The new “Kent” strain of SARS-CoV-2 (officially named VUI 202012/01 for Variant Under Investigation, year 2020, month 12, variant 01) was identified as have multiple spike protein mutations

1/n
These include deletion 69-70, deletion 144-145, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H

2/n

gisaid.org/references/gis…
Structural modelling suggests N501Y (orange in Fig) might affect host receptor and antibody binding

3/n

Credit gisaid.org/references/gis…
The deletions in cyan in above Figure are in positions contributing to potential spike surface variation (Y145del is where some antibodies like neutralizing 4A8 bind).

4/n
It strain was identified by @PHE_uk monitoring during surge in cases in Kent and London.

Great work by Public Health England

5/n
Dr Susan Hopkins, Test and Trace and PHE joint medical adviser, said: "There is currently no evidence that this strain causes more severe illness"

Credit medscape.com/viewarticle/94…

6/n
Much remains unclear still, but such mutations are to be expected as the virus spreads. Most of the spike protein will “look” the same to the immune system, so current vaccine should continue to provide protection.

7/n
Over time the vaccine might need modification, just as the flu jab does each year.

This is new so sincere apologies if there are errors. As these & new information come to light, I’ll update you.

8/8
“At this point in time, there is no reason to believe that any of the mutations discussed here will affect vaccine efficacy” COG-UK

cogconsortium.uk/wp-content/upl…
So far, 126,219 genomes from +ive samples generated by the COG- UK consortium. This identified 1,777 different amino acid changing mutations in Spike protein.

Of these, 37% (654) were only observed in a single sequence, while 5% (87) were observed in at least 100.
“5 amino acid replacements (D614G, A222V, N439K, Y453F and N501Y), 1 deletion (del) and co- occurrence of some of these changes are actively being investigated by COG-UK”
Some interesting details on individual mutations & presumed origins
Biological significance of some specific changes
And “A222V: It has been speculated that the increased transmissibility of the B.1.177 lineage may be associated with the presence of the A222V mutation, but more evidence is needed”
Recommended read!

“... a distinct phylogenetic cluster (named lineage B.1.1.7) was detected within the COG-UK surveillance dataset...[it’s] been growing rapidly over the past 4 weeks & since been observed in other UK locations, indicating further spread”

virological.org/t/preliminary-…
Interesting in vitro data from @GuptaR_lab — Δ69/70 twice as infectious
NERVTAG = New and Emerging Respiratory Virus Threats Advisory Group

1/n
Points discussed re transmission:

“Growth rate from genomic data which suggest a growth rate of VUI-202012/01 that
that is 71% (95% CI: 67%-75%) higher than other variants”

= By sequencing many samples of +ive tests, the rate of increase was compared to other strains

2/n
“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”

Modelling seems to suggest this strain has higher R (remember, R is determined both by viral transmissibility AND our behaviour)

3/n
“PCR ct values: which suggest a decrease of ct value of around 2 associated with the new variant”

In PCR testing, lower Ct values mean more starting RNA, so this suggests that ppl who swabbed +ive fir this strain may have had higher viral loads

4/n
“Viral load inferred from number of unique genome reads: which suggests 0.5 increase in median log10 inferred viral load in Y501 versus N501”

Suggests the mutation Y501 (one of several species n this new strain) is associated with 3-fold increase in viral load

5/n
“the emergence and subsequent dominance of VUI-202012/01 in a period of relatively high prevalence suggests [it has] a selective advantage over other variants”

Suggests this strain is better at spreading than other strains so was able to out-complete them (evolution)

5/n
“ It was noted that VUI-202012/01 has demonstrated exponential growth during a period when national lockdown measures were in place”

Suggests stricter measures (and/or Bette adherence to them) required if we are to control this

6/n
“ It was noted that VUI-202012/01 has demonstrated exponential growth during a period when national lockdown measures were in place”

Suggests stricter measures (and/or Bette adherence to them) required if we are to control this

6/n
“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”

Suggests the variant might be seen as “different” by our immune systems

7/n
“Four probable reinfections have been identified amongst 915 subjects with this variant but further work is needed to compare this reinfection rate with comparable data sets”

We knew reinfection is possible, so it isn’t clear if this is relevant. Time will tell.

8/n

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More from @Prof_Marciniak

19 Dec
Great point

Sensitivity = proportion of actual cases (ppl with a disease) that a test picks up

99% sensitive means 99 out of 100 truly affected ppl will be detected.

1/n
What’s the “gold standard” to determine what is a true case?

It depends on the condition in question, but for a viral RT-PCR a range of concentrations of RNA or virus can be added to a negative sample to help determine the limit of detection

2/n
Specificity = proportion of unaffected ppl that a test correctly identifies as not having the disease

99% specific means 99 out of 100 truly unaffected ppl will be correctly labelled as being negative.

Many known negative samples will be examined to determine this value.

3/n
Read 10 tweets
18 Dec
>35,000 new British cases yesterday

18,510 in hospital

Feeling for my colleagues on the wards this Christmas.
On the bright side

138,541 vaccinated

That’s 0.21% of the UK
But then again
Read 4 tweets
6 Dec
The Background

1860s: nucleic acids discovered
1940-50s: the concept that “DNA makes RNA makes protein” is developed (& is called the central dogma)
1960s: messenger RNA discovered

1/n
Path to the vaccine

1989: use of lipid nanoparticles to get mRNA into cells
1990: RNA injected into muscle can cause local synthesis of a protein
1994-9: RNA vaccines shown to induce immune response
2008-11: early phase trials

2/n
2003-2012: studies to generate a vaccine against 2 new severe coronavirus diseases SARS and MERS identify the spike protein as a good target for protective antibodies

3/n
Read 7 tweets
5 Dec
How science works:

Observations are made.
A hypothesis is generated.
Experiments are performed to test (try to disprove) the hypothesis.
This cycle is repeated many many times until the experiments are unable to disprove the hypothesis.
The results are shared at talks or posters at conferences or as preprints, so others can comment & criticise.
The results are then published as papers (a gruelling process when the paper is assessed by tough anonymous scientists who point out every error, big or small, which must be corrected).
Afterwards, scientists try to reproduce those results to see if they’re real.
Read 6 tweets

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