New South African SARS-CoV-2 variant called C.1.2 could change the course of the pandemic due to its ability to evade the immune system

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outh African researchers from the National Institute for Communicable Diseases (NICD), University of the Witwatersrand, University of Cape Town, University of Pretoria, University of KwaZulu-Natal and the Charlotte Maxeke Johannesburg Academic Hospital have discovered a new emerged SARS-CoV-2 variant called C.1.2 that is currently gaining dominance in circulation and could change the course of the COVID-19 pandemic as it is far more transmissible and also immune evasive due to enhancement by newer mutations found on its genome.

Both the WHO and also the U.S. CDC has been informed of the development and from the GSAID platforms it can be seen that C.1.2 variants has since been detected across the majority of the provinces in South Africa and alarmingly also in seven other countries spanning Africa, Europe, Asia and Oceania!
 
The report from study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2021.08.20.21262342v1
 
Various emerging SARS-CoV-2 variants of interest have been associated with increased transmissibility, neutralization resistance and disease severity.
 
Fortunately ongoing SARS-CoV-2 genomic surveillance world-wide has improved researcher’s ability to rapidly identify such variants.
 
The South African study team reports the identification of a potential variant of interest assigned to the PANGO lineage C.1.2. This lineage was first identified in May 2021 and evolved from C.1, one of the lineages that dominated the first wave of SARS-CoV-2 infections in South Africa and was last detected in January 2021.
 
Alarmingly, the emergence of C.1.2 variant was associated with an increased substitution rate, as was previously observed with the emergence of the Alpha, Beta and Gamma variants of concern (VOCs).
 
While the VOI Lambda (C.37) is phylogenetically closest to C.1.2, the latter has distinct lineage-defining mutations.
 
The new C.1.2 variant contains multiple substitutions (R190S, D215G, N484K, N501Y, H655Y and T859N) and deletions (Y144del, L242-A243del) within the spike protein, which have been observed in other VOCs and are associated with increased transmissibility and reduced neutralization sensitivity.
 
However, of greater concern is the accumulation of additional mutations (C136F, Y449H and N679K) which are also likely to impact neutralization sensitivity or furin cleavage and therefore replicative fitness.
 
Though these mutations occur in the majority of C.1.2 viruses, there is additional variation within the spike region of this lineage, suggesting ongoing intralineage evolution.
 
Approximately 44% of the viruses also contain a P25L mutation in the NTD, ~19% have L585F in S1, ~16% have T478K in the RBM, ~11% contain P681H adjacent to the furin cleavage site, 8% have D936H, and a further ~8% have H1101Q in S2.

The majority of these mutations (P9L, C136F, R190S, D215G, L242del, A243del, Y449H, E484K, N501Y, H655Y, and T716I) appeared together early in the lineage evolution (Fig. 3a).

Thereafter, the majority of sequences have also accumulated the mutations Y144del, N679K and T859N. The mutations P25L, W152R, R 346K, T478K, L585F, N440K, P681H, A879T, D936H and H1101Q can be seen in some of the smaller clusters from more recent sequences, further highlighting continued evolution within the lineage.
 
Researchers are worried that continued evolution of this lineage could result in the much anticipated deadly ‘Omega’ variant.
 
The C.1.2 lineage was first detected in the Mpumalanga and Gauteng provinces of South Africa, in May 2021. In June 2021, it was also detected in the KwaZulu-Natal and Limpopo provinces of South Africa as well as in England and China.
 
As of August 13, 2021 the C.1.2 lineage has been detected in 6/9 South African provinces (including the Eastern Cape and Western Cape), the Democratic Republic of the Congo (DRC), Mauritius, New Zealand, Portugal and Switzerland
 
The study team warns that while the phenotypic characteristics and epidemiology of C.1.2 are being defined, it is important to highlight this lineage given its concerning constellations of mutations.


ECDC regularly assesses new evidence on variants detected through epidemic intelligence, rules-based genomic variant screening, or other scientific sources. If a decision is made to add, remove, or change the category for any variant, the tables are updated to reflect this change. The tables are regularly sent for consultation to ECDC and WHO Regional Office for Europe’s joint virus characterisation working group. The rules-based genomic screening is performed using an open source algorithm. The weekly ECDC variant surveillance data report can be found in the weekly COVID-19 country overviews published on ECDC’s website. On 10 June 2021 ECDC published “Rapid Risk Assessment: Assessing SARS-COV-2 circulation, variants of concern, non-pharmaceutical interventions and vaccine rollout in the EU/EEA, 15th update” and on 23 June 2021 “Threat Assessment Brief: Implications for the EU/EEA on the spread of the SARS-CoV-2 Delta (B.1.617.2) variant of concern”.

Description of the tables

The tables include:

Category: variant of concern (VOC), variant of interest (VOI), or variant under monitoring (see definition above each table).

  1. WHO label: As of 31st May 2021, WHO proposed labels for global SARS-CoV-2 variants of concern and variants of interest to be used alongside the scientific nomenclature in communications about variants to the public. This list includes variants on WHO’s global list of VOC and VOI, and is updated as WHO’s list changes.
  2. Lineage and additional mutations: the variant designation specified by one or more Pango lineages and any additional characteristic spike protein changes. An alternate description may be used if the variant is not easy to describe using this nomenclature. For updated information on Pango lineages and definition of lineages and for instructions on how to suggest new lineages, visit the Pango lineages website. Each lineage in the table is linked to the respective lineage page on the Pango lineages website.
  3. Country first detected: only present if there is moderate confidence in the evidence relating to the first country of detection.
  4. Spike mutations of interest: not all spike protein amino acid changes are included – this is not a full reference for assignment of the variants. It includes changes to spike protein residues 319-541 (receptor binding domain) and 613-705 (the S1 part of the S1/S2 junction and a small stretch on the S2 side), and any additional unusual changes specific to the variant.
  5. Year and month first detected: as reported in the GISAID EpiCoV database. This can be adjusted backwards in time if new retrospective detections are made.
  6. Evidence concerning properties in three different categories:
    • Transmissibility
    • Immunity
    • Infection severity
      The evidence is annotated to indicate whether it is derived from the variant itself (v) or from mutations associated with the variant (m). Evidence that is deemed “low confidence” is annotated to indicate that it is unclear. An empty field means that we have not yet found and evaluated any scientific evidence for the category, while “no” indicates evidence that there is no change associated with the property. The comparator virus assumed “wild-type’” is B.1 (with D614G and no other spike protein changes).
  7. Transmission in the EU/EEA: categorised as dominant, community, outbreak(s), and sporadic/travel. The categories are qualitative, and the assessment is based on surveillance data collected in TESSy, GISAID EpiCoV data, epidemic intelligence data, and direct communications with the affected countries.

Variants of Concern (VOC)

For these variants, clear evidence is available indicating a significant impact on transmissibility, severity and/or immunity that is likely to have an impact on the epidemiological situation in the EU/EEA. The combined genomic, epidemiological, and in-vitro evidence for these properties invokes at least moderate confidence. In addition, all the criteria for variants of interest and under monitoring outlined below apply.

WHO labelLineage + additional mutationsCountry first detected (community)Spike mutations of interestYear and month first detectedEvidence for impact on transmissibilityEvidence for impact on immunityEvidence for impact on severityTransmission in EU/EEA
 AlphaB.1.1.7United KingdomN501Y, D614G, P681HSeptember 2020Yes (v) (1)NoYes (v) (2, 3)Community
 n/aB.1.1.7+E484KUnited KingdomE484K, N501Y, D614G, P681HDecember 2020Yes (v) (1)Yes (v) (4, 5)Yes (v) (2)Outbreaks
 BetaB.1.351South AfricaK417N, E484K, N501Y, D614G, A701VSeptember 2020Yes (v) (6)Yes (v) (7, 8)Yes (v) (3, 9)Community
 GammaP.1BrazilK417T, E484K, N501Y, D614G, H655YDecember 2020Yes (v) (10)Yes (v) (11) Yes (v) (3)Community
 DeltaB.1.617.2IndiaL452R, T478K, D614G, P681RDecember 2020Yes (v) (12)Yes (v) (13-15)Yes (v) (14, 16)Dominant

n/a: not applicable, no WHO label has been assigned to this variant at this time

All sub-lineages of the listed lineages are also included in the variant, e.g., AY.1 is included in Delta as it is a sub-lineage of B.1.617.2.

Variants of interest (VOI)

For these variants, evidence is available on genomic properties, epidemiological evidence or in-vitro evidence that could imply a significant impact on transmissibility, severity and/or immunity, realistically having an impact on the epidemiological situation in the EU/EEA. However, the evidence is still preliminary or is associated with major uncertainty. In addition, all the criteria for variants under monitoring outlined below apply.

WHO labelLineage + additional mutationsCountry first detected (community)Spike mutations of interestYear and month first detectedEvidence for impact on transmissibilityEvidence for impact on immunityEvidence for impact on severityTransmission in EU/EEA
EtaB.1.525NigeriaE484K, D614G, Q677HDecember 2020 Yes (m) (4) Community
ThetaP.3The PhilippinesE484K, N501Y, D614G, P681HJanuary 2021Yes (m) (1)Yes (m) (4) Sporadic/Travel
KappaB.1.617.1IndiaL452R, E484Q, D614G, P681RDecember 2020Yes (v) (17)Yes (v) (18-21) Outbreaks
n/aB.1.620Unclear (b)S477N, E484K, D614G, P681HFebruary 2021 Yes (m) (4, 22) Outbreaks
n/aB.1.621ColombiaR346K, E484K, N501Y, D614G, P681HJanuary 2021Yes (m) (1)Yes (m) (4) Sporadic/Travel
LambdaC.37PeruL452Q, F490S, D614GDecember 2020 Yes (23, 24) Detected (a)

n/a: not applicable, no WHO label has been assigned to this variant at this time

All sub-lineages of the listed lineages are also included in the variant, e.g., C.37.1 is included in Lambda as it is a sub-lineage of C.37.

Variants under monitoring

These additional variants of SARS-CoV-2 have been detected as signals through epidemic intelligence, rules-based genomic variant screening, or preliminary scientific evidence. There is some indication that they could have properties similar to those of a VOC, but the evidence is weak or has not yet been assessed by ECDC. Variants listed here must be present in at least one outbreak, detected in a community within the EU/EEA, or there must be evidence that there is community transmission of the variant elsewhere in the world.

WHO labelLineage + additional mutationsCountry first detected (community)Spike mutations of interestYear and month first detectedEvidence for impact on transmissibilityEvidence for impact on immunityEvidence for impact on severityTransmission in EU/EEA
n/aB.1.617.3IndiaL452R, E484Q, D614G, P681RFebruary 2021Yes (m) [1]Yes (m) (4, 25) Not detected
n/aB.1.214.2Unclear2Q414K, N450K, ins214TDR, D614GDecember 2020   Detected (a)
n/aA.23.1+E484KUnited KingdomV367F, E484K, Q613HDecember 2020 Yes (m) (4) Detected (a)
n/aA.27Unclear (b)L452R, N501Y, A653V, H655YDecember 2020Yes (m) (1)Yes (m) (25) Detected (a)
n/aA.28Unclear (b)E484K, N501T, H655YDecember 2020 Yes (m) (4) Detected (a)
n/aC.16Unclear (b)L452R, D614GOctober 2020 Yes (m) (4) Detected (a)
n/aB.1.351+P384LSouth AfricaP384L, K417N, E484K, N501Y, D614G, A701VDecember 2020Yes (v) (6)Yes (v) (7, 8)Unclear (9)Detected (a)
n/aB.1.351+E516QUnclear (b)K417N, E484K, N501Y, E516Q, D614G, A701VJanuary 2021Yes (v) (6)Yes (v) (7, 8)Unclear (9)Detected (a)
n/aB.1.1.7+L452RUnited KingdomL452R, N501Y, D614G, P681HJanuary 2021Yes (v) (1)Yes (m) (25)Yes (v) (2)Detected (a)
n/aB.1.1.7+S494PUnited KingdomS494P, N501Y, D614G, P681HJanuary 2021Yes (v) (1)Yes (m) (26)Yes (v) (2)Detected (a)
n/aC.36+L452REgyptL452R, D614G, Q677HDecember 2020 Yes (m) (25) Detected (a)
n/aAT.1RussiaE484K, D614G, N679K, ins679GIALJanuary 2021 Yes (m) (4) Detected (a)
IotaB.1.526 (d)USA E484K, D614G, A701VDecember 2020 Yes (m) (4) Detected (a)
n/aB.1.526.1 (d)USAL452R, D614GOctober 2020 Yes (m) (25) Detected (a)
n/aB.1.526.2 (d)USAS477N, D614GDecember 2020   Detected (a)
n/aB.1.1.318Unclear (b)E484K, D614G, P681HJanuary 2021 Yes (m) (4) Detected (a)
ZetaP.2BrazilE484K, D614GJanuary 2021 Yes (m) (4) Detected (a)
n/aB.1.1.519MexicoT478K, D614GNovember 2020 Yes (m) (25) Detected (a)
n/aAV.1United KingdomN439K, E484K, D614G, P681HMarch 2021 Yes (m) (4) Detected (a)
n/aP.1+P681HItalyD614G, E484K, H655Y, K417T, N501Y, P681HFebruary 2021 Unclear (27, 28) Detected (a)
n/aB.1.617.2 + K417NUnited KingdomL452R, T478K, D614G, P681R, K417NJune 2021   Detected (a)
n/aC.1.2South AfricaD614G, E484K, H655Y, N501Y, N679K, Y449HJune 2021Yes (m) (1)Yes (m) (4) Detected (a)
n/aB.1.617.2 + E484QIndiaL452R, T478K, D614G, P681R, E484QApril 2021   Detected (a)
n/aB.1.617.2 + Q613HIndiaL452R, T478K, D614G, P681R, Q613HApril 2021   Detected (a)

n/a: not applicable, no WHO label has been assigned to this variant at this time

All sub-lineages of the listed lineages are also included in the variant, e.g., AZ.1 is included in B.1.1.318 as it is a sub-lineage of it.

De-escalated variants

These additional variants of SARS-CoV-2 have been de-escalated based on at least one the following criteria: (1) the variant is no longer circulating, (2) the variant has been circulating for a long time without any impact on the overall epidemiological situation, (3) scientific evidence demonstrates that the variant is not associated with any concerning properties.

WHO labelLineage + additional mutationsCountry first detected (community)Spike mutations of interestYear and month first detectedEvidence for impact on transmissibilityEvidence for impact on immunityEvidence for impact on severityRationale for de-escalation
EpsilonB.1.427/B.1.429USAL452R, D614GSeptember 2020Unclear (25)Yes (v) Decrease in the proportion of the B.1.427/B.1429 isolates circulating in the EU/EEA countries and available data indicating that vaccines and treatments are effective against such variant
n/aB.1.616FranceV483A, D614G, H655Y, G669SFebruary 2021Detection (c) (29)  Not detected since 2021-04-23 (30)

n/a: not applicable, no WHO label has been assigned to this variant at this time

All sub-lineages of the listed lineages are also included in the variant, e.g., B.1.429.1 is included in B.1.427/B.1.429 as it is a sub-lineage of B.1.429.

(a) No assessment of transmission is given for variants in the monitoring category, only detected/not detected.

(b) The earliest detections from several different countries are close in time and there is no clearly demonstrated travel link to a specific country that explains the detections.

(c) The property of concern for this variant is the fact that there are reports of difficulties associated with detecting it in upper respiratory tract samples. These difficulties are not caused by primer-template mismatch but rather by the virus not being present in sufficient quantities in the upper respiratory tract.

(d) The sublineages of B.1.526 are listed as separate variants as they have different mutation profiles.

reference link :https://www.ecdc.europa.eu/en/covid-19/variants-concern

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