By Lambert Strether of Corrente.
“”It is common sense to take a method and try it. If it fails, admit it frankly and try another. But above all, try something.” –Franklin Delano Roosevelt
As is well known, the Biden Administration has pursued a “Vax-only” policy from its first days in office (augmented, to be fair, with various over-hyped yet profitable pharmaceutical treatments of less-than-stellar effectiveness; remdesivir, paxlovid). The hallmark of Administration policy has been a thorough-going rejection of a layered strategy (“Swiss Cheese Model“) that would mandate non-pharmaceutical interventions to decrease airborne transmission, whether through recommendations (“3C’s“), ventilation, or masking. (Such is the Democrat commitment to the bit that Acela Corridor media figures are now coming forward to stigmatize mask-wearers, making them objects of derision and hatred; see the New York Times and The New Yorker.) In practice, the Biden Administration has pursued a policy of mass infection, since the vaccines are not sterilizing, and eliminate neither transmission nor reinfection.
The Biden Administration’s Covid policy of mass infection has so far — I will assert for the purposes of this post — been cost-free politically, for a number of reasons: Business support, an incoherent Republican response, denial of airborne transmission by powerful institutional forces in healthcare and academia, a shift in focus from shared responsibility for public health to “personal risk assessment” (engineered by the public health establishment, ironically enough), and destruction of data gathering, but above all through a Goebbels-level propaganda campaign, waged by all components of the Democratic party apparatus and its (hegemonic) PMC class base in favor of “Vaxed and done.” (To be fair, “convenience” and “living your life” are not hard sells for Americans, our culture being what it is. Nor is working through illness.) However, time may be running out.
The Biden Administration’s Covid policy of mass infection has always been vulnerable to facts on the ground. Another surge equivalent to January 2022’s Omicron surge would do it in; so would “something awful” in the form of vascular or neurological (epithelial) damage of an undeniable scale. (Long Covid doesn’t seem to be awful enough, sadly; but that could change, given a solid mechanism and possibly a few celebrities to help with the narrative.) In this post, I’ll first present the case for vaccine escape from recent variants, and then the case for immune dysregulation as a sequel to accute covid. In terms of facts on the ground, the first would create a surge; the second, “something awful.” In either case, even the most coughing, exhausted, several-times-injected, “I’ve got a cold I can’t shake” vaccine militant might be gently led to the conclusion that the Biden Administration’s policy of mass infection has failed, and we must try something else.
I started meditating this post when I saw the following post from Cell: “Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants“; “Alarming” is not typically a word that one sees in article titles for professional journals. (I think it translates to “hair on fire”?). From the Abstract (and I’ve gone a little overboard with the formatting just to make the point:
The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to deriving from their additional spike mutations. Here, we report that including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13- to 81-fold and 66- to 155-fold, respectively, far beyond what had been observed to date. , and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors. Together, .
For whatever reason — charitably, the December 13, 2022 publication date, too close to the holiday season — this peer-reviewed study from a top-drawer medical journal has gottten virtually no play in the press.
GM advises us to look at Figure S3, so — even though I feel I’m juggling power tools — here it is (the highlighting is mine. This is an “antigenic map.” The caption explains why the axes are not labeled).
Figure S3 Antigenic map of BQ and XBB subvariants in relation to SARS-CoV-2 variants and sarbecoviruses, related to Figure 2
(B) Antigenic map based on the serum neutralization data from (A). Virus positions are represented by closed circles whereas serum positions are shown as open squares. Sera are colored by group. Both axes represent antigenic distance with one antigenic distance unit (AU) in any direction corresponding to a 2-fold change in neutralization ID50 titer.
(New subvariants in circle at right; no sera. Old subvariants in circle at left; sera.) In prose:
Our data demonstrate that these new subvariants were barely susceptible to neutralization by sera from vaccinated individuals with or without prior infection, including persons recently boosted with the new bivalent (WA1/BA.5) mRNA vaccines…. . In fact, combining these results with our prior findings on the serum neutralization of select sarbecoviruses, there are indications that XBB and XBB.1 are now antigenically more distant than SARS-CoV or some sarbecoviruses in animals… Therefore, 
But, you say, even if the old vaccines don’t work for the new subvariants (BQ/XBB), we have bivalent boosters now, so perhaps they will save us. First, the Cell study says they won’t (see above), but we can further look at two articles, first from the CDC, and the second from the NEJM.
The first article asks how much of a boost the bivalent boosters give, given “waning immunity of monovalent doses.” From the CDC’s Morbidity and Mortality Report, “Effectiveness of Bivalent mRNA Vaccines in Preventing Symptomatic SARS-CoV-2 Infection — Increasing Community Access to Testing Program, United States, September–November 2022,” December 2, 2022:
Relative vaccine effectiveness (rVE) of a bivalent booster dose compared with that of ≥2 monovalent vaccine doses among persons for whom 2–3 months and ≥8 months had elapsed since last monovalent dose was 30% and 56% among persons aged 18–49 years, 31% and 48% among persons aged 50–64 years, and 28% and 43% among persons aged ≥65 years, respectively.
That doesn’t sound very encouraging.
The second article is a letter in the New England Journal of Medicine, written in answer to a Cell article from February 2022, among others, but not the article quoted above. From “Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster, December 21, 2022:
We tested serum samples obtained from participants who had received either one or two monovalent boosters or the bivalent booster to determine the neutralization efficiency of the booster vaccines against wild-type (WA1/2020) virus and primary isolates of omicron subvariants BA.1, BA.5, BA.2.75.2, BQ.1.1, and XBB using an in vitro, live-virus focus reduction neutralization test (FRNT).
… Persons who received the BA.5-containing bivalent booster had neutralizing activity against all omicron subvariants (especially against BA.2.75.2, BQ.1.1, and XBB) than those who received either one or two monovalent boosters, even though the neutralization GMT against WA1/2020 was similar in the cohort that received the two monovalent boosters and the cohort that received the bivalent booster. These responses are consistent with recent observations in persons with breakthrough omicron infection showing broadened neutralizing activity against omicron subvariants. . These serologic data show an overall neutralization benefit with bivalent booster immunizations.
Comparing the methodology of the Cell study with the NEJM letter is above my paygrade, but I think the Cell methodology is superior. Cell includes up to four shots (not just two), and includes breakthrough infections (Figure 2), so it’s looking at population that’s far closer to the real world than the NEJM paper. I also don’t know what NEJM’s “better” means in terms of effectiveness. If it means what the MMWR study means (“30% and 56% among persons aged 18–49 years”) that’s not very encouraging. Next — and here I’m going to juggle power tools again — the NEJM letter lacks a mechanism. If you look again at Figure S3, BQ/XBB have no sera. So how was the NEJM’s putative “neutralizing activity” to have been achieved? (If we think of antibodies and antigens like a lock and a key, we are not just trying to open a lock with the wrong key, the key is a Shlage, and the lock is a Yale.) Finally, the NEJM study doesn’t mention the new subvariants ace out monoclonal antibodies, eliminating important treatment options. So I remain “alarmed.”
Dr. Anthony Leonardi is the foremost proponent of Covid immune dysregulation. This deep dive in the Tyee, “What If COVID Reinfections Wear Down Our Immunity?” gives the backstory and explains the concepts.
By dysregulation Leonardi means three effects of COVID:
- The hyperactivation of many T cells [“one of two white blood cells that defend the body against foreign invaders”], which can prematurely age them
- The exuberant function of those hyperactivated T cells, which can then cause organ damage
- The exhaustion of those hyperactivated T cells, which implies they aren’t winning the battle against viral proteins they are supposed to defeat.
In other words, argues Leonardi, T cells are becoming hyperactivated by SARS-CoV-2 and are prematurely aging, harming organs, and becoming exhausted trying to rid the body of an immune-evasive virus.
Here is a study from Nature, which is alarming because it suggests that Covid can cause immune dysregulation not only in T Cells, but in monocytes, “a type of immune cell that [can] surround and kill microorganisms, ingest foreign material, remove dead cells, and boost immune responses.” Or, as the Cleveland Clinic puts it, “Monocytes are your cell’s firefighters.” They constitute between 2% and 8% of your white blood cell count. That’s a lot! From “Transcriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19,” December 26, 2022:
Here, we examine the function of classical CD14+ monocytes in patients with mild and moderate COVID-19 during the acute phase of infection and in healthy individuals. Monocytes from COVID-19 patients display altered expression of cell surface receptors and a dysfunctional metabolic profile that distinguish them from healthy monocytes…. These results identify a potential mechanism by which monocyte dysfunction may contribute to COVID-19 pathology.
On this paper, Leonardi comments:
It looks like Covid suppresses innate immunity toward other viruses and Bacteria
This doesn’t bode well for the severity of other infections that aren’t even covid
Think of all the people saying “The worst cold of my life”
— Anthony J Leonardi, PhD, MS (@fitterhappierAJ) December 30, 2022
Oh. Oh good. (Leonardi might well have mentioned the cases of Strep and resulting sepsis in the UK as well.)
I do not use the word “ruin” in the headline lightly. At the very beginning of our Covid journey, on January 26, 2020 (!!), Nassim Nicholas Taleb and his co-authors wrote “Systemic Risk of Pandemic via Novel Pathogens – Coronavirus: A Note” (PDF):
The general (non-naive) precautionary principle  delineates conditions where actions must be taken to reduce risk
of ruin, and traditional cost-benefit analyses must not be used. These are ruin problems where, over time, exposure to tail events leads to a certain eventual extinction. While there is a very high probability for humanity surviving a single such event, over time, there is eventually zero probability of surviving repeated exposures to such events. While repeated risks can be taken by individuals with a limited life expectancy, ruin exposures must never be taken at the systemic and collective level.
Taleb defines a “ruin problem” as “one where outcomes of risks have a non-zero probability of resulting in unrecoverable losses.” I suppose it would be possible for some to consider a million people dead from Covid not ruinous — after all, we can always breed more — but taking such risks repeatedly sounds like a very bad idea, especiallly since we’re taking that risk “at the systemic and collective level.”
If the papers I have presented are correct, the Biden Adminstration’s policy of mass infection has brought us to the brink of ruin. Vaccine escape is the direct result of the Administration’s mass infection policy. GM writes:
[N]ever before has such a virus received the opportunity to replicate so fast and so much. We’re talking several orders of magnitude more replication than usual. And these are the results.
In the worst case scenario, the health care system is right back where it was in Spring 2020, with no working vaccines. Moreover, it will be overwhelmed not merely with Covid cases — remember “flattening the curve”? Good times! — but with all sorts of new infections brought about by Covid’s immune dysregulation abilities, as is happening in the UK now.
Even worse, the subvariants with demonstrated immune escape capabilities (BQ/XBB) are peaking and becoming dominant during the Christmas and New Year’s holiday period. Worse than that, the Southwest Airlines debacle has meant that there have been entire families, nationwide, staying 24/7 in airports, which are Covid hotspots, for days. Worse than that, opening up China will — probably already has — expose us to whatever variants have been brewing in immunocompromised Covid patients in that country.
 At least as a putative public health measure.
 Readers will note we’ve been following the expansion of the The BQ and XBB subvariants in Water Cooler, using both CDC and Walgreens data. (The data for both comes from Pango but we can use Walgreens as a check on CDC’s tendency to hide up-and-coming subvariants in aggregated data). BQ is currently dominant, but XBB is coming up fast. CDC’s NOWCAST model predicts that XBB will dominate soon, which is why many are saying it is already dominant.
 There follows some qualifying language that says vaccines work in principle, but for us the point of the study is that they are not likely to work now, which is when we need them.
 Having explained the concept, I don’t want to get deeply into the balance of the Tyee article, which you should read if you have not. Suffice to say that the Tyee looks at “six key issues, comparing his statements with what the scientific literature now says or suggests.” I every case, Leonardi was either on the money or still in the running. So he has form.