Aladdin
Well-Known Member
At least they didnt mess around with obfuscating this bit:
What does this mean...in layman's English...for an immunocompromised person?
At least they didnt mess around with obfuscating this bit:
In the case of that mutation they were talking about how this mutation was seen popping up in variations of the virus that they had found in immunocompromised patients, probably during a lengthy infection, quite possibly when attempts to help the patient included plasma from recovered patients.What does this mean...in layman's English...for an immunocompromised person?
In the case of that mutation they were talking about how this mutation was seen popping up in variations of the virus that they had found in immunocompromised patients, probably during a lengthy infection, quite possibly when attempts to help the patient included plasma from recovered patients.
So them mentioning it is in connection with the risk of that sort of mutation appearing in such patients, about how such mutations pop up in the first place. And the implications of a strain with such mutations taking hold that can escape peoples immunity more broadly.
Its not being mentioned in the context of some additional implications and risks specific to people with compromised immune systems should they catch a version of the virus that takes off in the wild and carries that particular mutations, if thats why you were asking.
Sorry if this explanation is still a bit wordy. I can try again if necessary, let me know.
It does take me a few goes before I can whittle my waffle down to the basics.Yes thank you...that's clearer.. in some way.
ORF1a | NSP1 | D75G |
ORF1a | NSP2 | G339S, A411V |
ORF1a | NSP3 | H342Y, P822L, K927I, N1587S |
ORF1a | NSP4 | A446V |
ORF1a | NSP6 | △106-108 |
ORF1b | NSP12 | P323L, S434A |
ORF1b | NSP13 | T481M |
ORF1b | NSP14 | A119V |
S | Spike | D80G, T95I, G142D, △144, N439K, E484K, D614G, P681H, I1130V, D1139H |
M | Membrane | A63T, H125Y |
N | Nucleocapsid | I157V, R203K,G204R, |
AV.1 (VUI-21MAY-01) is technically B.1.1.482.1 (ie B.1.1.482 parent lineage). May be associated with B.1.1.28 (parent lineage of P.1). Mainly seen in South Yorkshire (but also E Midlands, NW and SE in very small numbers) plus France. Significant numbers of mutations (~23) in the ORF and spike:
Some of the mutations may reduce effectivity of monoclonal antibodies, improve ACE2 affinity and improve transmission.
ORF1a NSP1 D75G ORF1a NSP2 G339S, A411V ORF1a NSP3 H342Y, P822L, K927I, N1587S ORF1a NSP4 A446V ORF1a NSP6 △106-108 ORF1b NSP12 P323L, S434A ORF1b NSP13 T481M ORF1b NSP14 A119V S Spike D80G, T95I, G142D, △144, N439K, E484K, D614G, P681H, I1130V, D1139H M Membrane A63T, H125Y N Nucleocapsid I157V, R203K,G204R,
Detailed analysis here.
This is a great time to be a [whoever has a professional interest in looking for virus variants and such like ]Dr Andrew Lee, reader in global public health at the University of Sheffield, tweeted today: “Emergence of a new #covid variant #B11482 in South Yorkshire reported by team from @sheffielduni & Sheffield Teaching Hospitals. Great work @Thushan_deSilva @cariadmevans @InfectionDave & others."
AV.1 (VUI-21MAY-01) is technically B.1.1.482.1 (ie B.1.1.482 parent lineage). May be associated with B.1.1.28 (parent lineage of P.1). Mainly seen in South Yorkshire (but also E Midlands, NW and SE in very small numbers) plus France. Significant numbers of mutations (~23) in the ORF and spike:
Some of the mutations may reduce effectivity of monoclonal antibodies, improve ACE2 affinity and improve transmission.
ORF1a NSP1 D75G ORF1a NSP2 G339S, A411V ORF1a NSP3 H342Y, P822L, K927I, N1587S ORF1a NSP4 A446V ORF1a NSP6 △106-108 ORF1b NSP12 P323L, S434A ORF1b NSP13 T481M ORF1b NSP14 A119V S Spike D80G, T95I, G142D, △144, N439K, E484K, D614G, P681H, I1130V, D1139H M Membrane A63T, H125Y N Nucleocapsid I157V, R203K,G204R,
Detailed analysis here.
I havent looked on GISAID, I just took note of this bit from the analysis you linked to:Can't see any B.1.1.28 in GISAID clearly indicating origin from/near Coventry?
Importantly, three recent B.1.1.28 samples (QEUH-148F257, QEUH-14C1E55, QEUH-144D7A1) appear to form an intermediate cluster between the South Yorkshire samples and the sample from France suggesting that this could be a common ancestor of the two clusters.
Just noticed that Kucharski estimates baseline R for B.1.1.7 at around 4-5. On which basis B.1.617.2 could easily be above 5, maybe even 6-point-something.I dont suppose you've seen any simple estimates of what range the 'natural, unimpeded R' of the India strain might be? Or for that matter what sort of range that would have been for the Kent variant?
Just noticed that Kucharski estimates baseline R for B.1.1.7 at around 4-5. On which basis B.1.617.2 could easily be above 5, maybe even 6-point-something.
Just to underline, an epidemiologist writes:Thanks very much. Numbers that high or potentially even higher did enter my imagination which is why I asked. Wasnt sure if I'd gotten carried away with how high those numbers could be, and part of my brain still recalls how things were framed around such numbers early in the pandemic. So hearing about latest variants in those terms helps me update my sense of how much pandemic weight we need vaccines and ongoing behavioural changes to carry.
This is a variant that looks like it might have originated out of Nepal/India - has unfortunately been described as the 'Nepal' variant in some quarters. Though there is next to no sequencing surveillance in Nepal, it was picked up in Japan amongst a number of travellers from there. So far 90 cases worldwide also detected in Portugal, Poland, Japan, India, UK, Swittzerland, US and Canada.There is (what could classified as being) a new variant (sublineage) of B.1.617.2 just drifting across the radar (not yet uniquely named - see page 37, table 11 of PHE VOC Technical Briefing 13 ). It features a spike RBD point mutation of concern (K417N) in common with P.1 and B.1.351 (both of which have a greater degree of immune escape than most other variants). Probably a travel introduction (has been seen in several countries) that has already established elsewhere with less sequencing surveillance.
Two doses of BNT162b2 elicited ELISA-detected anti-Wild-type spike antibodies in all participants, and NAb activity against all strains, including the three VOCs tested, in all except six (3%) and nine (5%) of 159 participants who lacked NAb activity against B.1.617.2 and B.1.351, respectively (appendix p 2). NAbTs of sera correlated well between Wild-type and variants (appendix p 2; RS>0·82, p<2 × 10−16), as well as between VOCs (B.1.617.2 vs B.1.351: RS=0·85, p<2 × 10−16). However, NAbTs were 5·8-fold reduced against B.1.617.2 relative to Wild-type (95% CI 5·0–6·9), significantly more reduced than against B.1.1.7 (2·6-fold vs Wild-type, 95% CI 2·2–3·1), and on a similar order to the reduction observed against B.1.351 (4·9-fold vs Wild-type, 95% CI 4·2–5·7).
Notably, across all variants, increased age significantly correlated with reduced NAbT (appendix p 2; −0·33<RS<–0·27; 2·2 × 10−5<p<5·6 × 10−4), whereas no correlation was observed for sex or body-mass index (appendix p 4). NAbTs reduced over time after administration of the second dose of BNT162b2: participants (n=14) who attended an additional study visit 8–16 weeks after their second BNT162b2 dose showed significantly reduced NAbTs against all variants (appendix p 2; 0·0002<p<0·0134). While the final NAbTs against Wild-type, D614G, and B.1.1.7 remained within the quantitative range of our assay (IC50>40), two participants' NAbTs against VOCs B.1.617.2 and B.1.351 dropped below 40 on their later study visit about 3 months after their second BNT162b2 dose.
We found that neutralisation of VOCs was markedly different after only one dose of BNT162b2 (appendix p 2): although 177 (95%) of 186 participants tested positive for anti-spike antibodies by ELISA and mounted a detectable NAb response against Wild-type (median IC50=68 [IQR 42–140]) and D614G (median IC50=71 [IQR 46–111]), median NAbTs against all VOCs were below the quantitative limit of detection. Stratification of NAbTs into three groups (IC50 low [<40], medium [40–256], high [>256]) and assessment of the significance of the shift in their distribution relative to Wild-type by ordered logistical regression was more informative (appendix p 2). Whereas only 39 (21%) of 186 samples had low NAbTs against Wild-type, this proportion rose to 50% against B.1.1.7 (p=1·7 × 10−6) and further to 75% against B.1.351 (p<3 × 10−16) and 68% against B.1.617.2 (p<5 × 10−16). Notably, the downwards shift in titres was also significant when compared to B.1.1.7 for B.1.351 (p=3·7 × 10−4) and B.1.617.2 (p=1·2 × 10−5), confirming reduced NAb activity against B.1.617.2 relative to the present B.1.1.7 strain after one vaccine dose. Notably, participants with low NAbTs tend to be older than those who produced medium or high responses (appendix p 2), and logistical regression analysis suggests age is a significant factor in reduced NAbTs, independent of strain in our samples (appendix p 7; p=0.006), following a single dose of BNT162b2.
B.1.617.2 with K417N (in spike) now named AY.1 (alias of B.1.617.2.1).There is (what could classified as being) a new variant (sublineage) of B.1.617.2 just drifting across the radar (not yet uniquely named - see page 37, table 11 of PHE VOC Technical Briefing 13 ). It features a spike RBD point mutation of concern (K417N) in common with P.1 and B.1.351 (both of which have a greater degree of immune escape than most other variants). Probably a travel introduction (has been seen in several countries) that has already established elsewhere with less sequencing surveillance.
B.1.617.2 with K417N (in spike) now named AY.1 (alias of B.1.617.2.1).
This new BBC article mentions a possible range of between 5 and 8, which comes via disease modellers at Imperial.Just noticed that Kucharski estimates baseline R for B.1.1.7 at around 4-5. On which basis B.1.617.2 could easily be above 5, maybe even 6-point-something.
A new study from Imperial which suggests that the P681R point mutation, on the D614G backbone, improves the efficiency of the S1/S2 furin cleavage site, likely a mechanism for enhancing transmissibility and pathogenicity, in B.1.617.2 (and associated sub-lineages). The P681H of B.1.1.7 likely contributes to the increased transmissibility of that variant (over earlier types but to a lesser degree than for B.1.617.x).
DOI: 10.1101/2021.05.28.446163.
During the current SARS-CoV-2 pandemic, a variety of mutations have been accumulated in the viral genome, and at least five variants of concerns (VOCs) have been considered as the hazardous SARS-CoV-2 variants to the human society. The newly emerging VOC, the B.1.617.2 lineage (delta variant), closely associates with a huge COVID-19 surge in India in Spring 2021. However, its virological property remains unclear. Here, we show that the B.1.617 variants are highly fusogenic and form prominent syncytia. Bioinformatic analyses reveal that the P681R mutation in the spike protein is highly conserved in this lineage. Although the P681R mutation decreases viral infectivity, this mutation confers the neutralizing antibody resistance. Notably, we demonstrate that the P681R mutation facilitates the furin-mediated spike cleavage and enhances and accelerates cell-cell fusion. Our data suggest that the P681R mutation is a hallmark characterizing the virological phenotype of this newest VOC, which may associate with viral pathogenicity.