial risk assessment of the Lambda variant, and today we have a new assessment on the Beta variant, along with an update on Delta.
While it emerged in 2020 in South Africa, roughly at the same time the Alpha variant took hold in the UK, Beta hasn't made the kind of splash that both Alpha and Delta have around the world.
Whatever it lacks in excessive transmissibility, however, is made up for by with its ability to evade naturally acquired immunity from other variants, and reduced vaccine effectiveness. Both qualities that may allow it to be a `sleeper' variant, one that hangs around in the wings until Alpha and Delta lose steam.
Of course, that assumes that another hyper-transmissible variant doesn't emerge in the meantime.
The latest updated risk assessment on Beta follows. Of note, there is some evidence that prior infection with the Delta variant my provide less protection against Beta than other variants.
Some highlights from the above assessment:
Experimental evidence of evasion of naturally acquired immunity
There is laboratory evidence of reduction in neutralisation by convalescent sera, from multiple laboratories. Although this is true regardless of the nature of the first infection, preliminary data suggest the effect may be more pronounced in convalescent sera from Delta infections in unvaccinated individuals (LOW confidence). Systematic comparative data on clinical reinfections would be required to raise the risk to red.
Evidence of decreased vaccine effectiveness
There is robust evidence of reduced neutralisation by sera from vaccinated individuals, across multiple studies and vaccines. The change in neutralisation is greater than for other variants of concern, including Delta. Clinical trial and realworld data support a reduction in vaccine effectiveness against symptomatic infection after two doses, which varies by vaccine (MODERATE confidence). The reduction in vaccine effectiveness is greater for some vaccines than the reduction seen for Delta, but for other vaccines there is equivalent effectiveness for Beta and Delta. There is some evidence that vaccine effectiveness against severe disease is similar to that against Delta, however the data include one study which combines Beta and Gamma, and two studies where the studied population is young and does not reflect the composition of the UK population (LOW confidence for VE against severe disease).
Overall Assessment
There is strong laboratory and real-world evidence that Beta is antigenically different to other common variants. The immune experience of the UK population will be shaped by which variants have circulated and which vaccines have been used. This will determine the population vulnerability to Beta and should be further explored. Whilst Beta does not appear highly fit or transmissible compared to the currently prevalent variants, it has still achieved widespread global transmission and it is currently difficult to predict whether it may display a selective advantage in the changing virological, immunological and human behavioural landscape in the UK.
The revised risk assessment for the Delta variant follows. Of special note is the embedded warning: Distinct clades within Delta are beginning to be identified, predominantly distinguished by changes outside spike of uncertain biological significance. Laboratory investigations have been triggered.
Again, some highlights include:
Transmissibility appears greater than wild type (first wave) virus.
All analyses support increased transmissibility for Delta compared to both wild type virus and Alpha. There is in vitro evidence suggestive of increased replication in biological systems that model human airway, and evidence of optimised furin cleavage. There is epidemiological evidence from secondary attack rates, household transmission studies, and growth rate modelling. The finding of lower CT values in routine testing data, compared to Alpha, may be relevant to the mechanism of increased transmissibility, however there may be multiple contributors.
Increased severity (hospitalisation risk) when compared to Alpha.
There is an apparent increased risk of hospitalisation compared to contemporaneous Alpha cases. Analysis of deaths in England is limited by low numbers but suggests that Delta has at least an equivalent case fatality rate to Alpha (LOW confidence). Further analysis is required of both national surveillance and CO-CIN data to understand the severity and characteristics of disease in hospital.
Evidence of increased reinfections
Pseudovirus and live virus neutralisation using convalescent sera from first wave and Alpha infections shows a reduction in neutralisation. National surveillance analysis, adjusted for different variables including age and vaccination, shows a preliminary signal of increased risk of reinfection with Delta compared to Alpha. Further investigations are being undertaken
Epidemiological and laboratory evidence of reduced vaccine effectiveness
There are analyses from England and Scotland supporting a reduction in vaccine effectiveness for Delta compared to Alpha against symptomatic infection. This is more pronounced after 1 dose. Iterated analysis continues to show vaccine effectiveness against Delta is high after 2 doses. Current evidence suggests that VE against hospitalisation is maintained. Although this is observational data subject to some biases, it holds true across several analytic approaches and the same effect is seen in both English and Scottish data. It is strongly supported by pseudovirus and live virus neutralisation data from multiple laboratories. There are no data on whether vaccine effectiveness against transmission is affected.
Overall Assessment
Delta remains predominant in the UK and the rapid global spread continues. Distinct clades within Delta are beginning to be identified, predominantly distinguished by changes outside spike of uncertain biological significance. Laboratory investigations have been triggered. The changes in this update concern severity and reinfection risk.
Both hospitalisation and deaths analyses now point towards severity that is at least as great as that of Alpha, although there is a high level of uncertainty in these findings. Whilst laboratory data and anecdotal reports have long raised the possibility of an increased risk of reinfection, there is now a signal in the national surveillance data.
The priority investigations are to improve understanding of asymptomatic transmission in the vaccinated, to further investigate the developing diversity within Delta, and continued investigation of the clinical course of disease.
While Delta remains the primary COVID threat in the UK, the United States, Europe, and most of the rest of the world, it will probably be supplanted by another variant - perhaps Beta or Gamma, or by one that isn't on our radar yet - over the next year.
While the next variant could be less severe, we can't really count on that. Regardless, we have Delta, and rising non-Delta respiratory viruses to deal with in the weeks and months ahead.
Good reasons to book your flu shot early this year, to continue to wear facemasks indoors and in crowds, and to get the COVID vaccine if you haven't already.
