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
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/
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/
One of the major limitations of this study is that it's unknown how applicable this signature will be for immunocompromised individuals. Why?
Because T cells were the major source of this 3-gene signature being expressed! This is important, because...
4/
This is YET ANOTHER study showing SARS-CoV-2 adversely impacts the immune system.
Monocyte abnormalities (decreases) were found in BOTH symptomatic and asymptomatic SARS-CoV-2 infections! Because monocytes INCREASE in normal immune response, this suggests monocyte infection!
5/
This study also found the same odd immune response patterns found by other studies: The immune system is STRONGLY activated (especially the inflammatory response), but the pathway responsible for signaling *targeted* attacks on infected cells is suppressed!
6/
As shown in Figure 2C, BOTH symptomatic and asymptomatic SARS-CoV-2 activate identical cellular pathways, but with less inflammatory signaling for asymptomatic infections.
That is, even asymptomatic SARS-CoV-2 impacts processes usually unaffected by the other studied viruses! 7/
This study strongly suggests that there are "distinct molecular mechanisms" at play during SARS-CoV-2 infections, relative to other common respiratory viruses.
It *unambiguously* shows, however, that even asymptomatic SARS-CoV-2 infections are NOT "just a cold." 8/
The authors validated their discovery with a longitudinal study that was able to detect even asymptomatic Omicron infections with high accuracy, long before a given patient is able to test positive with RT-PCR testing.
9/
That's all the highlights! The study is Open Access and available at
The rest of this thread is going to be commentary/analysis of the details of the study...
10/16mdpi.com/1999-4915/16/7…
So what role do these genes play?
It seems to be a cascade that highjacks the innate and adaptive immune responses in a way that's advantageous for the SARS-CoV-2 virus itself. That's not to say that the virus *directly* increases expression of these genes...
11/
Rather, these are the common product of the cascade of dysfunctional processes triggered by SARS-CoV-2 infection. This study identified a unique signature of *differentially expressed genes*, but there's not a 1:1 cause and effect for differential expression of a given gene!
12/
The methods were thorough, in that they cross-validated all of their findings multiple ways to ensure they weren't picking up on some spurious signal in the data. Even if the genes turn out not to be meaningful for *pathogenesis*, they're VERY meaningful for *diagnosis*!
13/
IMO, there's one big error. Figures 2A and 2B have slightly different Y-axes, likely because the graphs were generated separately, but it actually has the effect of shrinking a range that is *unexpectedly* larger.
I aligned the scales on Figures 2A and 2B here
14/
When symptomatic and asymptomatic gene expression for each virus are put side by side, it's clear that SARS-CoV-2 has a wildly different pattern compared to the other viruses, and a vastly larger magnitude of effect.
Differential expression INCREASES in asymptomatic covid?!
15/
Most notably, T cells are the PRIMARY type of cell where the 3-gene signature is most differentially expressed... and it's specifically a pattern that will lead to T cell exhaustion through overactivation.
Say it with me: "COVID is airborne and exhausts T cells!"
16/end
Afterthought: The bit about “discovery should include not only SARS-CoV-2 infections but also other respiratory infections” is an echo of another paper about HCoV-OC43… from 1980! There, the author also complained about lack of dataset diversity
I’m not sure if it would, because at least one of the genes is involved in one type of cell entry, and there’s evidence that persistent infections may use *different* methods to move between cells that possibly wouldn’t engage that gene!
Simply put, if the cause of dysregulation is removed, the immune system can *likely* recover.
Time is the enemy, in this case! Cancer is a huge concern here, because without immune cells, cells with defective DNA will be ignored and grow into tumors
20/16
Opportunistic infections are the biggest concern with a compromised immune system (lack of defenses), but when an individual has effectively zero immune system, the body isn't able to perform basic janitorial tasks that clean up random defective processes!
21/16
Sure! Here's a meta-annotated version of the graph with simplified explanations of each element. The graph itself is fairly noisy, but the takeaways are simple!
Lack of symptoms may not even be because of immune system *destruction*! Symptoms of cold and flu are driven by interferon signaling, which SARS-CoV-2 suppresses.
But the end result is the same: lack of effective immune response!
The immune system has a vast range of functions spread across different systemic and cellular mechanisms.
It's likely that there are many people walking around with a compromised innate immune system, who don't realize it as leftover adaptive defenses fight infections
24/16
This discovery seems to have a clear path to commercialization, because this discovery is purely a new method of *analyzing* the results of existing types of Nucleic Acid Amplification Tests (NAAT), including RT-PCR and LAMP testing. It's software!
The advantage here is that, rather than requiring detection of a specific viral protein (which may be present in the body but not the swab location), it requires detection of elevated levels of HOST PROTEINS that indicate active viral infection!
26/16
Here's the entire thread about the article "A T-Cell-Derived 3-Gene Signature Distinguishes SARS-CoV-2 from Common Respiratory Viruses," on a single page for easier sharing: readwise.io/reader/shared/…
[Caveat: This doesn’t apply to people trying supplements as *treatment*]
Supplements will have no effect. The deficiencies associated with severe covid/LC are likely a product of the infection itself, because the virus is dysregulating the production processes
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/
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/
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)
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
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/
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.)
1/
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/
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!
1/
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/
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!