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Astra Zeneca / Oxford / Covishield Vaccine Update

Scientific data and knowledge on this topic is evolving rapidly and each individual should make their own decision based upon their risk tolerance and risk perception. It’s important that updates on this topic are followed and decisions amended accordingly. 


Vaccine Efficacy, Effectiveness and comparisons


First dose effectiveness  for preventing symptomatic disease of Pfizer and Oxford in UK age 70+

In this UK study of 7.5 million people age 70 and above protection against symptomatic COVID, 4 weeks after the first dose, ranged between 57 and 61% for one dose of Pfizer and between 60 and 73% for one dose of the Oxford-AstraZeneca vaccine.


First dose effectiveness  for preventing hospital admission  of Pfizer and Oxford in UK age 80+

In patients age over 80, single dose of either vaccine was more than 80% effective at preventing hospitalisation, around 3 to 4 weeks after the jab.

https://www.medrxiv.org/content/10.1101/2021.03.01.21252652v1

https://www.gov.uk/government/news/new-data-show-vaccines-reduce-severe-covid-19-in-older-adults


Trial Efficacy for Oxford Vaccine from USA

79% vaccine efficacy at preventing symptomatic COVID-19

80% efficacy in participants aged 65 years and over

100% efficacy against severe or critical disease and hospitalisation

https://www.astrazeneca.com/media-centre/press-releases/2021/astrazeneca-us-vaccine-trial-met-primary-endpoint.html


Pfizer effectiveness in UK

In this UK cohort study of 40,000 health workers of all ages, a single dose of Pfizer vaccine demonstrated vaccine effectiveness of 72%  21 days after first dose and 86%  seven days after two doses for Covid19 infection ( symptomatic or asymptomatic) 

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3790399


Putting medical risk into context 

In one study of nearly 52,000 people taking NSAIDs, 35 developed anaphylactic shock. That is approximately one in every 1,500  patients 

Approximately 1 in 5000 exposures to a parenteral dose of a penicillin or cephalosporin antibiotic causes anaphylaxis ( life threatening severe allergy )

Risk of serious complications related to Colonoscopy is 3 in 1000

https://www.asge.org/docs/default-source/education/practice_guidelines/doc-56321364-c4d8-4742-8158-55b6bef2a568.pdf?sfvrsn=8

Risk of death with general anaesthesia is around 1 in 100,000

https://www.nhs.uk/conditions/general-anaesthesia/


Oxford Vaccine and Cerebral Sinus Thrombosis

Up to and including 24 March, MHRA has received 22 reports of cerebral venous sinus thrombosis (CVST) and 8 reports of other thrombosis events with low platelets, out of a total of 18.1 million doses of COVID-19 Vaccine AstraZeneca given by that date. There were no such reports for the Pfizer/BioNTech vaccine.

It’s now known what the background rate is but even over-estimating causality as 100%, that’s one in 822,000 doses.

https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting


German scientists hypothesis on possible causation of rare type of blood clot ( associated with low platelets) caused by Oxford Vaccine 

https://www.researchsquare.com/article/rs-362354/v1


Germany's Paul Ehrlich Institute has reported 31 cerebral venous sinus thromboses and nine deaths out of 2.7 million people vaccinated there.

Again, background rate isn’t known precisely but overestimating causality at 100 % leads to a ten fold higher rate than UK in Germany of one in 87,000 doses

Trends in vaccine administration may explain the difference in incidence between UK and Germany.


The UK has, largely, been working from the oldest age groups down, while Germany was one of the countries that initially refused to use the vaccine in the over 65s because of a lack of trial data. Instead nearly 90% of Germans given AstraZeneca are thought to be under 60.

Side-effects related to an excessively strong immune response ( creation of auto-antibodies, in this case antibodies against own blood platelets)  tend to be more severe in younger patients. Auto-immune disease is also more common in women and blood clots are more common in women taking the oral contraceptive pill. Other risk factors include obesity and smoking. 

Based on the Germany data alone, if you vaccinate a million people then you would expect 12 to have a blood clot and four of them to die if we overestimate causality at 100% ( under investigation). 

But if a million 60-year-olds catch coronavirus then around 20,000 would die of Covid-19. If a million 40-year-olds catch coronavirus then over a thousand would be expected to die going by current case fatality rate of Covid19 ( which appears to be higher with variants ) 

https://www.bbc.com/news/health-56594189


300,000 of these shots have been administered in Canada already, with no reports of blood clots here so far, but as you can see, this sample size isn’t large enough to reveal a potentially rare complication. 

https://www.cbc.ca/news/politics/astrazeneca-under-55-1.5968128


Weighing pros and cons in decision making

It’s important that updates on this topic are followed and decisions amended accordingly.

Current Scientific Guidance , a must read on anyone receiving an Adenovirus vaccine such as Oxford / Astrazeneca / Covishield, Johnson & Johnson or Sputnik V 

https://covid19-sciencetable.ca/sciencebrief/vaccine-induced-immune-thrombotic-thrombocytopenia-vitt-following-adenovirus-vector-covid-19-vaccination/


Scientific data and knowledge on this topic is evolving rapidly and each individual should make their own decision based upon their risk tolerance and risk perception. Individuals may wish to to appraise not only their own personal risk but also view the decision from a population/ social / public health. 

Notably while Europe is experiencing a steep increase in Covid19 prevalence, the United Kingdom has so far experienced a steady decline in Covid19 incidence. This is driven by high vaccination rates ( over a third of population) and the vaccine used most there is in fact the Oxford Vaccine. Notably as population level prevalence reduces, individual risk will also decrease accordingly. 

https://coronavirus.data.gov.uk/details/cases


Link to book Covid19 vaccine in Ontario

https://covid-19.ontario.ca/book-vaccine



My Personal Mechanistic Viewpoint 

My personal opinions on why Oxford Vaccines efficacy and side effect profile may differ from other leading vaccines:

1. Comparable first dose effectiveness but will that maintain after second dose ?: Oxford vaccine is the only leading vaccine which is a DNA recombinant viral vector vaccine using same vector for both doses prime and boost: It’s possible that antibodies created to viral vector at time of administering prime could make the second booster less effective due to antibodies blocking viral vector entry into host cells.

2. Spike conformation difference leading to less efficacy ( particularly against variants)?: It’s been known since pre clinical animal studies that Oxford vaccine wouldn’t confer ‘ sterilising immunity’. In South Africa use of Oxford vaccine was halted as it’s efficacy vs the variant there in preventing symptomatic disease was 10-20 % ( although it was still 100% effective in preventing hospitalisation and death from Covid19). There is a notable difference between the spike produced by other leading vaccines and Oxford. While the pre-fusion stabilised spike conformation used by Pfizer, Moderna and Johnson was developed at University of Texas, Oxford used a different formula to create their full length Spike which may explain the difference in effectiveness independent of other factors such as choice of viral vector.  

3. Is the overactive immune response in younger patients triggered because of the Zoonotic vector ? Notably Oxford is the only mainstream vaccine at this time using a viral vector which is not naturally found in humans. May that be causal in leading to rare autoimmune response leading to blood clots with low platelets? 

Please note that I’m neither a virologist or immunologist and the three opinions described above are mere opinions with no significant scientific basis at present. 


INFORMATION & DISCLAIMER: 

I obtained my primary medical education from India and post graduate MD in Family Medicine from the United Kingdom. After working in the NHS for 15 years, I moved to  Canada five years ago.  As a Family Physician, my specialty is engaging patients, interpreting  medical information for them, guiding them through their health journey, promoting wise health choices and encouraging early detection and management of disease. The information on this blog is accurate as per time of publishing and patients should check the main blog for updates. Scientific information and evidence changes dynamically and my opinions would change accordingly. 

The information on this this blog reflects my opinions as per time of publishing. Scientific information and evidence changes dynamically. The recommendations on this blog are not prescriptions and any patients considering these should consult with a physician to check if these are applicable to their unique situation.
 
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The recommendations on this blog are not prescriptions and any patients considering these should consult with a physician to check if these are applicable to their unique case. Patient confidentiality must be upheld at all times and any patients wishing to discuss specific medical scenarios on social media are requested to do so anonymously in 'third party' sense. 

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