Network for Genomic Surveillance South Africa (NGS-SA)

SARS-CoV-2 Sequencing Update
25 November 2021

Summary of new variant• New variant detected in South Africa (lineage B.1.1.529) with high number ofmutations, which are concerning for predicted immune evasion andtransmissibility• B.1.1.529 genomes produced from samples collected 12-20 Nov from Gauteng, SA(n=77), Botswana (n=4) and Hong Kong (n=1, traveler from SA)• B.1.1.529 can be detected by one particular PCR assay (before whole genomesequencing) – this will help us to track and understand spread• Early signs from diagnostic laboratories that B.1.1.529 has rapidly increased inGauteng and may already be present in most provinces• We can make some predictions about the impact of mutations in this variant, but
full significance uncertain and the vaccines remain the critical tool to protect us
against severe disease

News24 – 23 Nov 2021

First signs of fast increase ofcases in Gauteng.

Is this a cluster
outbreak?
Real resurgence?
Start of 4th wave?

Timeline of discovery of new variant(36h from this media briefing).
- Tuesday 23 November 2pm – Discovery of new variant from samples from Lancet by NICD thatshowed different results in qPCR. Samples from 14 to 16 of November, which is the start of rise ininfections in JHB.
- Tuesday 23 November 3pm – Urgent meeting of the NGS-SA to discuss results, during the meetingmessage to NDoH and DSI.
- Wednesday 24 November – Detailed analysis of the NHLS data, more genomes produced at KRISP
and NICD, support the new variant to be concerning. Informed DSI and NDoH.
- Wednesday 24 November – First news reports from similar variant found in Botswana and China(from SA traveler) from sequences in databases on 23 November.
- Thursday 25 November – 8 am presentation to ministers of NDoH and DSI, 10:30 to president. 1pmtalking to media- Friday 26 November – Requested and approved an urgent sitting of WHO TWG on virus evolution.

Onset of Illness among the First 425 Confirmed Cases of Novelcurve – SouthAfrica
CoronavirusEpidemic(2019-nCoV)–Infected
Pneumonia(NCIP) inWuhan, China.

Estimated effective reproduction number Re = 1.47 (1.22 - 1.72)
Gauteng Re = 1.93 (1.67 – 2.19)
https://ibz-shiny.ethz.ch/covid-19-re-international/

Onset of Illness among the First 425 Confirmed Cases of Novel
SustainedMonitoring
Gauteng- SACMC
Coronavirus Increase(2019-nCoV)–Infected
Pneumonia(NCIP)
in
Wuhan, China.

Sustained increase in incidence across all Gauteng municipalities
Estimated effective reproduction number Gauteng = 1.93 (1.67 – 2.19)
https://www.sacmcepidemicexplorer.co.za/
https://ibz-shiny.ethz.ch/covid-19-re-international/

Onset of Illness among the First 425 Confirmed Cases of Novel
positivity rate- Gauteng
CoronavirusTest(2019-nCoV)–Infected
Pneumonia(NCIP) inWuhan, China.

Week 44 (31 Oct – 6 Nov)

Week 45 (7-13 Nov)

Week 46 (14-20 Nov)

Rapid increase in test positivity in Tshwane in last week

https://www.nicd.ac.za/diseases-a-z-index/disease-index-covid-19/surveillance-reports/weekly-testing-summary/B.1.1.529 – mutation profile

Very unusual constellation of mutations - multiple mutations across the SARS-CoV-2
genome, with >30 mutations in spike protein
Mutation profile clearly very different from other circulating VOCs/VOIs
Some mutations well characterized with known phenotypic impact (affectingtransmissibility, immune evasion), but many others rarely observed until now andnot well characterized – so full significance uncertain

B.1.1.529 – potential impact of mutations• Multiple RBD and NTD mutations associated with resistance to neutralizingantibodies (and therapeutic monoclonal antibodies)• Cluster of mutations (H655Y + N679K + P681H) adjacent to S1/S2 furin cleavage site –associated with more efficient cell entry → enhanced transmissibility• nsp6 deletion (Δ105-107) – similar to deletion to Alpha, Beta, Gamma, Lambda – may
be associated with evasion of innate immunity (interferon antagonism) → could alsoenhance transmissibility• R203K+G204R mutations in nucleocapsid - seen in Alpha, Gamma, Lambda –associated with increased infectivity

B.1.1.529 becoming dominantB.1.1.529 genomes detected in GP
South Africa variants by province
KwaZulu−Natal
Gauteng

Variants

Western Cape

20H (Beta, V2)
Limpopo20I (Alpha, V1)
B.1.1.529

Eastern Cape

C.1.2
Free StateDeltaOther Lineages

Northern CapeNorth West
Mpumalanga
Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec
2020 2020 2020 2021 2021 2021 2021 2021 2021 2021 2021 2021 2021 2021 2021

monthSequences from KZN due today or tomorrow. PCR proxy for variant in most other provinces.

PCR-based proxy for new variant• Variant can be detectedwith one particular PCR
assay (before wholegenome sequencing)• New increase in S-gene
dropout noted by NHLS
and private labs very
recently - from midNovember• Now rapidly increasing inmost provinces
Courtesy of Lesley Scott and NHLS teamS gene target failure by province• Rapid increase in proportion with SGTF
noted across multiple provinces (caution low
number of tests in most provinces)• 77 samples with SGTF sequenced fromGauteng (samples collected 12-20 Nov) –77/77 (100%) were B.1.1.529• Hundreds of recently collected samples
being sequenced currently by NGS-SA labs –results available by end of week (today wereceived 70 samples from Gauteng 67/70
were SGTF and sequencing tonight, in KZN
approximately 20%).

Courtesy of Lesley Scott and NHLS team

Work needed to understand phenotypic impact

Transmissibility

Risk of reinfection

Vaccines

Disease severity

Diagnostics

Summary• Epidemiological data suggest sustained increase in COVID-19 incidence acrossGauteng, possibly fueled by cluster outbreaks• New variant (B.1.1.529) detected in multiple samples from across Gauteng• Public and private testing labs in Gauteng have noticed a significant and rapid
increase in detection of variant (based on PCR proxy), and now increasing inother provinces• Mutation profile predicted to give significant immune evasion and enhanced
transmissibility – urgent work already started to understand full significance• We can make some predictions about the impact of mutations in thisvariant, but full significance uncertain and the vaccines remain the critical
tool to protect us against severe disease

Additional support and collaborators
NHLS
Koeleka Mlisana
Zinhle Makatini
Eugene Elliot
Florette K. Treurnicht
Kathleen Subramoney
Oluwakemi Laguda-Akingba
Shareef Abrahams
Greta Hoyland
Gloria Selabe
Elias Bereda
Jeannette WadulaHyrax Biosciences
Simon Travers
Cape Town HVTN Laboratory
Erica Anderson-Nissen
Anneta NaidooNdlovu Research
Hugo Tempelman
CJ Umunnakwe

LancetAllison J. Glass
Raquel Viana

CAPRISA
Salim Abdool Karim
Nigel Garret

Africa CDC
John Nkengasong
Sofonias Tessema

AmpathTerry Marshall
Cindy van Deventer
Eddie Silberbauer

UKZN - Big Data
Francesco Pettruccione
Ilya Sinayskiy

Netcare:Richard Friedland
Craig Murphy
Caroline Maslo
Liza Sitharam

Pathcare Vermaak
Andries Dreyer
Howard Newman
Riaan Writes
Marianne Wolfaardt
Warren Lowman

University of Oxford
José Lourenço
FioCruz, Brazil
Vagner Fonseca
Marta Giovanetti
Luiz Carlos Junior Alcantara

Bridge-the-Gap
Raymond RottCytespace Africa Laboratories
Christa Viljoen
ARC-OVI
Lia Rotherham

DSI
Glaudina Loots
SA MRC
Glenda Gray
Chan Soon-Shiong
Foundation
Dr. Patrick Soon-Shiong
Rockefeller Foundation
Dr. Rick Bright