Research and analysis

SARS-CoV-2 variant surveillance and assessment: technical briefing 53

Updated 22 September 2023

Applies to England

Summary

This report has been published to share the detailed variant surveillance analyses which contribute to the variant risk assessments and designation of new SARS-CoV-2 variants. This specialist technical briefing contains early data and analysis on emerging variants and findings have a high level of uncertainty. Unless stated otherwise, this technical briefing uses a data cut-off of 4 September 2023 to allow time for analyses.

During periods when technical briefings are being published by the UK Health Security Agency (UKHSA), the routine variant prevalence and growth rate reports will be included in the technical briefing.

Situational assessment BA.2.86 (Variant Technical Group of 5 September 2023)

1. There is a continued slow accumulation of cases globally including cases reported from new countries. The rate of detection of new sequenced cases cannot be used as an indicator of growth due to limited and lagging genomic surveillance globally.
2. BA.2.86 is now more globally dispersed than other lineages of similar age in 2023. This may have been the result of international seeding from one or more unknown sources through mass travel. However, with apparent established transmission chains now in many countries, these seeding events are now unlikely to be the key driver of spread.
3. The data suggest established community transmission of BA.2.86 within the UK. This is based on the detection of multiple unlinked cases in different regions of the UK, without identified travel links, and phylogeny (the relationship between cases as determined by viral genomic data). This finding does not confirm that BA.2.86 has a growth advantage within the UK compared to other circulating variants.
4. A single care home outbreak was investigated due to a high attack rate and found to be BA.2.86. This cannot be used to make an assessment of the variant’s fitness but in contrast to recent laboratory data suggesting lower infectivity in vitro, this is an early indicator that the variant may be sufficiently transmissible to have impact in close contact settings.
5. Pseudovirus neutralisation data is available from several laboratories. Whilst this data has limitations, antigenic cartography based on mouse sera is mostly consistent with the antigenic distances estimated from the mutational profile. The potential UK population impact after several vaccines and waves cannot be extrapolated from the available data.
6. Some early indicators of increasing COVID-19 transmission in the UK were noted and behavioural, immunological and virological factors may all be contributing. We cannot confirm that BA.2.86 is contributing to any increase given available data.
7. There is an insufficient number of cases to make an assessment of outcome or severity. In the UK, the current surveillance systems do not support an assessment of comparative severity between variants but trends in severity and outcomes can be monitored over time through hospital data. It is likely that any such signal will take weeks to be visible and confirmed through sequencing.

Data summary

BA.2.86

As of 4 September 2023, there are 34 BA.2.86 sequenced cases in England, with cases located in East of England, London, and North West England. Of 34 total cases in England, 5 were hospitalised (2 have unknown hospitalisation status), and no deaths due to COVID-19 have been reported. These cases include 28 sequenced as part of an investigation of an outbreak in a care home which reported a high attack rate.

Cases in Scotland are reported by Public Health Scotland. There are no cases reported by Wales or Northern Ireland.

The global situation is dynamic with new cases identified daily. As of 5 September 2023, there are 33 sequences from human cases identified as BA.2.86 available in GISAID from 9 countries. The earliest collection date is 24 July 2023, and the most recent collection date is 26 August 2023. Of the 33 sequences, 2 are from the UK. The remaining UK sequence data will be uploaded to GISAID shortly, including those from the outbreak cluster described in this briefing. There are also multiple reports of BA.2.86 detected in wastewater in other countries though limited sequence data is available.

Virus was successfully isolated from the first UK case and passage 1 isolate has been shared with UKHSA; UKHSA and academic partners will undertake assessment using sera from UK studies.

Notification of change to UK genomic data upload procedures

UK sequencing centres upload sequence data to the Cloud Infrastructure for Microbial Bioinformatics (CLIMB), where sequences are processed. UK sequences (excluding Wellcome Sanger Institute sequences which are managed separately) are automatically uploaded from CLIMB to Global Initiative on Sharing All Influenza Data (GISAID) and International Nucleotide Sequence Database Collaboration (INSDC, specifically European Nucleotide Archive), after a lag to permit quality checking and analysis. From Wednesday 5 September 2023, the lag was reduced from 7 days to 72 hours (excluding weekends), to allow faster global sharing of sequencing data whilst still allowing time for manual quality and data checks to be performed.

Sequence variant prevalence (UKHSA-designated variants)

As of 31 August 2023, for sequences with a specimen date between 14 August 2023 and 20 August 2023 inclusive, 24.8% of UK sequences were classified as V-22OCT-02 (XBB), 23.3% were classified as V-23JUL-01 (EG.5.1), 19.5% were classified as V-23APR-01 (XBB.1.16), 5.8% were classified as V-23JAN-01 (XBB.1.5), and 1.5% were classified as V-22DEC-01 (CH.1.1). The remaining sequences (25.1%) were from lineages that have not been designated as a variant or are of insufficient quality to assign.

Horizon scanning

Variant designations are made when variants are considered significant enough to report in routine surveillance and to facilitate variant-specific epidemiological studies. The designation means that UKHSA has confirmed a genomic case definition and will monitor the variant through regular surveillance analyses. Since the last report EG.5.1 and BA.2.86 have been designated as variants V-23JUL-01 and V-23AUG-01 respectively.

Variants are identified as signals when they show growth or potentially significant mutational profile through a standard horizon scanning process. The following variants have been added to the signals under monitoring: FL.1 (increasing numbers), FY.4.1 (additional spike mutations compared to XBB).

Growth rates

Using English sequencing data, only XBB.1.16.6 and XBB.2.3.11 were identified by both the generalised assistive model and the logistic regression as having positive growth rates relative to other lineages. However, the sample sizes for the majority of lineages are relatively small. The lineage BA.2.86 does not appear in this analysis as it did not meet the criteria of 50 sequenced cases and 1.5% lineage prevalence in the past 6 weeks.

BA.2.86 (V-23AUG-01)

BA.2.86 was first raised as a signal in monitoring on 14 August 2023 as part of horizon scanning due to the large number of mutations present in the available international sequences. It was subsequently raised from a signal in monitoring to a variant V-23AUG-01 on 18 August 2023 due to further reported cases internationally and one case in the UK.

UK cases

There are 34 confirmed cases of BA.2.86 in England, with 3 low-quality sequences being further investigated.

Of the 34 sequenced cases, 28 cases are part of a care home outbreak in the East of England.

There are an additional 6 cases identified through routine surveillance: 4 in London, one in the North West, and one in the East of England. None of these cases are known to be epidemiologically linked and none have recent travel history.

Of 34 cases, 5 cases were hospitalised, 2 cases had unknown hospitalisation status, and there were no deaths due to COVID-19 among these cases (note that this will not be representative of all BA.2.86 cases as most genomic surveillance is among people tested in hospital).

Figure 1. Number of confirmed BA.2.86 cases by specimen date as of 4 September 2023

The data used in this graph can be found in the accompanying spreadsheet.

Figure 2. Age-sex breakdown of BA.2.86 cases as of 4 September 2023

The data used in this graph can be found in the accompanying spreadsheet.

Figure 3. Number of confirmed BA.2.86 cases by property type and specimen date as of 4 September 2023

The data used in this graph can be found in the accompanying spreadsheet.

Scotland have reported 2 confirmed cases of BA.2.86, further information about Scottish cases is published on the Public Health Scotland webpages.

Care home outbreak

On 21 August 2023 UKHSA was notified of an outbreak in a care home in the East of England with reports of an increased number of cases and increased severity compared to previous outbreaks at the home. All residents and symptomatic or lateral flow device (LFD) positive staff members were polymerase chain reaction (PCR) tested and PCR positive samples were referred to UKHSA for sequencing.

As of 5 September 2023, 33 out of 38 residents have tested positive for SARS-CoV-2 (attack rate 86.6%). Of the 33 positive residents, 19 (57.6%) were symptomatic with symptom onset between the 20 August 2023 and 28 August 2023; 29 of the residents have now recovered, while 4 remain unwell. One resident was hospitalised as a result of their illness (hospitalisation rate, 3.0%), and no deaths due to COVID-19 have been reported. Twelve staff tested positive either by LFD and/or PCR, and all have now recovered. No staff members were hospitalised.

A total of 43 samples were sent for sequencing (33 care home samples and 10 staff samples) of which 28 of the samples were identified as BA.2.86 (22 care home residents and 6 staff). Of the remaining 15 samples sent for sequencing, 11 were not suitable for sequencing, one failed and 3 are low quality and being further investigated.

At least 29 out of 33 the residents who tested positive had received a dose of COVID-19 vaccination as part of the spring booster campaign around 4 months prior to the outbreak and all 4 of the residents who tested negative had received a spring booster. Known information about confirmed cases among care home residents is summarised in table 1.

Table 1. Summary of the 33 confirmed SARS-CoV-2 cases among care home residents only

	Yes	No	Unknown	Rate
BA.2.86 confirmed	22	0	11	NA
Symptomatic	19	14	0	57.6%
Hospitalised	1	32	0	3.0%
Received spring booster	29	3	1	90.6%

The sequences from the care home cluster together and are distinct from other UK cases. All sequences from this cluster share 2 mutations that are not seen in any other BA.2.86 genomes to date: a synonymous mutation in nsp2 (2527 G>A); and a non-synonymous change in nsp3 (P153L).

The sequences in this cluster are most closely related to sequences from France (n=2) and Sweden (n=4). They share a non-synonymous mutation in nsp2 (Y441C) with these European sequences that is not observed in other BA.2.86 sequences. There are 3 mutations observed within the cluster that are not seen in all sequences. Two are each observed in a single sequence: nsp2 A318V and nsp2 F406C. The other mutation (S D1139N) is observed in 5 sequences in this cluster and the nucleotide change is observed as a mixed base in an additional sequence.

Global cases

As of 5 September 2023, there are 33 sequences from human cases identified as BA.2.86 available in GISAID. The sequences are from 9 countries: Canada (1), Denmark (12), France (2), Israel (2), Portugal (2), South Africa (3), Sweden (5), UK (2) and USA (4). The earliest collection date is 24 July 2023, and the most recent collection date is 26 August 2023. Figure 4 shows the proportion of sequences from human cases in GISAID that are identified as BA.2.86 by week of collection. An additional 5 partial sequences from wastewater samples are available from Thailand.

Figure 4. Proportion of sequences uploaded to GISAID since 1 July 2023 that are identified as BA.2.86

Sequences are grouped by week of collection and coloured by country of upload. Where collection date is not available, submission date has been used. The proportion of sequences which are BA.2.86 is indicated by the bar (left hand axis) The total number of sequences in GISAID are shown by the black line (right hand axis) and the total number of BA.2.86 sequences are shown in the number above each bar. Data as of 5 September 2023.

The data used in this graph can be found in the accompanying spreadsheet.

Phylogeny

Figure 5 shows a phylogeny of the BA.2.86 sequences available in GISAID and additional sequence data from cases in England. The alignment was generated using mafft (v7.467) and the phylogeny was generated using Fasttree (v2.1.11). Due to the large number of mutations seen in this lineage compared to other BA.2 sequences, the tree was generated without an outgroup and rooted manually. To reduce the impact of erroneous bases on the tree structure, several positions have been masked in the alignment.

The single bases masked because of suspected bioinformatics errors are: 22200; 22786; 23222; 21610; 22770; and 26577. The regions that are masked due to poor coverage are: 1-265; and 29675-29903 (inclusive). Due to poor alignment, the following deletions have also been masked: 21633-21641; 22194_22196; 28362-28370; 11288-11296; 21765-21770; and 21991-21993 (inclusive).

The phylogeny shows diversity among the BA.2.86 sequences and suggests multiple introductions to the UK. The sequences from samples in the outbreak described above cluster together and are most closely related to sequences from France and Sweden. They do not cluster with UK sequences that are not considered part of the outbreak. One sequence from this cluster (CLIMB-CM7YRJMO) has not been included in the phylogeny for quality reasons.

Figure 5. Phylogeny of BA.2.86 sequences available in GISAID and additional UK sequence data. Sequences are shown by country

Data cut off for sequence data from Scotland and GISAID is midday 4 September 2023. Data cut off for England is midday 5 September 2023.

Supplementary data is not available for this figure.

Phylogenetic analysis of globally available genome sequences of BA.2.86 shows distinct polytomies (numerous independent branches descended from a single point) within the phylogeny. This pattern may represent rapid amplification close to the origination of the lineage, seeding this variant in multiple countries. There is currently no evidence as to the nature of this event or its location. Based on the observed rate of evolution for SARS-CoV-2, the most recent common ancestor of these sequences is estimated to have existed in June, if not earlier.

Geographic dispersion

A comparative phylogenetic analysis was carried out to determine if the geographic dispersion of BA.2.86 was unusual relative to other contemporaneous circulating variants of SARS-CoV-2 with a similar time of common ancestry. A set of 272 clades of SARS-CoV-2 were identified from a global phylogeny of SARS-CoV-2 (downloaded from GISAID on 2 September 2023) and:

• having a time of most recent common ancestor (TMRCA) between 29 April and 1 July 2023 (see section on phylogeny)
• having at least one recently sampled descendent after 15 August 2023

TMRCAs in the global phylogeny were estimated using known dates of sample collection and the chronumental software. The geographic dispersion of each clade was quantified using a statistic based on Shannon’s entropy. This statistic is higher for clades which are observed in more countries and which do not have samples concentrated in a small number of countries.

The distribution of this statistic was compared to data for BA.2.86 as of 4 September, which included samples from Canada (1), Denmark (12), France (2), Israel (2), Portugal (2), South Africa (3), Sweden (5), the UK (8), and the USA (4). Most clades within the comparison set are observed within only a single country and therefore have zero dispersion. The BA.2.86 lineage has the greatest geographic dispersion as measured by this statistic (10.8) relative to the comparison set (mean = 0.68, IQR = 0-0.91).

Lab investigations

Virus was successfully isolated from the first UK case (Kings College London) and passage 1 isolate has been shared with UKHSA. This was put into culture on Vero/hSLAM cells with cytopathic effect (CPE) at day +3. Virus was harvested to form the assay bank and is now undergoing quality control.

UKHSA Porton will test this virus against panels of donated vaccinee sera, sera from the SIREN study including post XBB 1.5 infection, and CONSENSUS study samples and it will also be used to verify lateral flow device performance.

To date isolation from the second UK case has not been successful. UKHSA continues to intercept clinical material from the sequencing pipelines for further isolation.

The G2P2 consortium are currently undertaking a range of laboratory investigations to establish virulence (both in vitro and in vivo), neutralisation data and spike fusion analyses. Results of these analyses will be reported in due course.

Variant prevalence report

Variant prevalence

Testing policy and sequencing should be considered when interpreting variant data. Information about surveillance systems for England are reported by UKHSA in the national influenza and COVID-19 surveillance report.

The prevalence of lineages amongst UK sequences by Phylogenetic Assignment of Named Global Outbreak Lineages (Pangolin) designation is presented in Figure 1. Lineages are shown if there are more than or equal to 5,000 sequences since 13 March 2023 or if they represent more than or equal to 1% of sequences within a single week over the last 6 weeks. Lineages that do not meet these criteria are combined with their parent lineage (for example, BA.2.4 is combined with BA.2).

The lineages have been assigned using the accurate Ultrafast Sample placement on Existing tRee (UShER) mode and version 1.22 of the Pangolin data.

Figure 6. Prevalence of Pango lineages in the UK sequence data with a specimen date from week beginning 13 March 2023 to week beginning 14 August 2023, as of 31 August 2023

The data used in this graph can be found in the accompanying spreadsheet.

The total number of valid sequence results per week is shown by the black line. The ‘Other’ category in this plot contains all lineages that do not meet the relevant criteria after combining smaller sub-lineages. ‘Unassigned’ are sequences that could not be assigned a lineage by Pangolin. Lineages present in at least 2% of sequences in the most recent week are labelled to the right of the plot. Please refer to previously published routine updates for the relationship between lineages.

Variant modelling

Methods used for variant modelling have previously been described in the UKHSA prevalence and growth rate briefings.

Growth rates were based on sequences sampled through Pillar 1 testing (primarily positive tests conducted in hospital) in England (Table 2). The sampling range for both the logistic regression generalised linear model (GLM) and generalised additive model (GAM) is from 7 March 2022 to 22 August 2023. The model fit for any lineage with a positive growth rate advantage (with 95% confidence intervals (CIs) that do not cross zero) are shown in Figure 7. The lineages with a positive growth rate estimated with reasonable confidence are XBB.1.16.6 (39.2%, GAM), EG.5.1.1 (38.3%, GAM), EG.5.1.4 (37.2%, GAM), XBB.1.16.15 (29.9%, GAM), EG.5.1.3 (27.1%, GAM), EG.5.1 (24.8%, GAM), XBB.2.3.11 (22.03%, GAM), FL.1.5.1 (12.62%) and XBB.1.16.11 (5.11%, GAM).

Table 2. Growth rate (GR) of English sequence lineages as of 22 August 2023†

Lineage*	Lineage group composition**	Pillar 1 sample size***	Weekly growth rate advantage (GAM)	Estimated prevalence¥ (GAM)	Weekly growth rate advantage (GLM)
XBB.1.16.6	XBB.1.16.6 (100%)	82	39.2% (95% CI: 36.3 to 41.98)	6.64% (95% CI: 4.63 to 9.44)	49.41% (95% CI: 11.87 to 86.95)
EG.5.1.1 (XBB.1.9.2.5.1.1)	EG.5.1.1 (98.95%); HK.3 (0.7%); HK.2 (0.35%)	285	38.34% (95% CI: 38.39 to 38.28)	17.42% (95% CI: 11.77 to 25.03)	-12.07% (95% CI: -30.57 to 6.43)
EG.5.1.4 (XBB.1.9.2.5.1.4)	EG.5.1.4 (100%)	60	37.18% (95% CI: 30.63 to 43.73)	5.11% (95% CI: 3.32 to 7.78)	16.6% (95% CI: -21.4 to 54.6)
XBB.1.16.15	XBB.1.16.15 (100%)	64	29.86% (95% CI: 25.96 to 33.76)	4.97% (95% CI: 3.54 to 6.92)	36.48% (95% CI: -3.1 to 76.06)
EG.5.1.3 (XBB.1.9.2.5.1.3)	EG.5.1.3 (100%)	83	27.05% (95% CI: 20.92 to 33.18)	5.75% (95% CI: 4 to 8.2)	19.37% (95% CI: -13.71 to 52.44)
EG.5.1 (XBB.1.9.2.5.1)	EG.5.1 (83.22%); EG.5.1.6 (12.75%); EG.5.1.2 (3.36%); EG.5.1.5 (0.67%)	149	24.8% (95% CI: 20.32 to 29.29)	9.42% (95% CI: 6.52 to 13.42)	16.51% (95% CI: -6.41 to 39.43)
XBB.2.3.11	XBB.2.3.11 (91.14%); GS.1 (8.86%)	79	22.03% (95% CI: 19.83 to 24.22)	5.12% (95% CI: 3.9 to 6.69)	41.06% (95% CI: 8.35 to 73.77)
FL.1.5.1 (XBB.1.9.1.1.5.1)	FL.1.5.1 (100%)	58	12.62% (95% CI: 4.02 to 21.21)	3.02% (95% CI: 1.65 to 5.46)	-12.47% (95% CI: -52.65 to 27.71)
XBB.1.16.11	XBB.1.16.11 (100%)	89	5.11% (95% CI: 3.76 to 6.46)	5.36% (95% CI: 2.51 to 11.06)	21.05% (95% CI: -9.21 to 51.32)
XBB.1.9.1	FL.4 (23.19%); XBB.1.9.1 (18.84%); FL.24 (11.59%); FL.15 (11.59%); FL.3 (10.14%)…	69	4.88% (95% CI: -6.99 to 16.74)	3.01% (95% CI: 1.75 to 5.12)	3.37% (95% CI: -31.4 to 38.14)
GE.1 (XBB.2.3.10.1)	GE.1 (100%)	141	-4.93% (95% CI: -12.38 to 2.51)	6.45% (95% CI: 4.52 to 9.13)	7.59% (95% CI: -17.02 to 32.2)
XBB.1.9.2	XBB.1.9.2 (46.74%); EG.1 (21.74%); EG.2 (20.65%); EG.7 (8.7%); EG.5 (2.17%)	92	-17.91% (95% CI: -31.58 to -4.24)	1.84% (95% CI: 1.02 to 3.29)	-14.99% (95% CI: -49.95 to 19.96)
XBB.1.5	XBB.1.5 (40.17%); XBB.1.5.28 (8.55%); XBB.1.5.59 (8.55%); XBB.1.5.11 (5.98%); XBB.1.5.71 (5.98%)…	117	-18.84% (95% CI: -28.71 to -8.96)	2.59% (95% CI: 1.69 to 3.94)	-26.71% (95% CI: -55.97 to 2.54)
XBB.1.16.1	XBB.1.16.1 (72.73%); FU.1 (19.32%); FU.2 (5.68%); FU.3 (1.14%); FU.4 (1.14%)	88	-23.08% (95% CI: -34.31 to -11.84)	1.79% (95% CI: 1.03 to 3.08)	-9.58% (95% CI: -48.18 to 29.02)
XBB.1.16	XBB.1.16 (71.79%); XBB.1.16.21 (6.59%); XBB.1.16.19 (4.76%); XBB.1.16.9 (4.58%); XBB.1.16.2 (2.75%)…	546	-26.43% (95% CI: -32.6 to -20.26)	12.84% (95% CI: 9.45 to 17.2)	-2.04% (95% CI: -16.38 to 12.29)
EG.6.1 (XBB.1.9.2.6.1)	EG.6.1 (100%)	51	-50.1% (95% CI: -72.15 to -28.06)	0.84% (95% CI: 0.35 to 2.02)	-16.87% (95% CI: -63.63 to 29.89)

*Listed parent lineages include all sub-lineages, other than those explicitly modelled.

** The top 5 contributing lineages to the modelled group in the most recent 6 weeks (11 July 2022 to 22 August 2023). More than 5 sublineages are indicated by “…”

*** Sample size is for Pillar 1 samples in England in the most recent 6 weeks (11 July 2022 to 22 August 2023).

¥ Estimated prevalence for the 22 August 2023.

† Sampling range for both logistic regression and generalised additive models is from 7 March 2022 to 22 August 2023.

CI = confidence intervals.

Figure 7. Modelled prevalence of lineage groups with a growth rate advantage over other circulating lineages

Supplementary data is not available for this figure.

The black line shows the central estimate and blue shaded regions the 95% confidence intervals. Points show the national level proportions, with the size being indicative of the sample size for that particular lineage. The grey portion of the ribbon denotes that this period of time is likely to be backfilled with more sequenced cases, making proportions unreliable.

Published information on variants

On 1 April 2022 UKHSA amended its variant classification system. Further details are available in technical briefing 39.

SARS-CoV-2 routine variant data update covers surveillance data and sequencing coverage data on all other variants up to 25 March 2022.

The collection page gives content on variants, including previous technical briefings. Technical briefings are published periodically.

The UKHSA variant definition repository contains the previous genomic definitions for UKHSA declared variants.

Sources and acknowledgments

Data sources

Data used in this investigation is derived from the CLIMB and UKHSA genomic programme data set, the UKHSA Second Generation Surveillance System, the Secondary Uses Service data set, Emergency Care Data Set, the UKHSA Case and Incident Management System and GISAID.

Authors of this report

Nurin Iwani Binti Abdul Aziz

Wendy Barclay

Jamie Lopez Bernal

Kevin Bewley

Naomi Coombes

Meera Chand

Gavin Dabrera

Katy Davidson

Martyn Fyles

Eileen Gallagher

Rachael Graham

Natalie Groves

Bassam Hallis

Susan Hopkins

Robert Jordan

Meaghan Kall

Amelia Kelly

Nick Loman

Edward Parsons

Laura Lopez Pascua

Rob Patton

Andrew Rambaut

Elise Tessier

Erik Volz

Tom Ward

Variant Technical Group members

Chair

Meera Chand (UKHSA)

Genomics and bioinformatics

Andrew Rambaut (University of Edinburgh)

Thomas Peacock (Pirbright Institute and Imperial College London)

Matt Holden (Public Health Scotland)

Nicholas Loman (UKHSA and University of Birmingham)

Richard Myers (UKHSA)

Eileen Gallagher (UKHSA)

Natalie Groves (UKHSA)

Virology and immunology

Bassam Hallis (UKHSA)

Derek Smith (University of Cambridge)

Gavin Screaton (University of Oxford)

Lance Turtle (University of Liverpool)

Maria Zambon (UKHSA)

Ravi Gupta (University of Cambridge)

Susanna Dunachie (University of Oxford)

Tim Wyatt (Northern Ireland Public Health Agency)

Wendy Barclay (Imperial College London)

Emma Thomson (University of Glasgow and London School of Hygiene and Tropical Medicine)

Epidemiology and modelling

Chris Williams (Public Health Wales)

Daniela de Angelis (University of Cambridge)

Erik Volz (UKHSA and Imperial College London)

Fergus Cumming (UKHSA)

Jamie Lopez-Bernal (UKHSA)

John Edmunds (London School of Hygiene and Tropical Medicine)

Julia Gog (Scientific Pandemic Influenza Group on Modelling and University of Cambridge)

Maria Rossi (Public Health Scotland)

Neil Ferguson (Imperial College London)

Meaghan Kall (UKHSA)

Susan Hopkins (UKHSA)

Thomas Finnie (UKHSA)

Thomas Ward (UKHSA)

International epidemiology

Chris Lewis (Foreign, Commonwealth and Development Office)

Acknowledgements

The authors are grateful to those teams and groups providing data for these analyses including: the National Health Service, CLIMB, the Wellcome Sanger Institute, Health Protection Data Science teams, the Genotype to Phenotype Consortium, Medical Research Council Biostatistics Unit, the Francis Crick Institute, Cambridge and Imperial College, London.

We are also grateful to the SIREN and CONSENSUS studies as well as Kings College London for providing materials for laboratory analysis.