[Pestilence] https://youhavetoliveyour.life/

The Something Awful Forums > Discussion > C-SPAM > [Pestilence] https://youhavetoliveyour.life/

(Thread IKs: PoundSand)

Fur20: Nov 14, 2007; すご▞い！
君は働か░い
フ▙▓ズなんだね！

Oracle posted:

Yeah wastewater is a very kind of rule of thumb guideline and rather crappy (no pun intended) when you consider a single person has been responsible for like 90%+ of wastewater detected virus in no less than three separate metropolitan areas now.

it turns out that specific individuals are, in fact, full of poo poo

# ? Aug 21, 2023 22:21

Adbot: ADBOT LOVES YOU

# ? May 10, 2024 16:01

The Oldest Man: Jul 28, 2003

Re, trusting doctors chat, a close relative of mine was on vacation when she had a trip-and-fall incident and was taken by paramedics to the nearest level 2 trauma center. They gave her ketamine since there was some worry about a head injury, which it turned out later was superficial but I guess they were worried about her hurting herself during transport. The fact that she was out of her gourd on k will become important momentarily. Anyhoo, at the hospital, she was operated on and given what her PCP and regular orthopedic dr are pretty sure was an unnecessary orthopedic surgery that put her in PT for the following 6 months. She was consented for this while still on ketamine and before her husband or emergency contact were there; when they showed up she was already in surgery. A number of complaints were filed (the board, medicare, etc.) but nothing was done about it and while a lawsuit was discussed, wouldn't you know it but the hospital happened to lose her pre-op x-rays at some point and tldr her lawyer advised her she very well might lose a lawsuit and end up eating the costs so she dropped it.

tldr you should always talk to a healthcare professional before taking medication. On the other hand, maintaining a self-defensive skepticism when interacting with the healthcare system (particularly in the US and particularly when you are outside the bubble of major metro areas with academic hospitals) as a whole - doctors included - is also very warranted. There are no guarantees that anyone in this system is operating with your best interests as priority #1 at all times and lots of perverse incentives trying to see that they don't, and that's before even considering how far outright quackery like vaccine refusal (and hcq and ivermectin for covid) has penetrated into mainstream medicine.

Rosalind posted:

Still, I am going to continue posting from my perspective as long as I am welcome to do so. I can't promise I'll never argue, but I recognize that people here mean well and we're all just trying to stay healthy in a deeply hosed up world.

part of the crew part of the ship

# ? Aug 21, 2023 22:22

Phigs: Jan 23, 2019

Corrigenda posted:

That is really concerning!

Anyway, I'm very off base per the replies. My apologies if I said things wrong or in an unkind edit:manner. I don't want this thread to get shutdown, and it just appeared to be retreading ground that lead to the reopening of the SAD thread.

One thing that is rough about this thread is that a lot has been said over the years so some of those things are just left unrepeated when regulars talk to each other, which can make it hard for a new person to parse exactly what is being said.

Definitely something we should try to improve on I think. It's something common to megathreads but I think it impacts this thread's helpfulness a bit. It's fine if a megathread is just for shitposting about Trump or some poo poo.

# ? Aug 21, 2023 22:24

Pingui: Jun 4, 2006; WTF?

Rosalind posted:

Thank you. I apologize for being a bit harsh in my replies as well.

You know a week ago I thought this thread shouldn't exist. I no longer believe that. It's generally benign and I think most people here are posting genuinely and considerately. I came in here expecting to be driven out with pitchforks and torches but mostly people are chill.
(..)

Glad you are enjoying yourself, despite stepping into the proverbial lions den

Also thank you for the Nebraska data!

# ? Aug 21, 2023 22:26

Gunshow Poophole: Sep 14, 2008; OMBUDSMAN
POSTERS LOCAL 42069; Clapping Larry

Phigs posted:

One thing that is rough about this thread is that a lot has been said over the years so some of those things are just left unrepeated when regulars talk to each other, which can make it hard for a new person to parse exactly what is being said.

Definitely something we should try to improve on I think.

yeah I think the OP could be put to use in this regard, because in a lot of places a response to a new poster of "read the OP" is seen as flippant and dismissive. here it coudl be a useful shortcut?

there's a lot of posting fatigue as the regular posters who have relitigated things over, and over, and over for the last four years kinda struggle to reorient their tone to the (I mean this non-derogatorily) naivete of people who haven't done that. or those who are new to the generally-accepted feeling of abandonment and cybernetic capitalism that pervades these discussions.

tbf honestly most of the earnest first-time posters who mention they or their family popped hot have been welcomed and helped with little issue.

# ? Aug 21, 2023 22:27

NeonPunk: Dec 21, 2020

A college just reinstated mask mandates on campus.

https://twitter.com/CovidDataReport/status/1693468249709523308

# ? Aug 21, 2023 22:27

StratGoatCom: Aug 6, 2019; Our security is guaranteed by being able to melt the eyeballs of any other forum's denizens at 15 minutes notice

Yeah, we should make a thread policy of extending friendliness to new people.

# ? Aug 21, 2023 22:28

Lib and let die: Aug 26, 2004

Gunshow Poophole posted:

yeah I think the OP could be put to use in this regard, because in a lot of places a response to a new poster of "read the OP" is seen as flippant and dismissive. here it coudl be a useful shortcut?

there's a lot of posting fatigue as the regular posters who have relitigated things over, and over, and over for the last four years kinda struggle to reorient their tone to the (I mean this non-derogatorily) naivete of people who haven't done that. or those who are new to the generally-accepted feeling of abandonment and cybernetic capitalism that pervades these discussions.

tbf honestly most of the earnest first-time posters who mention they or their family popped hot have been welcomed and helped with little issue.

you forget the contingent of people that have become completely numb to feeling of abandonment and cybernetic capitalism and are thus neither shocked nor despaired at a capitalist society's ability to handle or manage a public health crisis, op

# ? Aug 21, 2023 22:29

fosborb: Dec 15, 2006; Chronic Good Poster

Oracle posted:

Yeah wastewater is a very kind of rule of thumb guideline and rather crappy (no pun intended) when you consider a single person has been responsible for like 90%+ of wastewater detected virus in no less than three separate metropolitan areas now.

I'm extremely skeptical of that Twitter user who attempts to estimate COVID case counts from waste water. I look at it as directional only and watch hospitals if I need to make any sort of Personal Health Decisions

# ? Aug 21, 2023 22:31

Poppers: Jan 21, 2023

Shiroc posted:

sweating profusely about whose credentials win between the historian and the doctors discussed this tangentially related good article about the history of diy trans healthcare

https://thebaffler.com/salvos/doctors-who-gill-peterson

Jules ftw

# ? Aug 21, 2023 22:34

Oracle: Oct 9, 2004

NeonPunk posted:

A college just reinstated mask mandates on campus.

https://twitter.com/CovidDataReport/status/1693468249709523308

drat, in Atlanta even. Wonder how long it'll take for them to be brigaded by gun-toting muh freedum parents.

# ? Aug 21, 2023 22:34

JAY ZERO SUM GAME: Oct 18, 2005; Walter.
I know you know how to do this.
Get up.

lmao that to get an idea of covid trends in our loving hellworld requires you to monitor half a dozen different sources of statistics of varying accuracy/timeliness/reliability along with looking for people in the public sphere posting "wow covid again huh"

# ? Aug 21, 2023 22:35

fosborb: Dec 15, 2006; Chronic Good Poster

Boba Pearl posted:

please don't probe me for saying this, I know I'm an enemy in this thread, but I legitimately don't think the covid thread changed my avatar to my address, I would like that to be said publicly, because I know how it looks. I have a stalker who is obsessed with me, and I don't even really think it has anything to do with SomethingAwful.

yeah gently caress that av change. velkyn blanked the first two I believe. multiple mods are watching if it happens again, and if you have plat, a PM will email and buzz my phone immediately

# ? Aug 21, 2023 22:36

The Oldest Man: Jul 28, 2003

Boba Pearl posted:

I legitimately don't think the covid thread changed my avatar to my address

I will come and say outright there are a lot of things I wish I could talk about more openly here that I don't because they contain information that is too personally identifying and I know there are a bunch of hosed up weirdos waiting in the wings to dox people either to ruin the posting climate or to own their enemies and it's super hosed up that happened to you

# ? Aug 21, 2023 22:38

The Oldest Man: Jul 28, 2003

JAY ZERO SUM GAME posted:

lmao that to get an idea of covid trends in our loving hellworld requires you to monitor half a dozen different sources of statistics of varying accuracy/timeliness/reliability along with looking for people in the public sphere posting "wow covid again huh"

I just want this dashboard (https://kingcounty.gov/depts/health/communicable-diseases/disease-control/influenza.aspx) to have covid on it along with all the other communicable respiratory viruses and it is cartoonishly evil that reporting positivity and case rates have become casualties of the public health back-to-normal death drive

# ? Aug 21, 2023 22:40

Lib and let die: Aug 26, 2004

The Oldest Man posted:

I will come and say outright there are a lot of things I wish I could talk about more openly here that I don't because they contain information that is too personally identifying and I know there are a bunch of hosed up weirdos waiting in the wings to dox people either to ruin the posting climate or to own their enemies and it's super hosed up that happened to you

I got my avatar changed to a picture of my face when I said it would be anti-worker for Joe Biden and the Democrats to bust up a rail strike in d&d lmao

# ? Aug 21, 2023 22:41

Pingui: Jun 4, 2006; WTF?

Lib and let die posted:

I got my avatar changed to a picture of my face when I said it would be anti-worker for Joe Biden and the Democrats to bust up a rail strike in d&d lmao

This sounds bad, until you realize lald is Italian Elon Musk.

# ? Aug 21, 2023 22:43

The Oldest Man: Jul 28, 2003

Lib and let die posted:

I got my avatar changed to a picture of my face when I said it would be anti-worker for Joe Biden and the Democrats to bust up a rail strike in d&d lmao

hosed up weirdo or democratic party operative tho

# ? Aug 21, 2023 22:43

Lib and let die: Aug 26, 2004

The Oldest Man posted:

hosed up weirdo or democratic party operative tho

What's the difference

# ? Aug 21, 2023 22:44

Pingui: Jun 4, 2006; WTF?

Lib and let die posted:

What's the difference

There is actually substantial difference between C-SPAM and D&D.

# ? Aug 21, 2023 22:45

Parity warning: Nov 1, 2009; 3rd Place, TRP Sack Race 2021/22

Corrigenda posted:

the reopening of the SAD thread.

lol that was always gonna happen literally no matter how the "reboot" went

# ? Aug 21, 2023 22:54

mahler_biryani: Jan 28, 2023

Sunny Side Up posted:

this loving sucks and godspeed on every front. hopefully no long term issues.

Thank you! It really sucks that there is nothing I can do for the kid except suppress the symptoms. At least us grown ups have a chance with paxlovid.

# ? Aug 21, 2023 22:55

CGI Stardust: Nov 7, 2010; Brexit is but a door,
election time is but a window.

I'll be back

Insanite posted:

https://twitter.com/zalaly/status/1693640539537555921?s=20

this is all good, then, right, assuming that you're rooting for the virus?

*shaking fist* goddamnit Al-Aly!! you've done it again!!

quote:

Overall, the findings show that while risks of many (but not all) postacute sequelae decline and become nonstatistically significant over time, the decline is less pronounced among those who were hospitalized in the acute phase of infection. The findings highlight the substantial cumulative burden of health loss due to PASC and call for attention to the care needs of people with long-term health effects due to SARS-CoV-2.

quote:

Taken together the findings suggest that the risk horizon for postacute sequelae after SARS-CoV-2 infection is prolonged even among nonhospitalized individuals and is further prolonged among hospitalized individuals�highlighting the importance of reducing risk of hospitalization among people with SARS-CoV-2 infection (and reinfection) as a means to reduce the risk of long-term health loss.

want to give this more of a thorough read. guess we'll see the same criticism of this as of all his other VA-based studies - older population, probably not in fantastic health to start with, predominantly male; may have been people in the "healthy" cohort who had COVID but didn't test positive (or didn't report it); long-term infection effects may vary by variant, vaccination status, treatment quality etc. and this study lumps them all togther (although it does try to correct for some of this afaict from a quick skim)

but: there are some pretty pictures for the thread!

if i'm reading this right - 7% of non-hospitalised infections, 31% of hospitalised infections cause PASC, which seems to be about in line with other estimates. DALY is Disability-Adjusted Life Year, the amount of healthy life "lost" by the symptom.

NS (grey) means non-significant; not sufficiently different from the controls. kind of intrigued by the significant (albeit small) increase in dysautonomia

CGI Stardust has issued a correction as of 23:07 on Aug 21, 2023

# ? Aug 21, 2023 22:57

Bastard Tetris: Apr 27, 2005; L-Shaped; Nap Ghost

The Oldest Man posted:

I will come and say outright there are a lot of things I wish I could talk about more openly here that I don't because they contain information that is too personally identifying and I know there are a bunch of hosed up weirdos waiting in the wings to dox people either to ruin the posting climate or to own their enemies and it's super hosed up that happened to you

Yiiiiikes, I don�t know if it was from this thread but some hosed up weirdo came to my lab a year or two ago and posted a facebook live of him ranting about weird poo poo while security crowded around him.

Be normal, internet!

# ? Aug 21, 2023 22:58

tristeham: Jul 31, 2022

StratGoatCom posted:

Hahahha, I started like you, we'll have you shopping for a secure click yet. Welcome to the thread and enjoy your crack ping.

# ? Aug 21, 2023 23:06

Platystemon: Feb 13, 2012; BREADS

The Oldest Man posted:

Just doubling down on it being nbd would be a lot easier for me to understand than what he's actually doing which is:

1. Saying he thinks it's worth trying to not get it.
2. Saying it's worth it for him personally to try not to get it.
3. Outlining this very complicated risk management calculus he says he's following to avoid getting it.
4. All of that doing absolutely gently caress-all and getting it because somehow his finely-tuned risk management swiss watch didn't tell him getting into a crowded elevator without an n95 on might be a bad idea.
5. Suffering significant, painful, potentially fatal consequences.
6. Doubling down not on "the disease is nbd" but on the risk management rube goldberg machine.

If he didn't think it was a problem to get COVID he would jettison the entire risk management framing and just do whatever he wants with no qualms like everybody else is. Instead what he's doing is the same net outcome (doing whatever) but wrapping it in a zillion layers of nonsense risk management that has obviously failed him multiple times, and that's the part I don't get.

Bob Wachter is the funniest comedian in Northern California.

# ? Aug 21, 2023 23:09

Troutful: May 31, 2011

StratGoatCom posted:

We've got transmission of loving malaria in the mainland US again, loving malaria. If that thing gets back in, we'll never be rid of it.

We're capable of getting rid of Anopheline mosquitoes in the US without DDT. Don't know if we have the political will to do it but it's not a technical impossibility.

Did you know we completely eradicated this disease-causing fly in the mid-1900s without pesticides or habitat destruction? I'm bullish on insect control, it's much easier than controlling viruses.

# ? Aug 21, 2023 23:11

fosborb: Dec 15, 2006; Chronic Good Poster

Troutful posted:

I'm bullish on insect control, it's much easier than controlling viruses.

effective M99 mask

# ? Aug 21, 2023 23:14

Pingui: Jun 4, 2006; WTF?

fosborb posted:

effective M99 mask
(..)

Mosquitos aren't airborne.

# ? Aug 21, 2023 23:17

Sunny Side Up: Jun 22, 2004; Mayoist Third Condimentist

mahler_biryani posted:

Thank you! It really sucks that there is nothing I can do for the kid except suppress the symptoms. At least us grown ups have a chance with paxlovid.

yeah it's not like you can game the system somehow. we got into a vax trial to get our toddler the pfizer vax early, and we got him masking at 20 months, but once they get it, what do you do?

hmmm maybe there's a joke in here about causing the covidomor by hoarding beets. where is calibananabal

# ? Aug 21, 2023 23:17

Platystemon: Feb 13, 2012; BREADS

fosborb posted:

effective M99 mask

Gonna need to see an RCT on this, buddy.

Dr. Loeb will set up a large RCT where participants are instructed to wear as loosely as the model in the the product photo, and his lovely study will constitute the foundation of the gold‐standard Cochrane review.

Troutful posted:

We're capable of getting rid of Anopheline mosquitoes in the US without DDT. Don't know if we have the political will to do it but it's not a technical impossibility.

Did you know we completely eradicated this disease-causing fly in the mid-1900s without pesticides or habitat destruction? I'm bullish on insect control, it's much easier than controlling viruses.

Fake news.

The screw worm (a persecuted native species. :smith:

) was not eradicated, merely eliminated from North America north of the isthmus of Panama.

# ? Aug 21, 2023 23:18

Lib and let die: Aug 26, 2004

Roller Coaster Tycoon rules

# ? Aug 21, 2023 23:20

JAY ZERO SUM GAME: Oct 18, 2005; Walter.
I know you know how to do this.
Get up.

random fun question: anyone have a PCP in NYC that still wears a mask/thinks about covid? I called this afternoon to book my annual and asked about masks; no one wears them anymore

...together with some other things (he's never asked me to fast before my annual bloodwork, something that a couple of other people, including my PA friend, thought was bizarre), I'm thinking i'm in the market for a new primary physician.

# ? Aug 21, 2023 23:20

bedpan: Apr 23, 2008

JAY ZERO SUM GAME posted:

random fun question: anyone have a PCP in NYC that still wears a mask/thinks about covid? I called this afternoon to book my annual and asked about masks; no one wears them anymore

...together with some other things (he's never asked me to fast before my annual bloodwork, something that a couple of other people, including my PA friend, thought was bizarre), I'm thinking i'm in the market for a new primary physician.

are you getting cholesterol checked? lithium levels? bloodsugar?

# ? Aug 21, 2023 23:21

16-bit Butt-Head: Dec 25, 2014; Can't post for 5 hours!

please listen to your doctors covid thread

# ? Aug 21, 2023 23:22

Sunny Side Up: Jun 22, 2004; Mayoist Third Condimentist

ibid posted:

"First, some introduction in order to better understand the premise and the findings of this work:

In the last 3 years, an exhaustive amount of research has been carried out to elucidate the precise events that directly cause progression of COVID from an early mild acute illness in the first few days, to a severe/fatal form in a subset.

Two specific early events key to such progression have been identified: The first key event identified is the early interaction between SARS-CoV-2 and megakaryocytes (MKs) in the bone marrow. PMID: 36920790, 35708858

If MKs are infected by SARS-CoV-2, the patient is anticipated to progress to severe COVID in the ensuing days. Vice versa, if MKs remain uninfected, the patient is expected to experience a mild course and recover. PMID: 35708858

The other key event that is thoroughly well-established to drive severe COVID is: The early production of a distinct form of antibody against the spike protein ("afucosylated") that delivers a double blow to the host ... PMID: 33361116

This distinct anti-spike IgG antibody: (1) Does not neutralize SARS-CoV-2 (2) And instead, triggers and directly drives the immune-mediated pathology of severe COVID

It goes without saying that upon infection with SARS-CoV-2, our immune system tries to produce antibodies against proteins of this virus, including the spike protein, with one goal: To neutralize and clear the infection. And this happens without deviation in a majority

However, not all antibodies targeting the spike protein are created equal in COVID. Anti-spike IgGs come in two forms in this disease, with dire consequences for the patient.

Multiple studies have shown this phenomenon. That the *quality* of antibodies produced early on in response to SARS-CoV-2 spike protein differs between individuals, and this variation determines the fate of the patient. PMID: 33361116, 33979301, 35040666

In fact, the detection of a distinct form of anti-spike IgG *early* in the illness accurately predicts who progresses to severe disease in the ensuing days, and who doesn�t progress and experiences only a mild illness.

So how is this variability in the anti-spike IgGs defined? Understanding this requires a brief background on antibody structure first:

IgG antibody structure comprises of: (1) antigen-binding region (�Fab�), where antigens such as spike protein are recognized and bound, and �

In the Fc regions of IgG, there are specific sites (at Asparagine 297) where modifications called �glycosylation� can change the inflammatory capability of each IgG.

For instance, the addition of a �fucose� moiety to this site on the Fc region would create a less inflammatory IgG. 90% of all IgGs in humans are formed this way, containing a fucose moiety, and referred to as �fucosylated� IgGs.

On the other hand (and of relevance to COVID), the lack of fucose in the Fc region of IgG, brings about an *intensely* inflammatory quality to the antibody. IgGs lacking fucose (�afucosylated� IgGs) have a 100-fold *higher* affinity for the FcyRIlla receptors on immune cells.

This translates into an extremely intense activation of monocytes, macrophages, NK and dendritic cells � all of which are then recruited to attack the antigen recognized and bound by the antibody

Less than 10% of human IgGs encountered are afucosylated, as these afucosylated IgGs are intensely inflammatory and can cause severe immune-mediated pathology.

Our immune system relies on fucosylated IgGs � with much lower inflammatory quality than the afucosylated ones � to respond to a vast majority of infectious pathogens

However, afucosylated responses are found in response to specific situations. Infections with enveloped viruses such as SARS-CoV-2, dengue virus, and HIV can be associated with afucosylated IgG production against viral antigens

Afucosylated IgG responses are also seen in reaction to foreign antigens on blood cells such as platelets. PMID: 24243971

In the case of COVID, multiple prominent studies have demonstrated the detection of afucosylated IgGs against the spike protein in severe COVID. PMID: 33361116, 33979301

These studies have also shown that not only afucosylated anti-spike IgGs are present in severe COVID, but also � their presence is an early predictor and a direct driver of progression to severe COVID.

In two prospective cohorts of outpatients with early COVID who underwent blood draws ... the detection of these afucosylated IgGs against the spike protein was shown to determine the fate of these individuals later on.

Those with an early production of afucosylated anti-spike IgG detected on, for instance day 5 of illness as outpatient, reliably progressed to severe COVID on subsequent days, whereas � On the other hand, the patients ...

... who only formed normally fucosylated IgGs against the spike protein experienced only a mild course and recovered

The timing of antibody formation mattered too. In those who progressed to severe disease, the afucosylated (and non-neutralizing) IgGs were formed prior to the normally fucosylated (and neutralizing) IgGs against the spike protein.

Something � somehow � pushed these unfortunate individuals to form a non-neutralizing and pathogenic afucosylated response against the spike protein � And these pathogenic antibodies were formed much earlier than the neutralizing ones that clear the virus.

Mechanistically, these studies also clearly show how the formation of these afucosylated anti-spike IgGs are key drivers of the immune-mediated pathology in severe COVID �

Recall that lack of fucose in the anti-spike IgGs triggers an intense activation of monocytes, macrophages, NK and dendritic cells � all targeted any and all tissue harboring the spike protein

In other words, these afucosylated IgGs order our own immune system to most ferociously attack and eliminate any trace of spike protein in the body.

The only problem becomes that � the spike protein is broadly expressed on the cell surface of many infected human tissues during COVID. And our own body becomes the collateral damage to our immune system�s reaction by way of these afucosylated IgGs

This is why in severe COVID, most successful therapeutics are immune-modulators such as steroids, JAK/STAT inhibitors, anti-TNFs, etc.

These afucosylated responses are *not* unique to severe COVID. We�ve seen them before. They also drive severe dengue. PMID: 31765380, 34083490

Dengue virus also happens to another enveloped RNA virus like SARS-CoV-2, that also infects bone marrow megakaryocytes like SARS-CoV-2.

In addition to these, afucosylated responses are also seen in HIV, but this time, they act in a beneficial fashion by conferring improved viral suppression. HIV is yet another enveloped virus that not only infects MKs, but also ...

... uses MK infection as a reservoir to cause persistence despite patients taking highly-active antiretroviral therapy. PMID: 32188724

We thought there may be a pattern here, perhaps. And naturally, this is where shaping of our hypothesis began. Is there a relationship between enveloped viruses infecting MKs, and this infection causing afucosylated responses toward antigens of these enveloped viruses?

What do we know about the contexts and antigens that are associated with afucosylated responses? Owing to a comprehensive study by Larsen et al. (PMID 33361116), we know that ...

Afucosylated responses can occur in response to a limited set of stimuli including � (1) Enveloped virus antigens (2) Alloantigens on surface of platelets (3) Alloantigens on surface of RBCs

In contrast (bottom row): (1) Soluble proteins (2) Bacterials antigens, and (3) Non-enveloped virus antigens are not known to cause afucosylated responses � and instead form the typical fucosylated IgGs only.

To dig deeper � In the case of enveloped viruses, not all viral proteins are known to trigger afucosylated responses. Larsen et al. have demonstrated that the location of the viral protein matters. Surface expression is the differentiator.

Surface proteins of enveloped viruses can cause afucosylated responses. An example of a surface protein would be the spike protein of SARS-CoV-2. In contrast, viral proteins without any surface expression do not induce afucosylated responses.

Larsen et al. showed in the case of severe COVID patients, afucosylated IgGs are only detectable against the spike protein (has surface expression) � Whereas very little to no afucosylated IgGs are formed against the nucleocapsid protein (no surface expression).

We also know that afucosylated responses are seen in response to foreign antigens expressed on the surface of platelets. This is best illustrated in the case of a fetal platelet disorder called FNAIT. PMID: 24243971

Further refining our hypothesis based on these lines of evidence � We began to wonder whether ... SARS-CoV-2 can infect platelets and pathogenically embed its spike protein on the surface of platelets ➡️leading to an afucosylated response and the associated immunopathology.

But we hit a roadblock there. Several prominent studies clearly show that platelets are infected by SARS-CoV-2 during COVID. None, however, were able to visualize evidence of spike protein expression on the surface of platelets.

I even pursued personal communication with the authors of these studies over the last 2 years, who confirmed that �

... although the spike protein was found in the cytoplasm of infected platelets, and such finding was highly predictive of severe disease progression, no evidence of spike protein expression was found on the surface of platelet membrane

So, our attention switched to platelet progenitors, megakaryocytes, to explore our suspicion about the spike protein expression on the surface of these cells.

Multiple human studies thus far have established that SARS-CoV-2 infects MKs in the bone marrow (all in postmortem samples of bone marrow)

wo studies in particular demonstrated that not only SARS-CoV-2 infects MKs, but also � The viral infection of bone marrow MKs � similar to the case of afucosylated anti-spike IgGs � was an early predictor of progression to severe COVID. PMID: 36920790, 35708858

Strikingly, virus-infected MKs were shown to transfer viral antigens including the spike protein (red) to emerging platelets during differentiation to proplatelets and platelets (Fortmann et al.)

What was not explored in this study was whether the spike protein is specifically expressed on the surface of resultant platelet progenitors emerging from the virus-infected MKs.

Such finding � similar to platelet alloantigens encountered in FNAIT � would provide a plausible pathway by which afucosylated IgGs form against the spike protein.

Moreover, thus far no group has explored the possibility of whether virus-infected bone marrow MKs may be the key trigger for the production of the pathogenic afucosylated IgGs against the spike protein.

These two questions formed the basis of our study. The schematic below summarizes the four parts of our hypothesis.

Based on the described hypotheses, experiment was designed as depicted in this diagram

After obtaining IRB and approval from ethics committee, human bone marrow megakaryocytes were isolated from hospitalized subjects who were in the early days of experiencing severe COVID.

Subsequently, human bone marrow MKs were isolated from the bone marrow aspirate. PCR confirmed the infection of bone marrow MKs by SARS-CoV-2 in these living donors in early stage of severe COVID

Next � Virus-infected MKs were grown and allowed to differentiate under favorable conditions and assessed for evidence of spike protein expression on the surface of resultant platelet progenitors.

Proplatelets emerging from the virus-infected MKs were labeled to identify their periphery (α-tubulin, green) and to identify any evidence of spike protein (red). Indeed, we found the spike protein expressed on the surface of virus-infected proplatelets!

We then pursued our second question. Virus-infected human bone marrow MKs were injected intravenously to transgenic mice harboring human ACE2 to see whether it triggers the formation of fucosylated IgGs against the spike protein.

First: We found that injection of virus-infected human MKs into transgenic mice significantly promoted the formation afucosylated IgG antibodies against the spike protein To our knowledge, this is the 1st instance of afucosylated IgGs detection against a viral antigen in vivo.

Second: The mortality rate in the infected mice was proportional to the level of afucosylated anti-spike IgG produced.

This finding suggests that the afucosylated anti-spike IgG antibodies were pathogenic and contributed significantly to the severity of COVID-19 in mice - as is the case in humans.

Third: The plasma levels of PF4 and serotonin, as soluble markers of platelet activation and/or granule release, were significantly higher in the infected mice compared with the uninfected mice.

Lastly, and perhaps most importantly: Injection of virus-infected MKs into the circulation of these mice (without inhalation of the virus) mimicked the lung pathology seen in human cases of severe COVID:

Inflammatory cell infiltrate in the lung, followed by clot formation in the pulmonary vascular lumen, and distortion of the lung tissue.

In summary, to the best of our knowledge, this is the first study that demonstrates direct evidence that bone marrow megakaryocytes are infected early on by SARS-CoV-2 in those experiencing severe COVID.

Additionally, to the best of our knowledge, this is the first study that demonstrates proplatelets express SARS-CoV-2 spike protein on the surface of their membranes during differentiation from virus-infected human MKs. This surface expression of spike protein matters �

... as it likely explains the context within which our immune system decides to switch gears and form highly inflammatory afucosylated antibodies against the spike protein.

In millions infected by this virus, the immune response follows a predictable pattern. Virus infects the respiratory tract. Immune system reacts in a typical fashion, and forms neutralizing fucosylated antibodies against the spike protein. Virus clears. Acute disease resolves

In a subset who progress to severe COVID, the antibody response is atypical � and actually causes disease progression. Our proposed mechanism is that in these instances, the virus likely breaches the respiratory tract, reaches the bloodstream, and infects the bone marrow MKs.

As the virus infects MKs, and expresses the spike protein on the surface of emerging proplatelets, the immune system senses a much more 🔥dangerous situation. Body�s own circulating blood cells are now infected � beyond the respiratory tract, beyond the oropharynx

The infection of circulating blood cells is likely a highly alarming 🚨context to the immune system. To combat viral spread now aided by far-reaching infected platelets, a most potent inflammatory reaction is called into action by creating afucosylated IgGs against spike protein

This leads to an intense FcyRIlla-mediated activation of monocytes, macrophages, NK and dendritic cells systemically, attacking every tissue harboring spike protein. That is, unfortunately, a large part of body's tissues, including the vasculature, lung, neural tissue, etc.

... causing widespread immuno-thrombosis, and immune-mediated injury to vasculature, lungs, blood-brain barrier, nervous system, and other tissues in the body.

In summary, we provide preliminary evidence that SARS-CoV-2 infects human bone marrow megakaryocytes, and this infection of megakaryocytes is directly responsible for triggering the immune-mediated pathology of severe COVID

We acknowledge that this is a preprint, and has not been peer-reviewed. We also acknowledge that we have a significant amount of future work left to be done to better characterize the preliminary findings described in this work.

If your group has expertise in glycobiology, please consider reaching out to us as we are open to collaboration to decipher the detailed mechanisms of the findings in this work.

We appreciate your patience in reading through this long thread. And we encourage you to read our preprint below for further details.

Lastly, we would like to thank the entire team of Dr. Younes Zaid @ZaidYounes9, and acknowledge the generous funding by Balvi and @VitalikButerin to allow us to continue our work."

https://nitter.net/farid__jalali/status/1683707701866692608

https://www.biorxiv.org/content/10.1101/2023.07.14.549113v2

Fascinating. Not the complete story, yet, but hopefully more research illuminates the relationship between microclots and mitochondrial attack, fatigue, hyperclotting, viral reservoirs, bone marrow attack, and immune system disregulation/severe activation.

# ? Aug 21, 2023 23:24

icantfindaname: Jul 1, 2008

16-bit Butt-Head posted:

please listen to your doctors covid thread

The American way is that I pay service workers to perform services for me

# ? Aug 21, 2023 23:26

Lib and let die: Aug 26, 2004

Pingui posted:

There is actually substantial difference between C-SPAM and D&D.

I was implying there's no difference between hosed up weirdos and democrat party operatives

# ? Aug 21, 2023 23:27

NeonPunk: Dec 21, 2020

16-bit Butt-Head posted:

please listen to your doctors covid thread

Rude. You're assuming that everyone has access to a personal doctor that they can talk to.

# ? Aug 21, 2023 23:28

Adbot: ADBOT LOVES YOU

# ? May 10, 2024 16:01

Bastard Tetris: Apr 27, 2005; L-Shaped; Nap Ghost

Sunny Side Up posted:

Fascinating. Not the complete story, yet, but hopefully more research illuminates the relationship between microclots and mitochondrial attack, fatigue, hyperclotting, viral reservoirs, bone marrow attack, and immune system disregulation/severe activation.

Yep, one of the many reasons PASC has a lot of similarities to ME/CFS and other autoimmune issues, I�m blanking on the poster but they had an awesome series in the old thread about the lengths certain groups went to paint ME/CFS as malingering so patients suffering from it would have their benefits cut off.

# ? Aug 21, 2023 23:30

The Something Awful Forums > Discussion > C-SPAM > [Pestilence] https://youhavetoliveyour.life/

«‹›624 »