Coronavirus Sars-CoV-2/Covid-19 Megathread

[alfred russel]

In April I highlighted a group of states working to open up early as evidence people were fed up with the situation: South Carolina, Tennessee, Alabama, Georgia, and Florida. Malthus suggested a group of Trumpist governors doesn't prove anything.

My proposal: by the end of the year, the per capita death rate in those states will be below the national per capita death rate. The calculation will be total deaths in all those states divided by the population in all those states.

How much money are you willing to bet, and at what odds?

Straight up, line in signature acknowledging the winner's superior knowledge of coronavirus and the loser's inferiority and general stupidity.

Coming back to this a few days late. Back when there was so much hand wringing over the extent of the summer covid spikes in southern states like Georgia and Florida, and so many "I told you so" comments here (and elsewhere), I made an offer to bet that by the end of the year the states mentioned above would have a combined per capita death toll less than the national average. No one took the bet: which goes to show the level of confidence in their criticism of those states.

Things got close, but at year end not only is the average below the national average in those states as a whole, but every state is individually:

(deaths per million)
National average: 1,105
South Carolina: 1,065
Georgia: 1,033
Florida: 1,029
Alabama: 995
Tennessee: 1,049

[alfred russel]

No more outdoor climbing for you, Sheilbh.

I spent a few days of time off going climbing in Red Rock just outside Las Vegas with my fiance. The climbing areas were crowded-I've been there a few times before and it was way busier than before. Basically with west coast gyms (and offices) shut down, lots of climbers have migrated to the one place warm enough to climb and in a state that isn't closed. We stayed at an airbnb but I understand the campgrounds around the area were full.

That said, it is the outdoors, and there was plenty of room to socially distance.

My fiance hadn't been to the strip before, so we went down there for New Year's Eve. We probably arrived about 8:30, and left by about 9:30 (and were probably asleep by 10 -- we aren't exactly partiers). But the strip was jamming, and I bet a zillion more people arrived as things approached midnight. I'm sure cases in the country will continue to be high post holidays, but I really doubt hikers and climbers will be responsible.

[Iormlund]

Things got close, but at year end not only is the average below the national average in those states as a whole, but every state is individually:

(deaths per million)
National average: 1,105
South Carolina: 1,065
Georgia: 1,033
Florida: 1,029
Alabama: 995
Tennessee: 1,049

Those figures are pretty bad, once you take into account how big a role climate has on transmission.

Excess mortality in the Canary Islands -- noticeably warmer than the rest of the country -- is just ~5% of Spanish average. Or in other words, 95% below average.

[edit] Didn't notice how MoMo presents data. Corrected it.

[mongers]

No more outdoor climbing for you, Sheilbh.

He can still social climb in all of those draughty, near open air castles he's so familiar with. 

[alfred russel]

Those figures are pretty bad, once you take into account how big a role climate has on transmission.

Excess mortality in the Canary Islands -- noticeably warmer than the rest of the country -- is just ~5% of Spanish average. Or in other words, 95% below average.

[edit] Didn't notice how MoMo presents data. Corrected it.

I don't think that the temperature difference between the Canary Islands and mainland Spain accounts for the difference in outcome. There is a larger temperature difference between Spain and Sweden than the Canary Islands and Spain, but Sweden actually has less per capita deaths. Is their response that much better that it can overcome the huge temperature disadvantage?

[DGuller]

I think the name of Canary Islands kind of gives away why it was much more successful controlling Covid.

[Eddie Teach]

The British Isles didn't do so well.

[mongers]

The British Isles didn't do so well.

Doh, it's because we don't have any Canary living here.

[celedhring]

This cartoon sums up my feelings perfectly 



"So this was the light at the end of the tunnel?"

[Richard Hakluyt]

The British Isles didn't do so well.

Doh, it's because we don't have any Canary living here.

Because Thatcher closed the coal mines and all the canaries were made redundant 

[Sheilbh]

Germany and Denmark apparently also considering moving to a single dose plus 12 weeks for the booster. In the UK the big pressure is the risk around the new variant. I think with Germany and Denmark the issue is more that supply of the vaccine has been slow. In both cases it feels like the potential benefits to the whole population probably outweigh the risk of lower effectiveness (for three months) for individuals.

[Tamas]

I don't get it though, if the Pfizer folks say they have no idea how effective their stuff on the 12 weeks schedule and it should not be used like that, why can the same people who thought their decade old anti-flu pandemic excel sheets are perfectly fine should now decide they know better than Pfizer?

[garbon]

https://www.bmj.com/content/371/bmj.m4978/rr-3

Where is the evidence that extending the dosing interval for the Pfizer mRNA vaccine from 3 weeks to 12 weeks is effective and safe?

Dear Editor

The four Chief Medical Officers (CMOs) of the United Kingdom and the Deputy CMO for England wrote to the profession on 31 December 2020 to explain their rationale for the dosing schedule for the Oxford vaccine and the change to the dosing schedule for the Pfizer vaccine, to maximise the public health benefits of the vaccine roll-out this winter (1). They supported their arguments with a report from the Joint Committee on Vaccination and Immunisation (JCVI) Optimising the COVID-19 vaccination programme for maximum short-term impact, 31/12/20 (2).

Table 1, Annex A of the report tabulates vaccine efficacy (VE) for the Pfizer vaccine at 15-21 days, 22-28 days and 15-28 days after the first dose (2). The VE at 15-28 days (one week either side of the booster dose on day 22) is 91% (95%CI 74-97). The post-hoc analysis behind this estimate preserves randomisation, is based on apparent reasonable assumptions about time lags before a clinical response to vaccination and is supported by data-derived evidence for the separation of symptomatic Covid-19 incidence curves in the two trial arms (3). Such a high VE so early is reassuring, particularly as the lower bound of the 95% confidence interval for the Pfizer vaccine at 15-28 days is 74%. Although the booster on day 22 may have some effect before day 28, in line with a reported increase in 50% neutralizing antibody titre between days 21 and 28 (4), a VE of 89% (52-97) at 15-21 days is also reassuring (2).

The JCVI present a convincing argument that most of the benefit of the Pfizer vaccine occurs early and that we can anticipate a greater public health benefit in the short term if we accelerate recruitment by postponing the booster and vaccinating twice as many people with a single dose initially (2).

But what then? Patients will be reassured that initial protection with the first Pfizer vaccine dose alone is almost as good as that following a prime-boost regime with a 3-week dosing interval (89% at 15-21 days (2) compared to 95% from day 29 onwards with a prime/boost regime (3)) but they will want to know how long this level of protection after only one dose will last, and how any extended dosing interval will affect the response to a booster in terms both of efficacy and duration.

As a GP, I will struggle to answer their questions because of weaknesses in the quality of evidence presented by the JCVI, who state that "the second dose is still important to provide longer lasting protection and is expected to be as or more effective when delivered at an interval of 12 weeks from the first dose" (2).

Expected is the key word here. We must bear in mind that: (a) SARS-CoV-2 is a newly emerged pathogen – clinicians and researchers experienced in infectious diseases advise us to be humble and cautious in our assumptions about the behaviour of new pathogens; (b) the correlates of protection against infection, infectiousness, symptomatic or severe Covid-19 disease are not known, nor whether these might vary (say) by age (5); (c) neither the Pfizer BNT162b2 nor Moderna mRNA1273 vaccine trials that have been reported so far were designed to evaluate different dosing intervals (3,6); (d) mRNA-based vaccines are a new technology – even though there is a strong foundation of pre-clinical research using various mRNA platforms (7,8), BNT162b2 and mRNA1273 are the first such vaccines to have been approved for use against infectious disease in a broad section of the population.

The JCVI document reads, in part, like an Olympian pronouncement (2). This contrasts with the reasoning in reports that clinicians are accustomed to reading from NICE, whose technology appraisals and guidelines contain explicit acknowledgements of uncertainty and limits to evidence. Clinicians and the public understand the imperative to act despite imperfect evidence because of the rapidly evolving pandemic. However, a lack of transparency about some of the evidence behind current decision making does not sit well with earlier reassurances that no corners have been cut in the expedited development and deployment of Covid-19 vaccines.

So, what is the evidence for and against an extended prime-boost vaccine dosing interval against respiratory viruses in humans, and how might this be relevant to mRNA vaccines against SARS-CoV-2? How well might any such evidence about vaccine use in children translate to adults?

Key questions include the effects of an extended prime-boost vaccine dosing interval on:
1. Safety, immunogenicity, efficacy and duration of the immune response in humans?
2. The patterning of antibody binding and T cell specificity to different target epitopes, bearing in mind the potential for new variants of SARS-CoV-2 to emerge?
3. The direction of skewing of T-cell responses?
4. Coordination between different arms of the adaptive immune response, including mucosal immunity?

Does such evidence depend on the type of vaccine technology? Is there any evidence specifically for mRNA vaccines, besides the limited data in a report by Feldman et al that prolonging the dosing interval (in only 5 participants) for an mRNA vaccine against H7N9 influenza from 21 days to 6 months increased, or at least preserved, immunogenicity 3 weeks after the second dose, as judged by haemagglutination inhibition assay titres or microneutralization assay titres, respectively (9)?

[Sheilbh]

I don't get it though, if the Pfizer folks say they have no idea how effective their stuff on the 12 weeks schedule and it should not be used like that, why can the same people who thought their decade old anti-flu pandemic excel sheets are perfectly fine should now decide they know better than Pfizer?

But there's a difference between having no data - not having tested something - and having no idea. There are people who absolutely think we should just follow the three week course. I found this by a couple of Yale experts interesting and the key point is the risk profile on this is different:
https://twitter.com/VirusesImmunity/status/1345086669607890945
https://twitter.com/thehowie/status/1345404768416641024

It's not what we should be doing all things being equal. But given either lack of supply or this new more transmissible strain which is significantly more deadly (on a general level), I think it's a risk decision and the risk is lower but broader immunity among the at-risk or better immunity among a smaller group of the at-risk. My view is that in terms of saving lives we are better with the weaker/broader immunity - you know hospitals are providing emergency/disaster level care not standard levels of critical care. I don't think we're in a position to provide standard levels of vaccination strategy in that context - if we were rolling these out during the summer it would be crazy to delay the second dose (similarly in Australia or Israel where you have good supply and low prevalence), but I think the context right now is really different here and in other bits of Europe.

Edit: Incidentally it feels like something is starting to happen (only a month late) on organising vaccinations. Morrisons have confirmed some of their stores and car parks will be used as vaccination hubs - I'm particularly keen on the car-parks being used because I've slightly panicked about the thought of loads of vulnerable people sat in the GP reception waiting for the vaccination. So doing it in better ventilated, biggger or outdoor spaces strikes me as likely to be safer (until the great 2021 pneumonia epidemic ).

Edit: Oh also the FT are reporting that ministers are now looking at proposals to require a pre-flight PCR test for anyone entering the country. Only 11 months into a pandemic where the countries with the strictest border control/monitoring measures have most successfully managed the pandemic - and Britain is considering finally doing the bare minimum

[Tamas]

I know it is probably fine, Sheilbh, but the same people who have an idea about this now, had a similarly good idea about how to handle this thing back in February/March.

And that is assuming that this going against manufacturer's recommendation plan is the preferred way for the experts and not just one of the several alternatives offered to and chosen by, well, whoever runs the country since Cummings resigned as Prime Minister.