#15,641
Today marks 7 days since we first learned of a new, more transmissible SARS-CoV-2 variant (VUI – 202012/01 aka B.1.1.7 ), spreading in the UK (see UK Health Secretary Announces A New COVID Variant), and while there remain a good many unanswered questions, we have seen a commendable amount of preliminary data being released.
ECDC Threat Assessment Brief On UK SARS-CoV-2 Variant
UK Prime Minister's Statement: New COVID-19 Variant Up To 70% More Transmissible
UK : England CMO Professor Chris Whitty - New COVID Strain Is Considered More Transmissible
Denmark Orders Christmas Lockdown Over COVID - SSI Update On UK Strain
COG-UK: Brief Update & Expert Reaction On The New SARS-CoV-2 Variant In Southern England
While claims of `up to 70% increased transmissibility', increased lockdown restrictions where the variant is circulating - and travel bans enacted over the weekend by several nations to and from the UK - have created quite a commotion, it should be noted that much of this response has been based on preliminary information gleaned from a relatively small (but growing) dataset.
Kai Kupferschmidt at Science magazine has an excellent overview (see Mutant coronavirus in the United Kingdom sets off alarms but its importance remains unclear) on what we know, and don't know, about the impacts that are likely to arise from these mutations.
Yesterday the UK agencies released two new reports on this COVID variant; one from the PHE (Public Health England) that takes a more `lay' approach, and 9-page - far more technical - report from COG-UK.
We'll make the Q&A from PHE our first stop.
COVID-19 (SARS-CoV-2): information about the new virus variant
The new strain transmits more easily than the previous variant but there is no evidence that it is more likely to cause severe disease or mortality.Published 20 December 2020
from: Public Health England
Main points
Data from Whole Genome Sequencing, epidemiology and modelling suggest the new variant ‘VUI – 202012/01’ (the first Variant Under Investigation in December 2020) transmits more easily than other strains.
We currently have no evidence that the variant is more likely to cause severe disease or mortality – but we are continuing investigations to understand this better.
The way to control this virus is the same, whatever the variant. It will not spread if we avoid close contact with others. Wash your hands, wear a mask, keep your distance from others, and reduce your social contacts.
Is there any evidence that the variant is more serious?
We currently have no evidence that this variant causes more severe disease or higher mortality – but we continue to study cases to understand this better. We know that mortality is a lagging indicator and we will need to continually monitor this over the coming weeks.
Why is this more transmissible?
We know that mutations in the spike protein, the part of the virus that makes it infectious, can change how the virus interacts with human cells. However, we do not yet know the mechanism for this increase in transmission.
The evidence shows that infection rates in geographical areas where this particular strain has been circulating have increased faster than expected, and the modelling evidence has demonstrated that this variant has a higher transmission rate than other variants in current circulation.
How long has this variant been in circulation?
All viruses mutate over time and new variants emerge regularly.
Backwards tracing using the genetic evidence suggests this variant emerged in September 2020 and then circulated at very low levels in the population until mid-November.
The increase in cases linked to the new variant first came to light in late November when PHE was investigating why infection rates in Kent were not falling despite national restrictions. We then discovered a cluster linked to this variant spreading rapidly into London and Essex.
Evidence of increased transmissibility was provided to NERVTAG and ministers on December 18.
Is this strain resistant to the Pfizer vaccine?
There is currently no evidence to suggest that the Pfizer vaccine would not protect people against the new strain.
Further laboratory work is currently being undertaken as a priority to understand this.
How widespread is the variant geographically?
144 Lower Tier Local Authorities have identified at least 1 case genomically, although the vast majority of cases identified are in London, the South East and the East of England.
Can tests detect this new variant?
Labs have been issued with guidance to adapt processes to ensure that PCR tests can detect this variant.
PCR tests can be adapted rapidly to respond to the new variant.
A more technical report comes from COG-UK - the COVID-19 Genomics UK-Consortium - which not only describes the new B.1.1.7 lineage, but also goes into considerable detail on the other variants and mutations that have appeared in SARS-CoV-2 since it emerged just over a year ago.
Due to its length (9 pages), I've only reproduced the summary. Follow the link to download and read the report in its entirety.
COG-UK update on SARS-CoV-2 Spike mutations of special interestReport 1
Prepared by COG-UK, 20th December 2020 Summary
This report provides background context on mutation tracking by COG-UK and describes a priority set of SARS-CoV-2 Spike mutations that are of particular interest based on potential epidemiological significance in the UK and/or biological evidence based on the literature or unpublished work. It provides details on the frequency of mutations, and their potential biological and immunological significance as we currently understand it. At this point in time, there is no reason to believe that any of the mutations discussed here will affect vaccine efficacy. Appendix 1 provides explanations for terms (mutation, variant, lineage) and the basis for prioritising the mutations described here.
The analysis described below (using complete data up to 15th December 2020) is based on 126,219 genomes from positive samples generated by the COG-UK consortium. This identified 1,777 different amino acid changing (non-synonymous) mutations in Spike glycoprotein’s gene S (this does not include mutations that do not lead to an alternation of amino acid (which are more numerous), or mutations elsewhere in the genome). Of these non-synonymous changes, 37% (n=654) mutations were only observed in a single sequence, while 5% (n=87) were observed in at least 100 sequences.
Five amino acid replacements (D614G, A222V, N439K, Y453F and N501Y), one deletion (del) and cooccurrence of some of these changes are actively being investigated by COG-UK. Further details, including the reason for their inclusion, is provided in Table 1. This is a shortlist of Spike-focused priority mutations, but others are being monitored in S and other SARS-CoV-2 genes.
The lineage B.1.1.71 is of particular interest (see footnote) and is notable for a higher number of mutations in one lineage than observed previously (Table 1b). It has been speculated that it may have arisen from a chronically infected individual. One of these (the N501Y mutation) occurs in the region of the Spike protein, the receptor binding domain (RBD), that the virus uses to bind to the human ACE2 receptor. Changes in this region of the Spike protein can result in the virus changing its ACE2 binding specificity and alter antibody recognition.
Two other mutations (N439K and Y453F) also occur in the RBD region and increase binding affinity to ACE2 and have been shown to escape the neutralising effect of a few monoclonal antibodies (mAbs). The 69- 70del has co-occurred with all three of these RBD mutations.
As we saw in yesterday's ECDC Threat Assessment Brief On UK SARS-CoV-2 Variant, we see speculation that the large number of concurrent mutations in the B.1.1.7 variant may have arised from a single chronically-infected, likely immunocompromised, individual.
B.1.1.7 lineage. This variant has 23 mutations with 14 amino acid replacements and 3 in-frame deletions which are listed in Table 1b. Two of these mutations have already been described to alter SARS-CoV-2 biology: N501Y sits in the receptor binding motif (RBM) of the Spike protein, and has been described to increase binding affinity to the human ACE-2 receptor; 69-70del has been identified in variants associated with immune escape in immunocompromised patients and is responsible for a “dropout” in the S gene PCR target in certain diagnostic tests (e.g. Thermo Fisher TaqPath). These tests target multiple regions of the virus genome, so the test itself is not compromised. Reported cases and phylogenetic analyses have indicated an exceptional rate of introduction of mutations into this lineage. It has been hypothesised that this lineage may have resulted from the transmission of the virus from a chronically infected individual. This is based on observations that a high rate of mutations may accumulate in immunocompromised patients with chronic infections of SARS-COV-2.
Along this same vein, late last week COG-UK released a report on multiple escape mutants generated in a chronically ill, immunocompromised patient, after receiving convalescent plasma therapy.
