new variant
1 messages over —, 2021-11-26 – 2021-11-26.
-
Good morningWe had an ad hoc/emergency meeting of the WHO Technical Advisory Group on Variant Emergence (TAG-VE) this morning with a presentation from South African scientists. We were asked to not report our discussion until the WHO puts out a statement later today so the report below is confidential. Here is the low-down: • S.A. had gotten to a stage of very low infection rate so that they noticed this new variant-- B.1.1.529--because of its very rapid increase in cases; the rate of infection is higher than expected. (as background, seroprevalence in S.A. was at 80-85% so that the low infection rate they were seeing with Delta was likely due to the fact the virus ran out of susceptibles; vaccination rate is at 30%). • The first evidence was an increase in positive cases associated with S gene target failure (drop out) in the qPCR assay; Sequencing of those early samples in Gauteng showed new mutation 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 a Rolland B.1.1.529 mutations.pp... , and this is a moving target that Glenda Gray and Tulio said they would keep us informed on as soon as they get real data. Multiple countries in Europe and elsewhere are blocking travel from RSA and neighboring countries. I briefed Jeff about this immediately after the 10:30 AM zoom with the South Africans. Jeff wants me to brief the POTUS immanently. The president is spending the Thanksgiving holiday with his family in Nantucket. Conference call with President Biden: Jeff arranged for me to brief the president on a conference call that included Jake Sullivan (NSC), Natalie Quillian, Ron Klain and Jeff. I described the medical and public health situation to the President and Natalie and Ron discussed the issue of blocking travel from RSA and neighboring countries. I explained to the President that this is all the more reason to get people vaccinated and boosted. The president will make a public announcement soon, likely this afternoon, that he has spoken with me and that the decision has been made about the travel restriction. Announcement about travel restrictions went out at 2:00 PM today. 212F is the authorization for restrictions Slides on mutations: Incredibly busy Thanksgiving Day. We had zoom calls with the Pfizer group led by Mikael Dolsten to scope out what their plan is regarding scaling up boosters against prototype as well as the advisability or not of developing Omicron-specific boosters. Also met with the Moderna people for similar discussions. Clearly, the virus is spreading widely with five cases in Israel all of which were picked up by screening at the airport. E-mail from Danny Douek: Dear Tony, I have been on the phone with the Israelis this morning. They have identified 3-5 cases of B.1.1.529 One case was AZ x2. Symptomatic. Another was Pfizer x3. Asymptomatic. All identified on screening on entry at the airport. 1 case from Malawi, 1 from Jordan, 1 from Egypt via Belgium. PRESS: CNN "New Day" with Brianna Keilar (she was rude and asked questions about Brett Giroir out of context); Interviews with Sheryl Stolberg - NY Times; Kaitlan Collins - iter CNN; NBC "Evening News" with Lester Holt Bloomberg: U.S. Needs Data on Variant Before Limiting Any Flights, Fauci Says By Kathleen Hunter