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Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
@NickAnderegg
Jul 8, 2024 • 28 tweets • 11 min read • Read on X
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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...

1/ Preprint Title: "MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID." Abstract: "Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines the underlying viral triggers. [...] Applying the same principles for long-COVID patients, MENSA is positive for SARS2 in 40% of PASC vs none of the COVID recovered (CR) patients without any sequelae demonstrating ongoing SARS2 viral inflamma...
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!

2/ "In summary, MENSA is a novel immune diagnostic which captures unique signatures of the early-minted ASC in the blood to reveal the cause of illness. In chronic conditions such as PASC where serum antibody titers are high, MENSA is an independent matrix that identifies persistence of SARS2 viruses or antigens and can also recognize the reactivation of latent herpes viruses, such as EBV, CMV, and HSV2 in 60% of patients. This host immune snapshot reveals the fundamental drivers of viral persistence and reactivation in this chronic disease." That means 60% of LC patients have one o...
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)

3/ From "The Antibody-Secreting Cell Response to Infection: Kinetics and Clinical Applications" (2017): "In this review, we summarize previous studies that have used techniques to enumerate ASCs during infection. We describe the emergence, peak, and waning of these cells in peripheral blood during infection with a number of bacterial and viral pathogens, as well as malaria infection. We find that the timing of antigen-specific ASC appearance and disappearance is highly conserved across pathogens, with a peak response between day 7 and day 8 of illness and largely absent followi...
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:

4/ "Nearly all individuals in the general population have been exposed to EBV and our results were consistent with this finding. Here, EBV serologies are positive for 59/60 (98%) in the PASC group and all 23 [control] samples."
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 "In this study, we use a novel diagnostic platform whereby we capture antibodies secreted from plasmablasts or newly-minted antibody secreted cells (ASC). This method can identify new or repeat infections despite elevated serum antibodies since these ASC appear in circulation shortly after infection or vaccination, then rapidly disappear from the blood. By capturing antibodies from these special ASC in a new matrix called Media Enriched with Newly Synthesized Antibodies (MENSA), we provide a signature response from only the new illness. MENSA antibodies often appear prior to seroconve...
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 Additional description of Figure 3 from the paper: Figure 3A: The short-lived antibodies detected by the MENSA matrix jump with each exposure (via infection OR vaccination) to the spike protein. Then, they rapidly decline. This makes it possible to more accurately pinpoint *active* infections! Figure 3B: Serum antibodies for the spike protein increase with each exposure to that antigen (through infection or vaccination), then remain steady. This is our main line of defense against additional infections! Figure 3D: Note how this individual's second infection causes their nucleocapsid anti...
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

7/ "For the initial PASC experiment, we tested for only SARS2 antigens in MENSA and serum samples prepared from the subset of 19 CR subjects mentioned above and 39 PASC patients recruited during the first year of the Long-COVID clinic at Emory University December 2020-May 2021. [...] All patients were enrolled from day 60-279 DPSO after their initial acute infection and prior to any COVID-19 vaccination. Of the 39 PASC patients, 56% had initial M/M acute infections and 44% had initial S/C acute infections. Of the 19 CR patients, 95% had M/M acute infections and 5% had S/C acute infections...
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 "... blood PCR tests have limited utility for SARS2 and latent herpes viruses, such as EBV, CMV, and HSV2 due to strong T cell responses that mediate rapid viral clearance. SARS2 antigen assays have been shown to identify the spike protein, but quantities are extremely low and require ultrasensitive assays.... Autopsies up to 230 days after acute SARS2 infection detected SARS2 RNA in multiple tissues such as the gut, central nervous system (CNS), muscle, myocardium, and the respiratory tract demonstrating viral reservoirs. Thus, measuring the MENSA has advantages over pathogen detectio...
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 "...lymph nodes to form memory B cells and newly-minted ASC that produce antibodies. Interestingly, the majority of these ASC die, but a few successfully migrate to the bone marrow or tissue sites where they can undergo further maturation to become long-lived plasma cells (LLPC). [...] Memory B cells persist over a lifetime and differentiate into plasmablasts when re-encountering the same antigens?5. During breakthrough or repeat infections, newly-minted ASC mostly originate from memory B cells and circulate transiently in the blood'5. Since MENSA measures antibodies only from these ne...
They found reactivated latent infections! Here's the percentage of patients positive for *MENSA antibodies* (CR = Covid Recovered)

- EBV: 37% LC / 17% CR
- CMV: 23% LC / 4% CR
- HSV2: 15% LC / 4% CR

But *serum* levels were high for all, because these viruses are common!

10/20 "When examining the latent herpes viruses, MENSA reactivity was greater overall in the PASC group than in the CR group (Fig. 7A). For EBV, more PASC patients had positive MENSA samples 22/60 (37%) compared to CR subjects 4/23 (17%). ... Nearly all individuals in the general population have been exposed to EBV and our results were consistent with this finding. Here, EBV serologies are positive for 59/60 (98%) in the PASC group and all 23 CR samples. MENSAs for CMV are positive in 14/60 (23%) of the PASC patients compared to 1/23 (4%) in the CR group. ... Similar frequencies of positive ...
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 "In a cohort of 60 PASC patients (39 patients in 2021 and 21 patients from 2022-2024), 21 CR patients (2020-2022), and 16 healthy adult controls (2020), we tested MENSA and serum for a combined SARS2, EBV, CMV, and HSV2 IgG immunoassay. We had 23 samples from 21 CR patients since two individuals suffered repeat SARS2 infections in 2020 and 2022. As expected, all healthy controls drawn prior to SARS2 exposure were negative for SARS2 IgG in both MENSA and serum (Fig. 7). Only 2/16 (13%) were positive in the MENSA for any of the viruses tested (EBV) in the healthy control group, whereas 1...
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 "Figure 7. MENSA and serum in PASC, CR, and healthy adults for SARS2, EBV, CMV, and HSV2. MENSA (A) and serum (B) samples were collected from healthy donors prior to SARS2 exposure (top), COVID recovered (middle), and PASC (bottom) patients, tested for IgG reactivity against SARS2, EBV, CMV, and HSV2 antigens, and presented in a heat map. Green cells represent Net MFI values ≥ the C 0 thresholds calculated for each sample type and antigen combination, while white or grey cells represent values below the C0 . In MENSA, a C 0 was calculated as the average Net MFI of 22/23 CR samples plus...
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 "Since the convalescent baseline MENSA negative values could be slightly higher than in pre-pandemic controls, we identify a subset of the convalescent patients from Fig. 1 as COVID Recovered (CR) who had fully recovered with no sequelae (N=19). CR MENSA samples were used as controls to calculate the MENSA C0 using the average Net MFI plus 3 standard deviations. In contrast to MENSA, serum levels rise and remain high indefinitely in both CR and PASC patients; therefore, the serum C0 values are calculated using the average Net MFI plus 5 standard deviations of the 60 healthy controls pr...
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 "Figure 5. Prolonged, elevated MENSA IgG responses for SARS2 in a subset of PASC patients. Dot plots show MENSA and serum IgG antibody responses to S1-RBD (A,B) and Nucleocapsid (C,D) in samples collected between 60-279 DPSO since initial COVID-19 Wild Type infection from patients who completely recovered from their acute illness (CR; n=19) and patients who suffer PASC (n=39). Blue dots represent a Mild/Moderate acute disease severity. Red dots represent a Severe/Critical acute disease severity. All values are reported as average Net MFI (Median Fluorescent Intensity – Background). Das...
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 "Understanding the main viral drivers of the inflammatory and metabolic changes in patients with long-COVID has been challenging. Multiomic studies provide a wealth of information but have not identified the underlying triggers of this chronic condition. Although suggestions of viral persistence have been raised, it has been difficult to demonstrate ongoing reservoirs or reactivation of the latent virus by PCR due to the limited sensitivity of the current tests. Thus, detecting the pathogen has been challenging in patients with normal or even heightened immune responses. In this paper,...
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 "Autoantigen triggers have also been implicated in PASC patients, and so we tested MENSA from a limited number of PASC patients for autoantigens using the PhiP-seq human peptidome library which consists of 605,656 peptides tiling protein-coding sequences, splice variants, non- 37,38 coding open reading frames, and endogenous retroviral sequences in the human genome No differences were observed between the PASC and CR MENSA against the human peptidome (our unpublished results). However, a larger number of patients using the 3-D conformational epitopes of the human proteome may be needed...
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 "There are several limitations of this study. One is that we do not have longitudinal samples from the PASC patients and thus, it is unclear how consistent the MENSA responses are in the patients with chronic illness over time. Second, large clinical trials are needed to evaluate responses to anti-viral therapies in MENSA positive patients identified with SARS2 persistence and reactivation of EBV, CMV, or HSV2 infections."
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.

18/20

"Finally, the utility of MENSA may be challenging in immunocompromised patients since the MENSA requires B cell activation to form new ASC."
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 "The real-time immune snapshots provided by MENSA may be leveraged to inform therapeutic strategies and successful treatment of chronically ill PASC patients. Whether MENSA can also be useful to identify persistence of viral reservoirs in other chronic illnesses such as multiple sclerosis, HIV, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other infections with post-sequelae are yet to be determined. For example, EBV was recently implicated in multiple sclerosis. Interestingly, infection with SARS2 is associated with increased susceptibility and severity of neurodegen...
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!

AND IT CONFIRMS SARS2 VIRAL PERSISTENCE!

Preprint on medRxiv:

20/endmedrxiv.org/content/10.110…
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

21/20
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%

23/20
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

24/20
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

25/20

Image
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 "Additionally, for S/C compared to MM patients, serum levels rise higher during the acute illness and remain elevated during convalescence, suggesting more ASC survived in other tissues such as the spleen, bone marrow, or mucosal sites. During convalescence, 87% of MENSAs become negative, but are overall slightly higher than pre-pandemic levels. In all, MENSA rises during acute infection and then rapidly falls to negative whereas serum titers rise and remain elevated."
Here's the entire thread on the "Media Enriched with Newly Synthesized Antibodies" preprint available on one page:

And all of the content here is freely licensed for reuse: readwise.io/reader/shared/…
They were only *validating the ability to DETECT chronic infections,* so we can't infer causality.

HOWEVER!

All of the control group had high SERUM titers for EBV. Thus, in this study, adverse outcomes were *uncorrelated* w/ PRE-COVID EBV exposure!
27/20

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More from @NickAnderegg

Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Sep 7
Let’s talk about systemic risk from negligent public health: Catastrophe doesn’t require population-wide illness.

The worst case isn’t sickness. Worst case is infrastructure collapse due to overstressed resources.

You know power plants need stable power to operate?

1/many “8. Performance of Nuclear Power Plants Affected by the Blackout On August 14, 2003, nine U.S. nuclear power plants experienced rapid shutdowns (reactor trips) as a consequence of the power outage. Seven nuclear power plants in Canada operating at high power levels at the time of the event also experienced rapid shutdowns. […]. Many non-nuclear generating plants in both countries also tripped during the event. Numerous other nuclear plants observed disturbances on the electrical grid but continued to generate electrical power without interruption. […] - The severity of the grid transient...
If there is a widespread disruption in the service area of, e.g., a nuclear power plant, it shuts down for safety. Massive blackouts like in 2003 or in Spain this year are caused by safety systems!

If too much trips out at once, it has a ripple effect across the grid
2/ Source: https://www.insurancejournal.com/news/international/2025/04/29/821703.htm Why Restarting a Power Grid After Massive Collapse Is So Hard April 29, 2025 by Rachel Morison and William Mathis It’s a worst case scenario that grid operators plan for but hope never to encounter. After one of the worst blackouts in Europe in more than a decade, electricity grid operators in Spain and Portugal are trying to get networks back up and running from the ground up. The initial estimate from grid operator Red Electrica was that restoring all power supply in Spain may take between six and 10 hour...
Frequency Factor So far, the only information about what caused the crisis was a comment from grid operator Red Electrica that the blackout was a result of “oscillation,” which suggests a disruption in the grid’s frequency or voltage — both crucial factors for maintaining stability. The frequency, which normally stays pretty steady around 50 hertz, is the heartbeat of the grid. Frequency monitoring specialist Gridradar said it identified a rapid movement in frequency just after noon in Spain — right before the blackout hit. Such oscillations can cause chain reactions that ultimately lead ...
In 2003, it took 2 days to fully restore most power. The infrastructure is 20 years older than it was back then and higher demand creates risk of cascading failure.

As of 2003, recommendations from blackouts in 1965, 1977, 1982, 1996, and 1998 had not been implemented.
3/ “Recommendations to Prevent or Minimize the Scope of Future Blackouts As reported in previous chapters, the blackout on August 14, 2003, was preventable. It had several direct causes and contributing factors, including: • Failure to maintain adequate reactive power support • Failure to ensure operation within secure limits • Inadequate vegetation management • Inadequate operator training • Failure to identify emergency conditions and communicate that status to neighboring systems • Inadequate regional-scale visibility over the bulk power system.”
“Further, as discussed in Chapter 7, after each major blackout in North America since 1965, an expert team of investigators has probed the causes of the blackout, written detailed technical reports, and issued lists of recommendations to prevent or minimize the scope of future blackouts. Yet several of the causes of the August 14 blackout are strikingly similar to those of the earlier blackouts. Clearly, efforts to implement earlier recommendations have not been adequate. Accordingly, the recommendations presented below emphasize comprehensiveness, monitoring, training, and enforcement of r...
“1. Market mechanisms should be used where possible, but in circumstances where conflicts between reliability and commercial objectives cannot be reconciled, they must be resolved in favor of high reliability. 2. Regulators and consumers should recognize that reliability is not free, and that maintaining it requires ongoing investments and operational expenditures by many parties. Regulated companies will not make such outlays without assurances from regulators that the costs will be recoverable through approved electric rates, and unregulated companies will not make such outlays unless th...
“3. Recommendations have no value unless they are implemented. Accordingly, the Task Force emphasizes strongly that North American governments and industry should commit themselves to working together to put into effect the suite of improvements mapped out below. Success in this area will require particular attention to the mechanisms proposed for performance monitoring, accountability of senior manage-ment, and enforcement of compliance with standards. 4. The bulk power systems are among the most critical elements of our economic and social infrastructure. Although the August 14 blackout ...
Read 20 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Sep 4
If Florida drops vaccine mandates, society is probably officially over. I really, really, really don’t think most people get that herd immunity is the only thing keeping measles from ripping through the population, and a measles infection wipes out all pre-existing immunity

1/3
Measles specifically infects the cells that are responsible for “remembering” which pathogens your body has encountered before. So they ALL get wiped out, and all you’re left with is cells that remember your measles infection and nothing else.

2/3
Every infection, vaccination, and other pathogenic exposure you’ve ever had? Your body no longer knows how to detect them after a measles infection. The only immunity you’ll be left with is immunity to measles. That’s it. Open season for every other pathogen encountered.

3/3
Read 8 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jun 30
Can I say something? I have a BA in psych, a BPhil in linguistics, and went to grad school for cognitive psych. My research, including an undergrad fellowship, was on the cognitive relationship between written and spoken language…

Audiobooks are NO DIFFERENT than reading print.
In the last hour, there have been a dozen replies from people nitpicking the first tweet

The topic of discussion is "do audiobooks 'count' as reading?," and the answer is "Audiobooks are NO DIFFERENT than reading print."

Maybe read the thread before arguing with it? lmfao
And for all those people with indignant responses who want to nitpick every detail, the fact that so many people hold THIS exact view—that audiobooks are somehow “cheating”—is the ENTIRE point. It leads to people who would benefit from audiobooks depriving themselves the medium
Read 4 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Feb 1
Many people are asking for recommendations about what storage media to buy, so here's a buying guide from an experienced data hoarder (me)

The MOST IMPORTANT thing to know is that SOLID-STATE MEDIA IS NOT DURABLE. Flash drives, SSDs, SD cards, etc. are NOT long-term storage.

1/
That's not to say that it's impossible to use solid-state media for long-term storage. It's just that anything with durability guarantees gets prohibitively expensive quickly. Spinning hard drives—as well as DVDs and Blu-ray discs!—are your friend.

2/
- The way data is stored in solid-state media makes it much more susceptible to bit rot than other media.
- In a spinning hard drive, the moving parts are the most common point of failure.
- When you burn a DVD, that shit is fairly permanent.

3/
Read 42 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 9
I wish people would understand that insurance underwriters have armies of actuaries calculating risks, and if an insurance company drops you, it's because things have changed in such a way that insuring you will take more out of the financial pool than you're putting in

1/
It sucks, but it's a direct result of the fact that humans are widely inhabiting locations that are rapidly becoming impossible to inhabit safely. If you can't find insurance for your home, it means there's a high likelihood you'll need to move soon anyway.

2/
You get insurance so that you can replace all of your stuff in the event of a disaster. When the insurance company effectively says "the risk of disaster is so high that insuring you would almost certainly cause us to lose a lot of money," it ALSO means your life is in danger

3/
Read 7 tweets
Nick #RespiratorsFilterPathogens😷 Anderegg Profile picture
Jan 5
So here’s the thing about some of the subtle neuro damage related to SARS-CoV-2 infection that I think a lot of people miss: some of the known deficits are correlated with things like impulsiveness and poor emotional control, so we might expect to see deficits there are well

1/
Consider how impatient people seem to be on the road in the last couple years relative to the 2010s, and I think we have a perfect example of where this is LIKELY already manifesting.

2/
This impact is particularly insidious for the person experiencing it, because poor impulse control, by definition, doesn’t really come on gradually. My biggest concern is how interactions under these circumstances will play out if this impact continues to become more common

3/
Read 15 tweets

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