COVID-19: the spread of the mutated coronavirus strain in Britain is on average 56% more contagious than the original version

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A mutated coronavirus strain spreading in Britain is on average 56 percent more contagious than the original version, scientists have warned in a study, urging a fast vaccine rollout to help prevent more deaths.

The new variant, which emerged in southeast England in November and is spreading fast, is likely to boost hospitalisations and deaths from COVID next year, according to the study published Wednesday by the Centre for Mathematical Modelling of Infectious Diseases at the London School of Hygiene and Tropical Medicine.

Researchers, focusing on the English south east, east and London, said it was still uncertain whether the mutated strain was more or less deadly than its predecessor.

“Nevertheless, the increase in transmissibility is likely to lead to a large increase in incidence, with COVID-19 hospitalisations and deaths projected to reach higher levels in 2021 than were observed in 2020, even if regional tiered restrictions implemented before 19 December are maintained,” they said.

The authors warned that a national lockdown imposed in England in November was unlikely to prevent an increase of infections “unless primary schools, secondary schools, and universities are also closed”.

Any easing of control measures, meanwhile, would likely prompt “a large resurgence of the virus”.

This meant that “it may be necessary to greatly accelerate vaccine roll-out to have an appreciable impact in suppressing the resulting disease burden”.

In announcing more stringent lockdown measures over the Christmas holiday, British Prime Minister Boris Johnson said on Saturday the new viral strain “may be up to 70 percent more transmissible than the original version of the disease”.

The discovery of the new strain set off alarm bells worldwide just as more countries began vaccination campaigns to halt a pandemic that has claimed more than 1.7 million lives since it emerged a year ago in China.

Many countries quickly imposed bans on travel from Britain, but EU governments have since begun to relax the restrictions.

The co-founder of BioNTech – one of the firms behind the vaccine that is being rolled out worldwide this week – has said its drug is “highly likely” to work against the mutated strain detected in Britain and otherwise can be adapted in six weeks.


Over the last few weeks, the UK has faced a rapid increase in COVID-19 cases (Figures 1 and 2, Annex Figures 5 and 6). This increase was pronounced in South East England, with an increase in the 14-day case notification rate from 100 cases per 100 000 population in week 41/2020 to over 400 per 100 000 in week 50/2020 (Fig. 1 and Annex Fig. 6).

This increase led to an enhanced epidemiological and virological investigation. Analysis using viral genome sequence data identified a large proportion (>50%) of cases belonged to a new single phylogenetic cluster [1]. This variant is referred to in the UK as SARS-CoV-2 VUI 202012/01 (Variant Under Investigation, year 2020, month 12, variant 01).

Overall, around 5 to 10% of all COVID-19 cases are regularly sequenced in the UK, with a sequencing coverage in Kent, the part of South East England that was most affected, of around 4%. As of 13 December 2020, 1 108 individuals had been identified with this virus variant in England, with the earliest case identified from 20 September 2020.

The observed rapid increase in COVID-19 cases overall was temporally associated with the emergence of the new variant in this area in November 2020. The reported COVID-19 cases related to the VUI 202012/01 variant are concentrated in Kent and wider South East England, including the regions of London and the East of England, but there are indications of a more widespread occurrence of cases across the UK as well as small numbers of cases detected in other countries.

In Wales, as of 14 December 2020, 20 individuals had been identified with this virus variant of 4 733 sequenced samples collected since 1 November. Additionally, Denmark has reported nine cases [2], the Netherlands reported one case [3], and one case from Australia was identified through the GISAID EpiCov database. Media report that four cases have been identified in Belgium in recent months [4].

On 19 December 2020, in response to the increase of this variant, the countries of the UK have announced stricter measures to be applied from 20 December and over the coming weeks, with affected areas going into a ‘Tier 4’ level with movement restrictions within and between more and less heavily affected areas [5,6]. These measures include recommendations for residents of the most affected areas to restrict movements and travel, including international travel, outside of these areas. The government of Scotland announced a travel ban between Scotland and rest of UK from 26 December.

In addition, the Netherlands issued a travel ban from the UK effective from 6:00 a.m. on 20 December 2020 until 1 January 2021 [3] and Belgium halted flight and train travel to the UK for a 24-hour period as of midnight on 20 December 2020 [7].

Epidemiology

The investigations into the properties of this new variant are ongoing, and poorer clinical outcomes, higher mortality or particularly affected groups have not been reported to date. The cases with the VUI 202012/01 variant are predominantly identified in people younger than 60 years, but the increase of overall COVID-19 cases in England is similarly driven by this age group (Figure 2). Preliminary modelling results show a strong association between the presence of the new variant in the Kent/South East England region and increasing incidence of COVID-19. Among the 20 VUI 202012/01 cases identified in Wales, cases have a median age of 41 years (range 11-71 years), and are mainly located in South Wales, where incidences are also rising. The increasing proportion of cases with the VUI 202012/01 variant among all sequenced isolates uploaded to the GISAID database is shown in Figure 3.

Genomic properties of the new SARS-CoV-2 variant

This new SARS-CoV-2 virus variant is referred to in the UK as SARS-CoV-2 VUI 202012/01. It is defined by multiple spike protein mutations (deletion 69-70, deletion 144, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H) present as well as mutations in other genomic regions [8]. One of the mutations (N501Y) is located within the receptor binding domain. The variant belongs to Nextstrain clade 20B [9,10], GISAID clade GR [11,12], lineage B.1.1.7 [13,14].

Phylogenetic analysis (Figure 4) reveals that there are very few intermediary forms between this variant and other circulating viruses reported to GISAID. The cluster differs by 29 nucleotide substitutions from the original Wuhan strain, which is higher than current molecular clock estimates of around two substitutions per genome per month [10].

The fraction of non-synonymous mutations in the spike protein for the variant is much higher than expected from random mutations (27% of the 22 substitutions acquired since the Nextstrain clade 20B common ancestor are located in the S-gene, which comprises 13% of the viral genome, and all of these substitutions are non- synonymous).

Three sequences from Denmark and one from Australia, from samples collected in November 2020, cluster with the UK variant, most likely indicating that international spread has occurred, although the extent remains unknown.

The UK has an established SARS-CoV-2 genome sequencing consortium called COG-UK. It consists of the national public health institutes, National Health Service organisations, academic institutions and the Wellcome Sanger Institute [15]. They are working to keep sequencing coverage high and geographically representative and to keep turnaround times low.

The consortium is by far the largest contributor to the GISAID EpiCov database in the world, with more than 120 000 of around 270 000 genomes published so far. This initiative increases the likelihood that emerging variants are identified and can be assessed in a timely fashion.

Figure 4. Phylogenetic tree, subsampled dataset focused on N501Y-variants of SARS-CoV-2 from Nextstrain [16] – Nodes within the cluster formed by the new SARS-CoV-2 VUI 202012/01 variant (black box) are coloured by country: United Kingdom (orange), Australia (grey), and Denmark (green). Other colours indicate countries not involved in the cluster.

Possible sources of SARS-CoV-2 virus variants with a high number of mutations in the spike protein

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.

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 (including RBD mutation Y453F and deletion 69-70) in Denmark during transmission among mink [19].

Several different spike protein mutations associated with mink have also been described in the Netherlands [20]. 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 [1].

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.

South Africa reports through the GISAID EpiCoV database [11] and a public press release [21,22] a similar rapid increase since October of a variant with the spike protein mutation N501Y, two additional RBD mutations and multiple additional spike protein mutations. This variant has no close evolutionary relation to VUI 202012/01 but demonstrates that the emergence of successful variants with similar properties may not be rare.

Options for response and considerations to support public health action

The four nations of the UK have announced stricter measures to be applied from 20 December and over the coming weeks. These measures include recommendations for residents of the most affected areas to restrict movements and travel, including international travel, outside of these areas.

The government of Scotland has announced a travel ban between Scotland and rest of UK from 26 December. In addition, the Netherlands and Belgium issued an immediate travel ban for flights carrying passengers from the UK.

Given that there is currently a lack of evidence to indicate that the new virus variant is widely spread and the occurrence is limited to a few countries or local areas, timely efforts to prevent and control the spread of the variant should mirror those effective in an early epidemic phase, including avoidance of non-essential travel to and from the affected areas as well as increased testing efforts, contact tracing and isolation of confirmed cases with epidemiological link to affected areas.

Efforts to carry out sequencing of cases in a timely manner, including cases who have recently been to or are in contact with people from affected areas, is important to understand the spread of the variant. ECDC will, in collaboration with the EU/EEA Member States, continue to monitor and report on new affected areas.

ECDC has previously recommended reducing non-essential travel and social activities [33].

SARS-CoV-2 genetic evolution has the potential to impact on the antigenic properties, transmissibility or severity of the virus. It is therefore important to monitor the evolution through sequencing of virus isolates and to assess whether there is a need for EU/EEA Member States to adjust their response to COVID-19. The following suggestions should be considered for public health response.

National public health authorities should:

  • Immediately identify people with an epidemiological link to cases with the new variant or travel history to areas known to be affected in order to test, isolate and follow up their contacts so as to stop the spread of the new variant. Virus isolates from such cases should be sequenced in a timely manner to identify cases of the new variant.
  • Continue to advise the population on the need for non-pharmaceutical interventions according to their national policies, and consider in particular guidance on the avoidance of travel and avoidance of non- essential social activities.
  • Continue to monitor for abrupt changes in rates of transmission or disease severity as part of the process of identifying and assessing the impact of variants.
  • Notify cases of the new variant as well as new SARS-CoV-2 variants of potential concern through the Early Warning and Response System of the European Union.
  • Follow up reports of suspected cases of COVID-19 reinfection and initiate sequence analysis of virus isolates from these cases.
  • Follow up reports of cases with treatment failures using convalescent plasma or monoclonal antibodies as recently described [17] and initiate sequence analysis of virus isolates from these cases.
  • Ensure that close monitoring of COVID-19-vaccinated individuals regarding vaccination failure and breakthrough infections is in place and initiate sequence analysis of virus isolates from these cases, and then conduct antigenic characterisation to confirm or exclude vaccine escape mutants.
  • Develop standardised mechanisms, in partnership with global stakeholders, including triggers to investigate and assess newly emerging variants of SARS-CoV-2 in terms of animal reservoir, antigenic characteristics, transmissibility, infection severity, cross-protection and also with regard to adapting vaccine strain recommendations. If needed, establish systems for reassessing vaccine composition and strategy.

National public health laboratories should:

  • Sequence virus isolates from cases with an epidemiological link to countries where the variant is present, currently the UK, Denmark, and the Netherlands according to official reports, and possibly also Belgium.
  • Increase the number of sequenced SARS-CoV-2 virus isolates to identify new variants similar to the UK variants in EU/EEA Member States. Laboratories can refer to the upcoming technical note Sequencing of SARS-CoV-2 which is in preparation by ECDC and the WHO Regional Office for Europe for guidance about technologies and sample selection. ECDC can offer sequencing services to countries with limited national capacity in this area.
  • Increase representativeness of isolates selected for sequencing based on population and geographic location of infections to identify emerging variants and assess spread.
  • Assess the implications of the drop out of the S-gene target RT-PCR in use for diagnostic purposes and adapt the gene target regions for SARS-CoV-2 PCR diagnostics. If sequencing capacity is limited, multi-target RT-PCR assays that include a S-gene target that is affected by the deletions present in the variant can be used for identifying isolates that show a S-gene drop out as signal for further investigation. Note that the deletion at positions 69-70 of the spike protein is not exclusive to this variant. Confirmation using sequencing is recommended.
  • Increase capacities to perform in-depth virus characterisation analyses genetically and antigenically or share isolates with SARS-CoV-2 reference laboratories for further genetic and antigenic investigations.

References

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