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!
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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...
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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!
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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!
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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!
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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."
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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.
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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...
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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!
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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*!
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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
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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?!
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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!"
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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
17/16
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!
18/16
2. Lots of things can cause lymphopenia! () It's just usually *temporary* with most non-HIV causes.
1. Like the HIV patients on death's door in the 90s, who are alive today thanks to HAART, recovery may be possible
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en.wikipedia.org/wiki/Lymphocyt…
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!
tl;dr: larger graph = more intense response
[Quoted tweet was referring to the graph]
22/16
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!
23/16
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
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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!
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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
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