24 April 2021 Episode 132 Real world effectiveness of vaccines

Sat, 04/24/2021 - 22:09

Dear colleagues,


I was wondering about further evidence on real world effects of SARS-CoV-2 vaccination and about the ongoing discussion on Adenoviral-associated side effects.


Let me first show you a Table, I prepared from the data on https://www.worldometers.info/coronavirus/




As you can see (in Ep 132-0), I took 3 reference dates: Jan 10 (peak of infection in UK), Jan 23 (peak of deaths in UK) and April 23.  All the figures are expressed per 100,000 people, to facilitate realistic comparison.  Focus on the 3 countries where present vaccination coverage is high (UK, US, Israel) versus 4 European countries with less advanced vaccination (Be, NL, Sweden and Norway).


Very strikingly UK, US, Israel had very high infection and death rates in January and those figures have dropped very dramatically, especially in UK and Israel, to a lesser extent in US. 

Whereas death rates are also decreasing in Europe (except in Norway, where they are very low already in Jan), infection rates are on the rise in Belgium (as we know), while they are more stable in the other countries.


Of course, the dynamics of peaks and lows is slightly different in each country (see Ep 132 1-7), but the favorable trend in the highly vaccinated countries cannot be denied. And, obviously, the good news is that for “us”, it is  really a matter of a few months to get out of the heat of the epidemic…


Next, I present you some very recent preprints of interest


Ep 132-8   Impact of vaccination on infection in the community UK (Pritchard medRxiv 23 April)


  • SARS-CoV-2 infections fall substantially (65 %) after a first dose of either vaccine; two doses of the Pfizer-BioNTech vaccine provided even greater protection (70%), to a similar degree as previous infection with SARS-CoV2
  • Vaccination and previous infection were most effective at reducing symptomatic infections,and infections with high viral burden, with lower reductions in infections not causing symptoms and with lower viral burden.
  •  Both vaccines (Pfizer and Astra-Zeneca) appear to be highly effective against infections compatible with B.1.1.7


Ep 132-9: Retrospective cohort in the US: mRNA vaccines were 96% effective at preventing Covid-19 related hospitalization and 98.7% effective at preventing Covid-19 related death when participants were fully vaccinated. (Vahidy medRxiv 23 April).


Ep 132-10 argues that the difference in trial outcome with different vaccine candidate may be due to upcoming variants.  Obviously, it is clear that the mRNA vaccines were tested at a time, when few variants were circulating and for Astra-Zeneca, Johnson§Johnson as well as Novavax (S protein), the negative effect of particularly the South-African variant was evident in the various trial arms.  Nevertheless this meta-analysis does not provide really new insights on for instance what exactly the efficacy of the mRNA vaccines against the South-African or Brazilian variant is…. (Lirong Cao medRxiv 22 April 2021).


Ep 132-11: on breakthrough infections after Pfizer vaccine in Israel is therefore interesting.

  • As could be expected, the “British variant” B.1.1.7 (which has virtually taken over the epidemic see Fig 1A p. 9) is slightly more likely to occur as “breakthroughin partly vaccinated subjects (from 2 weeks after 1st dose till 1 week after 2nd dose).
  • The South-African variant (B 1.315) is clearly more likely to occur in fully vaccinated individuals.
  • The exact number, proportion of breakthrough infections are not mentioned and it is also not clear whether these subjects were symptomatic. In the introduction, it is just repeated that the Pfizer vaccine was 95 % effective against symptomatic infections in Israel.



Ep 132-12 and 13: two reflective papers on the clotting problems associated with Astra-Zeneca and J§J:  several theories are presented: induction of antibodies against platelet factor-4, a role for the spike protein or for a sequence related to tissue plasminogen activator (tPA) or a “mixed bag”.  However, the latter theories would rather point to AZ and not to J§J.  The exact pathogenesis needs to be clarified and a big question remains whether the same problem is present with the Russian Sputnik V, using the same Adeno 26 as J§J. 


Ep 132-14: Greinacher et al, who described the clotting phenomenon first, now publish a preprint, where  they conclude that ChAdOx1 nCoV-19 (Astra-Zeneca) vaccine constituents (i) form antigenic complexes with PF4, (ii) EDTA increases microvascular permeability, and (iii) vaccine components

cause acute inflammatory reactions.


Clearly, on the short run, these very rare side effects will not prevent the use of Adenoviral vectors in the present “urgent” vaccination campaign, where this very small risk does not outweigh the need to acquire herd immunity quickly.


On the longer run, the future of Adenoviral vector vaccines is at stake, because it is evident, especially from the latter paper  (Ep 132-14) that an Ad vaccine contains so many constituent, partly from the vector, partly from the culture in human cells and other “impurities” that it is extremely difficult to have a “clean” and reproducible product.…. Also in that respect, mRNA vaccines are probably easier to “quality control”?  


Let me be clear: I am a fan of the mRNA vaccines, first subjectively because I have a history with those vaccines during my former HIV research career, but now more and more objectively, because their track record for COVID is excellent: no other platform can show such a positive balance. But… I am in the process of being vaccinated with Astra-Zeneca and I’m happy with it for now.  However, if we need a booster with a “variant-adapted” vaccine and there is a choice, I will go for mRNA. No doubt.  


Best wishes,



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