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

Jul 7
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)...
1/16 SARS-CoV-2 infections—both symptomatic and asymptomatic—produce distinct host immune responses compared to human rhinovirus infections (the common cold), influenza virus infections, and RSV infections.  That is, SARS-CoV-2 induces a set of changes in gene expression with significantly higher magnitude of change compared to other common respiratory viruses.  For each of the four viruses, the column on the left shows differential gene expression (relative to controls) for symptomatic infections, while the column on the right shows differential gene expression for asymptomatic infections. Note...
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!

2/ A T-Cell-Derived 3-Gene Signature Distinguishes SARS-CoV-2 from Common Respiratory Viruses  Abstract: ..., we performed a multi-cohort analysis with integrated bioinformatics and machine learning. We collected 3730 blood samples from both asymptomatic and symptomatic individuals infected with SARS-CoV-2, seasonal human coronavirus (sHCoVs), influenza virus (IFV), respiratory syncytial virus (RSV), or human rhinovirus (HRV) across 15 cohorts. First, we identified an enhanced cellular immune response but limited interferon activities in SARS-CoV-2 infection, especially in asymptomatic cases. Se...
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!

3/ "The 3-gene signature offered two major improvements to SARS-CoV-2 infection triage: specificity and early diagnostic power. ...showed superior diagnostic performance only in SARS-CoV-2 ... achieved excellent diagnostic performance in Omicron patients ... showed exceptional performance to identify SARS-CoV-2 infection before detectable viral RNA on RT-PCR testing....  ... The bioinformatics methods, including DEGs and WGCNA, provided biological insights into the stable SARS-CoV-2 specific candidate genes. The machine learning approaches on these candidates offered a better extrapolation po...
Read 28 tweets
Jun 3
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!

1/many Endogenous Retroviruses are Dysregulated in ALS doi: 10.1016/j.isci.2024.110147  Amyotrophic Lateral Sclerosis (ALS) is a universally fatal neurodegenerative disease with no cure. Human endogenous retroviruses (HERVs) have been implicated in its pathogenesis but their relevance to ALS is not fully understood….. Using different methods of feature selection, including differential expression analysis and machine learning, we discovered that transcription of HERV-K loci 1q22 and 8p23.1 were significantly upregulated in the spinal cord of individuals with ALS. Additionally, we identified a subs...
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!

2/ Image
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).

3/ Visualization of gene structure from Wikipedia.  The structure of a eukaryotic protein-coding gene. Regulatory sequence controls when and where expression occurs for the protein coding region (red). Promoter and enhancer regions (yellow) regulate the transcription of the gene into a pre-mRNA which is modified to remove introns (light grey) and add a 5' cap and poly-A tail (dark grey). The mRNA 5' and 3' untranslated regions (blue) regulate translation into the final protein product.
Read 37 tweets
May 27
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.)

1/ SARS-CoV-2 Selectively Induces the Expression of Unproductive Splicing Isoforms of Interferon, Class I MHC, and Splicing Machinery Genes  A plethora of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), strategically manipulate the host’s RNA processing machinery to circumvent antiviral responses….. Our findings explore a suggested but uncharacterized mechanism, whereby SARS-CoV-2 infection induces the predominant expression of unproductive splicing isoforms in key IFN signaling, interferon-stimulated (ISGs), class I MHC, and splicing machinery gene...
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.

2/ SARS-CoV-2 Promotes Unproductive Splicing of Class I MHC Genes  Pathways associated with antigen presentation through class I MHC exhibited greater upregulation among unproductive isoforms compared to productive isoforms (Figure 2A)…. Genes encoding core class I MHC complex elements, such as B2M, HLA-A, and HLA-B, also displayed a higher unproductive fold change. The HLA-B gene revealed five distinct overexpressed retained intron isoforms in ACE2-MOI2.0 cells (Figures 2F and S2C). This upregulation of unproductive isoforms could potentially decrease HLA-B protein production in SARS-CoV-2-in...
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.

3/  Similarly, melanoma cells possess a mutation at the 5 ′ splice donor site of intron 2 of the HLA-A2 gene, causing the absence of the HLA-A2 antigen and likely protecting these cancerous cells from immune surveillance. Our findings indicate that SARS-CoV-2 infection may also lead to the loss of class I MHC antigens due to intron retention, potentially rendering infected cells incapable of presenting viral antigens to the immune system. Reduced expression of HLA-DR in monocytes represents a molecular hallmark of severe COVID-19. Other studies have demonstrated that SARS-CoV-2 ORF6 inhibits c...
Read 19 tweets
May 18
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/
The model using only the “top eight” symptoms predicted ME/CFS development most accurately. The top eight features are shown below in Table 2 along with the corresponding symptom domains:  1. Fatigue/extreme tiredness 2. Mentally tired after the slightest effort 3. Feeling unrefreshed after you wake in the morning 4. Minimum exercise makes you physically tired 5. Next-day soreness or fatigue after non-strenuous, everyday activities 6. Needing to nap daily 7. Dread, heavy feeling after starting to exercise  Excerpt from: Hua, Schwabe, et al. (2023). Predicting Myalgic Encephalomyelitis/Chron...
Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome from Early Symptoms of COVID-19 Infection  Highlighted portion of abstract: "Early symptoms, particularly those assessing post-exertional malaise, did predict the development of ME/CFS, reaching an accuracy of 94.6%. We then investigated a minimal set of eight symptom features that could accurately predict ME/CFS. The feature reduced models reached an accuracy of 93.5%. Our findings indicated that several IOM diagnostic criteria for ME/CFS occurring during the initial weeks after COVID-19 infection predicted Long COVID and t...
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…
SNP: rs9264942(C;C)  Description: 90% reduction in HIV viral load The rs9264942(C;C) genotype is reported to be associated with a 90% reduction in viral load in HIV-infected individuals. [] See also rs9264942 and HIV.
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?



3/ ncbi.nlm.nih.gov/gene/3107
HLA-C major histocompatibility complex, class I, C  "Class I molecules play a central role in the immune system by presenting peptides derived from endoplasmic reticulum lumen. They are expressed in nearly all cells. ... The HLA system plays an important role in the occurrence and outcome of infectious diseases, including those caused by the malaria parasite, the human immunodeficiency virus (HIV), and the severe acute respiratory syndrome coronavirus (SARS-CoV). The structural spike and the nucleocapsid proteins of the novel coronavirus SARS-CoV-2, which causes coronavirus disease 201...
Read 6 tweets
May 6
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…
Read 13 tweets
Apr 15
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!

1/ New Study on Systemic Inflammation and Bipolar Disorder: "Higher Seasonal Variation of Systemic Inflammation in Bipolar Disorder"  Dallaspezia, S., Cardaci, V., et al. (2024). “Higher Seasonal Variation of Systemic Inflammation in Bipolar Disorder.” International Journal of Molecular Sciences, 25(8). doi: 10.3390/ijms25084310
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!

2/ Figure 1. Changes in systemic inflammation across seasons in participants, divided according to diagnostic groups. Left: neutrophil to lymphocyte ratio. Right: systemic immune-inflammatory index. Points are means; whiskers are standard errors of the mean.
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!

3/ …clear seasonal effects in the pattern of recurrence of severe illness episodes and hospitalization in bipolar disorder (BD), with excess depressive and mixed episodes in autumn and spring, and mania in summer. Changes in mood… parallel to the effects of changes in the photoperiod…, with serotonin (5-HT) release increasing, and the serotonin transporter density decreasing, together with the amount of daily light,… and associated with the severity of depression in winter….  In recent years, an unprecedented amount of evidence has supported immunoinflammatory mechanisms as a point of converge...
Read 22 tweets

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