26 April 2021 Episode 133 Miscellaneous topics

Mon, 04/26/2021 - 20:46

Dear colleagues,

 

Ep 133-1:  Finally, thanks to our colleague in Shanghai, I can present you a preprint on phase 3 trial with CoronaVac,  one of the Chinese inactivated vaccines, that is being rolled out over many parts of the world.  The SSRN paper is written by the Brazilian Profiscov consortium, which performed a trial in over 12,000 health care workers between July and Dec 2020.  The overall efficacy against symptomatic COVID is about 50 %.  Obviously this result needs to be put into the right perspective:

  • It is quite similar to the Astra-Zeneca (AZ) result that was obtained in the same time frame in Brazil: with the standard dose and less than 6 weeks interval, the AZ efficacy was 53 % (see Table 3 p. 8 Ep 95-5).
  • As was the case for AZ, it is also claimed here that a longer interval between the two doses would increase the efficacy.  For AZ it rose to 65 % if there was > 6 weeks between both doses, for CoronaVac it rose to 63 % if the interval was > 21 days. (Table 2 p. 28).
  • From the same Table 2, it is also evident that protection against very severe disease was better than against mild disease. We have no information on protection against infection.
  • Protection was similar in the oldest participants and in people with previous exposure to SARS-CoV-2, but both of these categories were few.  It was also similar in people with co-morbidities (p.29-30).
  • Obviously, during both AZ and CoronaVac trial, the infamous Brazilian variant P1 was not yet circulating to a high extent.  The paper does not contain information on sequencing, but the last paragraph of Results provides some data on life virus neutralization by sera from vaccinated individuals: it is rather similar against the three major circulating variants: B1.1.28, P1 and P2.  Only in P1 and P2 the E484K mutation is present.  For more details on all these variants, see  https://outbreak.info/situation-reports#lineage

 

Some more background on the Indian second wave:   

 

Ep 133-2 and 3 are recent preprints:

  • Murhekar finds a seroprevalence  in Dec of about 20 % in rural areas, but 34 % in poor slum urban areas, with a 25 % in HCW.  That would translate in 271 million infected Indians.  The official number of infected Indians was 10 million in Jan and is 17 million now….
  • Ranjan models the second wave and provides evidence that the peak will be half May.  Very nice, but also frightening graphs indeed.

 

Ep 133-4 and -5 are reflections from Nature and Science.  It is argued that the “Indian variant” (B.1.617), originating from the Maharashtra area (see Fig 2 p. 4 of Ep 133-3) is not the only explanation. Other factors include:

  • A public narrative that the first wave had already created herd immunity, hence reopening of the society, with mass gatherings and abandoning all prevention.
  • In fact, as suggested by Murhekar (Ep 133-2), the first wave mainly hit the urban slums, leaving the wealthier relatively uninfected, hence susceptible.
  • Similar to Europe, younger cohorts get preferentially infected, because they care less about the consequences.
  • Only 10 % of Indians has been vaccinated, mainly with Covishield (= Indian version of Astra-Zeneca).  It is suspected that people got infected, when getting their vaccines (crowding).  The question is also to what extent, AZ is very active against the new variant, hence how many breakthrough infections?  

 

Three key lessons:

  1. First, without an emphasis on effective monitoring, coronavirus will exploit those blindspots to spread again.
  2. Second, that even in the midst of a vaccination campaign such as India’s, while large numbers remain unvaccinated Covid-19 remains a powerful threat, able to overwhelm health systems.
  3. A third and final lesson is one for the political leaders. Boosterism (like Modi’s around India’s vaccine production) and the encouragement of normalcy bias (which leads people to minimise threats when confronted by serious risks) have real impacts in public health emergencies that rely on encouraging people to be careful.

 

Other news on vaccines

 

Ep 133-6: After successful trials in adolescents, Pfizer and Moderna are planning trials in kids, while, for obvious reasons, A-Z and J&J are hesitating.  The paper points to the small but significant risk in children on the MIS-C hyperinflammatory syndrome (1:1000) and the need to vaccinate kids as well if we want to acquire solid “herd immunity”.   In fact, for the latter reason, it is probably equally or more important to enable vaccination in the South.

 

Ep 133-7: An economic analysis on the failure of French institutions (Pasteur) and companies (Sanofi) to develop a COVID- vaccine: under-investment.  But what is the scientific reason?  Elsewhere, I read that the tentative Pasteur COVID vaccine was based on a measles platform, by Frederic Tangy. He has been developing this platform for many years, with success in animal models for Lassa, Chikungunya, malaria etc. See https://pubmed.ncbi.nlm.nih.gov/?term=(Tangy%2C%20Frederic%5BAuthor%5D)%20AND%20(measles)&sort=date&page=2

There is no publication related to COVID, however.

Probably, my French readers know more about this story?

 

Ep 133-8: a perspective paper by Jon Cohen in Science related to the possible development of a pan-Coronavirus vaccine.  As could be expected, several principles and platforms are being tried, either “mosaic” : mixtures of epitopes from receptor binding domains in S1 of various human Corona viruses or focusing on the more conserved S2 domain of the Spike.  One of the rationales of this approach is to provide a “basic cross-neutralizing ant-Corona immunity” (both antibodies and T cells), which could prevent or mitigate new emerging Coronaviruses, hence trying to prevent a new pandemic….

 

That’s it for today.

 

Have a nice evening.

 

Guido