☢️ take

What we call #Paxlovid rebound is actually a mismatch between the pharmacokinetics of the drug and the execution of the genetic programs of the #SARSCOV2 virus vis-a-vis its distribution across vascular beds & tissues the body. In the days pre #paxlovid, the biphasic nature of acute #covid disease was well understood and documented in the early, natural history clinical papers. Pax improves the symptoms of the first phase, and thus the contrast to the 2nd phase becomes more obvious.

This is an interesting visualization , straight from the USRDS 2023 report. Mortality in the 90% days after COVID19 diagnosis in the 5% sample of Medicare beneficiaries without CKD and all beneficiaries with ESRD (dialysis), and % of attributable deaths among those on dialysis.





This is a closed population and you can see several points:
- the effects of relaxation of NPIs during the politicalization of NPI (post summer of 2020) as we were heading towards the election, and the premature declaration of victory by the present administration in early 21 ...

#IgA Nephropathy went from having few medical therapies to > 60 potential combos (@NephRodby did the math) , none of which will ever be tested in trials (pharma companies with approved single agents are unlikely to run them & the budget exceeds what the public sector can fund) This is one of the areas in which biomarkers will settle the multi drug regimen for individuals, as the potential number of arms is prohibitive for any exhaustive RCT program given dz prevalence, the cost will be prohibitive, while the incentive to do these RCTs is nonexistent.

Let's assume that these findings hold ie BA.2.86 manifests both higher immune effectiveness and less infectivity. This could happen if the ACE2 is totally FUBARed so that it can't engage with Antibobies and the ACE2. It then follows it's using an alternate receptor for entry.

https://twitter.com/Yash25571056/status/1700338430616695262

Alternative receptors for ACE2


If this the case, the neutralization assays using the pseudovirus are going to be potentially misleading and a true neutralization , or microneutralization assay should be donepubmed.ncbi.nlm.nih.gov/36423144/

Shared with permission ....
This is wild report of an astute , young (<40) person without any comorbidities who was among the first to get infected in the US by covid (2nd month of the US pandemic) and got a protracted case of longcovid as a result. Symptoms of the LC included... Your garden variety orthostatic tachycardia, fatigue , and numerous GI symptoms that didn't really improve substantially for a year and would not go away until the 1st quarter of 2023. Sometime in the spring of the current year the said person ate what was apparently ...

Seems that a major problem with data driven decision making is people's inability to use Fermi calculations & their insistence on "exact" numbers, when the conclusions would not materially differ if those numbers were 10 times higher or lower than any approximate figure at hand. One nice example is the zoster vaccine (ZV) paper: the answer given is approximate and based on regression discontinuity methods, which are problematic if one considers the Age Period Cohort structure of the dataset. Yet the number is irrelevant: the ZV could be 10x less or ...

Unless you were in a tight labor market before #covid , where most jobs required substantial high speed processing (e.g. any workplace that was leanly staffed) you are unlikely to view #longcovid as a problem : there was a substantial buffer to hide disability and 1/ at least in Europe extensive informal and governmental support systems. #GigaFAFO may obtain in such locales as they will delay response and systemic risks, i.e., a global financial meltdown / regional wars have become more likely.