UK: Updated Risk Assessment On Delta Variant & Initial Assessment on Lambda

 The UK's Summer Wave Of COVID

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With the UK planning to eliminate all COVID restrictions 10 days from now there are concerns that the recent 15-fold rise in cases since May could double or triple in the weeks ahead. The UK's new Health Secretary, Sajid Javid, was quoted a few days ago stating that the number of new cases could reach 50 to 100 thousand per day this summer. 

The hope, or gamble, is that due to the the uptake of vaccines - particularly among the more elderly and vulnerable population - that most of these new cases will be mild.  

And we have seen a significant reduction in the death rate, even as case counts rise, as the average age of COVID Cases has fallen and more of the adult population becomes vaccinated.  

The rub in all of this are rapidly spread COVID variants - such as Delta, Gamma, and now Lambda - that threaten to reduce the effectiveness of current vaccines, and are feared may produce more severe illness, which could severely impact the NHS,

Making facemasks and all social distancing `optional' now may also invite a return of influenza (and other respiratory viruses) this fall and winter, which could further increase the load on the NHS and complicate the pandemic (see PHE Study: Co-Infection With COVID-19 & Seasonal Influenza).

None of this is to say UK approach can't work, only that there are risks.  Some that we know, and some we probably aren't aware of yet.

In an attempt to try to quantify some those risks, today the UK's PHE released two new risk assessments - the first since late June - including an update on the Delta variant, and their first look at the Lambda variant.

Our first stop is the update on Delta, which comprises more than 95% of all UK cases, and is well on its way to world domination (see CDC Nowcast Estimates Delta Variant Comprises > 50% Of US Cases).

Delta's increased transmissibility is already well established, but the two biggest concerns are increased risk of hospitalization and reduced vaccine effectiveness. The confidence level on evidence on infection severity is low, while the confidence on vaccines is high. 

From the risk assessment (bolding mine):

Increased severity (hospitalisation risk) when compared to Alpha.

Iterated analysis continues to suggest an increased risk of hospitalisation compared to contemporaneous Alpha cases. Analyses using 2 different sources of hospital data (SARIwatch sentinel surveillance and routine hospital episode data) do not yet find any evidence of increased severity once in hospital, in hospital inpatients since Delta became predominant. There is a high level of uncertainty in the estimates for the past 2 months due to data lag and these will be iterated. Data from COCIN (hospitalised patients) are broadly consistent with this, but additional analyses are being undertaken to adjust for age and vaccination status.

Epidemiological and laboratory evidence of reduced vaccine effectiveness

There are now analyses from England and Scotland supporting a reduction in vaccine effectiveness for Delta compared to Alpha against symptomatic infection. This is more pronounced after one 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 to prevent transmission is affected.

Leading to this overall assessment:

Delta is predominant in the UK and there is very rapid global spread. All analyses continue to support increased transmissibility and reduced vaccine effectiveness against symptomatic infection. Whilst risk of hospitalisation appears increased, early data on hospitalised patients does not show indicators of increased severity once in hospital and further analyses are required to resolve this. The priority investigations are to improve understanding of asymptomatic transmission in the vaccinated, to monitor for new mutations occurring on Delta, and continued investigation of the viral kinetics and clinical course of disease.

Ready or not, this formidable foe will likely become the dominant strain globally in the next couple of months, and reign until something more transmissible comes along to replace it. 

In the wings are other variants, including Lambda which has spread widely in South America, and has shown worrisome traits (see PrePrint: Infectivity and Immune Escape of the New SARS-CoV-2 Variant of Interest Lambda).  

Our knowledge of Lambda's potential threat, and its ability to take on Delta, are still quite limited.  For now, Lambda is viewed as a Variant of Interest (VOI) by the WHO (see WHO Adds Lambda VOI (Variant of Interest) To Their Watchlist), with the WHO recently stating:

Lambda has been associated with substantive rates of community transmission in multiple countries, with rising prevalence over time concurrent with increased COVID-19 incidence. The earliest sequenced samples were reported from Peru in August 2020.

(Snip)

It is characterised by mutations in the spike protein, including G75V, T76I, del247/253, L452Q, F490S, D614G and T859N; however, there is currently limited evidence on the full extent of the impact associated with these genomic changes, and further robust studies into the phenotypic impacts are needed to better understand the impact on countermeasures and to control the spread.

Further studies are also required to validate the continued effectiveness of vaccines.

Given the lack of data - and the small number of cases detected in the UK (n=8) -  it is not surprising that the UK's first risk assessment on Lambda is pretty thin, and their confidence level in the evidence is low. 

A few excerpts include:

Transmissibility between humans

Insufficient information Lambda (C.37) appears to have transmitted successfully in South America with some wider spread. There is a single study with some evidence of enhanced ACE2 binding. There is insufficient genomic structured genomic surveillance to understand the contribution of Lambda (C.37) to the high levels of transmission that have been seen in some South American countries. 

Infection severity (Insufficient information)

Vaccines 

Very limited experimental evidence of evasion of vaccine derived immunity There are only 2 pseudovirus studies available (US, Chile). Both find neutralisation by vaccinee sera to be reduced for Lambda compared to viruses from earlier in the pandemic. These are small studies and it is difficult to make any clinical extrapolation from this early data. 

Overall assessment 

Lambda has spread successfully in South America with evidence of some wider global transmission. There is no evidence as yet of a country where it is outcompeting Delta, though careful monitoring of the epidemiology in Chile and Peru is required. There are a small number of cases in the UK which are largely travel associated. Lambda contains a novel combination of mutations and very limited laboratory data are available. The priority studies are pseudovirus and live virus neutralisation with UK vaccinee sera, assessment of growth using in vitro systems and genomic surveillance of those countries where both Lambda (C.37) and Delta are present.

It is against the backdrop of these variants - and very likely others to come - that decisions have to be made on how we deal with the  COVID pandemic going forward. 

There are plenty of economic and societal arguments that can be made for lowering our guard, and returning to `normal', but choosing that direction will have costs - in terms of increased infections, greater pressure on healthcare systems, and likely more deaths -  attached to it. 

How big that cost - and whether we are willing to pay it - have yet to be determined.