Thread by @Tuliodna

Release of 8 new genomes of a new lineage of SARS-CoV-2 with > 100 mutations from South Africa. This is probably the most divergence lineage identified this year. In this thread, we highlight some of the characteristics of the new BA.2.X lineage and epidemiology in SA.

So far, this has been detected from eight samples from three districts in Limpopo and Gauteng provinces (Capricorn, City of Johannesburg and City of Tshwane) between 20 September and 29 November 2023. All eight genomes were sequenced by the NICD from SARS-CoV-2 genomic surveillance (routine diagnostic samples) or syndromic GP-based surveillance (Viral Watch) @nicd_sa

•The variant is genetically distinct from currently circulating Omicron lineages (particularly BA.2.86 and JN.1), and initial analysis suggests it has likely emerged from BA.2 or from the basal node of Omicron.

•Relative to BA.2, this cluster has >30 non-synonymous substitutions (concentrated in spike) and 7 deletions (3 in spike)
•There is diversity within the cluster, in keeping with the likely mode of emergence and sample collection over a 10-week period

In order to determine if this is widespread, South Africa has increased genomics surveillance, with very little signal that this new lineage is spreading widely and replacing the current dominating BA.2/JN.1

A closer look on the distribution of the new lineage and increased genomics surveillance in South Africa.

•Many mutations concentrated in important regions of the spike protein
•Two large deletions in the antigenic supersite of the N-terminal domain (15-26del and 136-146del)
•Multiple mutations at important antigenic sites in receptor-binding domain (e.g. K417T, K444N, V445G, L452M, N460K, N481K)
•Mutations close to the furin cleavage site (N679R, S691P)

Major rearrangement on the Spike NTD -
- Deletion of both segments of the NTD antigenicity supersite and additional NTD mutations
- Deletion of the NTD disulphide bond
- Large impact expected on the ability of existing immunity to recognize the the spike NTD
- This alone should not strongly impact protection from prior infection/vaccination

Impact on transmissibility and pathogenicity unknown and outgrown process already started @sigallab @nicd_sa

•At the same time, a single sequence (EPI_ISL_18839074) has been identified that is also genetically distinct from currently circulating Omicron lineages
•This genome was sequenced by the NICD from a sample collected on 29 November 2023 through pneumonia surveillance in Gauteng
•Initial analysis suggests this is not directly related to the cluster of eight genomes, and that this sequence is most closely related to BA.2.15 (a BA.2 sublineage that emerged and circulated in South Africa in early 2022)
•None of the new cluster have the lineage-defining mutations of BA.2.15

The 9 genomes are already registered at PANGO discussion group with more details at: github.com/cov-lineages/p…

South Africa still continue surveillance of SARS-CoV-2 in a number of well-stablished surveillance sites by NICD data from national surveillance programs (influenza-like illness and pneumonia)
Routine PCR testing data from private laboratories suggests some variability in SARS-CoV-2 test positivity in 2023, but no evidence of sustained increase at any point between September-December 2023

The Pneumonia surveillance public hospitals do not see any major rate of increase since the new lineage has been detected. Detailed report at: nicd.ac.za/diseases-a-z-i…

Routine laboratory data and SARS-CoV-2 PCR test positivity does not show any major increase and a decrease in the positivity in the recent weeks.

We also do not see an increase in the wastewater surveillance sites

Likely originated in a chronic infection?
18 of the Spike mutations (including disulphide bridge loss) and 8 mutations elsewhere in the genome have been repeatedly observed in sequences from chronic infections but have been rare in circulating sequences.
Protection from vaccines and past infections are not expected to be more severely underminedby these Spike mutations than it is by spike mutations found in other circulating lineages like XBB and JN.1

Most plausible hypothesis, as with the emergence of BA.2.86, would be chronic infection followed by transmission into the population (± a period of undetected circulation). However, we can not reject an animal reservoir.

All of the results have been communicated over a week ago to the National Department of Health and the Department of Science and Innovation. Policy makers are aware of the new lineage and at present we are not concerned as all the epidemiological data points to a low wave of infections.

In summary, SARS-CoV-2 continue to evolve. A new lineage has been detected in SA with >100 mutations (>30 on spike) and multiple deletions. No sign of widespread, on the opposite, BA.2.86/JN.1 continue to dominate and SA is following the epidemic in many fronts with no sign of increasing cases, hospitalisation and deaths.

This work was mostly done by the @nicd_sa and the NGS-SA. Results have been discussed with leading of scientists and police makers in South Africa. Analysis were also supported by @LongDesertTrain @DarrenM98230782

Genomes public and detailed discussion happening at PANGO community. Together, scientists in SA and internationally and government and public health authorities informed - Continue genomics surveillance and science advancing so this pandemic stop surprising us - github.com/cov-lineages/p…

Dr. Dikeledi from @nicd_sa has been the main person leading the analysis of this data in SA and under the auspice of the @nicd_sa and in collaboration with network for Genomics Surveillance in SA (NGS-SA).