COVID: the spreading UK variant, South Africa news

 The highly transmissible UK variant SARS-CoV-2 is overtaking the United States at this point (see covid UK variant in US medrxiv2021 in dropbox, or https://www.medrxiv.org/content/10.1101/2021.02.06.21251159v1.full.pdf )

 

Details: 

-- the UK B.1.1.7 variant of the SARS-CoV-2 virus has been spreading around the world. It was 1^st identified it in the US in January 2021 after 1^st being sequenced in the UK September 20  (this variant is also called the Variant of Concern, VOC 292912/01), which carries the N501Y mutation

    -- this mutation is shared by other VOCs identified in South Africa and Brazil, though B.1.1.7 does have several other signature mutations in the spike protein

--because of the particularities of this variant and the specifics of the PCR testing we use, the PCR test will not detect the S gene (referred to as S gene target failure, SGTF), giving us a very convenient way to tell if the virus is this variant or not

    -- a positive test for the regular SAR-CoV-2 virus by PCR is when 2 of 3 targets (N, Orf1ab, and S) are positive; for the B.1.1.7 variant, the PCR is positive for both the N and the Orf1ab, but negative for the S target

 

Results: 

-- 460 SGTF samples were sequenced in all of those who were PCR positive from December through January, finding 209 (45%) were of the B.1.1.7 variant from 10 states in the US, the vast majority from California (96) and Florida (87)

    -- other testing labs have reported finding B.1.1.7 sequences in 33 of the 53 US states and territories

    -- in terms of the high rates in California and Florida, the genomic analysis found that these 2 states had 2 different B.1.1.7 viruses, likely introduced independently to the US and with local spread to neighboring states (especially in the case of Florida)

-- in the week of October 18, the daily SGTF positive tests was 0.2% of daily SARS-CoV-2 positive tests

-- during the single month of January 2021 nationwide proportion of SGTF increased from 0.8% to 4.2% by the last week

    -- by the last week in January, B.1.1.7 made up an average of about 2.1% of all Covid cases in the US, 2% of all cases in California, and 4.5% of all cases in Florida [note: the difference in these national numbers, 2.1 vs 4.2% ,reflects the difference in what was measured: actual B.1.1.7 vs SGTF]

-- growth rate of B.1.1.7: 0.07 in the US (6% per day in California, 8% per day in Florida), translating to:

    -- a doubling time of 9.8 days in the US overall, 12.2 days in California, and 9.1 days in Florida

    -- an increased transmissibility of 35-46% over the historic SARS-CoV-2 virus

    -- and these numbers are consistent with this B.1.1.7 variant becoming the dominant lineage in the US by March

-- analysis over time have suggested that increased spread of B.1.1.7 within the US coincided with increase periods of travel (specifically associated with Christmas and Thanksgiving)

 

Commentary:

-- the growth rate of this virus is on the order of 40-70% higher than other SARS-CoV-2 lineages, perhaps attributable to the N501Y mutation having increased receptor binding affinity to the spike protein ACE2 receptors (see http://gmodestmedblogs.blogspot.com/2021/01/covid-longer-term-sequelae-and-new.html)

-- this level of B.1.1.7 prevalence was predicted in advance by the CDC, with a suggestion that over half of the US cases would be this variant by March

    -- in the UK, the proportion of virus attributable to the B.1.1.7 variant has increased from 3% in October to more than 90% by the end of November

    -- there have also been huge increases in Portugal and Ireland of the B.1.1.7 variant

-- the growth rates and transmissibility levels calculated in the US are similar to those found in other countries

-- of concern: initial thoughts were that this vaccine variant was more transmissible but without much effect on disease severity; more recent data suggest there could be a 30% higher mortality rate, though this analysis is preliminary, with small numbers of people and based only on SGTF analysis which is not highly specific (see https://www.bmj.com/content/372/bmj.n230 )

-- and it still remains unclear what the vaccine efficacy is for the B.1.1.7 variant: we do not have rigorous numbers on this. The press suggests between 50-90%....

    -- but, breaking news, the AstraZeneca vaccine in South Africa, where they are poised to administer a million doses, stopped because of preliminary data finding both that the vaccine did not prevent infection from their B.1.351 SARS-CoV-2 variant, and that those with prior actual infection were not protected from reinfection. the study was limited because there was no information that severe disease was prevented by the vaccine (but the people immunized were relatively young and less likely to have a severe outcome).  see https://www.nytimes.com/live/2021/02/08/world/covid-19-coronavirus 

        -- this South African variant has also been found in the US

    --but... another paper just released in preprint, pre-peer reviewed form found that the Astra-Zeneca vaccine was almost equally effective in reducing symptomatic NAAT positive infection from B.1.1.7 variant and the non-B.1.1.7 lineage virus, at 74.6% (41.6%-88.9%) vs 84% (70.7%-91.4%) (see https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3779160 )

    --so: is it a more fundamental difference between the UK and South African variants than we suspect? is there a sampling error (only 2000 people were given the vaccine vs placebo in South Africa, and only 19 of 748 people got infected in the vaccine group and 20 of 714 given placebo) or methodologic problem with this breaking news releases (which I cannot analyze further since it has not been presented as a scrutable paper?)

Limitations:

-- this SGTF frequency varied a lot from state to state, however the testing done for this study did not evenly cover the US

-- and, given the state-oriented approach to testing in the US, genomic analyses overall have lagged far behind other countries, there is no national US genomic surveillance program, and there been quite uneven sampling from state to state; this creates inconsistency in the data available for analysis (ie, it is really important we get better, consistent data to understand the evolution of Covid-19 for both this B.1.1.7 variant as well as others. This is necessary to develop appropriate public health guidelines)

    -- the data available from Florida and California are relatively robust, however

-- as noted above the SGTF testing anomaly used above to monitor the spread of B.1.1.7 is not a perfect proxy for that variant, though the increased growth rate of that variant suggests it will become the dominant one within a matter of weeks (ie, for better or worse, this test will become a more accurate proxy of B.1.1.7 as it overwhelms the other causes of a SGTF anomaly...)

    --also, for the PCR to be SGFT-positive, there is a different threshold than the regular SARS-CoV-2, the former requiring that 2 of 3 targets be positive (both the N and the Orf1ab), whereas the latter requires only 2 of S, N, and Orf1ab

--and, we need much more robust data on the B.1.351 variant

 

So, we are now being overtaken with the UK variant:

-- the UK variant B.1.1.7 has had multiple different introductions into the United States, found especially in California and Florida, with further national spread

-- increased travel seems to be associated with bursts in viral spread

-- we will have a huge increase in infections, as anticipated by the CDC

    -- and, by the way, it is nice to see that mathematical modeling does work, at least sometimes

-- though it seems that even if this variant were less susceptible to the vaccine, even the 50% protection is extremely important in decreasing population-based transmissibility

    --and, of course, we need more data on the efficacy for the B.1.351 variant from South Africa from all of the vaccines (though the drug companies Pfizer and Moderna state that their preliminary analyses suggest they are effective but perhaps less so against B.1.351)

-- and, it is really important for us to decrease the amount of virus in the population: the more virus, the more likely will get new mutations, and some of these may be completely vaccine resistant

-- so our task is (as has been the case for bit):

    -- it is even more urgent to have people immunized, meaning the governmental tasks of making sure vaccine is available and accessible, and our task to counter the array of fake news about this vaccine (and perhaps vaccines in general)…

    -- And the national task to combat Covid-fatigue: reinforcing the extreme importance of wearing masks, distancing, especially minimizing indoor exposure to others, minimizing traveling/shopping/interacting with as many people as possible

geoff

 

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