Updates to “Unfinished”
With apologies for the email bandwidth impact.
The “Official Unglossed Totally Reckless Theory” for Paxlovid viral rebound has undergone a substantial rebuild. One of the key assumptions of the original version of the theory (RE endogenous proteases) turned out not to be supported by experimental evidence. Correcting the theory on this point not only made the argument more elegant, but strengthened the entire structure by implying other reasons why Paxlovid only stops replication temporarily by design.
See the original post for the new version. Over 50% of what is after “Presenting” will be new content. The changelog for the update is below.
The “latest,” per Johnson’s uncredited half-recycling of the Boston Globe story, neither of which articles (obviously) give credit to any substacks that uncovered the trend (Igor Chudov) or offered a theory of mechanism that correctly predicted true rebound (non-reinfection) (myself):
These rebounds exceed normal noise in PCR testing, says expert NBA-swab-result-look-atter Yonatan Grad. Thanks, I already thoroughly demonstrated that in Part 2 of this series, Johnson.
Pfizer issues remarks! Emphasis added:
Pfizer is collecting data, in clinical trials and in real-world monitoring of the drug’s use. The company’s trial data indicates there is a late uptick in viral load in “a small number” of people who take the drug [4 - 8%, per my math in Part 2], but the rates appear to be similar among study participants given a placebo, according to company spokesman Kit Longley [really? or is this a misunderstanding of the methodology of the FDA independent analysis, which only appeared to show similar rates among other Paxlovid recipients]. The people who experienced such increases also did not develop severe disease the second time around. […]
“Although it is too early to determine the cause, [the alleged observation of rising viral load in the placebo group] suggests the observed increase in viral load [in the Paxlovid group] is unlikely to be related to Paxlovid,” Longley wrote in an email [fake news, the 8 “rebounders” identified in my analysis in Part 2 are not normal variations in untreated infections, and likely did not occur in the placebo group during trial]. “We have not seen any resistance to Paxlovid [irrelevant, the drug leads to rebound by design], and remain very confident in its clinical effectiveness.”
Charness’s case study has been posted to pre-print. It contains some feisty pot-shots at the failed Covid vaccines. Meanwhile, Charness’s daughter, who was issued the drug on the ridiculous pretext of “asthma,” experienced the rebound as her father was researching it. Totally what always happens with “rare” outcomes.
Nothing interesting RE the mechanism is provided. The expert commentary seems indifferent to actually “solving” the alleged puzzle; instead, the consensus seems to be coming around to the idea, “Eh, I guess it’s [the virus] still In There Somewhere or something.”
End of Post story recap.
Changelog for “Unfinished Business” Part 1:
Remodeled the introduction to add a Table of Contents and remove the now-unnecessary caveats about the quality of the early evidence (moved to footnotes for the record).
Removed reference to endogenous proteases as the main means by which nsp5 is initially liberated from the polyprotein.
Added reference to auto-cleavage as the main means etc.
Re-modeled the dynamics of continued cleavage that take place after Paxlovid binds to nsp5, whether with a preference for free nsp5 or not.
Added consideration of events that precede and follow nsp5 cleavage. For precede: cleavage of nsp1 to 3, which initiates suppression of intracellular immunity. For follow: retrieval of the viral RNA molecule and beginning of replication and expression of structural proteins, including spike. Therefor, both innate and memory immunity (especially spike-only memory immunity) are less likely to intervene and destroy a cell that has been “paused” by Paxlovid, due to this flaw in the design.
If you derived value from this post, please drop a few coins in your fact-barista’s tip jar.