23 April 2022 Episode 256 New WHO treatment guidelines; vaccine effectiveness; new vaccine principle and Haseltine’s view on the “endemic”

Sat, 04/23/2022 - 14:11

Dear colleagues,

First thanks to Patrick Smits and Kevin Ariën, who provided much of the interesting information that I will discuss here.

WHO treatment guidelines 22 april

Ep 256-1 A and B: with a lot of supporting data in A and a “executive” summary in B

 

 

From the data presented, it is evident to me that

  • Paxlovid (Nirmatrelvir/Ritonavir) presumably is superior to Remdesivir and Molnupiravir for the indication of preventing hospitalization in non-severe BUT at risk patients.
  • Corticosteroids can be favorably combined with IL-6 receptor blockers OR Baricitinib (Jak/stat inhibitor) in severe and critical patients.
  • Existing monoclonal Ab therapies have become very uncertain since Omicron.
  • I would be reluctant to use heavy immune suppressants such as Ruxolitinib and Tofacitinib.

My feeling is that, with regard to COVID, Ivermectin and convalescent plasma will soon belong to medical history, just like hydroxychloroquine and lopinavir-ritonavir already are, but we will wait for the final scientific evidence, of course.

Vaccine effectiveness

Ep 256-2: Interesting comparison between Pfizer (mRNA) and CoronaVac (inactivated) in Hong Kong.

Remember the recent dramatic increase in mortality in Hong Kong, due to under-vaccination of elderly, which inspired Chinese authorities to the strict lockdown policy in Shanghai.

 

Well, the present study in medRxiv, covering the same omicron period (Jan-March 2022) shows that indeed this could have been prevented by two or three doses of either Pfizer or CoronaVac.

While CoronaVac is much less effective against moderate infection, it is equally effective against severe/fatal disease.

 

Ep 256-3: Kirsebom shows that vaccine effectiveness in England was similar  against symptomatic disease with BA.1 and BA.2 after one or two doses of BNT162b2, ChAdOx1-S or mRNA-1273, and after booster doses of BNT162b2 or mRNA-1273 during a period of co-circulation.

 

 

 

Ep 256-4: Bjork reports similar data from Sweden: VE remained relatively stable after the transition from BA.1 to BA.2 among people with at least three doses but decreased markedly among those with only two doses. Protection from prior infection was also lower after the transition to BA.2.

 

Ep 256-5: Gram provides very extensive Danish data on protection against infection and hospitalization with either 2 or 3 doses of Pfizer vaccine during alpha, delta and omicron period, also subdivided according to age.  As expected, protection was always lower for omicron and waned faster, but as shown in the first figure, protection against hospitalization remained > 75 % for omicron in 60+ even more than 120 days after the booster.

 

Ep 256-6:  Simmons calculated the VE against hospitalization in Canadian children and adolescents (4-7 years) between May 2021 and January 2022 after 1 dose 37 %, after 2 doses 59 %, which seems rather moderate.

With regard to risk factors for hospitalization as shown in the Table, gender, age and time were no risk factor, but immune suppression and asthma were very serious risk factors,  

 

 

 

Ep 256-7: Similar data in Norwegian adolescents on protection against infection with Pfizer: lower efficiency against omicron

 

 

 

NEW VACCINE PRINCIPLE

 

Ep 256-8: McCafferty in Mol Ther a dual-antigen self-amplifying RNA SARS-CoV-2 vaccine induces potent humoral and cellular immune responses and protects against SARS-CoV-2 variants through T cell mediated immunity

 

Dual = both Receptor binding  domain of S and Nucleoprotein

Self-amplifying: containing replicase from Venezuelan Equine Encephalitis Virus

 

 

 

 

Immunization with saRNA vaccines encoding Wuhan SARS-CoV-2 nucleocapsid lowers viral load in hamster challenged with a SARS-CoV-2 beta B.1.351 variant: both S-RBD and ZIP-1642 (combined RBD + N) elicit strong neut Ab.  Nevertheless ZIP protects better against infection (F).  Presumably due to Th1 response against both RBD and N.  For details see p. 46.

 

HASELTINE ON Omicron variants and policy

 

Ep 256-9: Haseltines view on the emerging new omicron subvariants BA.4 and BA.5 in Europe and BA.2.12.1 in the US (see below).  He is warning that we might see a scenario with a protracted epidemic with these (and other) new omicron variants during the summer, just like last year with delta.   

 

In a very interesting interview, he clarifies his view further on the future of the -still dangerous- COVID “endemic” in a very accessible way.

 

https://www.youtube.com/watch?v=-3qNOQeqWJY

 

Please listen to the first 10 minutes, it is instructive even for “advanced covidologists”….

 

Best wishes,

 

Guido

 

 

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