This is good news.

The longer it takes to statistically tell difference between vax effectiveness against variants the smaller the actual dip (if any) in protection will be.

In randomised control trials we can be confident in vax effect after only 100+ infections because selection bias and confounding variables between the vaxxed and unvaxxed comparison populations are (e)limited by the randomisation process.

This is not the case when we do retrospective observational studies - like vax effectiveness against variants in the field.

The statistical analysis is more challenging. There are biases in who is vaxxed or infected, living, working, mixing patterns, medical health/immunity.

To account for these need to do matching/case-control or logistic regression to find true odds ratio between infxn risk of vaxxed vs unvaxxed.

cf RCT where Chi-squared or T test test could do.

NB I still do simple short cuts for twitter analysis with point estimates of field vax effectiveness...

But if we're being proper clinical scientists trying to get robust publishable/usable data we should have higher standards!

For proper analysis the retrospective cohorts have to be much larger with many events (infections). ~10X or more vs RCT.

So far there have only been 3.4k B1.617.2 cases identified. Predominantly in unvaxxed young people - so the vaxxed v unvaxxed groups will be v unbalanced.

To get to a point when confidence intervals no longer overlap it will take many more weeks if there is a small difference.

Applies to 1 dose only effectiveness too which is even more challenging due to differing time windows of population in that state/community infxn rate.

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More from @DevanSinha

23 May
Grateful for the hard work of dedicated public health scientists at @PHE_uk like @kallmemeg and unsung others who work overtime to produce excellent reports on the variant of concern B1.617.2 🇮🇳

🧵analysis of vax effectiveness, and why interpretation of reduced VE limited.

PHE did a 'test negative case control study' w/ logistic regression as I outlined yday.

From test and vax databases they retrospectively created a control cohort of 99k who tested negative and compared to 6.4k test positive for B117 & 1k for B1.617.2


PHE found a statistically significant dip in symptomatic protection after 1 vax dose.

51% ➡️ 33% against B1.617.2 variant (yellow).
For both Pfizer and Ox/AZ (21 days after 1st dose).

No statistically significant change after 2 vax doses (14 days after 2nd dose).

3/ Image
Read 21 tweets
16 May
JCVI extension of vax dosing interval to 12 weeks is a great public health decision.

3.5X higher peak antibody levels w/ Pfizer if delayed boost vs 3 week.

Really important for protection against variants and duration esp in vulnerable🧵

We kept seeing 1 dose vax after prior infxn boosting Ab tires 3X higher than 2 doses at the standard 3 week interval. Some of us wondered if this was from optimised prime-boost interval at the time...

It now looks like a probable explanation.


3 weeks on short side of intervals, where immune response hasn't completely matured after prime stimulus.

Delay may selectively expand population of long lived plasma cells (B cell derivatives) too.

Delayed boost shown to have better Ab response across prev vax types👇

Read 15 tweets
29 Apr
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...

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!

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

Read 18 tweets
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


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)

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

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 👇


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

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 :)

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

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

Read 10 tweets

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