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Devan Sinha Profile picture
Devan Sinha
@DevanSinha
Neuroradiologist | Molecular Medicine | into science and data | via Oxford Med | https://t.co/V1TDFk8fVq
Jan 9, 2022 • 5 tweets • 2 min read
How many total COVID-19 deaths in the UK?:

▪️ 173,248
mentions on death certificates to 24th Dec'21

▪️ 150,154
within 28 days of positive test reported by 9th Jan'22

▪️ 119,600
age standardised excess deaths from Continuous Mortality Investigation (CMI) to 24th Dec'21

1/ 1. Mentions on death cert: filled by physicians who knew the patient w/access to medical history. But includes primary cause (1a) and contributing factor or co-existing. So likely overestimate.

Proportion of 1 or 'due to' covid cause has varied over time 80-90% (ONS).

2/
Dec 16, 2021 • 11 tweets • 4 min read
Can this Kaplan-Meier curve apply to countries as a whole?

Thought experiment on survivorship bias in South Africa and question of Omicron 'mildness' (as we wait for better data - UKHSA case control/retrospective matched studies in 2-3 weeks)...

1/ Firstly, we need to recognise that the attack rate in RSA is very very high. Modelling from excess deaths, even if adjusting for a higher low income country IFR would place AR at over 85% and closer to 100%.

278k excess deaths = 0.5% of a demographically young population

2/
Dec 3, 2021 • 4 tweets • 2 min read
COV-BOOST RCT

3rd dose immunogenicity v AZ or PF/BNT 2dose primary course

▪️2883 randomised w/ multiple cntrl groups
▪️7 different vax boosters + some 1/2 doses
▪️1/2 age >70
▪️>84 days from 2nd dose PF and >70d for AZ til boost

For boost after 2xAZ 👇

thelancet.com/action/showPdf… ▪️For boosters UK chose after 2xAZ:
~25x fold higher Anti-spike IgG w/ PF
~30x fold higher w/ Moderna

▪️PBMC also higher ~2-4x

▪️Some age response effect, but not meeting statistical significance

separated by 1o course; some persistence of difference in anti-spike IgG and PBMC
Dec 1, 2021 • 4 tweets • 2 min read
On point 1. Glad JCVI exist and appraise vaccine/immunology data.

Booster trial effectiveness is based on 6 month gap (may not be same with shorter gap) and immunogenicity studies show longer the gap between dose2 and 3 stronger the immune response.

But Omicron appears to be.. A significant evasion concern vs 2 dose symptom VE. An emergency situation that wasn't known until 7 days ago.

Reducing gap to 3 month is akin to an emergency kitchen sink response.

It's like complaining why didn't you shock a patient who wasn't in cardiac arrest or Vfib/Vtach.
Nov 25, 2021 • 5 tweets • 2 min read
🧵 of 🧵's I found useful to understand B.1.1.529 (Nu) today. From actual subject matter experts or data journalists.

1/5 Tulio de Oliveira, the director of the Centre for Epidemic Response and Innovation in South Africa.

On the rapidly changing situation in SA and sequencing.

2/5
Nov 25, 2021 • 9 tweets • 3 min read
The most robust data for vax effectiveness waning is from randomised control trials. Pfizer👇

2doses holds up well- but still complete the course and boost!

This is real world data. Prospective randomisation only reduces confounding we face in retrospective observations.

1/ Sources of bias/confounding in observational data (eg UKHSA case control study below):

▪️ accrued natural immunity in control (>45% 🏴󠁧󠁢󠁥󠁮󠁧󠁿 infected) & only a fraction tested
▪️ difficulty of retrospective matching/case controlling (high clinical risk vaxxed first, not just age)

2/
Oct 21, 2021 • 4 tweets • 1 min read
The Pfizer booster trial is pretty spectacular.

10k previously 2x dosed (median 11 months from dose 2).

Randomised 1:1 placebo and 30ug.

95.6% relative risk reduction in symptomatic infection in intervention arm vs control (2dose only).

5 v 109 events 7+ days from boost. To repeat: 95.6% RR reduction in symptomatic infection was for 3 vs 2 DOSES

UK data has 2dose Pfizer at ~80% VE vs symptomatic infection in Delta era. But follow up time <11 months in Pfizer trial.

If boost anywhere near 90% RR⬇️ we're looking at ~98% VE vs immunonaive.
Aug 9, 2021 • 7 tweets • 3 min read
80% [78,82] of England's Total population have now been vaccinated or infected

Wall of immunity:

10% Infected only
19% Both infxn+vax
51% Vaccinated 1or2 doses

Usual caveats: time lag after vax, not 100% protective, assumes random vaxing probability of previously infected etc Remaining 11.5m unexposed/unvaxxed susceptible population is heavily skewed to younger age groups.

80% under 25yo
47% in school age kids 5-14yo

Outbreaks and cases will expectedly be concentrated in these groups now and increasingly <15 after current vax roll out plan completed
May 26, 2021 • 5 tweets • 2 min read
70% [68,72] of England's Total population have now been infected or vaccinated.

Wall of immunity:

13% Infected
44% Vaccinated 1+
13% Both

Usual caveats: time lag after vax, not 100% protective, assumes random vaxxing probability of previously infected etc.

1/ Estimated numbers of people:

7.0m Infected only
24.7m Vaccinated only
7.5m Infected & vaccinated

17.1m unexposed and susceptible

2/
May 23, 2021 • 21 tweets • 8 min read
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.

1/ 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

2/
May 22, 2021 • 7 tweets • 2 min read
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.

1/ 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.

2/
May 16, 2021 • 15 tweets • 6 min read
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🧵

1/
nature.com/articles/d4158… 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.

2/
Apr 29, 2021 • 18 tweets • 5 min read
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…
Apr 28, 2021 • 4 tweets • 2 min read
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/
Mar 30, 2021 • 4 tweets • 1 min read
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/
Mar 15, 2021 • 10 tweets • 4 min read
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/
Mar 5, 2021 • 14 tweets • 5 min read
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/
Feb 22, 2021 • 5 tweets • 4 min read
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
Dec 31, 2020 • 8 tweets • 2 min read
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/
Dec 30, 2020 • 5 tweets • 1 min read
Disentangling Astra/Oxford vaccine data (it's a messy trial/ data presentation):

Efficacy after 1st dose overall: 52.69% (95%CI 40.52-62.37)
108 v 227 cases/10k cohorts

Subgroup analysis from 3 weeks after 1st dose until 2nd dose or 12 weeks: 73.00% (48.79-85.76)
12 v 44/8k

1/ Overall vaccine efficacy with 2 completed doses: 70.42% (95%CI 58.84-80.63)
30 v 101 cases/5.8k cohorts

0 hospitalised and 0 severe disease in full vaccine cohort

For 1 dose subgroup only 2 hospitalisations (day 1 and 10 post vaccine when no immunity conferred), 0 severe

2/
May 12, 2020 • 6 tweets • 3 min read
This CT scan is definitely the most traumatic during lockdown I've been shown. Archery accident.

Arrow through the heart.

Miraculously and thankfully the patient survived.

Let's look at all the ways they were lucky: Image The arrow missed the sternum and so didn't cause multiple shards of bone to rupture the right ventricle and communicate with a large external wound.

It passed through the right ventricle (the low pressure side of the heart).