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While here in the United States we are monitoring the rise of the BA.2.12.1 Omicron subvariant, other parts of the world are monitoring the recently emerged BA.4 and BA.5 subvariants which first appeared in South Africa.All three are believed to have a transmissibility advantage over BA.2, but their future impact on the pandemic is largely unknown.
While the number of confirmed cases in the UK is still quite low, today the UKHSA has added BA.4 and BA.5 to their watchlist, and has issued their first (incomplete) risk assessment.
COVID-19 variants identified in the UK
Latest updates on SARS-CoV-2 variants detected in the UK.
From:UK Health Security Agency Last updated 6 May 2022
Latest update
The UK Health Security Agency (UKHSA) has released variant technical briefing 41.
This edition includes an update on the current circulating lineages, including several cases of Omicron BA.4 and BA.5 which have been detected in the UK.
UKHSA has also released a variant risk assessment for Omicron BA.4 and BA.5, summarising the emerging epidemiology and laboratory evidence.
As of 2 May 2022, 21 confirmed cases of Omicron BA.4 and 19 confirmed cases of Omicron BA.5 have been detected in England.
Dr Meera Chand, Director of Clinical and Emerging Infections at UKHSA, said:
UKHSA continues to monitor and study variants of SARS-CoV-2 closely and is working with academic partners to rapidly assess the significance of the lineages BA.4 and BA.5.
Our continued genomic surveillance allows us to further investigate variants that are growing within the UK.
Although there is still much we don't know about BA.4 and BA.5, the UKHSA has identified two areas where they believe these variants could pose a greater risk than BA.2.
First:
Evidence of a growth advantage compared to BA.2, in the context of South Africa Available data from South Africa suggests that BA.4 and BA.5 are increasing as a proportion of sequenced cases and based on SGTF may already be predominant. As of 26 April, the reported weekly incidence in South Africa has more than doubled compared to the previous week and test positivity has increased. The provinces with the greatest increases in BA.4 or BA.5 based on sequence data are also those showing the greatest rise in incidence.
This data suggests BA.4 and BA.5 are showing a growth advantage over BA.2 in South Africa. However, it should be noted that South Africa has different background population immunity to the UK and has not experienced a large BA.2 wave. The conditions favouring BA.4 and BA.5 growth in South Africa may not be replicated elsewhere. There is evidence of international spread including small numbers of cases in the UK and Europe (note differences in testing and sequencing across countries). There is no other country where BA.4 and BA.5 are showing a clear growth advantage as yet.
Secondly:
There is evidence of some antigenic change compared to BA.2 based on structural modelling and pseudovirus neutralisation data BA.4 and BA.5 are most closely related to BA.2. Structural modelling indicates there is likely to be antigenic change related to L452R (found in Delta) and F486V (a more radical version of the F486L found in some mink adapted viruses), both of which may affect the binding of neutralising antibodies. In addition, the differences between BA.2 and BA.4 and BA.5 at position 493 may have some effect, as well as the 2- residue deletion in the N-terminal domain in BA.4 and BA.5 compared to BA.2.
In preliminary unpublished pseudovirus data from one laboratory there is a reduction in neutralising activity of vaccinee sera (including vaccinees who have also had BA.1) for BA.4 compared to BA.2. In a second laboratory, sera from BA.1 infected animals neutralised BA.4 poorly but sera from BA.2 infected animals did not show the same reduction in neutralisation. These findings support the modelled predictions of a degree of antigenic change. There is no data for vaccinees who have also had Delta or BA.2, both of which profiles are relevant in the UK context and require additional assessment.
At this point it is too soon to speculate which variant will become the next king of the viral hill. The takeaway, however, is that the SARS-CoV-2 virus continues to reinvent itself, and more variants are undoubtedly on their way.
