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Covid Mutations

Wastewater studies hint that the 'rona is well established in various sections of the wild murine population.
 
A potential variant of interest has popped up in Southern France, first detected in a vaccinated traveller returning from Cameroon in mid-November. Daily hospitalisation and ICU admission rates in the region are apparently climbing faster than the national average (case numbers and vaccination rates are comparable to any other French area), though it is too early to conclude whether these are linked.

This variant is B.1.640.2 with defining changes: P9L, E96Q, Δ136-144, R190S, D215H, R346S, N394S, Y449N, E484K, F490S, N501Y, D614G, P681H, T859N and D1139H all in spike, plus NSP2: p129L, NSP4: D459N, NSP6: Δ106-108, NSP6: T181I, NSP12: p323L, NSP13: V371A, NSP14: p46S, NSP14: V437F, ORF3a: T32I, ORF3a: Q57H, M: I82S, ORF8: Q27*STOP, N: D22Y, N: T205I. A significant number of those changes are known to have an effect on various neutralising epitopes and some on cleavage and cell fusion.

Not yet clear how it competes with omicron/B.1.1.529. Small numbers of cases also spotted in the UK.
 
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Perhaps notable that BA.2 appears to have been taking off in several countries over recent weeks.

It is growing in Germany and displacing BA.1 (omicron/B.1.1.529) in Denmark - is just becoming dominant there:
Share of BA.2 of all BA.x in Denmark.
Already appears to be dominant in India (and the Philippines).
Share of BA.2 of all BA.x in India.
Growing in the UK too (interestingly significantly so since xmas and almost co-incident with the 'peak' in parent-lineage omicron cases):
Share of BA.2 of all BA.x in the UK.

Very preliminary data might suggest that BA.2 doesn't appear to result in any more severe disease than BA.1. Hard to determine relative degree of vaccine evasion, if any, right now. Nor is it obvious that there would be a loss of cross-reactivity from BA.1 (ie previous recent infection). Amino acid differences might facilitate improved evasion of innate immunity (eg signalling modulation).
 
Is it BA.2 that was being called "stealth Omicron" a wee while back?
BA.2, not having the 69-70 deletion in spike, does not feature the S gene dropout (SGTF) so growth can't be implied from PCR; it has to be sequenced (as per post #431). That may have been what that 'label' referred to?
 
BA.2, not having the 69-70 deletion in spike, does not feature the S gene dropout (SGTF) so growth can't be implied from PCR; it has to be sequenced (as per post #431). That may have been what that 'label' referred to?

Yeah, that’s exactly what the term meant. It was a media/internet slang thing - nothing scientific.

So BA.2 is the only Omicron variant we know of with the S-gene dropout, is that right? My question was basically about whether the new one spreading in Germany was a “stealth Omicron 2”, or the one that they were talking about a few weeks ago.
 
So BA.2 is the only Omicron variant we know of with the S-gene dropout, is that right? My question was basically about whether the new one spreading in Germany was a “stealth Omicron 2”, or the one that they were talking about a few weeks ago.
Without, not with. And yes its the same one mentioned back in early December and given that moniker by some.

December example: Scientists find ‘stealth’ version of Omicron that may be harder to track

The 'stealth Omicron' name is actually being used more by the press in recent days than it was back then. Or rather, this variant is in the news more at the moment and unless its given another name, the press are more likely to call it stealth Omicron in their headlines than BA.2.
 
The name stealth omicron really isnt appropriate now given that the BA.1 Omicron dominated to such a great extent, and Delta fell away so much, that S-gene stuff can again be used as a shortcut to viewing the rise of another variant with the opposite s gene target detectability.

 
Preliminary calculations suggest BA.2 could be 1.5 times more infectious than BA.1, Denmark's top infectious disease authority, Statens Serum Institut (SSI), said in a note on Wednesday.

However, an initial analysis by the institute showed no difference in the risk of hospitalisation for BA.2 compared to BA.1.

"There is some indication that it is more contagious, especially for the unvaccinated, but that it can also infect people who have been vaccinated to a greater extent," SSI's technical director Tyra Grove Krause said at the briefing.

This could mean the peak of Denmark's epidemic will extend a bit further into February than previously forecast, Krause said.

 
Theres a lot of BA.2 focus in the latest UK variants technical report.


The proportion of SGTP cases is now increasing. As of the 24 January 2022, the overall proportion of SGTP cases in England is 4.4% compared to 2.2% on the 17 January. There is geographical variation with the highest proportion in London (9.5%) and the lowest in the North-East region (0.9%).

Growth rate
BA.2 has an increased growth rate compared to BA.1 in all regions of England where there are sufficient cases present to make an assessment. Whilst growth rates can be overestimates early in the emergence of a variant, the apparent growth advantage is currently substantial.

Secondary attack rates
Analysis from routine contact tracing data indicated higher secondary attack rates amongst contacts of BA.2 cases in households (13.4%; 95% CI: 10.7%-16.8%) than those for contacts of other Omicron cases (10.3%; 95% CI: 10.1%-10.4%) in the period 27 December 2021 to 11 January 2022. These secondary attack rates are not adjusted for vaccination status and reflect overall growth advantage rather than transmissibility.

I consider the early vaccine effectiveness estimates to be based on too small a sample size for me to place huge weight on the initial analysis, but also wont be too surprised if they remain similar in future.

Vaccine effectiveness
A preliminary assessment did not find evidence of a difference in vaccine effectiveness against symptomatic disease for BA.2 compared to BA.1. However, numbers included in this study are relatively small and it will be iterated. The University of Oxford has reported preliminary unpublished pseudovirus neutralisation data. In this study, BA.1 and BA.2 pseudoviruses did not differ substantially in neutralisation by sera from vaccinated individuals.

Screenshot 2022-01-28 at 18.14.jpg
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There was also stuff on Omicron in general in there, including intensive care stuff:

The weekly proportion of Delta versus Omicron ICU/HDU admissions from 24 November 2021 to 24 January 2022 are shown below in Figure 13. A linkable sample was available for 19% of critical care admissions in this time period. Overall, the majority of admissions in this subset of critical care patients had Delta infection. However, towards the end of December, Omicron infection was detected while overall numbers of critical care admissions decreased. From cases where there was a valid sequencing result, those admitted to ICU that were Omicron increased from 9% week commencing 15 December 2021 to 50% on week commencing 12 January 2022. Individuals admitted to ICU/HDU are often late in their course of infection and therefore lower yields from sequencing is expected. However, hospitals should endeavour to locate and send prior positive COVID-19 samples from individuals admitted to ICU for sequencing and genotyping, where these samples are available, in order to understand the differences in severity between variants.

They also looked at a preprint about Omicron impact on care homes, which concluded the same sort of thing we'd already heard in other settings in regards notably reduced severity. Here I link to an updated version of the preprint, since the original version they link to has a error in the results summary which erroneously said the hospitalisation risk was lower pre-Omicron instead of higher.


Updated corrected results paragraph:

Risk of hospital admission was markedly lower in 1241 residents infected in the Omicron-period (4.01% hospitalised, 95% CI: 2.87-5.59) compared to 398 residents infected in the pre-Omicron period (10.8% hospitalised, 95% CI: 8.13-14.29, adjusted Hazard Ratio 0.50, 95% CI: 0.29-0.87, p=0.014); findings were similar in residents with confirmed variant. No residents with previous infection were hospitalised in either period. Mortality was lower in the Omicron versus the pre-Omicron period, (p<0.0001).
 
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The name stealth omicron really isnt appropriate now given that the BA.1 Omicron dominated to such a great extent, and Delta fell away so much, that S-gene stuff can again be used as a shortcut to viewing the rise of another variant with the opposite s gene target detectability.
Latest technical report confirms this:


As of 7 February 2022, 7,194 genomically confirmed cases of BA.2 have been identified in England. Sequencing data is complete up to 31 January, at which point 95.4% of sequences were BA.1, 4.1% were BA.2 and 0.5% were other lineages. BA.2 does not contain the spike gene deletion at position 69-70 and is S-gene target positive (SGTP) on polymerase chain reaction (PCR) diagnostic assays with targets in this area. SGTP is now a reasonable proxy for BA.2, accounting for 97% of sequenced SGTP cases with an increasing trend. The proportion of SGTP cases is now increasing. As of 6 February 2022, the overall proportion of SGTP cases in England is 18.7% compared to 5.1% on 24 January. There is geographical variation with the highest proportion in London (31%) and the lowest in the North-East region (3.9%).

Also discussed are serial interval differences:

Preliminary analysis from contact tracing data suggests that the average time from symptom onset of a primary case to symptom onset in their identified contacts (the mean serial interval) is around half a day shorter for BA.2 than BA.1, with a mean serial interval of 3.27 days compared to 3.72 days for BA.1. Both are shorter than the mean serial interval for Delta of 4.09 days. The serial interval suggests the time between primary and secondary infections is shorter, which could contribute to the increased growth rate of BA.2.

And the intensive care picture for Omicron:

Since 29 December, among Intensive Care Unit/High Dependency Unit (ICU/HDU) cases linked to variant and mutations, Omicron (B.1.1.529/BA.1) has become the dominant strain, but weekly numbers of admissions are much lower than previous weeks. Small numbers overall preclude an accurate comparison of risk of ICU admission between variants at present.

Hospitalisation and death risk estimates:

Analyses of the comparative risk of hospitalisation or death between Omicron or Delta found that after adjustment for confounding factors risk of hospital attendance among cases with Omicron was reduced compared to Delta (Hazard Ratio: 0.56, 95% CI: 0.54-0.58). The risk of death was approximately 60% lower among Omicron cases compared to Delta (Hazard Ratio: 0.31, 95% CI: 0.26-0.37). The relative risk of hospital admission varied by age, with similar risk of hospital admission among children aged under 10 years old, and approximately 75% reduction in the risk of hospital admission among those 60 to 69 years old (HR: 0.25, 95% CI: 0.21-0.30).

There is more detail than I have quoted in the ful report, and other stuff including reinfections.

Also:

Screenshot 2022-02-11 at 18.36.jpg
 

Tweet unavailable.

Speculation on the pathogenicity of BA.2? Perhaps arising from:
Statistical analysis shows that the effective reproduction number of BA.2 is 1.4-fold higher than that of BA.1. Neutralisation experiments show that the vaccine-induced humoral immunity fails to function against BA.2 like BA.1, and notably, the antigenicity of BA.2 is different from BA.1. Cell culture experiments show that BA.2 is more replicative in human nasal epithelial cells and more fusogenic than BA.1. Furthermore, infection experiments using hamsters show that BA.2 is more pathogenic than BA.1. Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1.
DOI: 10.1101/2022.02.14.480335.

But always remember: mice lie, monkeys exaggerate (and ferrets are not people). Needs a couple of weeks and a few more separate studies to corroborate (or not).
 
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