NERVTAG meetingon SARS-CoV-2 variant under investigation VUI-202012/01

Note of meeting

Date & Location of meeting: 11:00 –13.00 18December2020 -Via telecon only

In attendance:

Chair: Peter Horby (PH)

NERVTAG Members: Peter Openshaw (PO), Andrew Hayward (AH),Wei Shen Lim (WSL),Julian Hiscox (JHi),John Edmunds (JE), Neil Ferguson (NF), Robert Dingwall (RD),Muge Cevik (MCe), Wendy Barclay (WB), Jim McMenamin (JMM),Calum Semple (CSm),Cariad Evans (CE),Ben Killingley (BK), Lisa Ritchie (LR), Chloe Sellwood (CSw), Ian Brown (IB)

Invited experts: COG UK: Andrew Rambaut (AR)

NERVTAG Secretariat: Ruth Parry, Elaine Stanford, Stephen Barnard

PHE Observers: Meera Chand (MCh),Maria Zambon (MZ), Gavin Dabrera (GD), Jake Dunning (JD), Colin Brown (CB), Vanessa Saliba (VS)

DHSC Observers: Sadia Dorsani (SD), Ursula Wells (UW), Jonathan Van Tam (JVT)

DFIDObservers: Cathy Roth (CR)

C-19 Taskforce Observers: Nick Allan (NA), Nick Taylor (NT)

SAGE Secretariat Observers: Arne Blackman (AB), David Busse (DB), Stephanie Croker (SC), Carl Mayers (CM)

DA Observers: Wales: Catherine Moore (CM)

Apologies: James Rubin (JR), David Connell (DC), Kevin Rooney (KR)

Brief summary ofNERVTAG opinion-signed off by Chair.

The committee received and considered threedocuments:

   o The PHE document ‘New evidence on VUI-202012/01 dated 18 December
   o Ct monitoring data from ONS/Oxford University COVID-19 Infection Survey
   o Bonsall paper: Early analysis of a potential link between viral load and the N501Y mutation in the SARS-CoV-2 spike protein

Fouranalytic approaches were reviewed regarding the transmissibility of VUI-202012/01

   o Growth rate from genomic data:which suggest a growth rate of VUI-202012/01that that is 71% (95%CI: 67%-75%)higher than other variants.
   o Studies of correlation between R-values and detection of the variant: which suggest an absolute increase in the R-value of between 0.39 to 0.93.
   o PCR ct values: which suggest a decrease of ct value of around 2 associated with the new variant.
   o Viral load inferred from number of unique genome reads: which suggests 0.5 increase in median log10inferred viral load in Y501 versus N501.

It was noted that variations in observed ctvalues can change with epidemiology since the stage of illness at which infection is detected can vary with incidence of cases, awareness of transmission, and the availability of tests.

It was noted that VUI-202012/01can be challenging to sequence so estimates of frequency of this variant may be underestimates.

It was noted that whilst previous variants have successfully emerged in periods of low prevalencewithout clear evidence of having a selective advantage, the emergence and subsequent dominance of VUI-202012/01in a period of relatively high prevalence suggests VUI-202012/01does have a selective advantage over other variants.

It was noted that VUI-202012/01has demonstrated exponential growth during a period when national lockdown measures were inplace.

In summary, NERVTAG has moderate confidence that VUI-202012/01 demonstrates a substantialincrease in transmissibility compared to other variants.

NERVTAG concluded that there are currently insufficient data to draw any conclusion on:

   o Underlying mechanism of increased transmissibility (e.g. increased viral load, tissue distribution of virus replication, serial interval etc)
   o The age distribution of cases
   o Disease severity: 4 deaths in around 1000 cases have been identified but further work is needed to compare this fatality rate with comparable data sets.
   o Antigenic escape. The location of the mutations in the receptor binding domain of the spike glycoprotein raises the possibility that this variant is antigenically distinct from prior variants. Four probable reinfections have been identified amongst 915 subjects with this variant but further work is needed to compare this reinfectionrate with comparable data sets.

The committee discussed the geographic extentof spread of the variant:

   o Within the UK, the variant is concentrated in the London, South East and East of England but has been detected in various parts of the UK.
   o Few cases of this variant have been reportedinternationally but one confirmed export from the UK to Australia has been reported. It was noted that other countries have lower sequencing capability than the UK.

NERVTAG endorsed theactions proposed by PHE and in addition noted that:

   o Better comparative data on reinfection, readmission and case fatality rates will be available next week.readmission and case fatality rates will be available next week.
      o Better data on the age distribution of infections with this variant will be available next week.
      o In vitro data on the ability of convalescent and post-immunisation sera to neutralisethis variant will take at least a further week.

Work is ongoing to evaluate the ability of Lateral Flow Devices to detect VUI-202012/01.

NERVTAG recommends that ajoint NERVTAG-SPI-Msubgroup of SAGE is convened to provide further advice on risk and riskmitigation measuresfor VUI-202012/01.