This briefing provides an update on previous briefings up to 1 April 2021
Summary
• There are 4 variants of concern and 7 variants under investigation (Table 1).
VOC-20DEC-01 (B.1.1.7) remains predominant in the UK. Other variants of concern and
variants under investigation remain a very low proportion of the available sequence data.
VUI-21APR-01 (B.1.617.1) cases have been imported to England with increasing
frequency. Phylogeny and surveillance data are presented.
The enhanced investigations for all variants under investigation and variants of concern
have been updated, including secondary attack rates, spatial risk mapping, and growth
rate estimates. Numbers of all variants under investigation remain low and estimates have
low certainty. Travel data are now included.
A new clinical risk assessment for VOC-20DEC-01 (B.1.1.7) is provided in the Appendix.
Variant information
The collection page gives content on variants, including prior technical briefings.
Definitions for variants of concern, variants under investigation and signals in monitoring
are detailed in technical briefing 8.
Variant status and numbers
Table 1 shows the current variants of concern and variants under investigation (including
new simplified naming convention). Summary epidemiology on each variant is shown in
Table 2 (case numbers are also updated online Case numbers on variants of concern
(VOC) and variants under investigation (VUI)).
Lineage | Designation | First detected in sequence from | Status |
B.1.1.7 | VOC-20DEC01 | UK | VOC |
B.1.351 | VOC-20DEC02 | South Africa | VOC |
P1 | VOC-21JAN-02 | Japan ex Brazil | VOC |
B1.1.7 with E484K | VOC-21FEB02 | UK | VOC |
P2 | VUI-21JAN-01 | Brazil | VUI |
A.23.1 with E484K | VUI-21FEB-01 | UK | VUI |
B.1.525 | VUI-21FEB-03 | UK | VUI |
B.1.1.318 | VUI-21FEB-04 | UK England | VUI |
B.1.324.1 with E484K | VUI-21MAR-01 | UK | VUI |
P3 | VUI-21MAR-02 | Philippines | VUI |
B.1.617.1 with E484Q | VUI-21APR-01 | India | VUI |
B.1.429 | California USA | Monitoring | |
B.1.1.7 with S494P | UK | Monitoring | |
A.27 | France (Mayotte) | Monitoring | |
B.1.526 | New York USA | Monitoring | |
B.1.1.7 with Q677H | UK | Monitoring | |
B.1 with profile: P26S, V126A, S477N, E484K, P681H, T1027I, D1118H, nsp6d, Sd68, Sd143 | Imported cases to UK | Monitoring | |
B1.214.2 | Belgium | Monitoring | |
B.1.1.1 with L452Q and F490S | Imported cases to UK | Monitoring | |
R.1 | Multiple locations | Monitoring | |
B.1.1.28 with N501T and E484Q | Belo Horizonte (Brazil Lineage) | Monitoring | |
R346K, T478R and E484K | Variant associated with travellers | Monitoring | |
B.1.617.2 | India | Monitoring | |
B.1.617.3 | India | Monitoring |
Variant prevalence
Variant prevalence for all available case data is presented in Figure 1 and Figure 2. The
predominant variant remains VOC-20DEC-01; other variants of concern and under
investigation represent a low proportion of available sequences. The ‘Other’ category in
Figure 1 includes genomes where the quality is insufficient to determine variant status and
genomes that do not meet the current definition for any designated variant under
investigation or variant of concern; this category has been removed from Figure 2. These
figures represent all available genomic data including enhanced testing and sequencing
from individuals who have travelled, and surge testing and sequencing in outbreak areas.
The supplementary data for figures is available.
Figure 2. Variant prevalence for all England available case data from 1 February 2021 to 21 April 2021. excluding VOC20DEC-01.(Find accessible data used in this graph in underlying data)
New Variant Under Investigation: VUI-21APR-01 (B.1.617.1)
A variant first detected in sequences from India was designated under investigation on 1 April
2021 as VUI-21APR-01 (B.1.617.1).
Growth rates
The complete mutation profile of VUI-21APR-01 (B.1.617.1) is shown in Table 2 and genomic
case definition in Table 3.
Gene | Amino Acid | Actual Nucleotide | Note |
orf1ab | – | C3457T | nsp3 |
T1567I | C4965T | nsp3:T749I | |
T3646A | A11201G | nsp6:T77A | |
M5753I | G17523T | nsp13:M429I | |
K6711R | A20396G | nsp15:K259R | |
S Gene | – | T21895C | |
E154K | G22022A | ||
L452R | T22917G | ||
E484Q | G23012C | ||
P681R | C23604G | ||
ORF3a | S26L | C25469T | |
ORF7a | V82A | T27638C | |
N Gene | R203M | G28881T |
CONFIRMED | All variant defining changes called as alternate base |
PROBABLE | AT LEAST 5 variant defining changes called as alternate base and all other positions either N or mixed base |
LOW_C | Fewer than 5 variant defining changes called as alternate base and all other positions either N or mixed base |
Phylogeny
Genomic phylogeny of VUI-21APR-01 (B.1.617.1) and signals in monitoring B.1.617.2 and
B.1.617.3 are shown in Figure 3a.
Based on available data from international and UK datasets, the lineage B.1.617 contains 3
clades with different mutation profiles which are:
• B.1.617.1 – includes a large number of sequences and has a spike profile
including L452R and E484Q
• B.1.617.2 – has a different profile without E484Q and appears to have recent
expansion
• B.1.617.3 – has L452R and E484Q but is distinct from B.1.617.1 and currently
remains small
B.1.617.1 is designated VUI-21APR-01 on the basis of the mutation profile and apparent
successful transmission and spread. B.1.617.2 with a lesser mutation profile, and B.1.617.3,
not clearly spreading rapidly, are under surveillance and not designated as variants under
investigation.
Numbers within this briefing are for the designated VUI-21APR-01 (B.1.617.1).
Figure 3b shows the number of sequences of Lineage B.1.1.7 and B.1.617 over time in
sequences from individuals that have travelled from India as of 21 April 2021. There is an
increase in detected B.1.617 sequences.
Figure 3.Number of sequences of Lineage B.1.1.7, and B.1.617 over time in sequences from individuals that have travelled as of 21 April 2021 (Find accessible data used in this graph in underlying data). B.1.1.7 is shown in green, B.1.617 in blue and Other as dashed line.
Biological profile
VUI-21APR-01 (B.1.617.1) contains a number of spike mutations associated with antigenic
escape or found in other variants of concern.
Mutations at position 484 are well described as having a large impact on virus antigenicity
and are associated with the VOC-20DEC-02 (B.1.351) and VOC-21JAN-02 (P.1) variants,
however VUI-21APR-01 contains E484Q rather than the better described E484K. The
majority of antigenic escape studies (monoclonal antibody and/or polyclonal sera) that find
changes at position 484 implicate E484K, and to a lesser extent E484G/D/A/Y, while E484Q
is not seen. The studies where E484Q is routinely implicated, albeit at lower levels than
E484K, are deep mutagenesis scanning studies which generally give a much larger variety of
results, Unlike E484K, E484Q is not known to be associated with any change in receptor
binding avidity.
B.1.617 also contains the mutation L452R which is associated with antigenic escape from
both monoclonal antibodies and convalescent antisera, and found in several other variants
including signals in monitoring B.1.429 and A.27. L452R is also associated with enhanced
receptor binding affinity.
Additionally B.1.617 contains the furin cleavage site mutation P681R, similar to P681H.
681R/H are found in multiple variant lineages, such as VOC-20DEC-01 (B.1.1.7),
VUI-21FEB-04 (B.1.1.318) and VUI-21FEB-01 (A.23.1). Both P681H and P681R have been
shown to optimise spike cleavage by furin; it has been hypothesised that this optimisation
may enhance virus transmissibility.
VUI-21APR-01 contains several N-terminal domain mutations. G142D is associated with
escape from some N-terminal domain targeting monoclonal antibodies but is unclear if this
has a large impact on convalescent or vaccine-driven immunity.
Outside the spike gene, VUI-21APR-01 contains a number of mutations across its genome,
however none of these mutations are currently associated with any phenotypic change.
Surveillance in England
As of 22 April 2021, 119 genomically confirmed cases of VUI-21APR-01 (B.1.617.1) have
been identified in all regions of England; concentrated in the London, North West and East of
England regions (Table 4). Number of cases by specimen date are shown in Figure 4,
geospatial distribution in Figure 5 and Figure 11, age-sex distribution in Figure 6 and travel
association in Figure 7. The supplementary data for figures is available here. Note contact
tracing is included in Table 8.
Case detection indicates an increase in imported cases from March 2021. As of 22 April 2021
most cases of VUI-21APR-01 (B.1.617.1) in England occur as single cases with a few
localised clusters detected. Only 3 cases in England have been identified without a known
travel link, 94 have a link to travel, and 22 cases remain under investigation. No cases are
known to have died in England with VUI-21APR-01 (B.1.617.1) as of 22 April 2021.
Cases of signals in monitoring (B.1.617.2 and B.1.617.3) have been noted in sequences from
the UK (Figure 3). In addition to 119 VUI-21APR-01 (B.1.617.1) cases, there are 94
sequences from B.1.617.2 and 3 sequences B.1.617.3 detected.
The Amber border measures that remain until 23 April 2021 should limit both VUI-21APR-01
(B.1.617.1) and signals in monitoring (B.1.617.2 and B.1.617.3). Amber border measures
require individuals to isolate on arrival to the UK for 10 days at their home address and
perform PCR testing on day 2 and day 8. If either testing is positive, then individuals are
required to isolate for 10 days from the date of the positive test. From Friday 23 April 2021,
all arrivals from India will be required to isolate in managed quarantine facilities with day 2
and day 8 PCR tests. Any individual with a positive PCR test will be required to stay for 10
days from the date of the positive test in the managed quarantine facility.
Re-sampling of all PCR positive entrants from India is underway to provide materials for
virological culture work and analysis (for both VUI-21APR-01 (B.1.617.1) and signals in
monitoring (B.1.617.2 and B.1.617.3).
International surveillance
As of the 19 April 2021, international cases have been reported in 15 countries (including
the UK).
GISAID includes data on sequences available internationally. As of 21 April 2021 284
sequences from; India (188), Singapore (35), USA (21), Australia (8), Bahrain (7),
Germany (7), New Zealand (4), South Korea (4), Belgium (3), Ireland (3), Guadeloupe
(2), Canada (1), and Sint Maarten (1) have been identified on GISAID.
Region | Case Number | Case Proportion | Cases that have travelled | Proportion of travellers among cases |
East Midlands | 8 | 6.7% | 8 | 100% |
East of England | 13 | 10.9% | 10 | 76.9% |
London | 55 | 46.2% | 37 | 67.3% |
North East | 4 | 3.4% | 2 | 50% |
North West | 17 | 14.3% | 7 | 41.2% |
South East | 10 | 8.4% | 7 | 70% |
South West | 2 | 1.7% | 2 | 100% |
West Midlands | 3 | 2.5% | 3 | 100% |
Figure 4. Confirmed and probable VUI-21APR-01 (B.1.617.1) cases by specimen date as of 22 April 2021. Larger plot includes last 60 days only. (Find accessible data used in this graph in underlying data)
Figure 5. Geospatial distribution of confirmed and probable VUI-21APR-01 (B.1.617.1) cases by specimen date as of 22 April 2021. Larger plot includes last 60 days only. (Supplementary data is not available for this figure)
Figure 6. Age-sex distribution of confirmed and probable VUI-21APR-01 (B.1.617.1) cases by specimen date as of 22 April 2021. Larger plot includes last 60 days only. (Find accessible data used in this graph in underlying data)
Figure 7. Travel data for confirmed and probable VUI-21APR-01 (B.1.617.1) cases by specimen date as of 22 April 2021. Larger plot includes last 60 days only. (Find accessible data used in this graph in underlying data). N/A indicates information is pending or not available.
Mutations at position Q498 of SARS-COV-2 spike
Mutations at position Q498 of SARS-CoV-2 spike have been predicted, in combination
with N501Y, to greatly enhance human ACE2 binding (Zahradník et al., 20201). It is
hypothesised that greatly enhanced ACE2 binding could potentially lead to escape from
neutralising antibodies in an ‘avidity effect’ like that described in influenza, or lead to a
virus that was more transmissible or pathogenic. In the study Q498R was the specific
substitution described, however it is likely Q498K may have a similar effect based on the
similarity between R and K as both are positively charged.
Recently, more changes at position 498 have been identified in GISAID. This may be due
to enhanced sequencing but remains under surveillance. As of the 20 April 2021 there
were 21,767 sequences on GISAID that did not have the reference codon at position 498.
The majority of sequences contained either a missing base, an unresolved base or a
nucleotide change that did not change the amino acid. There were a total of 26 sequences
with an alternate amino acid coded at position 498 of which 12 were sequences derived
from viral infection of humans. These 12 sequences were assessed by Pangolin lineage
and for mutations at positions 498, 484 and 501 (Table 5).
Lineage | Country | Date | Reference sequence NC045512 Amino Acid | Detected 498 mutation Amino Acid | 501 Variant | 484 Variant |
B.1.1.144 | Switzerland | 2020-09-09 | Q(glutamine) | Z(glutamine or glutamic acid) | ||
B.1.1.222 | USA | 2021-02-26 | Q(glutamine) | H(histidine) | ||
B.1.1.7 | Ireland | 2021-02-02 | Q(glutamine) | K(lysine) | Y(tyrosine) | |
B.1.1.7 | USA | 2021-03-12 | Q(glutamine) | K(lysine) | Y(tyrosine) | |
B.1.1.7 | USA | 2021-02-24 | Q(glutamine) | H(histidine) | Y(tyrosine) | |
B.1.240 | USA | 2021-03-16 | Q(glutamine) | R(arginine) | ||
B.1.240 | USA | 2021-03-04 | Q(glutamine) | R(arginine) | ||
B.1.240 | 2021-03-10 | Q(glutamine) | R(arginine) | |||
B.1.429 | USA | 2021-02-09 | Q(glutamine) | H(histidine) | ||
B.1.429 | USA | 2021-03-25 | Q(glutamine) | R(arginine) | ||
B.1.608 | USA | 2021-03-09 | Q(glutamine) | L(leucine) | Y(tyrosine) | |
None | Iran | 2020-02-24 | Q(glutamine) | P(proline) |
Antigenic change mutation monitoring
Mutations potentially associated with antigenic change are monitored as part of horizon
scanning. Figure 8 shows the proportion of these mutations over time in the all England
genomic dataset, illustrating the decline of N439K and an increase in E484K. Only those
mutations which were present at a count of > 50 within the 6 month time frame are shown.
The supplementary data for figures is available.
Case numbers, proportion, deaths and case fatality rate
The number of cases of variants of concern and variant under investigation are shown in
Table 6. including the proportion of variant cases compared to all sequenced cases,
deaths and case fatality rate.
Variant | Case Numbera | Case Proportionb | Deathsc | Case Fatality (95%CI)d |
VOC-20DEC-01 | 185,216 | 99.243% | 3,846 | 2.1%(2.0-2.1%) |
VOC-20DEC-02 | 592 | 0.317% | 10 | 1.7%(0.8-3.1%) |
VOC-21JAN-02 | 51 | 0.027% | 0 | 0.0%(0.0-7.0%) |
VOC-21FEB-02 | 43 | 0.023% | 1 | 2.3%(0.1-12.3%) |
VUI-21JAN-01 | 53 | 0.028% | 1 | 1.9%(0.0-10.1%) |
VUI-21FEB-01 | 79 | 0.042% | 1 | 1.3%(0.0-6.9%) |
VUI-21FEB-03 | 334 | 0.179% | 12 | 3.6%(1.9-6.2%) |
VUI-21FEB-04 | 135 | 0.072% | 0 | 0.0%(0.0-2.7%) |
VUI-21APR-01 | 119 | 0.064% | 0 | 0.0%(0.0-3.1%) |
Excludes variant cases not linked to a known COVID-19 case.
aCase number England genomic cases 22 April 2021.
bProportion of sequences UK/England as of 22 April 2021.
cDeaths As of 22 April 2021 (within 28 days) with confirmed or probable VOC or total cases.
d95% Confidence Intervals calculated with Clopper–Pearson exact method, using R package PropCIs.
Enhanced investigations
Growth rates
The growth rate estimates from a logistic growth model for variants of concern and
variants under investigation (with sufficient numbers of cases) are shown in Table 8 and
Figure 9 . Growth rates for each VUI or VOC are computed relative to a B.1.1.7 baseline
and based on 2 sample sets. Set 1: Sequences randomly selected from Pillar 2 testing.
Set 2: As Set 1 which further excludes surge testing and recently-returned travellers.
Table 7 and Figure 9 shows Set 1 data, that the variants with significant positive growth
rates compared to other circulating lineages in the same area are VUI-21APR-01
(B.1.617.1) and VUI-21FEB-04 (B.1.1.318). This version is updated to use PHE variant
definitions. The supplementary data for figures is available.
Variant | Lineage | Growth rate (1/week) Set 1 | Growth rate (1/week) Set 2 |
VOC-20DEC-02 | B.1.351 | 0.076(n=250,p=9.139e-06) | 0.056(n=141,p=0.014) |
VOC-21JAN-02 | P.1 | 0.27(n=19,p=0.035) | 0.17(n=9,p=0.34) |
VOC-21FEB-02 | B.1.1.7 with E484K | -0.16(n=33,p=0.06) | -0.23(n=28,p=0.032) |
VUI-21JAN-01 | P.2 | 0.034(n=22,p=0.70) | 0.044(n=22,p=0.62) |
VUI-21FEB-01 | A.23.1 with E484K | -0.19(n=43,p=0.077) | -0.25(n=46,p=0.022) |
VUI-21FEB-03 | B.1.525 | 0.051(n=142,p=0.039) | 0.0063(n=77,p=0.84) |
VUI-21FEB-04 | B.1.1.318 | 0.16(n=79,p=0.0001) | 0.23(n=54,p=4.65e-05) |
VUI-21APR-01 | B.1.617.1 | 0.81(n=68,p=1.217e-12) | 0.51(n=21,p=0.006) |
Figure 9. Growth estimates of variants of concern and under investigation as of 21 April 2021 (set 1 data) (Find accessible data used in this graph in underlying data)
Secondary attack rates
Secondary attack rates are shown in Table 8. These are based on positive tests amongst
contacts named to NHS Test and Trace by an original case identified with a confirmed or
probable variant of concern or variant under investigation.
Secondary attack rates are shown for cases with and without travel history. In non-travel
settings, only close contacts (household members, face to face contact, people within 1
metre of the case for 1 minute or longer, or people within 2 metres for 15 minutes) named
by the original case are included. In travel settings the contacts reported are not restricted
to only close contacts named by the case (for example, they may include contacts on a
plane linked by additional contact tracing efforts), leading to likely deflation of secondary
attack rates amongst travellers compared to non-travellers. In addition, people recently
returning from overseas are subject to stricter quarantine measures and may moderate
their behaviour towards contacts. Travel history indicates, but does not confirm, where
infection of the original case occurred.
Secondary attack rates for contacts of non-travel cases with variants of concern or under
investigation except VOC-21FEB-02 are not significantly different from that for contacts of
non-travel cases with VOC-20DEC-01. No transmission events were identified to contacts
of cases with VOC-21FEB-02. Estimates of secondary attack rates for contacts of those
that have travelled with variants of concern or variants under investigation were all
considerably lower than those that have not travelled.
Variant | Lineage | Cases in those that have travelled | Cases in those that have not travelled or unknown | Case proportion that have travelled | Secondary Attack Rate among contacts of those that have travelled (95% CI) [secondary cases/contacts] | Secondary Attack Rate among contacts of cases that have not travelled or unknown (95% CI) [secondary cases/contacts] |
VOC-20DEC-01 | B.1.1.7 | 2220(81.6% with contacts) | 136936(73.4% with contacts) | 1.6% | 1.7%(1.6%-1.9%)[702/40371] | 10.3%(10.2%-10.5%)[28345/273897] |
VOC-20DEC-02 | B.1.351 | 197(71.6% with contacts) | 180(61.7% with contacts) | 52.3% | 2.5%(2.0%-3.1%)[76/3075] | 8.9%(6.2%-12.6%)[27/305] |
VOC-21JAN-02 | P.1 | 25(80.0% with contacts) | 7(71.4% with contacts) | 78.1% | 1.2%(0.4%-3.6%)[3/242] | Unavailable[1/9] |
VOC-21FEB-02 | B.1.1.7 with E484K | 1(100.0% with contacts) | 33(81.8% with contacts) | 2.9% | Unavailable[0/96] | 0.0%(0.0%-3.3%)[0/111] |
VUI-21JAN-01 | P.2 | 3(66.7% with contacts) | 31(77.4% with contacts) | 8.8% | Unavailable[0/137] | 10.8%(5.3%-20.6%)[7/65] |
VUI-21FEB-01 | A.23.1 with E484K | 0(0% with contacts) | 63(60.3% with contacts) | 0.0% | Unavailable[0/0] | 8.6%(4.4%-16.1%)[8/93] |
VUI-21FEB-03 | B.1.525 | 138(71.0% with contacts) | 139(71.9% with contacts) | 49.8% | 1.3%(0.9%-1.8%)[36/2805] | 9.2%(6.2%-13.5%)[23/249] |
VUI-21FEB-04 | B.1.1.318 | 32(75.0% with contacts) | 71(73.2% with contacts) | 31.1% | 0.9%(0.5%-1.6%)[11/1 214] | 7.8%(4.4%-13.4%)[11/141] |
VUI-21MAR-01 | B.1.324.1 with E484K | 1(100.0% with contacts) | 0(0% with contacts) | 100.0% | Unavailable[0/7] | Unavailable[0/0] |
VUI-21MAR-02 | P.3 | 4(50.0% with contacts) | 1(100.0% with contacts) | 80.0% | Unavailable[0/10] | Unavailable[0/3] |
VUI-21APR-01 | B.1.617.1 | 42(83.3% with contacts) | 14(71.4% with contacts) | 75.0% | 1.4%(0.9%-2.2%)[17/1 210] | Unavailable[1/29] |
Secondary attack rates are marked as ‘Unavailable’ when count of contacts is less than 50 or count of exposing cases is less than
20. Travel-linked cases for secondary attack rates are identified positively in NHS Test and Trace data using multiple PHE sources.
A case is considered as being travel-linked if:
• EpiCell or Health Protection Teams have found evidence of international travel
• their NHS Test and Trace record mentions an event associated with international travel
• their NHS Test and Trace record was created after notification via IHR NFP
• they have been marked for priority contact tracing in NHS Test and Trace for reasons of travel
Some travel-linked cases may be missed by these methods and would be marked as non-travel-linked or unknown. Secondary attack rates from NHS Test and Trace should generally be considered lower bounds due to the nature of contact tracing and testing. Data provided is for period 5 January 2021 to 28 March 2021 in order to allow time for contacts to become cases, hence
case counts are lower than other sources.
Spatial variation in risk for variants
Spatial variation in risk
The spatial risk surface is estimated by comparing the smoothed intensity of cases (variants
of concern) and controls (PCR +ve, non-variants of concern) across a defined geographical
area to produce an intensity (or risk) ratio. If the ratio is ~1, this suggests that the risk of
infection is unrelated to spatial location. Evidence of spatial variation in risk occurs where the
intensities differ. Ratio values >1 indicate an increased risk and values <1 indicate lower risk.
Figure 10 highlights areas of significantly increased risks for variants of concern, areas of
significantly increased risk were identified for all variants of concern other than VOC-21JAN02
(P.1). Supplementary data is not available for this figure. Figure 11 highlights areas of
significantly increased risks for variants under investigation, areas of significantly increased
risk were identified for multiple variants under investigation. Supplementary data is not
available for this figure.
Figure 11. Spatial variation in risk for VUI data from 1 October 2020, as of 22 April 2021, excluding cases that have travelled(Supplementary data is not available for this figure)
Appendices
Appendix 1. Variant assessment tools
Repository of human and machine readable genomic case definitions
A repository containing the up-to-date genomic definitions for all VOC and VUI as curated by
Public Health England was created 5 March 2021. The repository can be accessed on
GitHub. They are provided in order to facilitate standardised VOC and VUI calling across
sequencing sites and bioinformatics pipelines and are the same definitions used internally at
Public Health England. Definition files are provided in YAML format so are compatible with a
range of computational platforms. The repository will be regularly updated. The genomic and
biological profiles of VOC and VUI are also detailed on first description in prior technical
briefings.
Variant risk assessment framework
Variant risk assessment includes the following confidence grading categorisations and
utilises the framework in Table 9.
1. Low: Little or poor-quality evidence, uncertainty or conflicting views amongst
experts, no experience with previous similar incidents.
2. Moderate: Adequate quality evidence, including consistent results published only
in grey literature, reliable source(s), assumptions made on analogy and agreement
between experts or opinion of at least 2 trusted experts.
3. High: Good quality evidence, multiple reliable sources, verified, expert opinion
concurs, experience of previous similar incidents.
Indicator | Risk assessment framework | |||
Zoonotic emergence and transmission to humans | Animal reservoir identified but no evidence of transmission from animals to humans | Sporadic transmission from animals to humans | Frequent transmission from animals to humans | |
Transmissibility between humans | No demonstrated person to person transmission | Limited human case clusters | Established human to human qtransmission, which appears similar to wild type virus | Transmissibility appears greater than the wild type virus |
Infection severity | Evidence of less severe clinical picture or lower infection fatality than from wild type SARS-CoV2 infections | Similar clinical picture and infection fatality to wild type SARS-CoV-2 infections OR experimental animal data suggesting potential for increased disease severity humans | More severe clinical picture or higher infection fatality than from wild type SARS-CoV-2 infections (limited to specific risk roups) | More severe clinical picture or higher infection fatality than from wild type SARS-CoV-2 infections |
Susceptibility and immunity – natural infection | Evidence of no antigenic difference from other circulating wild type virus | Structural data suggesting antigenic difference from other circulating wild type virus | Experimental evidence of functional evasion of naturally acquired immunity | Evidence of frequent infection in humans with known prior infection with earlier virus variant. |
Vaccines | Evidence of no structural or antigenic difference in vaccine targets | Structural data suggesting difference in vaccine target epitopes | Experimental evidence of functional evasion of naturally acquired immunity | Evidence of frequent vaccine failure or decreased effectiveness in humans |
Drugs and therapeutics | Evidence of no structural or antigenic difference in therapeutic targets | Structural data suggesting difference in vaccine target epitopes | Experimental evidence of reduced drug susceptibility | Evidence of frequent vaccine failure or decreased effectiveness in humans |
Appendix 2. Data on individual variants
VOC-20DEC-01 (B.1.1.7)
This variant was designated VUI 202012/01 (B.1.1.7) on detection and on review redesignated
as VOC-20DEC-01 (202012/01, B.1.1.7) on 18 December 2020. The clinical risk
assessment for VOC-20DEC-01 (B.1.1.7) is shown in Table 10.
Indicator | RAG* | Confidence | Assessment and rationale |
Zoonotic emergence | NA | There is no evidence that VOC-20DEC-01 (B.1.1.7) emergence emerged from a zoonotic source. Reports of infection with VOC-20DEC-01 (B.1.1.7) in companion animals are noted. | |
Transmissibility between human | HIGH | Transmissibility appears greater than the wild between humans type (first wave) virus. The lineage rapidly became dominant in the UK and spread internationally. Epidemiological and genomic modelling in multiple studies and countries, and secondary attack rate studies using contact tracing data in the UK, support increased transmissibility | |
Infection severity | MODERATE | More severe clinical picture or higher infection severity fatality than from wild type (first wave) SARSCoV-2 infections. Multiple studies have now been undertaken. Although there are varying results from individual cohorts, the larger cohorts indicate an association with more severe disease (represented by either hospitalisation or death), compared to infection with non B.1.1.7 viruses. | |
Naturally acquired immunity | MODERATE | Evidence of no increase in reinfection rate. Although there is laboratory evidence supporting some antigenic distance between VOC-20DEC-01 (B.1.1.7) and older virus, with small reductions in the neutralising activity of convalescent plasma in some studies, there was no increase in reinfections in a large cohort study during the time that VOC20DEC-01 (B.1.1.7) became prevalent in the UK. Antigenic distance may be affected by the acquisition of further mutations in this lineage | |
Vaccine derived immunity | HIGH | Evidence that vaccine performance is preserved. Although there is laboratory evidence supporting some antigenic distance between VOC-20DEC-01 (B.1.1.7) and older virus, including small reductions in the neutralising activity of vaccinee sera, vaccine efficacy has been shown to be similar against VOC-20DEC-01 (B.1.1.7) compared to non B.1.1.7 lineages, in more than one study and with more than one vaccine. Antigenic distance may be affected by the acquisition of further mutations in this lineage. | |
Drugs and Therapeutics | The drugs and therapeutics risk assessment is under revision. | ||
Overall assessment of level and nature of risk, and level of confidence | VOC-20DEC-01 (B.1.1.7) remains the predominant virus in the UK. There is strong supporting UK and international evidence for increased transmissibility, and accumulating evidence on increased severity, but limited understanding of the biological mechanisms underlying these characteristics. There is a growing body of evidence suggesting the limited changes in susceptibility to polyclonal sera observed in vitro do not translate to substantial changes in either reinfection or vaccine efficacy. Continued worldwide transmission of VOC-20DEC-01 (B.1.1.7) is allowing it to acquire further mutations but at present none predominate sufficiently to change the risk assessment. |
Genomic profile
Lineage defining mutations are shown in technical briefing 6. In addition, VOC-20DEC-01 has
acquired other mutations in some cases (Table 11).
VOC-20DEC-01 (B.1.1.7) Spike variants | ||||
Amino acid change | Total number of instances in VOC-20DEC-01 (B.1.1.7) (UK data) to 20 April 2021 | 21 January 2021 to 20 February 2021 | 21 February 2021 to 20 March 2021 | 21 March 2021 to 20 April 2021 |
L18F | 5,789(2.43%) | 1,383(1.96%) | 931(1.67%) | 506(1.62%) |
Q677H | 1,915(0.8%) | 467(0.66%) | 760(1.37%) | 351(1.13%) |
P384L | 388(0.16%) | 74(0.11%) | 164(0.29%) | 105(0.34%) |
A701V | 456(0.19%) | 35(0.05%) | 122(0.22%) | 71(0.23%) |
F490S | 320(0.13%) | 78(0.11%) | 130(0.23%) | 60(0.19%) |
S255F | 154(0.06%) | 35(0.05%) | 32(0.06%) | 47(0.15%) |
P9L | 125(0.05%) | 25(0.04%) | 43(0.08%) | 40(0.13%) |
K458N | 66(0.03%) | 0(0%) | 24(0.04%) | 34(0.11%) |
S494P | 895(0.38%) | 313(0.44%) | 98(0.18%) | 30(0.1%) |
P384S | 339(0.14%) | 26(0.04%) | 21(0.04%) | 29(0.09%) |
A684T | 40(0.02%) | 4(0.01%) | 3(0.01%) | 27(0.09%) |
E484K | 124(0.05%) | 36(0.05%) | 24(0.04%) | 26(0.08%) |
S12P | 55(0.02%) | 5(0.01%) | 18(0.03%) | 25(0.08%) |
L455F | 105(0.04%) | 32(0.05%) | 35(0.06%) | 21(0.07%) |
G476S | 69(0.03%) | 6(0.01%) | 40(0.07%) | 16(0.05%) |
Q677R | 39(0.02%) | 6(0.01%) | 11(0.02%) | 16(0.05%) |
K147E | 23(0.01%) | 0(0%) | 2(0%) | 15(0.05%) |
A684S | 35(0.01%) | 1(0%) | 13(0.02%) | 11(0.04%) |
P9S | 99(0.04%) | 35(0.05%) | 29(0.05%) | 11(0.04%) |
K150R | 36(0.02%) | 10(0.01%) | 14(0.03%) | 11(0.04%) |
Q493R | 41(0.02%) | 4(0.01%) | 19(0.03%) | 11(0.04%) |
A684V | 94(0.04%) | 28(0.04%) | 31(0.06%) | 10(0.03%) |
H146Y | 122(0.05%) | 34(0.05%) | 37(0.07%) | 10(0.03%) |
Q493K | 30(0.01%) | 4(0.01%) | 12(0.02%) | 10(0.03%) |
D253G | 40(0.02%) | 11(0.02%) | 8(0.01%) | 10(0.03%) |
Epidemiological profile
Lineage B.1.1.7 is dispersed across the UK. Confirmed cases are those identified by whole
genome sequencing. As of 22 April 2021, there were 185,216 confirmed and probable cases
of VOC 202012/01 (B.1.1.7) in England. The use of S gene target failure (SGTF) in the
Taqpath assay as a good proxy for cases of this variant of concern has been described in
prior technical briefings. In samples tested with this assay in the Lighthouse Laboratories,
samples with SGTF have predominated since mid-December 2020, reaching 99% of cases in
the week starting 3 March 2021. Proportions in all regions were >97% in March 2021 (prior
technical briefings). An online B.1.1.7 tracking tool is available at Covid-19 Genomic
Surveillance.
Figure 12 and Figure 13 show the weekly number and proportion of England Pillar 2
(community testing) COVID-19 cases with SGTF among those tested with the TaqPath
assay, and with S gene detection results, showing cases with SGTF account for more than
98% of cases from community testing nationally. The supplementary data for figures is
available.
International epidemiology
As of the 19 April 2021, there are 137 countries or territories (including the UK) reporting
cases of VOC-20DEC-01 globally. Of countries or territories outside of the UK, 35 report, or
there is evidence of, community transmission. However, for many countries the information
available on the extent of transmission within the country is not clear.
Figure 13. Weekly number and proportion of England Pillar 2 COVID-19 cases with SGTF among those tested with the TaqPath assay and with S gene detection results, by region of residence (1 September 2020 to 21 April 2021) (Find accessible data used in this graph in underlying data)
Appendix 2. Data on individual variants
Through routine scanning of variation in VOC-20DEC-01 (B.1.1.7) a small number of B.1.1.7
sequences had acquired the spike protein mutation E484K. Information suggested more than
one independent acquisition event. One cluster was predominant with evidence of community
transmission and was designated variant under investigation on detection and on review redesignated as variant of concern VOC-21FEB-02 (VOC202102/02, B.1.1.7 cluster with E484K)
on 5 February 2021. The genomic and biological profile is as previously described in Technical
briefing documents on novel SARS-CoV-2 variants.
Epidemiological profile
As of 22 April 2021, 43 genomically confirmed cases of VOC-21FEB-02 (B.1.1.7 cluster with
E484K) have been identified; concentrated in the South West and North West (Table 12).
Cases by specimen date are shown in Figure 14 and shows cases have not been detected
since 1 March 2021. The supplementary data for figures is available.
International Epidemiology
As of the 19 April 2021, international cases have been reported in 8 countries (including the
UK) as of 21 April 2021, 6 sequences from the Netherlands have been identified on GISAID.
Region | Case Number | Case Proportion | Cases that have travelled | Proportion of travellers among cases |
London | 1 | 2.3% | 0 | 0% |
North West | 15 | 34.9% | 0 | 0% |
South East | 1 | 2.3% | 0 | 0% |
South West | 26 | 60.5% | 0 | 0% |
VOC-20DEC-02 (B.1.351)
B.1.351 was initially detected in South Africa. This variant was designated variant under
investigation on detection and on review re-designated as VOC-20DEC-02 (B.1.351) on 24
December 2020. The clinical risk assessment is detailed in Technical briefing 8.
Epidemiological profile
VOC-20DEC-02 (B.1.351) is dispersed across the UK in low numbers. Confirmed cases are
those identified by whole genome sequencing. As of 22 April 2021, 592 confirmed cases of
VOC-20DEC-02 (B.1.351) were identified. An international travel link was identified for 386
cases, and 154 had no travel link (47 cases awaiting further information). Confirmed and
probable cases by specimen date are shown in Figure 15, and regional breakdown in Table
13. Figure 15 shows cases predominate in the London area. Travel data is shown in Figure 16.
The supplementary data for figures is available.
Figure 16. Travel data for confirmed and probable VOC-20DEC-02 (B.1.351) cases by specimen date as of 22 April 2021 Larger plot includes last 60 days only. (Find accessible data used in this graph in underlying data)
Region | Case Number | Case Proportion | Cases that have travelled | Proportion of travellers among cases |
East Midlands | 27 | 4.6% | 21 | 77.8% |
East of England | 61 | 10.3% | 34 | 55.7% |
London | 259 | 43.8% | 135 | 52.1% |
North East | 8 | 1.4% | 3 | 37.5% |
North West | 67 | 11.3% | 28 | 41.8% |
South East | 79 | 13.3% | 47 | 59.5% |
South West | 23 | 3.9% | 13 | 56.5% |
West Midlands | 43 | 7.3% | 23 | 53.5% |
Yorkshire and Humber | 25 | 4.2% | 14 | 56% |
International Epidemiology
As of 19 April 2021 there are 97 countries (including the UK) that have reported cases of
this variant globally. GISAID includes data on sequences available internationally. As of the
21 April 2021 9,198 sequences of VOC-20DEC-02, excluding UK, are listed from 70
countries and territories.
VOC-21JAN-02 (P.1)
First identified in Japan amongst travellers from Brazil, the P.1 lineage is a descendant of
B.1.1.28. This variant was designated variant under investigation on detection and on
review re-designated as VOC-21JAN-02 (P.1) on 13 January 2021. The clinical risk
assessment for P1 is detailed in technical briefing 7.
Epidemiological profile
As of 22 April 2021, 51 genomically confirmed and probable cases of VOC-21JAN-02 (P.1)
have been identified in England. 36 cases have been linked to international travel, 1 case
has no travel link, 14 under investigation. Regional breakdown of cases in shown in Table
14 and cases by specimen date are shown in Figure 17. Travel data is shown in Figure 18.
The supplementary data for figures is available.
Region | Case Number | Case Proportion | Cases that have travelled | Proportion of travellers among cases |
East of England | 5 | 9.8% | 4 | 80% |
London | 28 | 54.9% | 16 | 57.1% |
South East | 4 | 7.8% | 4 | 100% |
South West | 11 | 21.6% | 1 | 9.1% |
West Midlands | 2 | 3.9% | 1 | 50% |
Yorkshire and Humber | 2 | 3.9% | 1 | 50% |
Figure 18. Travel data for confirmed and probable VOC-21JAN-02 (P.1) cases by specimen date as of 22 April 2021Larger plot includes last 60 days only. (Find accessible data used in this graph in underlying data)
International epidemiology
As of 19 April 2021, cases of VOC-21JAN-02 (P.1) have been reported in 55 countries or
territories (including the UK). Five countries have reported cases of a Brazilian variant but
additional information is awaited to clarify if this is with VOC-21JAN-02 (P.1).
GISAID includes data on sequences available internationally. As of the 21 April 2021
3,618 sequences of VOC-21JAN-02 are listed from 39 countries excluding the UK.
VUI-21JAN-01 (P2)
First identified in Brazil, the P.2 lineage is a descendant of B.1.1.28. This variant was
designated VUI-21JAN-01 (P.2) on 13 January 2021. It was first sequenced in the UK in
November 2020.
Epidemiological profile
As of 22 April 2021, 53 cases of VUI-21JAN-01 (P.2) have been identified in England. 9
cases have been linked to international travel, and 41 cases had no travel link (3 cases
awaiting further information). Regional breakdown of cases in shown in Table 15 and
confirmed and probable cases by specimen date are shown in Figure 19. Figure 19 shows
a limited number of cases in different regions. Travel data is shown in Figure 20. The
supplementary data for figures is available.
Region | Case Number | Case Proportion | Cases that have travelled | Proportion of travellers among cases |
East Midlands | 1 | 1.9% | 0 | 0% |
East of England | 2 | 3.8% | 1 | 50% |
London | 14 | 26.4% | 6 | 42.9% |
North West | 11 | 20.8% | 0 | 0% |
South East | 6 | 11.3% | 0 | 0% |
South West | 7 | 13.2% | 0 | 0% |
West Midlands | 1 | 1.9% | 0 | 0% |
Yorkshire and Humber | 11 | 20.8% | 0 | 0% |
International Epidemiology
As of 19 April 2021, cases of VUI-21JAN-01 (P.2) have been reported in 39 countries or
territories (including the UK).
GISAID includes data on sequences available internationally, as of 21 April 2021 2,072
sequences (excluding UK) of VUI-21JAN-01 from 33 countries.
Figure 20. Travel data for confirmed and probable VUI-21JAN-01 (P.2) cases by specimen date as of 22 April 2021Larger plot includes last 60 days only. (Find accessible data used in this graph in underlying data)
VUI-21FEB-01 (A.23.1 with E484K)
This variant was first identified in Liverpool, UK, derived from a lineage first identified in
Uganda without E484K. The variant was designated VUI-21FEB-01 (A.23.1 with E484K)
on 5 February 2021. It was first detected in the UK in December 2020.
Epidemiological profile
As of 22 April 2021, 79 genomically confirmed cases of VUI-21FEB-01 (A.23.1 with
E484K) have been identified. The majority of these are residents of the North West of
England (Table 16). Confirmed and probable cases by specimen date are shown in Figure
21. Figure 21 shows cases predominate in the North West. Travel data is shown in Figure
22. The supplementary data for figures is available.
International epidemiology
As of 19 April 2021, cases of VUI-21FEB-01 (A.23.1 with E484K) have been reported in
the UK and the Netherlands only.
GISAID includes data on sequences available internationally. As of 21 April 2021 1
sequence is listed of VUI-21FEB-01 (A.23.1 with E484K) (excluding UK) from Netherlands.
Region | Case Number | Case Proportion | Cases that have travelled | Proportion of travellers among cases |
North West | 78 | 98.7% | 0 | 0% |
West Midlands | 1 | 1.3% | 0 | 0% |
Figure 22. Travel data for confirmed and probable VUI-21FEB-01 (A.23.1 with E484K) cases by specimen date as of 22 April 2021. Larger plot includes last 60 days only. (Find accessible data used in this graph in underlying data)
VUI-21FEB-03 (B.1.525)
First identified as a geographically dispersed cluster in UK on the 2 February 2021. This
variant was designated VUI-21FEB-03 (B.1.525) on 12 February 2021. The earliest
sample date for VUI-21FEB-03 (B.1.525) in England was 15 December 2020. The
biological profile is described in technical briefing 7.
Epidemiological profile
As of 22 April 2021, there were 334 cases of VUI-21FEB-03 (B.1.525) in England In this
geographically dispersed genomic cluster with likely community transmission. Regional
cases are shown in Table 17 and confirmed and probable cases by specimen date are
shown in Figure 23. Figure 23 shows cases are in several regions, predominating in
London and South East and North West. Travel data is shown in Figure 24. The
supplementary data for figures is available.
Region | Case Number | Case Proportion | Cases that have travelled | Proportion of travellers among cases |
East Midlands | 9 | 2.7% | 5 | 55.6% |
East of England | 24 | 7.2% | 17 | 70.8% |
London | 113 | 33.8% | 73 | 64.6% |
North East | 3 | 0.9% | 3 | 100% |
North West | 62 | 18.6% | 16 | 25.8% |
South East | 71 | 21.3% | 24 | 33.8% |
South West | 14 | 4.2% | 4 | 28.6% |
West Midlands | 20 | 6.0% | 8 | 40% |
Yorkshire and Humber | 18 | 5.4% | 8 | 44.4% |
Figure 24. Travel data for confirmed and probable VUI-21FEB-03 (B.1.525) cases by specimen date as of 22 April 2021Larger plot includes last 60 days only. (Find accessible data used in this graph in underlying data)
First identified as a geographically dispersed cluster in UK on the 2 February 2021. This
variant was designated VUI-21FEB-03 (B.1.525) on 12 February 2021. The earliest
sample date for VUI-21FEB-03 (B.1.525) in England was 15 December 2020. The
biological profile is described in technical briefing 7.
International epidemiology
As of 19 April 2021, cases of VUI-21FEB-03 (B.1.525) have been reported in 51 countries
or territories (including the UK).
GISAID includes data on sequences available internationally. As of the 21 April 2021
1,331 sequences of VUI-21FEB-03 are listed, from 43 countries or territories excluding
UK.
VUI-21FEB-04 (B.1.1.318)
The VUI-21FEB-04 is lineage B.1.1.318 and was identified in England in mid-February
2021 through routine horizon scanning for the development of new clusters of genomes
containing E484K. This analysis identified an initial cluster of 6 cases containing E484K
and other spike mutations, designated VUI-21FEB-04 (B.1.1.318) on 23 February 2021.
Epidemiological profile
As of 22 April 2021, there were 135 genomically confirmed cases of VUI-21FEB-04
(B.1.1.318). Cases have occurred in most regions of England, concentrated in London and
the North West (Table 18). Regional cases are shown in Table 18 and confirmed and
probable cases by specimen date are shown in Figure 25. Figure 25 shows sporadic
cases in several regions. Travel data is shown in Figure 26. The supplementary data for
figures is available. Of the 135 cases, 54 had a link to travel, 42 cases had no known link
to travel, 39 are under investigation.
International epidemiology
As of 19 April 2021, cases of VUI-21FEB-04 (B.1.1.318) have been reported in 8 countries
(including the UK).
GISAID (gisaid.org) includes data on sequences available internationally. As of the 21
April 2021, there are 24 international VUI-21FEB-04 sequences, excluding UK. (USA 10,
Germany 6, Italy 4, Sweden 3, Bangladesh 1).
Region | Case Number | Case Proportion | Cases that have travelled | Proportion of travellers among cases |
East Midlands | 9 | 6.7% | 2 | 22.2% |
East of England | 16 | 11.9% | 8 | 50% |
London | 41 | 30.4% | 23 | 56.1% |
North East | 1 | 0.7% | 1 | 100% |
North West | 35 | 25.9% | 3 | 8.6% |
South East | 16 | 11.9% | 9 | 56.2% |
South West | 1 | 0.7% | 1 | 100% |
West Midlands | 5 | 3.7% | 3 | 60% |
Yorkshire and Humber | 11 | 8.1% | 1 | 9.1% |
Figure 26. Travel data for confirmed and probable VUI-21FEB-04 (B.1.1.318) cases by specimen date as of 22 April 2021 Larger plot includes last 60 days only. (Find accessible data used in this graph in underlying data)
VUI-21MAR-01 (B.1.324.1 with E484K)
First identified via horizon scanning of genomes with spike mutations characteristic of
VOCs (including both N501Y and E484K) on 3 March 2021, the variant VUI-21MAR-01
(B.1.324.1 with E484K) was designated VUI on detection as VUI-21MAR-01 (B.1.324.1
with E484K) on 4 March 2021.
Epidemiological profile
As of 22 April 2021, there are 2 confirmed cases in the UK in a group of returning
travellers, with links to additional unsequenced cases.
International epidemiology
As of 19 April 2021 there are no cases reported internationally.
GISAID includes data on sequences available internationally. As of the 21 April 2021, 0
sequences are listed internationally of VUI-21MAR-01.
VUI-21MAR-02 (P.3)
The VUI-21MAR-02 (P.3) was identified on 9 March 2021 in a report of 33 genomes from
the Philippines with 13 lineage defining mutations. This variant shares important mutations
with Variants of Concern including E484K, N501Y and P681H. Based on genomic profile,
PHE has designated VUI-21MAR-02 (P.3) on the 11 March 2021. This variant arises from
B.1.1.28, the same parent lineage that gave rise to P.1 and P.2 in Brazil. Phylogenetic
analysis of P.3 shows diversity indicating circulation prior to detection.
Epidemiological profile
AAs of 22 April 2021, there are 5 confirmed cases in the UK , of which 4 have recent travel
history.
International epidemiology
As of 19 April 2021, cases of VUI-21MAR-02 (P.3) have been reported in 9 countries or
territories (including the UK).
GISAID includes data on sequences available internationally. As of the 21 April 2021, 107
sequences are listed internationally of VUI-21MAR-02 excluding UK. (Australia 2, China 1,
Germany 7, Japan 3, Netherlands 4, New Zealand 3, Norway 2, Philippines 81, Singapore
1, South Korea 1, USA 2).
Sources and acknowledgments
Data sources
Data used in this investigation is derived from the COG-UK dataset, the PHE Second
Generation Surveillance System (SGSS), NHS Test and Trace, the Secondary Uses
Service (SUS) dataset and Emergency Care Data Set (ECDS).
Variant Technical Group
Authors of this report
PHE Genomics Cell
PHE Outbreak Surveillance Team
PHE Epidemiology Cell
PHE Contact Tracing Data Cell
Variant Technical Group Membership
The PHE Variant Technical Group includes representation from the following
organisations: PHE, DHSC, BEIS, Public Health Wales , Public Health Scotland, Public
Health Agency Northern Ireland, Imperial College London, London School of Hygiene and
Tropical Medicine, University of Birmingham, University of Cambridge, University of
Edinburgh, University of Liverpool, the Wellcome Sanger Institute.
Acknowledgements
The authors are grateful to those teams and groups providing data for this analysis
including: the Lighthouse Laboratories, COG-UK, the Wellcome Sanger Institute, tthe PHE
Epidemiology Cell, Contact Tracing, Genomics and Outbreak Surveillance Teams.
Published: April 2021
PHE gateway number: GW-7909