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Does an increase in Ct value of 3 result in a decrease in Viral Particles / ml by a factor of 10?
Test, test, test
No idea!
I have looked for papers on this but have not found anything useful. There are papers comparing the different sampling methods but the ones I have found use pcr for the analysis which does not tell you about the proteins.
I searched for papers reporting analysis using MS as it should give a better idea of the proteins they are seeing. There are some looking at swabs and others at saliva/gargle solutions. Because they all have used trypsin digests and none have done absolute quantitative analysis it is hard to draw any meaningful conclusions , (with tryptic digests the MS response can depend as much on the peptide you are looking at as the abundance of it, you get more peptides with larger proteins so more chance of having ones that give a good signal ).
It would not be hard to do the analysis. If Adeptrix have an N Bams, as the CEO indicated in his last talk , then you could look at both S and N in a range of sample types, you can buy in labelled peptides as standards to give a reasonably quantified response.
One final question if I may.
Innova (and others) are nasopharyngeal swabs, although in the NHS they have, off license, recommended doing anterior nasal swabs. Is the reason for np solely to increase quantity of antigen or is it because the sample is better (less variable matter and viscosity). AS comments that spike was more robust implied in the real world they would be easier to work with. I wonder if this might be what he meant?
Cheers Mowzerroks- please remember it is only my opinion/interpretation and may not be correct.
I also apologies for my all too frequent lapses of intelligible English, spelling and grammar (which I only seem to be able to see after I have posted!)
Robotics - fair point, it is hard to increase sensitivity when you are getting near LoQ's . If you think that 1 ct increase is a doubling of the signal it is quite hard to achieve this by LFT's . If, for example, the N and S tests have similar sensitivity then combining them (all other things being equal) you would only increase the sensitivity by 1 ct. Using two signal affimers would achieve the same results (so you would have 3 that bound S1, two of these would be reporters). Combine both methods and you only go to the equivalence of 2 ct's
Yes thanks monks, much appreciated.
Thanks for the clarification on pcr, appreciated. There is definitely an overlooked element iro virulence versus halflife which diasadvantages the S target imo so less S to pcr then even though the spike itself is robust according to AS. Maybe it is not only dead but dissolves to nothing.
Really helpful info monkshood - I really enjoy the science discussion. Obviously the trials are there for a reason - and I would hope they would be robust enough. I just had this nagging doubt in my head that if we are using something new like affimers, would the current testing process using spiked artifical samples have any issues given that we are using affimers and could the somewhat vague RNS that didn't directly dispute the failed test at PD report actually be that the test was inconclusive due to something that hadn't been considered. Monkshood - please do continue to contribute here - many here find it very helpful.
Doze.- You can pcr from 'dead' things it only needs a template, they have sequenced (same thing in practice) from stuff over 1m years old. Protein can survive even longer.
Thanks Monkswood, just wondered if I missed something. I'm hoping for best LFD bar none, we will see.
Surely the spike degenerates while the live dna for regeneration is within shell and the bits that get pcr'ed, you can't pcr a dead thing.
What it does show, with the benefit of hindsight, is that we have improved our lod 6x from Nov RNS. I think this is pretty impressive (in the Nov RNS they were confident that lod was in the range needed). This to me explains the delays. They have not been twiddling their thumbs. I think this shows development of a high performing lft is not easy. It also shows that there could well be merit in the hybrid Mologic/Avacta N/S test in the future. Looking forward to bigger clinical data.
The same would apply to the N half-life which I have not seen anything about and could be different than that for S1.
I have read a couple of papers looking at pfu's and ct and there are just so many outliers it is hard to draw clear conclusions especially as the numbers get lower.
The argument against pcr is that it picks up residual rna (which is actually quite labile), we do not know yet the half life of the antigens that the S1 affimers binds (it does not need to be entire S1) in relation to being able to isolate viable virions (i.e. a pfu) from the same samples.
Thanks. Although avacta gave the common measure of pfu, they are still not comparing complete like with like and down at those levels, even a small difference can be wrong by an order of magnitude. That is why, although slightly disappointed with the analytical Lod, it is mostly superceded by the clinical results. By their Lod, they shouldn't be detecting a CT value positive of 25-26 so there must be something lost in translation.
Agree monks, as yet nothing to prove it is the best, but am hopeful of excellent translation into clinical results (as already seen).
No Monkshood, so why do the idiots not pass the b.... test and get some proper usage data with a test that isolates the infectious. The test itself is not going to hurt anyone anymore than standing next to someone breathing out germs. It is so simple, no degree required.
The only common measure until they are trialled side by side is by ct numbers and s/s (which is itself referenced by ct number). I agree this is not perfect but what else is there? AS has never said it is the best LFT only the best S1 LFT.
It is clearly a competitive product, but there is no evidence yet to prove it is the best LFT.
Howzaty there is no measure possible apart from reduction of the R rate by mass testing and data analysis of R rates reducing. It is pointless measuring because you are then too late as the inventor said measuring with pcr/CT is for analysis and research.
Not pcr ct 25 I suppose?
So might I ask the measure you are comparing others against Avacta with, and what is the comparison?
Monkshood, AS stressed in the interview that spike proteins were robust so the detection of them should be easy if they are present but I don't think they multiply with CT as that is not dna and yet they are the infectious part of covid. The testing needs to be catching those with covid as early as possible and this only happens by capturing the spike proteins which are present in clinical samples but not artificial samples which are used after being selected using nucleic samples with a few residual spikes along for the ride.
I thought it interesting that he addressed the S/N question (does he look at the BB?). The comment about solubility was reasonable, not only is S1 on the outside it has lots of sugar groups which would make it more soluble (it is why I asked about the effect of these on movement in the LFT when he was answering questions one time ). Others have managed to get assays with N working, so it is possible to do it with this protein. As you say there is not a great deal of difference between the best N LFT and Avacta's S1 LFT so it may be 'swings and roundabouts' what you lose on the abundance you gain on the solubility.
They were making the point about spending time optimising buffers in the rns, so if there was a problem with artificial samples having them in VTM could have caused been the cause.
We know that it works well on clinical samples so I am quite happy with that, although I am still surprised that, if it was mainly about getting the buffers etc right it has taken quite so long to develop the test.
Theres a bit more meat on the bones in both the video today and the business update. AS said they believe targeting the spike protein is better because it is on the outside of the virus and is more stable, robust and soluble. Do you think these things compensate for the reduced numbers of spike compared to n proteins? Their analytical sensitivity compared to n protein tests isn't stunning. But I'm wondering whether you put all the info together, it means that Avacta's test will translate really well into clinical testing and particularly field trials (which is where Innova fell down)?
Avacta certainly made a point about saying that any test needs to be able to translate their LOD to clinical samples and clinical testing. Would be grateful for your views.