18 March 2021 Episode 120 Astra Zeneca saga and other vaccine stories

Thu, 03/18/2021 - 19:29

Dear colleagues,

As we all know, it becomes extremely difficult to keep a “cool head” amidst all the emotions, while we in Belgium are now definitely in the ascending phase of the seemingly unavoidable “third wave” (not less than 6 primary  schools are closed in my neighborhood). And then there is all the commotion about the vaccines, casting doubts again, at the time when we could finally get the campaign at reasonable speed….

In the meantime, it remains difficult to find truly scientific and trustable information. I try to do my best.  If you have more info, please let me know.  

 

  1. Controversy on thrombotic side effect by Astra-Zeneca vaccine:   A very interesting “journalist paper” (Ep 120-1) by Gretchen Vogel and Kai Kupferschmitt about the Astra-Zeneca saga.  So, I understand it is now all about 13 patients,  between ages 20 and 50 and previously healthy, 7 of whom died, not of “ordinary” blood clots, but a picture with widespread clots, low platelets and internal bleedings.

 

Remarkably, “a somewhat similar picture, related to immune thrombocytopenia”, has been seen in 36 recipients of Pfizer and Moderna in the US.  It remains also very strange that in UK, where both Pfizer and Astra-Zeneca have been extensively used, neither of these syndromes has been reported.

Two interesting potentially related theories are put forward:

  • These patients could actually  have been infected with SARS-CoV-2 around the time of vaccination.
  • Brodsky suggests an hypothesis in a Blood paper (Ep 120-2), showing that the SARS-CoV-2 Spike can trigger the alternate complement cascade indirectly, which could cause micro-angiopathy, thrombocytopenia and thrombophilia. This is, however, all based on in vitro experiments.  It could well play during infection with massive amounts of the Spike present, but could it also be the case after vaccination with relative minute amounts?  

 

Anyhow, Paul Hunter, an infectious disease expert at the University of East Anglia, notes that even if the risk of this potentially deadly complication is 5 or more  cases per million people vaccinated, the COVID-19 infection fatality rate for men in their mid-40s is 0.1%, or 1000 deaths per million infected.  

 

In the meantime both the European and British Medicines agencies have confirmed their confidence in the AZ vaccine See: https://www.vrt.be/vrtnws/nl/2021/03/18/europees-geneesmiddelagentschap-herhaalt-vertrouwen-in-astrazene/

 

  1. Risk on symptomatic and asymptomatic infection after vaccination.  According to the  retrospective study by Tandle et al in the US (Ep 120-3), risk of ASY infection decreased by about 80 % from 10 days after the first dose of either Pfiezr or Moderna (mRNA).  

 

Similar findings are reported by a journalist paper by Reuters (Ep 120-4):

  • Single dose Pfizer prevents 71 % of hospitalization and for Astra-Zeneca it was even 80 % in British patients with a median age of 87-88 years
  • Single dose Pfizer cuts asymptomatic infection in British health care workers by 75 %
  • Israel reported first dose Pfizer efficacy against symptomatic infections of 57 % after 2 weeks and 90 % after two doses.

In another Reuters press release (Ep 120-5), it is even claimed that the two doses of Pfizer in Israel prevented 97 % of symptomatic and 94 % of asymptomatic infections.

But I cannot find formal papers on all these claims yet…..  

 

On the other hand, I could not find real-world data on the protection towards asymptomatic infection after Astra-Zeneca vaccination.  According to the papers on the trials, this was rather weak (50-60 %).  We have also seen that AZ was less effective in South-Africa.

 

  1. With regard to scheduling, we know that AZ seems to work better when the second dose is postponed from 4 to 12 weeks, but in an Editorial, by Hung (Ep 120-6), the many limitations of the AZ studies are listed: not prospective,  not randomized, for 3 out of 4 not blinded, not balanced etc.  The question remains whether  a longer than 12 weeks interval could be beneficial.

 

Moghadas (Ep 120-7) models to what extent delaying the second dose (DSD) of either Pfizer or Moderna could improve the COVID burden on a population level, based on the published trials data on efficacy:

  • If the efficacy of the first dose did not wane until the administration of the second dose, then the DSD strategy will be more effective than the recommended schedules for both Pfizer-BioNTech and Moderna vaccines, achieving maximum benefits with a delay of 12-15 weeks.
  • If the efficacy of the first dose wanes over time, delaying the second dose
    • of Moderna vaccines could prevent more infections, hospitalizations, and deaths compared to the recommended 4-week interval between the two doses. The maximum benefits were achieved with a DSD of 9-15 weeks.
    • with Pfizer-BioNTech vaccines beyond the 3-week tested schedule, on the other hand, may lead to a higher number of infections compared to the recommended schedule, if the first-dose efficacy waned over time.

 

  1. This position is echoed by a   paper in Science by Saad-Roy (Ep 120-8) Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes: discusses in depth the difficult dilemma of more rapid population vaccination with a single dose, with gain on the short term with regard to hospitalizations and  death, but risk to increase the emergence of resistant variants.  The conclusion remains rather general:
  • Ongoing elevated COVID-19 case numbers stresses the rapid need for effective, mass vaccine deployment.
  • The impact of vaccine dosing regimes are strongly dependent on the relative robustness of immunity conferred by a single dose.

It is therefore imperative to determine the strength and duration of clinical protection and transmission-blocking immunity through careful clinical evaluations (including, for instance, randomized control trials of dose intervals and regular testing of viral loads in vaccinated individuals, their contacts, and those who have recovered from natural infections) in order to enforce sound public policies.

More broadly, our results underscore the importance of exploring the phylodynamic interaction of pathogen dynamics and evolution, from within host to global scales, for SARS-CoV-2, influenza, and other important pathogens.

  1. Allergic reactions to mRNA vaccines (Ep 120-9): while CDC reported a very low incidence of 0.025 to 0.11 per 10,000 of severe anaphylactic reactions, this prospective study amongst 64,900 employees of Mass Gen Boston (MGB) 2.47 per 10,000, which is clearly higher but still low.  The characteristics are shown in Table 2:  as expected these reaction appeared fast and could be promptly treated.  Remarkable 15/16 were female; 5 had a history of anaphylaxis and 10 of allergy.

 

In addition, a much higher frequency of other allergic reaction of 2.1 per cent (hence 100 times more frequent) was noted.  Symptoms included:  Itching or rash other than at the injection site (n = 788), respiratory symptoms (n = 342), hives (n = 244), or swelling (n=191).

 

On the other hand, while  5% of adults have severe food allergy histories and 1% of adults have evere drug allergy histories, this MGB employee cohort likely included almost 4000 individuals with severe food or medication allergy histories who were safely vaccinated.

 

  1. Two very thorough papers (Ep 120-10 and -11) on decrease or loss of neutralizing capacity of particular monoclonal antibodies, convalescent sera and sera from vaccinated individuals against the mutants containing the E484K mutation (Brazilian and South-African).  Interesting also that attention is asked for the type of virus and cell line used:  pseudoviruses are more easy neutralzable (even if they contain “escape” mutations) and also the cell line used: importance of expression of the TMPRRS enzyme that “activates” the virus and makes mutant viruses less susceptible to neutralization. Clearly, the exact in vitro correlate of protection still has to be established.

 

That’s it for today.  If all goes well, I receive my first AZ jab tomorrow….

 

Best wishes

 

Guido