SARS-CoV-2 Variants Of Concern And Variants Under Investigation

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SARS-CoV-2 variants of concern andvariants under investigation inEnglandTechnical briefing 206 August 2021This briefing provides an update on previous briefings up to 23 July 20211

SARS-CoV-2 variants of concern and variants under investigationContentsSummary. 3Published information on variants . 4Part 1: Surveillance overview . 51.1 Variants under surveillance . 51.2 Sequencing coverage . 71.3 VOC and VUI case numbers, proportion, deaths and case fatality rate . 111.4 Variant prevalence. 211.5 Antigenic change over time (international) . 261.6 Secondary attack rates . 301.7 Vaccination . 351.8 Updates from Variant Technical Group members. 36Part 2: Surveillance of individual variants. 372.1 VUI-21JUL-01 (B.1.621) Surveillance. 37Sources and acknowledgments . 42Data sources . 42Variant Technical Group . 422

SARS-CoV-2 variants of concern and variants under investigationSummaryThere are 4 current variants of concern (VOCs) and 10 variants under investigation (VUIs)(Table 1).This report has been published to continue to share the detailed variant surveillanceanalyses which contribute to the variant risk assessments and designation of new VOCsand VUIs. The specialist technical briefings contain early data and analysis on emergingvariants and findings have a high level of uncertainty.A new risk assessment for VUI-21JUL-01 (B.1.621) has been published and is availablehere. There are no updates to the Delta (B.1.617.2) risk assessment this week.A separate report is published covering routine data on all other VOCs and VUIs.Principal changes and findings are: there are no new VOCs or VUIs since the last briefingthe proportion of cases sequenced and genotyped remains relatively low buthas started to recover as case numbers fall and capacity expandsDelta variant accounted for approximately 99% of sequenced and 98%genotyped cases from 25 July to 31 July 2021PCR cycle threshold (Ct) values from routinely undertaken tests in Englandshow that Ct values (and by inference viral load) are similar between individualswho are unvaccinated and vaccinated.the UK Genotype to Phenotype Consortium reports new data relating to VUI21JUL-01 (B.1.621). There is evidence of reduction in pseudovirusneutralisation by serum from individuals who have been vaccinated orpreviously infected with DeltaAll risk assessments are published separately on the PHE webpage, Investigationof SARS-CoV-2 variants of concern, except for Gamma, which was publishedwithin Technical Briefing 7 and Alpha within Technical Briefing 9. As Delta is thedominant variant in the UK, epidemiological data in the weekly surveillance reportis also relevant.3

SARS-CoV-2 variants of concern and variants under investigationPublished information on variantsThe collection page gives content on variants, including prior technical briefings.Definitions for variants of concern, variants under investigation, and signals in monitoringare detailed in technical briefing 8. Data on variants not detailed here is published in thevariant data update. Variant risk assessments are available in prior technical briefings.Public Health England (PHE) curated a repository on the 5 March 2021 containing the upto-date genomic definitions for all VOCs and VUIs. The repository is accessible on GitHub.World Health Organization (WHO) nomenclature from 31 May 2021 is incorporated. Atable incorporating WHO and UK designations with Pango lineages is provided below(Table 1). Following the table, variants are referred to using their WHO designation wherethis exists and the UK designation where it does not.Technical briefings are published periodically. From 15 onwards, briefings include variantdiagnoses made by whole-genome sequencing and a genotyping PCR test, including thecategorisation of sequenced and genotyped variant results and a rules-based decisionalgorithm (RBDA) to identify variant and mutation (VAM) profiles from genotype assaymutation profiles. Genotyping is used to identify variants Alpha, Beta, Delta, and Gamma.Targets were updated in mid-May 2021 to prioritise accurate identification of Delta overAlpha.4

SARS-CoV-2 variants of concern and variants under investigationPart 1: Surveillance overview1.1 Variants under surveillanceTable 1 shows the current VOC, VUI, and variants in monitoring as of 2 August.Table 1. Variant lineage and designation as of 4 August 2021WHOnomenclatureas of 19 July2021LineageDesignationStatusUK orInternational(not currentlydetected in EC-02VOCUKGammaP.1VOC-21JAN-02VOCUKDeltaB.1.617.2, AY.1,AY.2, and AY.3VOC-21APR-02VOCUKZeta -03VUIUKB.1.1.318VUI-21FEB-04VUIUKTheta UI-21JUL-01VUIUKB.1.1.7 with ilon IotaB.1.427/B.1.429MonitoringB.1.1.7 with 1.7 oring5

SARS-CoV-2 variants of concern and variants under investigationWHOnomenclatureas of 19 July2021LineageDesignationStatusR.1MonitoringB.1 with214insQASMonitoringAT.1MonitoringLineage A withR346K, T478R andE484KMonitoringDelta like variantwithP.1 E484AN501T andMonitoringUK orInternational(not currentlydetected in itoringMonitoringProvisionally extinct variants are excluded from this table.VOCs and VUIs are monitored weekly for observations within the last 12 weeks. If variantshave not been detected in the UK within this period, they are moved to international statuswith continued monitoring. If a VOC or VUI has not been observed in the UK orinternational datasets within the preceding 12 weeks, it is designated as provisionallyextinct, but monitoring remains in place.VOC-21FEB-02 (B.1.1.7 with E484K) and VUI-21MAR-01 (B.1.324.1 with E484K) havenot been observed in the UK or within the international GISAID dataset within the last 12weeks. These variants are no longer included in the data update. Epsilon, Zeta and Theta were de-escalated by ECDC and by WHO.6

SARS-CoV-2 variants of concern and variants under investigation1.2 Sequencing coverageSequencing capacity has been maintained, but the proportion of cases sequenced hasfallen with increasing case numbers. Figure 1 shows the proportion of cases sequencedover time. Figure 2 shows the proportion of cases sequenced over time by regions. Figure3 shows the proportion of cases sequenced amongst cases who tested positive while inhospital.There is a reduction in overall sequencing coverage (Figure 1). Sequencing coverage isslightly higher for cases in hospital (Figure 3). During the current surge period, thesequencing strategy is: hospitalised cases and hospital staffcases among international travellersnational core priority studiesas near random a sample as possible from each region, to the maximumcoverage allowed by laboratory capacityThe increase in cases observed in England since the middle of June 2021 has resulted ina lower proportion of samples being sent for whole-genome sequencing (WGS) andgenotyping.7

SARS-CoV-2 variants of concern and variants under investigationFigure 1. Coverage of sequencing and genotyping over time (1 October 2020 to 2 August 2021)(Find accessible data used in this graph in underlying data)Grey shading was applied to the previous 14 days to account for reporting delays in sequencing data.8

SARS-CoV-2 variants of concern and variants under investigationFigure 2. Coverage of sequencing and genotyping over time by region (1 October 2020 to 2 August 2021)(Find accessible data used in this graph in underlying data)Grey shading was applied to the previous 14 days to account for reporting delays in sequencing data.There were 5493 cases with missing regional data that were excluded.9

SARS-CoV-2 variants of concern and variants under investigationFigure 3. Coverage of sequencing and genotyping for cases who test positive in hospital (1 October 2020 to 2 August 2021)(Find accessible data used in this graph in underlying data)Grey shading was applied to the previous 14 days to account for reporting delays in sequencing data.From 14 to 18 June 2021 an operational issue at a sequencing site resulted in a reduction in the number of samples with sequencing data of sufficient quality forvariant assignment. There were 19,502 samples reported to PHE as impacted by the incident. PHE has received approximately 10,000 sample identifiers from thelist of those affected of which sequencing data has been obtained for approximately 4,300 and genotyping data for 3,300 have a reflex assay result. Forapproximately 2,400 samples variant assignment is not possible. This issue resulted in a reduction in genome coverage for specimen dates 10 to 15 June 2021 andmay impact variant counts in figures and tables for this limited period. The unusable samples were from locations distributed around the UK and the proportions ofdifferent variants by region should be correct. In addition, the genotyping results means that this has limited impact in the interpretation of the overall data.10

SARS-CoV-2 variants of concern and variants under investigation1.3 VOC and VUI case numbers, proportion,deaths and case fatality rateSummary epidemiology on Delta is shown in Table 2 and for each variant is shown inTable 3, case numbers are also updated online. Table 3 shows the number of sequenced,genotyped, and total cases and deaths for each variant. However, case fatality rates arenot comparable across variants (see Table 3 footnote). Tables 4 and 5 show the numberof cases who visited an NHS Emergency Department, were admitted, and died in anysetting. The data is shown from 1 February 2021 onwards to enable comparisons acrossvariants. Figure 4 shows the cumulative number of cases per variant indexed by dayssince the first report.Information on attendance to emergency care is derived from the Emergency Care DataSet (ECDS), provided by NHS Digital. These data only show whether a case has attendedhospital and was subsequently admitted as an inpatient. The data excludes casescurrently in hospital or were directly admitted without first presenting to emergency care.The crude analysis indicates that the proportion of Delta cases who present to emergencycare is greater than that of Alpha, but a more detailed analysis indicates a significantlygreater risk of hospitalisation among Delta cases compared to Alpha (see page 50 ofVariant Technical Brief 15.ECDS reporting is lagged as NHS trusts routinely provide monthly data by the 21st of thefollowing month. However, some trusts report daily data, and the linkage betweencoronavirus (COVID-19) cases and ECDS data is updated twice-weekly.Table 2. Confirmed and provisional Delta cases by region as of 2 August 2021RegionConfirmedcasesProvisionalcases1East Midlands11,0696,27017,3395.8%East of 7314.6%North East11,4299,57421,0037.0%North West41,69340,35482,04727.3%South East19,82112,81132,63210.9%South West16,8084,34021,1487.0%1Total case Proportion of totalnumbercasesGenotyping is used to identify variants Alpha, Beta, Delta and Gamma; targets were updated in mid-May2021 to prioritise accurate identification of Delta over Alpha.11

SARS-CoV-2 variants of concern and variants under West Midlands12,41813,58326,0018.7%Yorkshire and 5130,352300,117-Unknown regionTotalTotal case Proportion of totalnumbercasesTable 3. Number of confirmed and provisional cases by variant as of 2 August 2021VariantConfirmed(sequencing)case numberProvisional(genotyping)case number2TotalcasenumberProportionof 1(A.23.1 withE484K)790790.0%2VOC-21FEB-02(B.1.1.7 2950.1%1VUI-21MAR-01(B1.324.1 0Alpha2Genotyping is used to identify variants Alpha, Beta, Delta and Gamma; targets were updated in mid-May2021 to prioritise accurate identification of Delta over Alpha.12

SARS-CoV-2 variants of concern and variants under investigationVariantConfirmed(sequencing)case numberProvisional(genotyping)case number2TotalcasenumberProportionof 20320.0%013

SARS-CoV-2 variants of concern and variants under investigationTable 4. Attendance to emergency care and deaths of confirmed and provisional cases in England (1 February 2021 to 2 years)CasesSince 1FebCases withCases with anspecimen date A&E visit §in past 28 days (exclusion‡)Cases with an Cases whereA&E visit§presentation to(inclusion#)A&E resultedin overnightinpatientadmission§(exclusion‡)Cases whereDeaths presentation toA&E resultedin %n% 1 4.8All cases150,541820.18,1085.4 10,4156.92,9502.04,4673.01,6141.1 50596101.7264.4284.750.881.310.2 50161-0.01811.22616.174.3159.374.3All cases766101.3445.7547.0121.6233.081.0 5021341.994.294.210.510.5-0.0 5021-0.014.814.8-0.0-0.0-0.0All cases23441.7104.3104.310.410.4-0.0 50265,749 84,77231.98,4493.2 10,9754.11,9700.73,0841.2710.0 5033,736 l cases300,010 98,7223.5 14,3194.83,0301.05,1591.77420.20.00.0-0.0-0.0-0.0 5016-32.9 10,3910.0-14-

SARS-CoV-2 variants of concern and variants under p(years)CasesSince 1FebCases withCases with anspecimen date A&E visit §in past 28 days (exclusion‡)Cases with an Cases whereA&E visit§presentation to(inclusion#)A&E resultedin overnightinpatientadmission§(exclusion‡)Cases whereDeaths presentation toA&E resultedin %n% 508-0.0112.5112.5112.5112.5-0.0All cases24-0.014.214.214.214.2-0.0 50273-0.0114.0134.851.862.2-0.0 50114-0.043.576.110.932.665.3All cases389-0.0153.9205.161.592.361.5 5023210.462.693.910.420.9-0.0 5055-0.011.823.6-0.011.811.8All cases28810.372.4113.810.331.010.3 504-0.0125.0125.0-0.0-0.0-0.0 503-0.0-0.0-0.0-0.0-0.0-0.0All cases7-0.0114.3114.3-0.0-0.0-0.0 50383-0.092.3102.610.320.5-0.0 5064-0.057.857.823.123.111.6All cases447-0.0143.1153.430.740.910.2 5011-0.0-0.0-0.0-0.0-0.0-0.015

SARS-CoV-2 variants of concern and variants under LambdaVUI21JUL01AgeGroup(years)CasesSince 1FebCases withCases with anspecimen date A&E visit §in past 28 days (exclusion‡)Cases with an Cases whereA&E visit§presentation to(inclusion#)A&E resultedin overnightinpatientadmission§(exclusion‡)Cases whereDeaths presentation toA&E resultedin %n% 502-0.0-0.0-0.0-0.0-0.0-0.0All cases13-0.0-0.0-0.0-0.0-0.0-0.0 50161-0.010.621.2-0.010.6-0.0 5023-0.0-0.0-0.0-0.0-0.014.3All cases184-0.010.521.1-0.010.510.5 50110-0.087.398.221.832.7-0.0 5031-0.0-0.0-0.0-0.0-0.0-0.0All cases142-0.085.696.321.432.1-0.0 508-0.0112.5112.5112.5112.5-0.0 50-------------All cases8-0.0112.5112.5112.5112.5-0.0 50261661.5-0.0-0.0-0.0-0.0-0.0 506350.0116.7116.7-0.0-0.0-0.0All cases321959.413.113.1-0.0-0.0-0.016

SARS-CoV-2 variants of concern and variants under investigationData sources: Emergency care attendance and admissions from ECDS, deaths from PHE daily death data series (deaths within 28 days). NHS trusts are required tosubmit emergency care attendances by the 21st of each month. As a result, the number of cases with attendances may show substantial increases in technical briefsprepared after the monthly cut-off, compared with other briefs from the same month. Cases without specimen dates and unlinked sequences (sequenced samples that could not be matched to individuals) are excluded from this table.* Cases are assessed for any emergency care attendance within 28 days of their positive specimen date. Cases still undergoing within 28-day period may have anemergency care attendance reported at a later date.§ At least 1 attendance or admission within 28 days of positive specimen date# Inclusion: Including cases with the same specimen and attendance dates‡ Exclusion: Excluding cases with the same specimen and attendance dates. Cases where specimen date is the same as date of emergency care visit are excludedto help remove cases picked up via routine testing in healthcare settings whose primary cause of attendance is not COVID-19. This underestimates the number ofindividuals in hospital with COVID-19 but only includes those who tested positive prior to the day of their emergency care visit. Some of the cases detected on theday of admission may have attended for a diagnosis unrelated to COVID-19. Total deaths in any setting (regardless of hospitalisation status) within 28 days of positive specimen date.17

SARS-CoV-2 variants of concern and variants under investigationTable 5. Attendance to emergency care and deaths of confirmed and provisional Delta cases in England by vaccination status(1 February 2021 to 2 August 2021)VariantDelta casesCases with an emergencycare visit§ (exclusion‡)Cases with an emergencycare visit§ (inclusion#)Cases where presentation toemergency care resulted inovernight inpatientadmission§ ((exclusion‡)Cases where presentation toemergency care resulted inovernight inpatientadmission§ (inclusion#)Deaths within 28 days ofpositive specimen dateTotalCases withspecimen datein past 28 days 50265,74984,77228,33023,82240,44925,536147,612 5033,73613,8032,9891955,64021,4723,440All cases300,01098,72231,84124,01846,08947,008151,054 508,449N/A707561,1276945,802 501,940N/A10153261,098491All cases10,391N/A827711,4531,7926,293 5010,975N/A1199531,3688647,671 503,342N/A24304861,815987All cases14,319N/A1459831,8542,6798,658 501,970N/A351362031531,443 501,059N/A712125620295All cases3,030N/A431483287731,738 503,084N/A612112982242,290 502,074N/A20232301,131670All cases5,159N/A822345281,3552,960 5071N/A2441348 50670N/A566538920518Unlinked 21 dayspostdose 1 21 days Received Unvaccinatedpost2 dosesdose 1Age group(years)**

SARS-CoV-2 variants of concern and variants under investigationVariantAge group(years)**TotalCases withspecimen datein past 28 daysAll cases742N/AUnlinked 21 dayspostdose 1810 21 days Received Unvaccinatedpost2 dosesdose 169402253Data sources: Emergency care attendance and admissions from ECDS, deaths from PHE daily death data series (deaths within 28 days). NHS trusts are required tosubmit emergency care attendances by the 21st of each month. As a result, the number of cases with attendances may show substantial increases in technical briefsprepared after the monthly cut-off, compared with other briefs from the same month. Cases without specimen dates and unlinked sequences (sequenced samples that could not be matched to individuals) are excluded from this table.* Cases are assessed for any emergency care attendance within 28 days of their positive specimen date. Cases still undergoing within 28-day period may have anemergency care attendance reported at a later date.§ At least 1 attendance or admission within 28 days of positive specimen date# Inclusion: Including cases with the same specimen and attendance dates‡ Exclusion: Excluding cases with the same specimen and attendance dates. Cases where specimen date is the same as date of emergency care visit are excludedto help remove cases picked up via routine testing in healthcare settings whose primary cause of attendance is not COVID-19. This underestimates the number ofindividuals in hospital with COVID-19 but only includes those who tested positive prior to the day of their emergency care visit. Some of the cases detected on theday of admission may have attended for a diagnosis unrelated to COVID-19. Total deaths in any setting (regardless of hospitalisation status) within 28 days of positive specimen date.** Age 50 50 do not total ‘all cases’ per category as some cases lack reported age data19

SARS-CoV-2 variants of concern and variants under investigationFigure 4. Cumulative cases in England of variants indexed by days since the fifthreported case as of 2 August 2021(Find accessible data used in this graph in underlying data)20

SARS-CoV-2 variants of concern and variants under investigation1.4 Variant prevalenceThe prevalence of different variants amongst genotyped and sequenced cases ispresented in Figures 5 and 6 and split by region in Figures 7 and 8. Genotyping providesprobably variant result with a shorter turnaround time of 12 to 24 hours after initialconfirmation of COVID-19. The initial panel of targets began trials in March 2021, usingsingle nucleotide polymorphisms that included N501Y, E484K, K417N, and K417T.Results have been reported and used for public health action since 29 March 2021. On 11May 2021, after rapid validation of targets to allow identification of Delta variant, P681Rwas introduced in the panel to replace N501Y. Genotyping results have now been fullyintegrated into the variant data reports and analyses. Changes in the use of genotypingover time should be considered when interpreting prevalence from genotyped data.The ‘Other’ category in Figures 6 and 8 includes genomes where the quality is insufficientto determine variant status and genomes that do not meet the current definition for a VUIor VOC. Sequencing numbers and coverage fall in the last week shown due partly tosequencing lag time, and new sequences are still being produced relating to sample datesin that week. The supplementary data for figures are available.Delta variant accounted for approximately 99% of sequenced and 98% genotyped casesfrom 25 July to 31 July 2021.21

SARS-CoV-2 variants of concern and variants under investigationFigure 5. Variant prevalence for available genotyped cases in England (1 February 2021 to 2 August 2021)(Find accessible data used in this graph in underlying data)A small number of cases identified as Beta (B.1.351) on genotyping since May 2021 without confirmatory sequencing may be VUI21JUL-01 (B.1.621) with an additional K417N mutation.22

SARS-CoV-2 variants of concern and variants under investigationFigure 6. Variant prevalence for available sequenced cases in England (1 February 2021 to 2 August 2021)Find accessible data used in this graph in underlying data).Dashed lines indicate period incorporating issue at a sequencing site.23

SARS-CoV-2 variants of concern and variants under investigationFigure 7. Variant prevalence for genotyped cases in England by region (1 February 2021 to 2 August 2021)(Find accessible data used in this graph in underlying data)Note that 1,253 cases were excluded due to missing region or specimen date information.24

SARS-CoV-2 variants of concern and variants under investigationFigure 8. Variant prevalence for sequenced cases in England by region (1 February 2021 to 2 August 2021)(Find accessible data used in this graph in underlying data)Note that 1,512 cases were excluded due to missing region or specimen date information.25

SARS-CoV-2 variants of concern and variants under investigation1.5 Antigenic change over time (international)A list of mutations of potential antigenic significance has been compiled using theavailable published evidence. The full list of mutations of potential antigenic significance iscompiled and continuously updated by an expert group comprising members of the varianttechnical group, COG-UK, and UK-G2P using literature searches and data mining frompublicly available datasets. Data analysis includes GISAID data uploaded before 4 August2021 (excluding UK data). The increase in the number of antigenic mutations over time isillustrated for all variants in Figure 9 and for variants excluding VOCs and VUIs in Figure10.The plots in Figures 9 and 10 were obtained by first counting the number of highconfidence antigenic mutations for each sequence. The sequences were then groupedand the prevalence for each number of mutations was estimated weekly from March 2020until 1 July 2021. All non-synonymous mutations at positions in the spike protein that havebeen associated with antigenicity were considered antigenic. VOCs or VUIs wereidentified by analysing their spike mutation profile to deal with low-quality and partialsequences.Table 6 shows additional spike mutations with a potential impact on antigenicity, avidity, orthe furin cleavage site significance acquired by Delta in the UK. This data uses thenumbers of genomes in the national genomic data set rather than case numbers. Onlymutations associated with antigenic change are presented here, such as those identifiedby published research. The unlinked sequences represent the number of sequences notpresent within the English surveillance system. These sequences include those samplesfrom the Devolved Administrations and cannot be associated with a date by PHE.26

SARS-CoV-2 variants of concern and variants under investigationTable 6. Additional spike mutations of interest detected in Delta genomes in the UK as of 3 August 2021Amino acidchangeDelta sequences inUK (COG UK)Delta sequencesoutside UK (GISAID)Delta sequences 4May to 3 June GE484AD80AE484KTotal 5135,6097482030500000401110011031,82027Delta sequences 4June to 3 July 2021Outside UK 32195390148518614103220181,079Delta sequences 4 Julyto 3 August 2021Outside UK 211948517203216913551564106501065,865Outside UK1,37380331220730111575151431,37321118157,899

SARS-CoV-2 variants of concern and variants under investigationFigure 9. Prevalence of antigenic mutations over time for all genomes in GISAID (excluding UK data) as of 4 August 2021(Find accessible data used in this graph in underlying data)28

SARS-CoV-2 variants of concern and variants under investigationFigure 10. Prevalence of antigenic mutations over time for all genomes in GISAID (excluding UK data), excluding VOCs andVUIs, as of 4 August 2021(Find accessible data used in this graph in underlying data)29

SARS-CoV-2 variants of concern and variants under investigation1.6 Secondary attack ratesThis section includes secondary attack rates for traveller and non-traveller cases, andseparate household contact rates, including new analysis of rates for household and nonhousehold contacts of non-traveller cases over time for Delta and Alpha variants.Secondary attack rates are based on positive tests amongst contacts named to NHS Testand Trace by an original case identified with a sequenced or genotyped VOC or VUI.Variant cases are identified using sequencing results supplemented with genotypingresults as of 26 July 2021 and exclude low-quality results.Secondary attack rates are shown for cases with and without travel history. In non-travelsettings, only close contacts named by the original case are included, that is, householdmembers, face-to-face contact, people within one metre of the case for one minute orlonger, or people within 2 metres for 15 minutes. In travel settings, the contacts reportedare not restricted to only close contacts named by the case. For example, they mayinclude contacts on a plane linked by additional contact tracing efforts. This likely deflatessecondary attack rates amongst travellers compared to non-travellers. In addition, peoplerecently returning from overseas are subject to stricter quarantine measures and maymoderate their behaviour towards contacts. Travel history suggests where infection of theoriginal case may have occurred.Table 7 shows secondary attack rates for all variants between 5 January 2021 and 13 July2021, which was a period chosen to capture data for all variants. Direct comparisonsbetween variants are not valid as vaccination levels and social restrictions in Englandhave varied over this period. Estimates of secondary attack rates for travel-relatedcontacts with VOCs or VUIS were considerably lower than non-travel cases due todifferences in contact defi

SARS-CoV-2 variants of concern and variants under investigation 4 Published information on variants The collection page gives content on variants, including prior technical briefings.

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