Followup Roundup: 22.2.5

Removed IVF Paper, Masked kids in the news, and mRNA-ed up macaques

IVF Vanishing Act

Edit, February 7: The paper has returned online, with no apparent alterations to the negative results. But the black-out was exciting while it lasted…

As noted by Paul Lutz in a comment sent yesterday, the Aharon, D. et al. IVF outcomes paper reviewed in “Glass House” has been pulled from online, so that it can complete some unspecified “transition” regarding “changed information”:

current result at https://journals.lww.com/greenjournal/Fulltext/9900/In_Vitro_Fertilization_and_Early_Pregnancy.378.aspx

Perhaps these edits will prove to be mundane (note that another recent article, reporting cycle changes for Covid-vaccinated users of a fertility app, has also been yanked¹).

In the meantime, it is exciting to imagine that the lower success rate of frozen embryo transfers in the Covid-vaccinated is being literally erased from the document, memory-hole style. Oops, we made the vaccine look bad:

Still online at “Glass House” and in the web archive snapshot…

²

Virginia is for Maskers

A Virginia court has provided an unwelcome affirmation of my Black Pill take in “The Vulgarity of Normal,” suspending the Governor’s mask-optional executive order. The court decision isn’t really substantial in of itself, as it merely constitutes a rational reading of the Virginia constitution. As judge DiMatteo said during the hearing, “I’m not here to decide who is right and wrong on masking. This case is a question of who has authority.”³

In the case of Virginia, the constitution vaguely divides authority between a state Board appointed by the Governor and confirmed by the Legislature, the Legislature itself, and local division School Boards.⁴ Whatever wiggle room there is in this document for judicial interpretation, it doesn’t include executive orders. So the suspension of Youngkin’s order is natural.

Nonetheless, the decision highlights the resilience and energy of the teachers and school officials who still support masking children. Seven school boards were involved in the suit (Alexandria City, Arlington County, the City of Richmond, Fairfax County, Falls Church City, Hampton City and Prince William County); Loudoun County’s defiance of Youngkin’s order prompted a suit in the opposite direction from parents; and the Virginia ACLU filed a separate suit irrationally claiming that useless mask-wearing is a prerequisite for “federally mandated” education access for the disabled (no, access is access).⁵

An Arlington school board press release,⁶ gloating over the court victory, complains in self-victimizing fashion that Youngkin’s order was forcing them to break an incoherent law passed by the Virginia legislature last summer demanding school boards follow CDC Covid-mitigation-recommendations to “the maximum extent practicable” (which itself voids the delegation of authority to local boards in the Virginia constitution, implying that the CDC is a chartered entity of the government of Virginia until expiration of the bill in August of this year⁷).

Prior to today’s decision, Virginia school boards were placed in a legally untenable position⁸ — faced with an executive order in conflict with the state constitution and state law. That conflict has also put the health and safety of our students and staff at risk, as the Omicron variant continues to affect Virginia localities.⁹ We are confident that the court will soon come to the right decision to resolve this pressing matter.

And yet, the board then appears to strike a conciliatory tone, referring to a “not-too-distant future” revocation of the mask mandates. But how is such a revocation possible, if the the school district is determined to insist that last years’ law obliges them to follow CDC guidelines over local judgment? As if to give up the game, the release simultaneously recycles the typical trope of the Covid Self-Hostage-Taking Public Health Restriction, insisting that unnecessary mitigation measures are necessary to avoid unnecessary total closures (emphasis added):

We look forward to a day in the not-too-distant future when universal mask-wearing is no longer needed as part of our layered health mitigation strategies in order to keep our schools open for in-person learning, but that day is not yet here.

News flash: “That day” passed in March, 2020.

¹⁰

Macaque Me an Offer I Can’t Refuse

The unreal, mythical, fake thing that is called “OAS” remains a hot topic this weekend, thanks to two papers involving “boosting” in animal models. As both were brought up in the comments over at “Original Antigroundhogic Sin,” I will reprint my own replies below:

Of Mice and Hamsters

Study:

“Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naïve hamsters compared to ancestral vaccine” by Hawman, D. et al.¹¹

My remarks:

First, it wouldn't require any new study to demonstrate that vaccination with a homologous antigen -let's use X' - to a previously vaccinated antigen - X - probably won't result in a lot of antibodies against X'. This is the relevance of OAS in terms of vaccination. It's extrapolating this problem to the real world where things fall apart. Immunology has moved beyond antibodies since 1960. We know that injected vaccination can't provide the mucosal immunity that results from real infection in the first place, so the idea that "can't keep updating antibodies against mutations" is a problem supposes that we shouldn't want vaccinated people to go out and get infected in real life and update their mucosal immune response that way. Why not? Don't we want them to have mucosal immunity at some point? The point of OAS is "how can we make endlessly updating vaccines" not "are endlessly updated vaccines necessary, given real-world immune response after 'infection boosting'." There is no evidence that suggests the answer to the second question is yes, so why are we asking the first question to begin with?

Does this study support any extension of the vaccination relevance of OAS into real life? No.

If we look at Figure 2B, where the grey bars are double A.1 vaxxed + Omicron boosted mice and the pink are double HA influenza vaxxed (control) + Omicron boosted mice, there's no "increase" in ELISA-measured binding against Omicron Receptor Binding Domain because A.1 already had higher anti-Omicron-RBD binding than the HA group ends up having.

Hawman, D. et al. Fig. 2. “*” indicates statistical significance. But draw 1 and 2 binding against “Omicron RBD” is still lower for the non-A.1-primed in pink, compared to A.1 double-primed in grey.

Then the neutralization assay (C). Discard the bars, the dots are what matter. 2 of 5 HA influenza vaxxed + Omicron boosted don't pass this test either. This suggests the authors didn't calibrate the neutralization assay very well. A more sensitive assay might reveal more neutralizers in the A.1 vaxxed groups. Even so, neutralization assays are not real life.

Onto the hamsters, where there’s 1-dose A.1 vaxxed, 1-dose Omicron vaxxed, and controls. A.1 vaxxed are a bit outperformed by the Omicron vax, but overall still do much "better" than the controls in terms of where the authors are able to find viral antigen or RNA on day 4. Better is in scare quotes because Omicron did not cause lesions or weight loss on any hamsters, it was totally mild (while earlier experiments with "Wuhan-strains" produced lesions) and focused on upper respiratory tract. But the A.1 vaxxed hamsters, again, had only 1 of 6 viral antigen in lung detection vs 5 of 6 in controls and 4 of 6 epitheilial viral antigen vs 2 of 6 omicron vaxxed and 6 of 6 controls. A.1 vaxxed still benefited against Omicron.

Hawman, D. et al.

Again as I mention in footnote 2, injected vaccines might still be a net negative via "more plausible mechanisms" but it's not clear-cut. If Wuhan-spike-mRNA-transfection had 0 adverse events, then you would have to weigh protection against viremia with "maybe more reinfections over the course of a lifetime" and you might come up with "better for some." If you believe that the immune system is smart and knows what it's doing, you can see why either outcome could be true: The immune system should only encounter the virus in natural context, to not be confused, or the immune system will self-correct after "natural boosting" post injection.

¹²

The Grapes of Macaqueth

Edit, March 9: This study’s non-confirmation of OAS has now been far more extensively appraised here:

Macaque to the Future

Elsewhere, in the OAS saga:

“Even-Steven.” (OAS is “proven” via generation of a more balanced immune response against Alpha or Delta after breakthrough infection.)

“Original Antigroundhogic Sin.” (OAS is “proven” via breakthrough blood samples taken too early for seroconversion, and an overhyped UKHSA comment.)

“Funeral for a Fact,” footnote 3. (OAS is “proven” because the boosters restore infection efficacy vs. Delta during the Omicron wave.)

“Darmok and the Spike Protein at Tanagra.” (OAS is “proven” when high pre-existing antibodies against coronaviruses… don’t correlate to severe outcomes in infection with SARS-CoV-2 in any way.)

Archive of the original Gagne, M. et al. comments:

Study:

“mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron” by Gagne, M. et al.¹³

My remarks:

Not to be macabre with the macaques, but the study is way too limited. What’s the biology of mRNA transfection with an Omicron protein vs a Wuhan protein to begin with, not in the context of a booster? Changes to the spike amino acid recipe can affect cellular output in different hosts, based on a million different factors.

And does mRNA + spike production + immune response on macaques really say anything about the outcomes for humans? The authors are in la-la-land when they say macaques have been well established as correlates for protection. Nothing is a correlate for protection for Omicron.

Lastly, only eight test subjects? I look at the pre-boost antibody levels and those eight monkeys are already very skewed in antibody output. So did the high-pre-booster-antibody monkeys fall in the Wuhan booster or the Omicron booster set? If the former, that would throw out the results for which booster “induced” more neutralizing antibodies.

Gagne, M. et al. Fig. 2.

And what would the results be of a non-boosted Omicron challenge? Oops, the study has no non-boosted macaques to work with, sorry. Geez, why couldn’t they just let these poor 8 monkeys go about their lives instead of pretending there was anything left to gain from infecting and sacrificing them without a large enough population to control for anything?

Gagne, M. et al. Fig 4. “Boosting” with either formulation enhanced B Cell cross-reactivity. But was boosting necessary anyway? Real-life infection also stimulates and expands pre-existing B Cells. The study used no non-boosted controls during actual viral challenge.

All that aside, in so far as the study suggests anything it’s that prior sensitization to the “wuhan spike” doesn’t impede immune response against Omicron in any meaningful way during actual infection.

Gagne, M. et al. Fig. 5. Similar to the Hawman, D. et al. hamster challenge, both “boosted” groups did better against challenge infection compared to non-vaccinated controls. “The control NHP had previously been administered 50μg of control mRNA formulated in lipid nanoparticles at the time of boost and had never been vaccinated.”

1. That defunct url is here: https://journals.lww.com/greenjournal/Fulltext/9900/Association_Between_Menstrual_Cycle_Length_and.357.aspx

The web archive, again, has the original in snapshot:

The paper’s findings also remain summarized (and downplayed) in the recent editorial by Victoria Male, “Menstruation and covid-19 vaccination.” BMJ 2022; 376:

Most affected were the 358 individuals who received both doses of the vaccine in the same cycle, experiencing a 2.32 day (98.75% CI 1.59 to 3.04) delay to their next period. Among this group, 10.6% experienced a change in cycle length of more than 8 days, which is considered clinically significant, compared with 4.3% in the unvaccinated cohort (P<0.001). In all groups, cycle lengths returned to normal by two cycles after vaccination.

2. (index link anchor)

3. NBC Washington Staff. “School Boards Granted Temporary Ruling Against Virginia Governor's Mask Order.” (2022, February 4.) nbcwashington.com.

4. See https://law.lis.virginia.gov/constitution/article8/

5. Natanson, Hannah. Weiner, Rachel. Jouvenal, Justin. “Judge temporarily halts Youngkin order making masks optional in Va. schools after lawsuit from school boards.” (2022, February 4.) The Washington Post.

6. https://www.apsva.us/post/arlington-court-issues-temporary-injunction-in-favor-of-school-boards/

7. https://lis.virginia.gov/cgi-bin/legp604.exe?212+sum+SB1303

8. (Oh, boo hoo.)

9. (Do imagine yourself circa-2019 reading this line. Just what is happening in this fictional Future Virginia; is it an invasion of brain-eating alien child-swappers?)

10. (index link anchor)

11. Hawman, D. et al. “Replicating RNA platform enables rapid response to the SARS-CoV-2 Omicron variant and elicits enhanced protection in naïve hamsters compared to ancestral vaccine.”

12. (index link anchor)

13. Gagne, M. et al. “mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron.”