CDE News – Over the last few weeks, the United Kingdom (UK) has faced a rapid increase in COVID-19 cases in South East England, leading to enhanced epidemiological and virological investigations. Analysis of viral genome sequence data identified a large proportion of cases belonged to a new single phylogenetic cluster.
The ECDC said that the new variant is defined by multiple spike protein mutations present as well as mutations in other genomic regions. The ECDC said that while it is known and expected that viruses constantly change through mutation leading to the emergence of new variants, preliminary analysis in the UK suggests that this variant is significantly more transmissible than previously circulating variants, with an estimated potential to increase the reproductive number (R) by 0.4 or greater with an estimated increased transmissibility of up to 70%.
This new variant has emerged at a time of the year when there has traditionally been increased family and social mixing.
There is no indication at this point of increased infection severity associated with the new variant. A few cases with the new variant have to date been reported by Denmark and the Netherlands and, according to media reports, in Belgium.
Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom
Preliminary modelling results communicated by the UK on 19 December suggest that the variant is significantly more transmissible than previously circulating variants, with an estimated increase in reproductive number (R) by 0.4 or greater with an estimated increased transmissibility of up to 70% .
Further epidemiological and virological investigations are needed to further quantify the increase in transmissibility and to understand the biological mechanism behind the increase. Any increased transmissibility would increase the likelihood of spread, particularly if increased family and social mixing that is traditional at this time of the year is not reduced, and further spread outside the UK, especially if non-essential travel is not reduced or avoided altogether, could eventually lead to the variant replacing currently circulating variants in much of the EU/EEA.
The ECDC said given that there is currently a lack of evidence to indicate the extent to which the new virus variant is spread outside the UK, timely efforts to prevent and control its spread are needed, and include the following:
- Public health authorities and laboratories are urged to analyse and sequence virus isolates in a timely manner to identify cases of the new variant. People with an epidemiological link to cases with the new variant or travel history to areas known to be affected should be identified immediately to test, isolate and follow up their contacts in order to stop the spread of the new variant.
- If cases infected with this new SARS-CoV-2 variant or other new SARS-CoV-2 variants of potential concern are identified, countries should notify through the Early Warning and Response System of the European Union.
- The importance of strict adherence to non-pharmaceutical interventions according to national policies needs to be communicated to the public, and in particular guidance on the avoidance of non-essential travel and social activities should be stressed.
- Laboratories should review the PCR performance and drop-out of the S-gene. PCR could be used as an indicator for cases with the new variant for further sequencing and investigation.
- Suspected cases of COVID-19 reinfection should be followed up, closely accompanied by sequencing respective virus isolates from these cases. Similarly, cases with treatment failures using convalescent plasma or monoclonal antibodies should be further studied.
- With the implementation of vaccination, close monitoring of COVID-19-vaccinated individuals needs to be ensured to identify possible vaccination failure and breakthrough infections. Virus isolates from these cases should be sequenced and characterised genetically and antigenically.
The unusually high number of spike protein mutations, other genomic properties of the variant, and the high sequencing coverage in the UK suggest that the variant has not emerged through gradual accumulation of mutations in the UK. It is also unlikely that the variant could have arisen through selection pressure from ongoing vaccination programmes as the observed increase does not match the timing of such activities.
Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom
Viruses constantly change through mutation and the emergence of a new variant is an expected occurrence and not in itself a cause for concern. A diversification of SARS-CoV-2 due to evolution and adaptation processes has been observed globally and is expected to occur with ongoing transmission of viruses in general and particularly for RNA viruses.
One possible explanation for the emergence of the variant is prolonged SARS-CoV-2 infection in a single patient, potentially with reduced immunocompetence, similar to what has previously been described [17,18]. Such prolonged infection can lead to accumulation of immune escape mutations at an elevated rate.
Another possible explanation could be adaptation processes in a virus that occur in a different susceptible animal species and is then transmitted back to humans from the animal hosts. This led to the emergence of a variant with multiple spike protein mutations in Denmark during transmission among mink.
Several different spike protein mutations associated with mink have also been described in the Netherlands. The UK has reported to ECDC and the WHO Regional Office for Europe that there is no clear epidemiological link to animals for VUI 202012/01, so this explanation is less likely for this variant.
Lastly, it is also possible that the variant has emerged through circulation in countries with no or very low sequencing coverage. This hypothesis is less plausible, however, as random mutations acquired during circulation of the virus would not explain the unusually high proportion of spike protein mutations, and undetected circulation for a long enough time for the high number of mutations to accumulate (around 10 months according to current molecular clock estimates) is also not very likely due to global travel patterns.
Full Threat Assessment via ECDC
