Fantasy commentary letter in Lancet (not a peer reviewed study)!

It's an unreasonable proposition for most countries like the UK to achieve elimination + constraints of reality negates claimed economic and liberty benefits if attempted...

1/

thelancet.com/journals/lance…
Despite pre-flight screening and quarantine Australia and New Zealand have failure rate of 4.8 per 100k travellers. SARS-COV-2 cases slip through!

2/

medrxiv.org/content/10.110…
Those cases slipping through results in necessary lockdown (regional or state wise) to eliminate community transmission.

Up to January 31, 2021:
Australia 7 failures, with 1 causing 800 deaths
New Zealand 9 failures, 1 causing an outbreak of 3 deaths

more since

3/
For the UK:

7k daily lorry drivers bring food +industrial supplies via channel

29k+ daily crossings of the Northern Ireland border

These flows could not conceivably be halted, nor quarantine pre-screened. Introduction rate >>4.8/100k depending on prevalence in ROI and EU

4/
Flight quarantine to be as effective as AUS/NZ wd severely limit number of inward travellers ~20k per week. Hugely damaging to skilled workforce movements, reuniting families, unis.

Despite UK sealed borders as much as possible (300k+/week) = introduction rate >>15 per week

5/
Most would not seed community clusters (K dispersion) but enough would.

Community outbreaks aren't picked up early enough as most cases mild. Not until moderate illness detected typically, hospitalisation or death. That's too late, too large. To eliminate need to lock down.

6/
Given UK introduction rate and cluster seeding:

To achieve and maintain elimination an 'actual ZERO' Covid policy would require a permanent state of national lockdown (Aus Stage 4 equivalent to Level 4+schools closed in Eng) despite sealing borders!

7/
Geographic compactness and density of the UK/England would necessiciate lockdown be near national in scale to actually eliminate all seeded domestic SARS-COV-2 infections - similar to Aus States.

8/
The effect of permanent Level 4 lockdown negates those economic and liberty gains supposed in the Lancet letter.

The scale of COVID cases, hospitalisations and deaths would be much less in this UK elimination counterfactual, but still much more than Aus/NZ...

9/
Aus/NZ did not move to elimination until after March 20th when they sealed borders.

The same geographic/economic connectivity and flows of peoples meant that UK outbreak was several orders of magnitude larger by then. UK 1st wave would have similar outcome by then.

10/
Subsequent waves would have been much less damaging in terms of deaths with continual sporadic low level outbreaks despite lockdown.

But excess ~47k deaths from 1st wave would have resulted before the switch to elimination strategy at the same time as Aus/NZ.

11/
This reasoning does not mean Aus/NZ should not have gone for elimination - actual zero covid.

They leveraged all their natural advantages w/ policies to achieve the best outcome for them in terms of health and GDP.

I wish all countries were as lucky as Australia.

12/
The reasons countries have serious covid outbreaks (infections or higher deaths rates) are multifactorial. Not all of them are under the control of public/health policy makers.

#coronacentrist manifesto👇

13/
Lancet letter also mischaracterises countries like Japan as elimination- it's not- has successful suppression strategy (higher domestic case rate than UK now).

And bundles successful suppression countries (Nordics, Germany etc) from whom we can learn and less successful.

14/
The range in what the suppression strategy involved, how successfully implemented, uncontrollable factors and resultant outcomes for deaths and GDP varied hugely in the 'suppression' countries. They are too mixed to lump together and analyse as one group.

15/
P.S. Lancet comment on elimination contained this disclaimer

"our analysis does not prove a causal connection"

It's not serious analysis work, nor a basis for policy recommendation... ie be an isolated island w/ low cross border traffic (🇰🇷 included thanks to DMZ)

16/
Summary:

Attempting an elimination strategy would have resulted in tens of thousands fewer deaths in UK, but it would have failed in definitional terms and required permanent national lockdown diminishing economic and liberty gains.

That would be an honest policy debate.

ENDS/
An updated analysis to 31st March for Aus/NZ. Slightly higher failure rate and 2.3 reactive lockdowns per 100k travellers.

At the scale of UK cross border flows would be 7+ lockdowns per week if truly aiming for domestic elimination!

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More from @DevanSinha

28 Apr
PHE study on household transmission after vax:

40-50% reduction if break through infxn

From contact tracing of 4.1k households where index vaxxed >21days and contact positive 2-14 days of index

4 Jan 4 - 28 Feb from 365k households w/ single index case and 1m+ contacts

1/ Image
No statistical difference between Ox/AZ and Pfizer efficacy for onward transmission

No statistical difference in effect by age

Well controlled:
adjusted for age of index case and contact, sex, region, calendar week, index of multiple deprivation quintile, household type

2/
limitations:

Pillar 2 symptomatic case only so may miss asymptomatic cases (=overestimate efficacy).
Assumed contact symptom >2days of index was transmission but cd be co-primary (=underestimate),
and all 2-14 days are household transmission not independent (=underestimate)

3/
Read 4 tweets
30 Mar
Updated meta-analysis B117 mortality w/ new PHE sequenced Pillar1/2 study Oct-Dec

Major limit= underpowered
Only 36/2.8k deaths B117 cohort v 40 non-VOC
HR 0.9 [0.57,1.41]

(W/ updated LSHTM and Exeter papers, but now excl hospitalised HR studies)

🔺c40% mortality risk

1/
Study still found B117 increased hospitalisation risk
HR 1.34 [1.07,1.66]

Unless in hospital mortality is lower in B117 (no clear difference) then over all fatality rate will necessarily be higher

A few other considerations 👇

2/

From pathophysiology understandable why B117 might have higher morbidity/mortality.

Higher binding affinity to ACE receptor means more tissues or systems w/ lower expression may be affected

More replication (⬆️viral load) means more tissue damage and systemic inflammation

3/
Read 4 tweets
15 Mar
COVID on the brain 🧠

Stroke like brain injury can be a life altering complication of SARS-COV-2 infection

Let's see how often is happens, what it looks like, and why.

A retrospective study was done in my own hospital trust :)

1/
3,403 PCR+ COVID inpatients between March and May 2020

167 had neurological symptoms warranting neuroimaging

38 revealed vascular (ischemic or haemorrhagic) abnormality = 1.12% of total C19 inpatients

Mean age 59.7

Onset of neuro symptoms mean 10.1 days from admission

2/
Even w/out COVID, many patients admitted for other reasons have strokes. However, in this COVID patient cohort when age adjusted the rate is ~5x ⬆️

87 vs 16 per 1000 hospitalised inpatients annualised rate

3/
Read 10 tweets
5 Mar
Temperature and SARS-COV-2 transmission:

Some seasonality expected for resp viruses, hard to say how much. England had unique circumstance Feb 7-13th.

- week long cold snap across country of similar magnitude
- no change in restrictions
- no increase in daily mobility

1/
Due to variables being reasonably controlled we can estimate how temperature may affect general transmission dynamics.

Note Seasonality: viruses transmit at ALL times of year but climate affects biology and behaviour which impacts on how much transmission occurs.

2/
Cases by specimen date in England showed a marked deceleration in the rate of decline the week after the cold period. From more than -5% per day to less than -2%.

(daily change adjusted for day of the week effect in testing)

3/
Read 14 tweets
22 Feb
1st dose hospitalisation vax efficacy

94% Oxford/Astra
85% Pfizer

Appears taken as point estimates for week 5 (28-34 days) post vax.

Pfizer data doesn't improve (declines even), but not too worrying yet... ImageImage
Scotland where data from care home residents and 85+ were vaxxed 1st. Follow up time after 5 weeks means age will confound VE. With few absolute events adjustment for age becomes statistically underpowered (and doesn't capture full care home risk). Hence wide confidence interval Image
Also interesting to think about vax tech.

Oxford uses chimp adenovirus vector. Although engineered not to replicate, it's tough and can persist for weeks-months before cleared. Continuing to stimulate immune response by causing Sars-Cov2 spike protein production. ImageImageImage
Read 5 tweets
31 Dec 20
The AZ/oxford vac shows high immunogenicity and efficacy when delayed to 12 weeks for 2nd dose. Ab titres highest for 12 weeks 👇

BUT the delay for Pfizer vac though potential large societal benefits is definitely a risk...

🧵 1/
1. Pfizer efficacy was only trialled at 21 days for 2nd dose. (cf AZ/Ox 4-26 weeks)

2. This can be estimated at ~80-90% for 10-22 days after 1st dose

2/

But Ab tires don't increase until 2nd dose for Pfizer, especially in the older age cohort who are the priority vaccine targets. How much protection are we giving them?👇

The 86% is a pooled estimate of all ages with younger population dominating.

3/
Read 8 tweets

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