Like many (grand)parents, I had to take care of my grandson today, because his class went in quarantine. It was a pleasure, but this episode will be rather brief.
Par 1 UPDATE ON VARIANTS: Omicron sublineages, “Deltacron”(?) and “French Variant”
- Omicron sublineages BA.1, BA.2, BA.3
Ep 229-1: Majumdar in J Med Virol 29 Dec 2021 describes the first two sublineages BA.1 and BA.2
As can be seen, both sublineages have 51 mutation, with 32 in common and most in S
The BA.1 lineage showed S gene target failure (SGTF) in RT-PCR assay due to multiple deletions in the NTD of S glycoprotein, whereas BA.2 lineage may skip SGTF due to lack of deletions in the NTD. This characteristic provides an easy tool to distinguish both sublineages.
Ep 229-2: Press articles on BA.2
- Tom Peacock (Imperial College London): minimal difference in vaccine effectiveness against both subvariants, no difference in pathogenicity but BA.2 may be more transmissible.
- I wouldn’t be that surprised if BA.2 slowly replaces BA.1 over the coming months
- Anders Fomsgaard (Statens Serum Institute Copenhagen):
- It is possible that you can be infected with BA.1 Omikron first, and then shortly after with BA.2: in Norway it has happened.
- When the Omikron variant came to Denmark in December, BA.2 accounted for about 2 percent of infection cases, but in January it outperformed BA.1, and now accounts for more than half.
- The vaccines still work against serious illness and death, he concludes.
- Similar information on Jan 23 in The Independent
Ep 229-3: Desingu describes a third Omicron sublineage BA.3. It has no specific own mutations, but has a combination of BA.1 and BA.2. But of the 33 Spike mutations in BA.3, 31 are in common with BA.1.
BA.3 represent only 0.013 % of all Omicron genome sequences; BA.2 0.85 % and BA.1 99.13 %.
Ep 229-4: Eric Topol: Where are we with Omicron
- Booster protection against symptomatic infection:
> 90 % with Delta; +/- 50 % with Omicron.
- Vaccine effectiveness against hospitalization omicron vs delta
- Lower after 2 doses
- Restored to 90 % after booster
- Very different clinical implication of omicron wave in Europe versus US:
- European countries: high level of 2 dose vaccination and about 50 % booster : much lower hospitalization and death by Omicron, despite high infection rate
- US: low level of vaccination and booster: high hospitalization and death rate
- Sharp decline of Omicron to be expected? It was seen in South-Africa, but it is not so evident in the more “omicron advanced” European countries
- More variants to come? Possible…. And we are always going to be behind the curve.
- Ultimate solutions?
- Oral/nasal pancoronavirus vaccine to elicit broad mucosal immunity
- Mass production and distribution of Paxlovid (Pfizer COVID protease inhibitor)
Ep 229-5: Freda Kreier Nature News 21 January: Deltacron the story of the variant that wasn’t.
On 7 January, virologist Leondios Kostrikis announced on local television that his research group at the University of Cyprus in Nicosia had identified several SARS-CoV-2 genomes that featured elements of both the Delta and Omicron variants.
However, most probably it was a lab contamination
Kostrikis now says he is “in the process of investigating all the crucial views expressed by prominent scientists around the world about my recent announcement”. He says he plans on submitting the research for peer review.
Wait and see…, but nevertheless:
Ep 229-6: Interview of Deutsclandfunk with Christian Drosten: Es istkeinesfalls sicher, dass Omikron imabgemilderten Zustand bleiben wird.
There are various ways in which omicron could develop from a rather mild variant into a more pathogenic one, said virologist Christian Drosten. One must currently fear that a recombination of omicron and delta will happen, said Drosten
Mainly due to the changes in the so-called spike protein, the omicron variant is currently able to circumvent the at least partially existing immune protection of the population. It is conceivable that a virus will emerge in the future which, on the one hand, "carries the spike protein of the omicron virus in order to continue to enjoy this immune advantage, but has the rest of the delta virus genome," said virologist Christian Drosten. Because the delta mutant has the higher ability to replicate, a mixture of omicron and delta could unfortunately recombine the strongest properties from both variants, according to the head of the Institute of Virology at the Berlin Charité.
The fallacy of natural immunization
However, it is also conceivable that Omikron could develop a stronger pathogenic effect on its own – without recombination it with other variants. The strategy “We all infect each other with the mild omicron and then everyone is immune” is a fallacy, said Drosten and he explains: “It could be that those who do not yet have any immunity (by vaccination) yet contract the omicron virus, like it is now - without getting a very severe course. But: It could also be the case that within a few weeks an omicron virus variant suddenly appears that again has a stronger pathogenic effect. Those who are not vaccinated would then have no immune protection against this virus and you couldn’t vaccinate those people against that pathogenic virus so quickly either.” (Therefore, the best strategy is to be vaccinated already before you contract Omikron)
It is also problematic that natural infections do not guarantee protective immunity in the population in the long term. If a second variant is also added, people would have to have undergone multiple infections with each of these variants until stable immunity was achieved, which also includes protection against transmission and serious illness. According to Drosten, this development could take years.
Germany lags behind in synchronous immunization
Christian Drosten: The pandemic will only be over for those who have been vaccinated
In this respect, everything speaks for an additional vaccination that is adapted to the omicron variant. According to reports, such vaccines can be expected from spring at the earliest.
Drosten: "While in Africa - for example in countries with fortunately younger population profiles (...) - population immunity is now almost complete, in the industrialized countries we have this hesitation in some places."
The price of the vaccination gap
Of course, population immunity can also be built up without vaccinations, said Drosten. "The only question is what that costs - in the form of deaths in populations that are relatively old." He does not believe that it will be possible to achieve complete immunization by vaccination by the beginning of next winter - that is, the majority of the population have also caught up on an omicron-specific vaccination. "If we could do that, I could say with conviction: next winter the pandemic will be over."
- Rise and fall of French variant
Ep 229-7: Colson medRxiv 4 Jan 2022 describe the history of the Marseille 4 variant, over 10 months since July 2020:
First Marseille 4A developed in 22 different lineages each accumulating 4.1 +/- 2.6 mutation and vanishing in 4.1 +/- 1.4 months.
Marseille-4B emerged when the other Marseille-4 lineages vanished. It had ORF8 knocked out and resulted in more hospitalizations and deaths (suggesting ORF8 is a virulence gene).
The accumulation of nonlethal and non-favoring mutations leads gradually to a dispersion of the lineages, a decrease in viral fitness and vanishing of the epidemic.
Par 2 UPDATE ON CHILDREN
Ep 229-8: Pediatric update New York State first week of January 2022:
- 7 fold increase in pediatric COVID hospital admissions
- 41 % of hospital COVID diagnoses made in children admitted for (other) acute and chronic medical conditions with COVID-19 as a possible exacerbating factor.
- 54 % had no co-morbidities.
- The report suggests increased severity, but does not specify which symptoms.
Ep 229-9: Testimony from field site in Flanders:
With regard to the recent morbidity evolution due to Covid-19 i.e. Omikron in the pediatric age group 5-11 year olds, I do not understand the discrepancy between the real field observations and the absent or adverse news reports.
Our pediatrician sees many children coming in, including PICU, also MIS-C.
I thought it was known by now that Omikron is a lot more morbid within this group of children and that we should therefore continue to motivate the parents for the vaccination of these children ...
Ep 229-10: Interview with prof Isabelle Meyts, pediatric immunologisy KULeuven in Knack (in Dutch)
Summary: "You have to vaccinate children to protect them, not to protect adults," Isabelle Meyts emphasizes
Are children equally contagious?
Meyts: The data on this are not unambiguous either. Some older studies say they are less likely to infect other family members. More recent studies, however, show it is common, especially with the more contagious variants. We observed that during the fourth wave. Most children have very mild corona infections. But both for corona and for other infections the important point is: when children become life-threateningly ill, it usually has to do with a natural defect in their defenses. The hard scientific data has not yet been received for corona, but we know for viruses such as flu and herpes. We find that previously healthy children who become very ill often struggle with problems in their innate immunity.
Should children also be vaccinated?
Meyts: Vaccination is without any doubt the most important achievement of medicine ever. It has significantly reduced the death rates by infectious diseases. There is much to be said about the issue that children should be vaccinated to protect adults, but I disagree. Children should be vaccinated in the first place to protect themselves. Some children can develop severe inflammatory reactions after infection, which means that they have to stay in the ward end up in intensive care. That has a huge effect on a child. You can't quite express it in numbers, but you can't underestimate. In Belgium, five children under the age of twelve have also died of corona. You can say it's only five, but for me it's five too many.
Some people argue that we also don't know what the side effects of the vaccines will be.
Meyts: I'm not afraid of the vaccines. The mRNA vaccines have been in development since the 1960s. No vaccine is 100 percent efficient and none are 100 percent safe. But I don't think it's wise, based on some uncertainty for the long-term, to withhold children a lot of undeniable short-term benefits. I refer to the recent research that establishes a clear link between infection with the Epstein-Barr virus and the risk of multiple sclerosis. We just know too little about the coronavirus to just say that it is not necessary to vaccinate children, because after an infection they usually do not end up in a hospital anyway. I would even put it differently: it is our job to give our children the maximum defence against the possible effects of the virus.
Finally: is it realistic to keep boosting against the coronavirus?
Meyts: Boosting is part of vaccination. You don't need boosters for measles. But the measles vaccine is a watered-down live virus that you administer, which produces a much stronger immune response than mRNA vaccines. In addition, the coronavirus mutates, it would have been miraculous that it was brought under control after two vaccines. Still, I don't think we'll have to continue boosting. Perhaps a fourth shot will suffice, especially if the virus still loses its pathogenic power. I think we will win the battle in the end. At least the current pandemic has highlighted what I've always preached: if a previously healthy child dies of corona or the flu, there is something wrong with his immune system. This statement is now being extended to adults. Our immune system is more than ever the key to success in the fight against infections.
Par 3 GOOD AND BAD NEWS ON VACCINES
Ep 229-11: The good news: T cell responses against omicron are much better preserved than B cell (antibody) responses:
In subjects ~6 months post-vaccination,
- T cells: 84 (CD4+) and 85% (CD8+) memory T cell responses preserved against Omicron.
- T cell epitope repertoire analysis revealed a median of 11 and 10 spike epitopes recognized by CD4+ and CD8+ T cells, with average preservation > 80% for Omicron.
- Omicron RBD memory B cell recognition of omicron was substantially reduced to 42% compared to other variants.
Ep 229-12: Jennifer Couzin-Frankel Science Insider 20 Jan 2022: In rare cases coronavirus vaccines may cause Long Covid–like symptoms
This report by 2 Science journalists quotes a few subjects, who experienced “brain fog”, headaches, palpitations, etc after one of the COVID vaccines. It states hat originally NIH was eager to investigate, but later they became reluctant.
We are also reminded about the known theories about auto-immunity, elicited by Spike protein and the interference with the renin-angiotensin-aldosterone system, which have also been evoked to explain some poorly understood aspects of COVID itself and of long COVID as well.
These are the last sentences:
Researchers exploring postvaccine side effects all emphasize that the risk of complications from SARS-CoV-2 infection far outweighs that of any vaccine side effect. “You see 10, 100, 1000 times less risk from the vaccine,” Prüss says.
But understanding the cause of postvaccine symptoms—and whether early treatment can help prevent long-term problems—could be crucial for designing even safer and more effective vaccines, Murphy says, as well as potentially providing clues to the biology of Long Covid.
Cheng has heard from dozens of people who describe chronic postvaccine problems, and she finds the overlap between their symptoms and those of Long Covid compelling. Now, she wants to move deliberately and scientifically in a search for answers. “We’ve got to retain rigor,” she says. “There’s just this complete dearth of data.”
Clearly, this is explosive stuff, as soon as the anti-vaxx movement will get to know it.
Just reminding Episode 226-12, an Israeli study, showing that 2 doses of Pfizer prevented long COVID symptoms….
Ep 226-12: Favorable effect of Pfizer vaccine on long-COVID
Vaccination with at least two doses of COVID-19 vaccine was associated with a substantial decrease in reporting the most common post-acute COVID-19 symptoms, bringing it back to baseline.
The last word about this topic has not been said….For sure….
9 August Episode 279: BA.2.75, novel monoclonal Ab, polymerase and anti-inflammatory treatment options
> More info
2 August 2022 Episode 278: Follow up on novel vaccine concepts: mucosal application and broadening towards “pansarbeco”
> More info
19 July 2022 Episode 275 SARS-CoV-2 infection or vaccination, risk of reverse transcription
> More info