In reply to dwisniewski:
> I'm not entirely sure what you mean here RE the pillar 1/2 testing?
These authors use many more self-reported symptoms to determine a "symptomatic" case than are used to select people for pillar 2 testing (12 vs 3). So, their definition of "symptomatic" is different. They could re-process their data with the definition used for eligibility for pillar 2 testing and see if the ratio of asymptomatic cases by that definition has changed - which is important as that is the definition used to select people for test/trace/isolate.
> To me one of the strengths of this surveillance study is that it's not biased by symptomatic testing.
I think there is value in having both sorts of testing - and it's clear that the ONS and P1/P2 data does not have a fixed correspondence over time. I see the random sampling as a great strength for information on societal prevalence, but the lack of that fixed correspondence makes it harder to use to understand what's going on with testing, which is a key part of what's going to help release restrictions. I also wonder how well they can really control for the selection bias of those who choose to participate.
> Also regarding what they say about asymptomatic transmission, I read it as saying that asymptomatic transmission accounts for a large proportion of cases as is the case for other lineages.
Yes, that was my understanding too, but it felt to me like they were hinting that it could play more of a role. As I said, perhaps I was way over- or mis- interpreting that - other parts as well as the part you quoted. It read to me a bit like they thought it was a more serious driver of transmission but couldn't support that. Probably all in my head.
> I think the differences are likely due to the period of time that testing was done. New exponential growth of a lineage, more cases that have newer infections and therefore higher viral loads. They do report the drop in Ct values in early Dec, that had first been reported around 20th December.
Yes, that was my understanding. But this mechanism for Ct starting higher and lowering only applies to a random sampling approach in a rising then level/decay phase - which this study was. I don't believe that this mechanism would translate to symptomatic pillar 2 testing, where people all go for testing at a similar, early stage in their infections. So, whilst this theory explains the higher early on Ct value in their data, that doesn't explain the higher Ct reported by NERVTAG from symptomatic P2 data. (Edit: When, unless we assume there is a significant random sampling component to P2, which is possible given that the symptoms used for entry capture > 20x as many people as are detected as infectious, so people coming in with non-covid induced symptoms and non-symptomatic covid could be effectively randomly sampled...?)
I'm not aware of data of Ct vs time from infection for either variant, so it's all scrabbling around in the dark, but I do think they could contextualise their observation on random sampling data to qualify how compatible it is with symptomatic sampling. But I regard Ct values and PCR in general as a bit of a dark bimolecular art.
> Yes their regional analysis for the south east in the pre-epoch align with the earlier estimates on transmissibility, which were a good warning. But given we're interested in estimating the biological transmissibilty of the new lineage I think the more recent matched regional growth rates (up to 2nd January) give a good indication that it's not *actually* as high as early estimates. Obviously different control measures will affect the apparent transmissibility, and it's always going to be difficult to disentangle the contributions of such measures from inherent transmissibilty.
Yes, even with the best visualisations of the data and the timelines, it's like trying to read digital tealeaves to unpick all of this. Having slept on it, I just don't like their production of an "average" value from data from different regions with each region being represented in the average by a different period in time. I think that's an over-reach. What I'd really like to see is a doubling time vs data estimate for old and new variants on a regional basis.
My take is that with lax control measures it really is a lot more transmissible, but that it responds strongly to them - although this is called in to question by how Kent and Medway remained exponential under Tier 4.
> I agree, I don't think there's any real conflict in the findings. I just think it raises further questions about the actual biological transmissibilty of the lineage, how much was it's early estimated value influenced by other factors in early-mid Decmeber, and if it is more transmissible how does it manage this?
Totally agree. This is going to be really important to understand for the unlocking process which I imagine will start in earnest when vaccinated down to 60 years of age or so.
> On the latter point, the viral load doesn't seem to be significantly different compared with other lineages so increased transmission not likely due to increased shedding. The prepint suggests it may be due to the increased binding of ACE2 receptors therefore requiring a lower amount of viral particles to cause infection. Who knows though.
Yes; this was a point of unrecognised conflict I thought I saw in the prerint. They also discussed how the lack of worse health outcomes is consistent with their not being a higher viral load, but to my mind the health consequences a product of (viral load ingested) x (probability of an individual virus particle binding) (*) as it's a numbers game and both affect the number that invade the host.
However, we found no evidence that Ct values (a proxy for viral load) were intrinsically substantially lower in SGTF-positives [...] consistent with observations that B.1.1.7 infection is not more severe
So more binding affinity would have a similar effect to a larger viral load ingested, so there's a contradiction to my mind between increased binding affinity and lack of more severe infection. I suppose this critically depends on what the non-linear saturation points are in the infection pathways and if viral load actually matters a lot or not to the severity of an infection that makes it past the initial endothelial cells.
(* - okay, really it's a more involved probabilistic calculation...)
> I agree it's been great to see, but I won't hold my breath over the future funding though especially with regard to basic/fundamental research. We can hope though.
After the original SARS, a shiny new CL-3 lab was built at great expense nearby. Interest and funding dried up and it was mothballed. It seems to have been stripped down, which is a shame if you're in the market for a CL-3 facility...
Post edited at 13:45