OOHHHH WOW! New preprint on the host immune response in Long Covid was just posted (few hours ago), and it's more significant than the 3-gene signature!
They found reactivation of viral herpes (EBV/CMV/HSV2) and CONFIRMED PERSISTENT SARS-CoV-2 INFECTIONS! Here's a summary...
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IMO, this is a hugely important study, so I'm going to do my best to explain it in detail, in a way that everybody can understand!
The headline here is that a persistent/reactivated infection of (one or more of) SARS2, EBV, CMV, and/or HSV2 were found in 60% of LC patients!
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Simply put, they looked at the antibodies produced by "Antibody-Secreting Cells" (ASCs), a type of short-lived immune response cells!
The primary types of antibodies stay in the blood. In contrast, ASCs peak *shortly* after infection, then rapidly decline! (see screenshot)
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Because serum (blood) antibodies increase after infection (or vaccination), remaining high for years as a defense against new infection, they're not a good measure of *current* infections!
For example, 98% of LC and 100% of controls had serum antibodies for EBV:
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This is where the MENSA (Media Enriched with Newly Synthesized Antibodies) matrix created in the current study comes in.
This new tool *specifically* measures the antibodies produced by ASCs (new infections) and memory immune cells (reactivated/persistent infections).
5/20
Looking at SARS-CoV-2 antibodies for one individual across multiple infections and vaccinations (comparing serum vs. MENSA antibody levels), the MENSA antibodies decline MUCH more rapidly after each exposure.
Thus, it distinctly detects *active* infection!
6/20
Just for the uninformed losers who show up to squawk "it's the jab! it's the jab!" every time:
- All of the LC patients had pre-vaccine infections
- 97% of the LC patients had nucleocapsid antibodies in serum. Those are acquired through INFECTION, and aren't in mRNA vaccines
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An issue with existing research is that SARS2 (and Herpesviruses) just don't show up in PCR tests of blood. Most of the studies showing viral reservoirs are *autopsy* studies because sampling those tissues is *destructive*
MENSA indirectly samples those same reservoirs!
8/20
Antibodies produced by ASCs are only found when there was RECENTLY a replicating pathogen that the immune system needed to attack, so this test can identify the "cause of the present-day illness" and is "an immune snapshot to uncover the sources of the patient's ailment"!
9/20
They found reactivated latent infections! Here's the percentage of patients positive for *MENSA antibodies* (CR = Covid Recovered)
But *serum* levels were high for all, because these viruses are common!
10/20
But even more significantly, they found the presence of MENSA antibodies for SARS-CoV-2 (indicating *persistent* infection) in 40% of LC patients and NONE OF THE CONTROL GROUP.
To put it another way, this test has SPECIFCALLY identified persistent SARS-CoV-2 infections!
11/20
Overall, the MENSA assays found:
- HALF of the LC patients were positive for at least one of EBV/CMV/HSV2
- 60% of the LC patients were positive for at least one of EBV/CMV/HSV2 *or* SARS2
- Only 17% of the recovered were positive for even one of EBV/CMV/HSV2
12/20
IMO, 40% is the LOWER bound for people with LC having persistent SARS-CoV-2 infection, because their positivity threshold is fairly conservative, statistically speaking: SARS2 positivity is three standard deviations beyond the mean MENSA values for *recovered* patients!
13/20
The AVERAGE level of antibodies *in the LC group* was BELOW the point they set as the test positivity threshold for the MENSA assay.
If we assume intensity of persistent infection is a spectrum, this is now an optimization problem!
14/20
This study pushes us a long way toward understanding the *specific drivers* of Long Covid, given that observable chronic symptoms don't manifest after *every* infection. MENSA allows precise sampling of *currently active* infections, regardless of serum antibody levels!
15/20
It's also worth noting that they checked for the presence of active responses to autoantigens and came up empty; however, that's not a definitive answer, because their technique had limited power. But, realistically, persistent infection explains most of the symptoms!
16/20
It's unknown how the MENSA assay results will look *over time* in LC patients or how treatment impacts it, so the specifics of how it can be used as a diagnostic tool are up in the air. But that's usually something the lab companies that commercialize the tests figure out!
17/20
And, of course, that gigantic fucking Catch-22 of the week, the MENSA assay may not be reliable in immunocompromised patients due to lack of B cell activation to form ASCs. SARS-CoV-2 ALSO fucks with B cells, in addition to T cells. Fantastic.
One interesting thing to note is that this method may *potentially* be capable of detecting other chronic (and/or neurodegenerative) conditions from very early in their onset, long before symptoms are present!
19/20
IMO, this is a STRONG study, and it's a starting point for much more specific diagnostics of chronic conditions resulting from SARS-CoV-2 infection—or any other pathogen!
This study is really just about the diagnostic tool, and their confirmation of viral persistence were part of proving that the tool works. This will likely end up being part of the measure treatment response, however
Also, huge shoutout to the people who routinely quote my threads with translations to other languages! We’ve got an efficient little global public health information network going!
22/20
IMO they missed a huge opportunity by not including VZV in their panel, because shingles is suuuch a common PASC! If (and only if) LC symptoms turn out to be driven PRIMARILY by latent herpesvirus reactivation (triggered by SARS2 persistence), VZV will prob be another 40%
TBD! This is really just a technical paper introducing a new *test method*, not a full blown virology research/theory paper. Also note that positives in the LC group were
- 40% for SARS2
- 47% for EBV/CMV/HSV2
- *60%* for SARS2 *and/or* EBV/CMV/HSV2
Good question! The *sensitivity* of this provisional test (i.e. not yet commercialized) was set conservatively to ensure the validity of the test results. If SARS2 persistence is ubiquitous, this positivity *threshold* will be artificially high
It's also worth noting they confirmed that the convalescent MENSA antibody levels do, in fact, remain HIGHER than the pre-pandemic baseline—and the convalescent MENSA baseline for an individual is also somewhat correlated with acute disease severity!
26/20
Here's the entire thread on the "Media Enriched with Newly Synthesized Antibodies" preprint available on one page:
GUESS WHAT?! A new study has shown SARS-CoV-2 infection is DISTINCT from common respiratory viruses!
Unequivocally, COVID is NOT "just a cold."
These findings are HUGELY significant, for multiple reasons! Here's a breakdown of the study (written for a general audience)...
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The paper is fairly complicated, so I'm going to start with the high-level takeaways before explaining everything in more detail.
Overall, they found a 3-gene signature that distinguishes SARS-CoV-2 infections from common viral infections—long before PCR test positivity!
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Because the signature:
1. is SPECIFIC to SARS-CoV-2, 2. is an EARLY indicator of infection, 3. is a DISTINCT pattern from other infections, and 4. even accurately identifies Omicron infections,
this discovery may be useful as a diagnostic tool AND a direction for treatment!
SIGNIFICANT new study has found a potential mechanism of ALS pathogenesis (with broader implications for other unexplained/idiopathic/"functional" neurological conditions?!)
This thread is pretty long, because I try to explain *everything* in a way anyone can understand!
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The short summary is that an endogenous retrovirus (HERV-K) is highly expressed in the brain and spinal cord of ALS patients, and may lead to neuroinflammation which leads to neurodegeneration.
These next several tweets are the background needed to understand the results!
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So, DNA… it's a *language* that encodes the instructions a cell uses to build proteins out of smaller molecules.
Like written language, different symbols are used to indicate when segments start and stop (i.e. capital letters, spaces, punctuation in human language).
HOLY SHIT. These mechanistic findings about covid's impact on immune signaling seem potentially HUGE!
Let's dig in...
(And I'm honestly ecstatic right now, because this paper seems to support my hypothesis about *how* I personally avoided LC.)
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When a cell is infected, the MHC-I protein presents antigens from the virus to the immune system to signal that the cell should be destroyed.
When infected with SARS-CoV-2, some genes involved in creating MHC-I are suppressed *by the virus* and form defective proteins.
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The result of the suppression is that infected cells are *unable* to present an antigen to the immune system, allowing infected cells to evade the immune system.
The authors view their result as indication of SARS-CoV-2 promoting unproductive splicing of key MHC-I genes.
When I had covid in Jul 2020, it was the worst experience of my life... but it was only *four days* of severe symptoms with an abrupt onset and resolution. Then a paper came out in October saying my symptoms strongly predict LC (93.5%)!
So how did I avoid chronic symptoms?? 1/
I think I avoided LC by random genetic chance
I put my 23andMe data into Promethease, and it turns out I have a gene that occurs in about 9.7% of white people, and it's associated with better control of viruses in general, incl. HIV, herpes, and hep C: 2/ omim.org/entry/142840#m…
But the interesting thing is that it seems to increase the expression of MHC-I receptors, related to the functionality of T cells and NK cells, and generally fine-tunes the immune response, I think?
I don’t know how to say this without sounding fear-monger-y, so here goes:
Brace yourself for things to get really bad, really fast.
In this case, “things” refers to *everything*, including public health and the climate. I think that,…
In multiple ways, certain patterns that were governed by self-limiting processes have fallen apart, because the context in which those patterns existed have slipped too far out of homeostasis.
But that’s not even my biggest concern.
In the last 75+ years of limitless growth, so little thought was given to things in the long-term. I think we’re approaching a tipping point on all the cans we’ve kicked down the road. Now, for example, the U.S. has so many buildings and other structures that were…
Oh shit, continuing in the theme of "everything is inflammation, it turns out"…
A GROUNDBREAKING research paper shows seasonal variation of systemic inflammation in Bipolar Disorder, explaining just… so, SO MANY ASPECTS of the disorder, including treatment resistance!
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They present a clear hypothesis, test it in a way that accounts for multiple potential confounding factors, and their conclusion is clear: seasonal variations in systemic inflammation are associated with Bipolar Disorder (BD)
Many fascinating immune system connections, too!
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Let's dive in!
Interestingly, epidemiological data already shows seasonality to BD symptoms, correlated with changes to neurotransmitters related to changing light. On top of this, there has been a convergence on the neuroinflammatory model of mood disorders more recently!