Investigation of novel SARS-CoV-2 variant

Nomenclature of variants in the UK

SARS-CoV-2 variants if considered to have concerning epidemiological, immunological or pathogenic properties are raised for formal investigation. At this point they are designated Variant Under Investigation (VUI) with a year, month, and number. Following risk assessment with the relevant expert committee, they may be designated Variant of Concern (VOC). This variant was designated VUI 202012/01 on detection and on review re-designated as VOC 202012/01 on 18 December 2020.

Current epidemiological findings

The specimen date for the first COVID-19 case with the VOC 202012/01 variant in England was 20 September 2020. As of 4 January 2021, a total of 6,008 cases with this variant have been identified in England, via routine genomic surveillance.

The following section describes demographic breakdowns of cases with the variant identified. As routine genomic surveillance may be non-random and not representative of all COVID-19 cases, similar breakdowns for the 68,246 cases with specimen dates between 20 September 2020 and 4 January 2021 that were routinely sequenced are provided for comparison ¹ .

Nomenclature of variants in the UK

Only a small fraction of all new cases of VOC 202012/01 are identified by whole-genome sequencing, and this data typically lags test date by approximately 2 weeks, therefore a proxy S gene target failure (SGTF) is used to indicate carriage of the VOC.

We previously observed that one of the S gene mutations in the VOC, which deletes amino acids 69 and 70 (Δ69-70), causes a reproducible S gene target failure (SGTF) in the Thermopath TaqPath assay used in 3 UK lighthouse laboratories (see Technical Briefing 1).

This coincidental occurrence provides a good proxy for monitoring trends in VOC 202012/01. SGTF correlates almost perfectly with presence of Δ69-70. Considering 14,950 tested samples where we know both the sequence and the SGTF status, 99.5% of Δ69-70 sequences (2190 of 2202) are SGTF, compared to 0.05% of sequences without the deletion (7 of 13278).

The majority of variant cases were resident in private dwellings (95.0% in variant cases and 94.3% in wild-type comparator cases). Variant cases were more likely to be part of a residential cluster (defined as all laboratory confirmed cases occurring at the same Unique Property Reference Number (UPRN) within 14 days of each other) compared to wild-type comparator cases (63.5% vs 56.1%, Chi-Squared test p=0.00).

Because Δ69-70 has arisen multiple times, and SGTF is a proxy for any lineage with that mutation, the utility of SGTF as a proxy for VOC 202012/01 varies over time and region. Table 4 shows, for all pillar 2 sequences, the weekly proportion of Δ69-70 sequences that were confirmed to be VOC 202012/01. Table 5 shows the proportion of Δ69-70 that is the VOC 202012/01 in England during December, broken down by region. It is, as expected, highest in the areas where the VOC was first observed, but it has been a substantial majority in all areas of England during the month of December. The numbers in these tables are based on sequenced samples, some of which may have come from the same individual (this effect is likely to be small).

Re-infection

Laboratory data were used to identify possible reinfections; these were defined as an episode of polymerase chain reaction (PCR) positivity at least 90 days before a recent PCR positive detection. Two reinfections were detected in in the variant case group (1.13/1000 cases) compared to 3 reinfections in the comparator group (1.70/1000 cases, Fisher’s exact P=1.00).

The same definition was applied to SGTF cases. These SGTF cases included samples with orf and N gene Ct values of <31, S gene defined as negative or positive based on presence or absence regardless of Ct value. The rate of detected re-infections in national SGTF cases was 0.60/1000 compared to a rate of 0.61/1000 in non-SGTF cases (P=0.94). When limited geographically to the Kent area, the rate of detected re-infections was 0.51/1000 compared to 0/1000 in non-SGTF cases (P=0.69).

Epidemiology of S gene target failure

The proportion of England specimens tested in the lighthouse laboratories using the assay which produces the S gene target failure is substantial and has been relatively constant over time (Figure 2). This however varies by geography, with lower coverage between 1 September 2020 and 4 January 2021 in local authorities in the East and South West of England.

The proportion of cases tested by this assay which are SGTF has continued to rise in December (Figure 3 and 4) in all regions (Figure 5). In the most recent seven-day period (29 December 2020 to 4 January 2021), 71.5% of 133,925 Pillar 2 cases detected in TaqPath laboratories had isolates with SGTF, compared to 27.7% of 57,919 in the seven-day period starting 1 December 2021.

The spatial distribution of SGTF cases shows a relatively higher burden in the south of England but with clear evidence of spread since the last update (Figure 3).

Cases by age and sex are displayed (Figure 6 and 7). Cases that had isolates with SGTF display a similar age-sex profile to other Pillar 2 cases tested by the TaqPath laboratories. Proportions of cases with SGTF were also similar across those aged under 25, between 25 and 59, and over 60: 71.0%, 72.2%, and 68.9% respectively among those diagnosed by TaqPath laboratories in the most recent seven-day period.

Analysis of secondary attack rates using routine contact tracing data

As of 5 January 2021, PHE has analysed secondary attack rates among contact tracing data (from NHS Test and Trace) for the variant of concern (VOC 202012/01) using both genomic sequence variant data and S-gene target failure (SGTF) data for pillar 2 cases tested by TaqPath labs.

Between 30 November 2020 and 20 December 2020, 386,805 cases were reported to NHS Test and Trace. 9,321 (2.4%) of these cases had genomic sequencing data included; 3,801 (40.8%) of those cases were VOC 202012/01. 212,943 (55.1%) cases had data from TaqPath; 90,401 (42.5%) of those cases were isolates with SGTF.

956,519 contacts reported to NHS Test and Trace were exposed between 30 November 2020 and 20 December 2020. 20,497 contacts were reported by cases with genomic sequencing data; 9,228 of those contacts were reported by cases with VOC 202012/01. 525,001 contacts were reported by pillar 2 cases tested by TaqPath labs; 262,769 of those contacts were reported by cases with SGTF.

121,072 (12.7%) of all contacts were known to become cases (secondary attack rate) ²:

• 14.7% among those whose index case had VOC 202012/01; 14.9% among those whose index case had SGTF
• 11% among those whose index case had a genomic result of wild type; 11% among those whose index case was tested by a TaqPath lab and did not have SGTF

Both when using genomic sequence data directly and SGTF as a proxy, the secondary attack rates estimated from contact tracing data are observed to be higher if the index case has the variant strain, from around 11% to 15% of named contacts. This increase is around 10% to 70% across most age groups and regions where sufficient sequencing data is available. Using the SGTF proxy to give a more comprehensive overview the increase is consistently around 30% to 50%.

² Data source and methods

Contacts with exposure dates within 30 November 2020 to 20 December 2020 were analysed for attack rate analyses. Genomic data from 1 November 2020 to 4 January 2021 and SGTF data from 1 November 2020 to 5 January 2021 were linked on SGSS specimen request ID to NHS Test and Trace (CTAS) individuals. Records with multiple inconsistent variants were not successfully linked.
CTAS data contains information collected from individuals with a positive test for SARS-CoV-2 referred to NHS Test and Trace (‘cases’) and individuals named by them as having been in contact with them between 2 days prior to symptom onset or test date and the date of tracing (‘contacts’). Persons can arise multiple times as cases and/or contacts in the data and are matched with themselves via combination of name, NHS number, date of birth, address and contact information. Transmission is defined to have occurred where a confirmed case (B) was previously reported as a contact by a case (A), where the date for case (A) interacting with case (B) is between 1 and 14 days inclusive prior to the onset of symptoms (or test date) for case (B). Where there was more than one contact event within the transmission window leading to a case, one event is counted per case who was previously a contact, with priority given to household contacts and to later interactions.
Sampling for variant breakdown in genomic and SGTF datasets is not random.

Attack rate: contacts becoming cases

*Direct: face to face contact (for example a conversation within 1 metre); skin to skin contact (including sexual contact); coughed on, sneezed on or spat on Close: within 1 metre for 1 minute or more (not necessarily face to face); within 1-2 metres for 15 mins or more (could be total 15 mins over 24 hours); travelling in a small vehicle; travelling in a large vehicle or plane (1 metre for 1 min and 1-2 metres for 15 mins)

Estimated attack rates for cases with VOC 202012/01 are 10%-70% higher than estimated attack rates with sequencing and wild type virus for most regions and age groups, excepting the East Midlands (which has relatively small numbers of people with genomic results).

*Direct: face to face contact (for example a conversation within 1 metre); skin to skin contact (including sexual contact); coughed on, sneezed on or spat on Close: within 1 metre for 1 minute or more (not necessarily face to face); within 1-2 metres for 15 mins or more (could be total 15 mins over 24 hours); travelling in a small vehicle; travelling in a large vehicle or plane (1 metre for 1 min and 1-2 metres for 15 mins)

Estimated attack rates for cases with SGTF are 30% to 50% higher than estimated attack rates for cases with TaqPath data without SGTF for most regions and age groups, excepting groups with few records such as the 80+ age group.

Virology

The workflow in process by PHE and partner laboratories is shown in Figure 8.

Activities in grey are completed and in blue are underway.

Data sources

Data used in this investigation is derived from the COG-UK dataset, the PHE Second Generation Surveillance System, NHS Test and Trace, the secondary uses service (SUS) dataset and Emergency Care Data Set (ECDS).

GISAID reference genome

Sequences from this VOC can be identified by searching for the B1.1.7 lineage on GISAID (gisaid.org). The canonical VOC genome is deposited with accession EPI_ISL_601443.

Contact: All enquiries relating to scientific or public health matters should be addressed to [email protected]

Authors: Variant Technical group
PHE:Meera Chand, Susan Hopkins, Gavin Dabrera, Hester Allen, Theresa Lamagni, Obaghe Edeghere, Christina Achison, Richard Myers, Maria Zambon, Vicki Chalker, Charlotte Anderson, Isabel Oliver, Richard Elson, Roberto Vivancos, Asad Zaidi, Meaghan Kall, Cong Chen, Charlie Turner, Marina Vabistsevits, Hannah Moore, Paula Blomquist, Gareth Hughes, Lara Utsi, Matt Edmunds, Mary Sinnathamby, Will Sopwith;
Imperial College London: Wendy Barclay, Neil Ferguson, Erik Volz;
University of Birmingham: Nick Loman;
University of Edinburgh: Andrew Rambaut;
Wellcome Sanger Institute: Jeff Barrett

Twitter: @PHE_uk

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, the PHE Contact Tracing Cell, Epidemiology Cell, Genomics Cell and Outbreak Surveillance team.
For queries relating to this document, please contact: [email protected]
Version 1, release date 5 January 2021

Published January 2021
PHE gateway number: GW-1856