19 Jan Episode 102 More practical info on variants and vaccines

Dear colleagues,

Yes, I realize episode 101 was though for those amongst you, who are not playing around with mutations every day.  This episode will reiterate and expand on the previous ones on mutations, variants and vaccines: more practical and a bit “lighter” to digest. 

1. More on the variants

• P1 variant in Amazonas: the communication by Nuno Faria (Ep 102-1) confirms that there is a new variant, the same that was found in a Japanese traveler (see Ep 101-10). It expands  during the second peak of infections in Manaus (Eep 102-2). This strain is  related to the one in Rio and derives from B 1.1.28 (Ep 101-9), but has additional mutations, besides N501Y: K417N/T, E484K and a deletion in ORF1b del11288-11296, amongst others shown in slide 2.

• Convergent evolution: comparing Brazilian P1 with the UK VOC B.1.1.7 and the South-African 501Y.V2 (also known as B.1.351) one can see that they all three have in common the N501Y and the ORF1b del11288-11296  while the Brazilian and the South-African also share  K417N/T and E484K: they apparently evolved independently from each other into the same direction.

• Herd immunity? Manaus is the city that was a possible example, since the sero-positivity reached 60-70 % in October.  Is the appearance of this new strain proof of “escape”?             → Essential to check for evidence of reinfection

→ Implications for vaccine?

•  The N501Y variants have a nick name “Nelly”: Quotes:
  • Kristian Andersen of Scripps Research: “Nelly might be innocent, except maybe when she’s hanging with her bad friends.” (i.e. the associated mutations).
  • Philip Krause, who chairs a WHO working group on COVID-19 vaccines. “The not-so-good news is that the rapid evolution of these variants suggests that if it is possible for the virus to evolve into a vaccine-resistant phenotype, this may happen sooner than we like,”
  • “It tells us that we should have these mutations in our vaccines, so that you shut off one of the avenues for the virus to go down.”
  • BUT…. for now: increased transmissibility is the biggest concern.
• Indeed, what about transmissibility of these variants in children?   
  • First there was the good news from Zimmerman (Ep 102-3) from North-Carolina (a US state, population-wise comparable to Belgium see slide 4).  They adopted also a similar half-and-half system of school re-opening during the summer and early autumn (15 August-23 Oct). In 11 participating school districts with 90,000 students and staff attend school in-person; of these, there were 773 community-acquired SARS-CoV-2 infections documented by molecular testing. Through contact tracing, NC health department staff determined 32 infections were acquired within schools. No child-to-adult transmission of SARS-CoV-2 were reported within schools.   
• • Then, there was the somewhat worrying investigation in England, showing a proportionally higher infectivity of the B.1.1.7 variant in children (see Volz Ep 101-7 and slide 5)
  • Now there is also the worrying situation in Lansingerland, close to Rotterdam (Ep 102-4): a serious  outbreak in the Willibrodus primary school was due to the B1.1.7 variant (dozens of both teachers and students) and in this case, community cases referred back to the school (in contrast with what was described in North-Carolina).  The whole town (60,000 people) is being tested at this moment.
  • Finally, we learned on Sunday about two outbreaks with the same UK variant, in schools in Edegem and Kontich. It is just 15 km from my doorstep and even closer to Ranst, where my grandsons (4 and 6 years old) happily go to  school every day. And then, just yesterday night, my daughter called my that the 6th grade of their school will close, because of a case (not yet sequenced). So there goes our “knuffelcontact” (close contact) with our grandsons, back into “splendid isolation” for a while, until we will receive the magic jab…. 

2. Vaccines

• Is there evidence that the variants might affect the efficacy of the present vaccines?
  • At first sight a reassuring preprint by Xie (Ep 102-5 and slide 6): sera from Pfizer vaccinated subjects neutralize a pseudovirus with the engineered Y501 even slightly better than the N501.  However, this is a pseudovirus with a single mutation, not a full virus with all mutations.
  • As pointed out  by Callaway (Ep 102-6) and in line with our discussion of yesterday, there are indeed several other mutations and the most “interesting’ (potentially troubling) ones are the K417N/T and E484K, in the South-African and Brazilian variants.  Anyhow, several samples of full viruses, belonging to the 3 variants, should be tested for neutralization by the sera from recipients of all the vaccines that are presently being rolled out in the world.
  • It would also be interesting to use sera from vaccinated people to induce resistance in circulating variants in cell culture.  The emerging resistance associated mutations (RAM) could instruct us about the next generation vaccine strains needed….

• The ongoing debate on modifying the dosing schema (see Ep 102-7, -8,-9):  in the UK there is the tendency to postpone the second dose or even replace it by another vaccine (mixing the mRNA and vector vaccines), according to availability. 
  • Pro: it would provide at least partial protection to as many (vulnerable) people as possible, while the “British variant” is raging.
  • Pro: there is evidence for Asta-Zeneca (Chimp Adeno vector) that protection was better is second dose was postponed: a broader and higher quality immune response? (But for mRNA there are no data on postponing).
  • Pro: mixing two types (heterologous prime-boost) is often better than 2 homologous doses: a broader and higher quality immune response?
  • Contra: partial immunity could favor development of resistance.
  • Contra: this is essentially an uncontrolled experiment, a violation on the basic principles of modern evidence-based medicine.
  • Contra: by diverting from the schedule, as approved by British, European, US medicine agencies,  legal claims could be made, if people get ill and die after un irregular vaccination scheme.  

Note: Janssen Ad26 trial is having a formal arm with a single dose, but will they be able to collect sufficient data, while every country in the West is vaccinating already?

• Status of “Asian vaccines” ( Ep 102-10 to 13):

As the first paper states: there is “mixed news” for prevention of symptomatic COVID by Coronavac (inactivated vaccine produced by Sinovac):

• • Only 50 % effective in 9200 Brazilian health care workers
  • 91 % effective in 1320 Turkish “volunteers”
  • 65 % effective in 1600 Indonesian “volunteers”

There are no efficacy data for the second inactivated Chinese vaccine (Sinopharm), the Indian inactivated Covaxin, nor the Russian Sputnik V (a combined Ad4-Ad6 vaccine). 

For Covishield, the Indian license of the Astra-Zeneca Chimp Adeno vaccine, there has been a bridging study” showing its vaccine can elicit an immune response comparable with the original AstraZenecavaccine in the Indian population vaccine.

I was looking for preprints, but could not find any….  Yet, all these vaccines are being rolled out over all continents, including parts of Europe.

About the “inactivated vaccines” unproven claims are being made that they are better against the British variant.  However, there is the risk of partly active vaccines that they will hasten the emergence of vaccine-resistant variants. 

So, clearly, sera from people, vaccinated with these suboptimal vaccines should be included in the exercise of RAM induction in circulating strains (including the UK, SA and BR variants) in order to determine how the next generation of vaccines should look like.

3. Two additional papers of interest.   

1. A very favorable field evaluation of a rapid antigen test in California (Ep 102-14)
2. A view on the “COVID” politics in various parts of the world, with a very critical evaluation of Belgium by our colleague Emmanuel André….(Ep 102-15)

Best wishes,

Guido