An
earlier article described how new SARS-CoV-2 synonymous nucleotide
mutations (which had no impact on the amino acid coding) may have arisen
with its move into the human population, but reported no ‘beneficial’
mutations.
reported on the spread of a SARS-CoV-2 spike (S) protein mutation,
D614G (i.e. an aspartic acid to glycine amino acid substitution at
position 614 in the viral S gene) across multiple countries, suggesting
that it was a more ‘transmissible’ form of the virus. This was based on
higher viral loads found during in vitro replication studies, as well as
in clinical samples containing this mutation and animal studies
suggesting this.
However, others cautioned this interpretation, stating that ‘founder’
effects could not be entirely ruled out to explain the ubiquity of this
virus in the global population,
van
Dorp L., Richard D., Tan C.C.S., Shaw L.P., Acman M., Balloux F. No
evidence for increased transmissibility from recurrent mutations in
SARS-CoV-2. bioRxiv 2020.05.21.108506; doi: 10.1101/2020.05.21.108506
Since
then a new, rapidly spreading variant in the UK (‘VUI-202012/01′ i.e.
‘variant under investigation’) has been reported in the UK in recent
weeks.
NERVTAG
UK. Meeting on SARS-CoV-2 variant under investigation VUI-202012/01.
https://khub.net/documents/135939561/338928724/SARS-CoV-2±variant±under±investigation%2C±meeting±minutes.pdf/962e866b-161f-2fd5-1030-32b6ab467896?t=1608470511452
(Accessed 20 December 2020).
COG-UK
update on SARS-CoV-2 Spike mutations of special interest. Report 1. 19
December 2020.
https://www.cogconsortium.uk/wp-content/uploads/2020/12/Report-1_COG-UK_19-December-2020_SARS-CoV-2-Mutations.pdf
(Accessed 20 December 2020).
This variant is derived from the SARS-CoV-2 20B/GR clade (lineage
B.1.1.7) and contains multiple mutations, including a combination of the
N501Y (i.e. an asparagine to tyrosine amino acid substitution at
position 501 in the viral S gene) and the 69–70del (i.e. a deletion of 6
bases coding for histidine and valine at positions 69 and 70,
respectively, in the viral S gene) mutations, both of which have been
circulating, separately and independently, globally for many months
previously.
Fig. 1
shows an illustrative maximum likelihood phylogenetic tree of selected
SARS-CoV-2 full genome sequences, highlighting the diversity and
timeline of globally circulating strains containing the N501Y (red) and
69–70del (green) mutations that have been existing separately and
independently prior to the emergence of the new B.1.1.7 (variant)
(pink), after August 2020, that contains both of these characteristic
mutations. Note that some of the earliest N501Y-containing viruses
originated from Brazil (April 2020) and Australia (June-July 2020), and
as early as March 2020 from Slovenia for the 69–70del mutation, though
we know that this 69–70del mutant was circulating as early as January in
Thailand and February in Germany.
Most of the sequences containing both of these mutations (pink) are
from the UK during October-November 2020, though there is at least one
sequence from Denmark from November 2020.
Fig. 1Maximum
likelihood phylogenetic tree of selected SARS-CoV-2 full genome
sequences rooted against the original Wuhan SARS-CoV-2 reference strain
(NC_045512_Wuhan_Hu_1, blue), highlighting the diversity and timeline of
globally circulating strains containing the N501Y (red) and 69–70del
(green) mutations that have been existing separately and independently
prior to the emergence of the new B.1.1.7 (variant) (pink), after August
2020, that contains both of these characteristic mutations. All
sequences were downloaded from GISAID (https://www.gisaid.org/)
and were aligned using BioEdit v.7.2.5., the tree was constructed using
FastTree v.2.1.11 and displayed in FigTree v.1.4.4. We gratefully
acknowledge and thank the various laboratories and contributors of these
GISAID for providing these SARS-CoV-2 sequences. Note that this tree is
illustrative and not intended to be comprehensive.
Early
investigations from the UK suggest an increased transmissibility of up
to 71% over and above the previous circulating strains of SARS-CoV-2,
which may contribute 0.39–0.93 to the R0 value estimates of the virus, and ongoing monitoring of the situation is in progress.
NERVTAG
UK. Meeting on SARS-CoV-2 variant under investigation VUI-202012/01.
https://khub.net/documents/135939561/338928724/SARS-CoV-2±variant±under±investigation%2C±meeting±minutes.pdf/962e866b-161f-2fd5-1030-32b6ab467896?t=1608470511452
(Accessed 20 December 2020).
However, so far there is no evidence that this new B.1.1.7 (variant)
demonstrates any increased clinical severity of illness, or vaccine
escape capability. The fact that these mutations have been reported
since October before the surge in test positivity noted in the Southeast
of England also raises the question as to whether this is also a
founder effect.
The practical risk
of a more rapidly spreading virus is the potential impact on healthcare
services especially if seasonal influenza were to return. If more people
are infected over a similar time period compared to other virus
strains, potentially more patients may need hospitalisation, with a
danger that healthcare services may be overwhelmed. A more rapidly
spreading virus will also accelerate the need to reach the
COVID-19-vulnerable populations (the elderly and those with multiple
comorbidities) with the new COVID-19 vaccines to stay ‘ahead’ of the
virus. At the same time, deferring elective surgeries or resources for
other illnesses may have unintended consequences if the rapidly
spreading virus does not behave as predicted.
At
the time of writing, further investigations are ongoing of this virus
to determine more clearly its impact on society and healthcare capacity.
In addition, the impact of the mutation on the effectiveness of
vaccines or prior immunity are being explored. Another intriguing
question is whether the mutation has arisen from an immunocompromised
host,
COG-UK
update on SARS-CoV-2 Spike mutations of special interest. Report 1. 19
December 2020.
https://www.cogconsortium.uk/wp-content/uploads/2020/12/Report-1_COG-UK_19-December-2020_SARS-CoV-2-Mutations.pdf
(Accessed 20 December 2020).
Many countries have decided to close the borders to visitors from the
UK even though the impact of the new B.1.1.7 (variant) is not fully
known. It is critical to have updated and transparent information from
across the world to answer these questions.
References
Wen F.
Yu H.
Guo J.
Li Y.
Luo K.
Huang S.
Identification of the hyper-variable genomic hotspot for the novel coronavirus SARS-CoV-2.
van
Dorp L., Richard D., Tan C.C.S., Shaw L.P., Acman M., Balloux F. No
evidence for increased transmissibility from recurrent mutations in
SARS-CoV-2. bioRxiv 2020.05.21.108506; doi: 10.1101/2020.05.21.108506
NERVTAG
UK. Meeting on SARS-CoV-2 variant under investigation VUI-202012/01.
https://khub.net/documents/135939561/338928724/SARS-CoV-2±variant±under±investigation%2C±meeting±minutes.pdf/962e866b-161f-2fd5-1030-32b6ab467896?t=1608470511452
(Accessed 20 December 2020).
COG-UK
update on SARS-CoV-2 Spike mutations of special interest. Report 1. 19
December 2020.
https://www.cogconsortium.uk/wp-content/uploads/2020/12/Report-1_COG-UK_19-December-2020_SARS-CoV-2-Mutations.pdf
(Accessed 20 December 2020).
Fig. 1Maximum
likelihood phylogenetic tree of selected SARS-CoV-2 full genome
sequences rooted against the original Wuhan SARS-CoV-2 reference strain
(NC_045512_Wuhan_Hu_1, blue), highlighting the diversity and timeline of
globally circulating strains containing the N501Y (red) and 69–70del
(green) mutations that have been existing separately and independently
prior to the emergence of the new B.1.1.7 (variant) (pink), after August
2020, that contains both of these characteristic mutations. All
sequences were downloaded from GISAID (https://www.gisaid.org/)
and were aligned using BioEdit v.7.2.5., the tree was constructed using
FastTree v.2.1.11 and displayed in FigTree v.1.4.4. We gratefully
acknowledge and thank the various laboratories and contributors of these
GISAID for providing these SARS-CoV-2 sequences. Note that this tree is
illustrative and not intended to be comprehensive.
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