Tony's Diary Package — page 935

patterns. While whole genome sequencing is still just ramping up (they have 77 genomes from Gauteng and will have 100 new ones by the end of the day), they do see the same S-gene dropout pattern in many other provinces; so far this pattern is 100% associated with the new lineage so they suspect it will be the case for these samples in other provinces. In summary: this is not a unique outbreak cluster in Gauteng. • Cases are starting to pop up in other countries, but numbers are still low. We suspect they will increase quickly. • Mutations: 10 in the receptor binding motif, many are similar to mutations observed in other lineages but also new ones. High number of mutations - • multiple in the RBD and NTD that are usually associated with resistance to neutralizing antibodies • Cluster of mutations (H655Y + N679K + P681H) adjacent to the furin cleavage site - usually associated with more efficient cell entry • NSP6 deletion (105-107) - convergent evolution as has been observed in Alpha, Beta, Gamma and Lambda - could be associated with evasion of innate immunity, possibly increased transmissibility • Mutations in the N gene - R203K and G204R (also seen in other lineages) that are associated with increased transmissibility So mutation profile is predicted to be associated with significant immune evasion and enhanced transmissibility, but no experimental evidence yet and epi data is still sparse. It clearly has a different mutation profile than other circulating VOC/VOI but full significance is not yet clear. • One big question is how this highly mutated virus emerged. There are signs of possible recombination at around nt 20,000. One of the spike mutations (N679K) is rare and also observed in C.1.2; a lot of convergent mutations observed. One hypothesis is that because of S.A.'s high rate of HIV/low CD4, this virus could have developed in immune suppression with a recombination event. • No evidence yet for different clinical presentation; age distribution tracks young so far but that's because the first outbreak was at a university, but it is also the age group that is most mobile and not vaccinated. • Most are symptomatic but severity is still being established. We are planning another meeting Monday. Will let you know if I have anything new to report. Best, Elodie Briefing with RSA colleagues: Glenda Gray, Tulio de Oliveira and others -Clearly we have a serious situation in South Africa. The virus is spreading rapidly in virtually all the provinces with a concentration in Gauteng province which is where Johannesburg and Pretoria are located. Reports now in multiple countries almost all related to travel from RSA. infections in RSA seen in people who have recovered from delta as well as breakthrough infections in those who have been vaccinated with the Pfizer product. What is unclear is what the severity of the infections are