Most cases are generated in waves. It doesn't matter if the base false positivity rate is 100% "when prevalence is low" because positives when prevalence are low are not even a rounding error of total positives. PCR works fine.
The case against bacterial infections driving deaths is simple. People hospitalized for "Covid-19" were given antibiotics aggressively, to no benefit, and screened for bacterial infections aggressively, with very low positivity rates. So bacteria aren't important here. https://unglossed.substack.com/p/the-myth-of-secondary-infection-in
The actual results reported by Gao, et al. don't dispute this. First, ICU patients are being screened for bacterial infections. So nothing is being "missed," it is looked for aggressively. There is only a marginal increase in mortality for ICU patients that experience said infections. The bulk of deaths are therefore unrelated to bacterial infections.
And so he quotes:
"They concluded: 'These data suggest mortality associated with severe SARS-CoV-2 pneumonia is more often associated with respiratory failure that increases the risk of unresolving VAP and is less frequently associated with multiple-organ dysfunction.'"
Note that "that increases the risk of unresolving VAP" *doesn't mean* the "risk of unresolving VAP" is relevant to mortality, vs. "respiratory failure" qua respiratory failure. If VAP were the driver, the text would say as much. Instead the text is just stringing spurious associations together in absence of a real message. The virus killed via respiratory failure.
Rancourt is quoted all the time, best I can tell he doesn’t actually have anything to say.
I don’t remember where I used the phrase but the analogy is that a picture of a man watering his garden does not prove rain is not real. The “no pandemic” theorists just like to show pictures they found of men watering gardens. Maybe spring 2020 death spikes were care protocols. These are drop in the bucket to later recorded Covid deaths.
I've seen a few other people covering this, and so I finally decided to look at the paper. Just as you stated, it seems entirely confusing how they got their results.
For instance, when considering VAP did they differentiate pneumonia from SARS-COV2 vs VAP? The methods suggest that at least 48 hours on a ventilator with bacterial culturing were used to suggest a VAP episode:
". By definition, VAP was considered to be an incident pneumonia that was diagnosed by a BAL performed after at least 48 hours of mechanical ventilation (39); only VAP episodes that were adjudicated to be due to bacteria were included in the analysis. "
They don't provide any evidence of what bacteria they cultured, and the study does not appear to use SARS-COV2 ICU patients without ventilation as a frame of reference (the 190 included appeared to have had SARS-COV2-related pneumonia, although one can argue that the design of SCRIPT would inherently focus only on pneumonia so this group should be assumed to not be included).
So I'm struggling to see how they were able to fully differentiate SARS-COV2 pneumonia from VAP, but I suppose that's an issue with any VAP study. They also don't indicate specific timepoints for when BAL samples were collected, just stating they did "serial collection".
I tried skimming through the supplemental section but it doesn't seem to indicate the number of BAL samples collected. This sentence in the methods makes it seem as if they only collected samples at the time of a suspected episode of pneumonia, but does that mean they continued to take samples throughout the course of the infection:
"ICU physicians at NMH routinely obtain bronchoscopic or non-bronchoscopic BAL samples
from mechanically ventilated patients whenever pneumonia is suspected (47)."
Given that all of the correlations made by their software are dependent upon the data they provide it, I would assume that there's an inherent bias in these results that should be taken into great account.
I think the last thing I noticed so far is that they never mentioned anything related to actual quantitation of cytokine profiles. Their limitations actually mentions that they did not quantitate any inflammatory biomarkers, but rather it appears that they are making assumptions about a "cytokine storm" with respect to the transitions into worse groups. This would seem like a non-answer for anything for or against the cytokine storm argument. It just looks like they didn't take any approach at all and are just making qualitative assumptions.
I haven't spent more time with this paper but it seems like so much was left up to how the AI interpreted the results that I can't help but consider this a fishing expedition.
Everyone has to be in ICU for "severe pneumonia and respiratory failure" before they can qualify for VAP. "VAP" can only be a panel-positive BAL >48 after already being on ventilator (p1 of Supp 1); maybe this included some persistent infections for the 252 patients with bacterial pneumonia but overall it's probably accurate for infections "associated" with ventilator.
We already have studies showing that cytokines are relatively crickets-ville during severe infections and ICU, from back in 2020. And not one study supporting the myth with actual measurement of cytokines, just assumption quoting assumption. I put quote-marks around the claim in the title because what this study is, is the one that is saying the thing that is already true, and people are listening to it. Is it adding the most impressive new results? I think they're ok - enough to refute the author's own attempt to twist the conclusion regarding VAP.
For cytokine storm, (lack of) multi-organ failure as a proxy is entirely fair. It would be nice to have the raw data. They must have had access to neurological, renal, and shock metrics in order for the ML to incorporate those into states. Either way the ones that involve those have few patient-days.
I probably should have clarified more, but I was not feeling well today. Or maybe it's my lack of general coherence?
So I generally took the set-up for the study to include anyone who was put on ventilators, so those within the SARS-COV2 pneumonia group were also on ventilators. The issue becomes how they determine that VAP is occurring. The criteria of 48 hrs post-intubation plus a positive bacterial culture from a BAL sample acts more as a confirmatory test, as in they had to suspect VAP which led to collection of another BAL sample. The language appears to suggest that unless they suspect this on/off case of VAP they didn't collect additional BAL samples. If that's the case I'm curious how they determined who should be considered for BAL sample for VAP.
Also, Supplemental Figure 6 appears to be the only one to provide an outline of VAP incidences. It appears that they are associating it with a positive culture of methicillin-sensitive S. aureus. This appears to be the strain most-associated with VAP (strangely more than MRSA?)
With respect to cytokine storm, it's apparent that the language and use of the word "storm" is creating the same issues as "sin" for OAS. The researchers defined their assumption of cytokine storm with respect to multi-organ failure, and irrespective of how other studies define it as long as they lay out that it is cytokine storm based upon their definition. It does create issues that they didn't confirm this assumption with inflammatory biomarkers, and it adds issues if all of their correlations in their AI are based on BAL samples.
I think people are running away with the term "storm" in cytokine storm, and are applying to any indication of cytokine production or elevation. This is one of those issues of terms of art coming into common usage and being interpreted as something different than the intended definition, although the assumption with cytokine storm is that hyper-inflammation may lead to multi-organ failure.
I may do a bit of a write-up. I think your end assessment is correct in that the VAP deaths would have to be compared to non-VAP deaths, which aren't strikingly huge, but this is the only comparison that can be made as non-VAP but SARS-COV2 deaths are the baseline to work with. It'd be nice if they had non-intubated patients to compare with to see if intubation in general led to worse outcomes.
Ok right, forgot that was limited to ventilated + at least one BAL. So this is applying essentially a test-negative design within the nest of severe pneumonia + respiratory failure, they really were committed to the hypothesis.
I still don't see any reason to doubt the accuracy of the VAP designation. That seems to be taking a "what are they hiding" approach to the study's control groups, but the study isn't about the control groups, and we don't really care about them. Presumably for SARS-CoV-2 all VAP is true VAP, and you can compare them to VAP- to see that the authors' conclusions about the importance of VAP in SARS-CoV-2 are contrived, so you don't care about any details in the control VAP+ group.
Again, I am not very concerned with how rigorous their results are for cytokine storm. This is a headline-generator, which will force those who have voiced the prevailing narrative to show evidence supporting their narrative. They won't have any because it's just a big myth. So the big myth will get binned. Finally.
As it pertains to VAP diagnosis I don't have any issues. I suppose my main issue is figuring out how they determined an episode of VAP was occurring prior to the BAL sample. Some sort of symptom must have been present, in which case how did they differentiate symptoms of VAP from symptoms of SARS-COV2? Supplemental Figure 6 seems to suggest that "routine sampling" was more along the lines of "sample when suspected VAP". If it was routine, such as maybe every 3 days and they happened to catch VAP that would make sense, but given this sampling method I wonder if there's the chance they happened to miss some episodes of VAP. It also would suggest that the timing of VAP would not be accurate- we wouldn't know how long they had VAP.
Like you said, this probably wouldn't do much, but I suppose I just wanted to find holes so that I get a better understanding of the study as a whole.
I'll see what comes of the cytokine storm issue. A lot of my prior thoughts are being questioned so I'll see how things are playing out.
By chance, did you happen to look at the "spike in the brain" study?
I looked at it a bit, but had to consider it from the context of that Alzheimer's study I looked at previously and didn't get back to it. I was curious if you had any thoughts.
"Some sort of symptom must have been present," as in respiratory distress. Why assume that distinguishing from SARS-CoV-2 comes first? In "Myth of secondary infection" which was built off of your links, it was shown that use of antibiotics was rampant for Covid-19 hospitalizations, and co-infections were looked for when they weren't there (low + rate) https://unglossed.substack.com/p/the-myth-of-secondary-infection-in
So in ICU they could easily have looked for infections without any special prompts.
NL63 is an ACE-2 binding ubiquitous coronavirus and they should have used that as a control, instead of flu HA. And then you could say "SARS-CoV-2 spike is doing something different from NL63" or "same as NL63," otherwise, who knows what it means... I found https://www.biorxiv.org/content/10.1101/2023.01.15.524078v1
RE E protein more interesting as a lead for the etiology of neuro symptoms and brain fog
But aren't we already starting from the assumption that the SARS-COV2 intubated patients are already in respiratory distress? My question in distinguishing is more to look at how they became aware of VAP. The language suggests that they did not do routine testing so they couldn't hit on it by chance, and Supplemental Figure 6J doesn't seem like coincidence to me. So I'm just curious because the BAL sampling seems to be used for the modeling constructed by CarpeDiem, so I was curious in knowing how they were timing these samplings, that's all. I never argued against antibiotic use, and the language suggests that the lack of VAP clearance wasn't due to negligence but due to unknown circumstances that made the clearance of bacteria more difficult in a subset of patients (which they did not elaborate on). All of this is related specifically to this SCRIPT endeavor. I wouldn't doubt that other hospitals may have conducted more routine assessments irrespective of any prompt for VAP, it just appears that in the case of this study the researchers were looking for things to suspect VAP. But all of this is based on the fact that more data is not provided, including the timeline of clinical assessment for more than just one patient, which is honestly annoying.
I wasn't too confident in the assessment of the brain study. I think the main issue in histology reporting is inferring that the presence of the antigen within a designated location is related to the pathology. I don't think they provide any behavioral or neurological changes in the autopsies they examined, and to find "spike in the brain" seems more incidental. I think the report relating to Alzheimer's that I covered seems to suggest that changes in brain pathology may occur by targeting of the vascular endothelial without needing to invade the brain, so I'm trying to discern if spike in any organ may just be a red herring for endothelial dysfunction that can explain those symptoms as well.
Thank you - that is already included in my spike knowledge map. It is a frustrating paper because Alpha, Delta, the Omicrons, all of them take away the P. Sattar et al. could have used any of these spikes as a control so the reader doesn't have to put their results in the "here's another could-be thing" file...
So, the virus caused lung damage, which we can infer because their O2sats got real low, but that was likely because they were denied any meds to treat the virus.
Then they were hooked up to ventilators and lots of them developed secondary infections which then killed them.
Er - it does not sound like you have read the post. The conclusion section:
The new paper by Gao, et al. supports dumping both the myth of cytokine storm and unresolved secondary infections in in-hospital deaths. These result from severe lung injury and hypoxia induced by ventilation-perfusion mismatch, as proposed in TASD and the review of Archer, et al.
These people have no idea what they're talking about. Look at CRP of severe covid sufferers, driven predominantly by IL-6, TNF-alpha, and IL-1ẞ. I experienced it first-hand. Thank God for colchicine.
The ancient Egyptians did not have a concept for the tide, nor know where the water of the Nile came from, because both these things would have required observing the world beyond their lands.
Years ago, they were doing a study on ARDS (acute respiratory distress syndrome.) I don't know the difference with the SARS supposedly caused by the sars virus.
It was about high-dose intravenous vitamin c treatment.
Brian, do you know anything about this?
In particular, to your current knowledge, is it possible to stop viral replication by using megadoses of ascorbic acid or sodium ascorbate directly on the bloodstream?
One last question, if you don't mind. to your knowledge, is it possible to prevent the progression of the disease by the mechanism of preventing viral entry to non-infected cells?
A lot of viruses can be stopped a lot of different ways. The thing to keep in perspective is that cells already have a huge toolkit here of virus-disabling genes, which every successful virus has evolved to counteract. Early versions of SARS-CoV-2 could be disabled by interferon and have cellular entry prevented by interferon-induced membrane proteins. P681H, in Alpha and Omicron spike proteins, gets around this limitation.
Yes, humans can probably add novel molecules tailored to specific viruses, like Paxlovid for the SARS-CoV-2 nsp5 protease, that stop replication (temporarily in that case). But how much benefit can we expect, should be tempered by understanding that we already make tons of antiviral molecules in our own cells.
Regarding vitamin C, maybe it stops coronaviruses, but for whatever reason evolution chose to drop it in bats and apes / humans. However, coronaviruses still thrive just fine in animals that can make their own vitamin C, so it doesn't seem like a magic bullet.
It is interesting that Ivermectin is also a protease inhibitor but also seems to bind to the N protein, and thus stop progeny virion assembly, but also seems to block the activity of the S protein in some cases.
It's really a numbers game. If you can cut the production of new virions by some percentage and prevent infection of cells by some percentage you are going to be OK.
Basically even in the sickest and most comorbid of patients who actually died from covid, true myocarditis was a factor in less than 2% of deaths, whereas cardiac clotting and inflammation was a factor in ~50% of deaths.
I take this to mean that spike protein is basically bad for you, whatever the source. 🤔
Spike protein is a bioweapon, "whatever the source", BUT it is vastly higher in the Vaxxed! There have been virtually NO myocarditis deaths among natural infections. Essentially all of them are from the shots.
Does it matter what you call it? High levels of inflammation and very elevated markers of inflammatory cytokines/chemokines are characteristics of the early variants of SARS-CoV-2.
The first autopsies on COVID deaths uniformly revealed major blood clotting (micro & macro clots) in the lungs, quite capable of being the cause of the severe hypoxia observed in those patients. They didn't even need secondary bacterial infections/pneumonia. They suffocated to death because of severely impaired perfusion from the blocked circulation.
The markers aren't "very elevated." The studies looking at the markers in 2020 just shows them "elevated," nothing that exceeds flu - and why shouldn't they be elevated when fighting an infection? This does not mean inflammation is causing the damage; and fails to affirm the myth of cytokine storm. The only "support" for the myth comes from the assumptions made in advance of evidence.
"Enthusiasm for the use of immunomodulatory approaches in COVID-19 seems to derive in large part from clinical experience with cytokine release syndrome (CRS), a term frequently interchanged with cytokine storm. In the 2016 study of CRS by Maude and colleagues […] the peak plasma IL-6 level in patients who developed CRS was approximately 10 000 pg/mL—almost 1000-fold higher than that reported in severe COVID-19. […]"
"Circulating cytokines in COVID-19 patients, at least early in their clinical course, did not show widespread elevation. Most COVID-19 patients had either no elevation or only mild increases in the major proinflammatory cytokines including TNF-α, IL-1α, IL-1β, IFN-ɣ, etc"
Microclotting was extensive in severe cases, but will I think be replaced by the HPV-suppression model proposed by Archer, et al. as the main explanation for hypoxia. Blood has to be sent to the non-ventilated lung tissue by suppressing the reflex that normally shuts it away; this is more critical for explaining the low blood oxygen. If you just have clotting but blood is shunted then you don't have hypoxia https://unglossed.substack.com/p/the-virus-and-hpv
Oxygen toxicity and improper PEEP settings? Negative, even if intubation contributed to their deaths. Those folks who were improperly intubated early on were already hypoxic due to coagulopathy cascade induced by runaway complement hyperactivation. Look at the platelet-neutrophil axis.
Pathophysiological processes are associated with increased levels of hyperoxia-induced reactive O2 species (ROS) which may readily react with surrounding biological tissues, damaging lipids, proteins, and nucleic acids. Protective antioxidant defenses can become overwhelmed with ROS leading to oxidative stress. Activated alveolar capillary endothelium is characterized by increased adhesiveness causing accumulation of cell populations such as neutrophils, which are a source of ROS. Increased levels of ROS cause hyperpermeability, coagulopathy, and collagen deposition as well as other irreversible changes occurring within the alveolar space. In hyperoxia, multiple signaling pathways determine the pulmonary cellular response: apoptosis, necrosis, or repair. Understanding the effects of O2 administration is important to prevent inadvertent alveolar damage caused by hyperoxia in patients requiring supplemental oxygenation.
Oxygen, often used to treat hypoxemia in the clinical setting, 👉 is itself a triggering factor 👈 in HALI given that the exposure is sufficiently concentrated and of adequate duration.
The lung is a vulnerable target for oxidant-induced injury, initiating a cascade of protein signals that determine the cellular response. The alveolar epithelial and alveolar capillary endothelial surfaces are injured.
👇
Hyperpermeability, microthrombi (resulting from altered coagulation and fibrinolysis), collagen deposition, and fibrosis alter alveolar structure and function.
☝️
Understanding precise mechanisms of injury and pulmonary cellular responses to hyperoxia is essential evidence for expert practice.
Or are "they" just stupid? Based on my acquaintances and friends who are MDs, I'd say ego and group think can explain the covid tragedy. The paper Brian is discussing here, a pile of turgid bombast, is unfortunately fairly typical in medical literature.
Cytokine storm is real and has been discussed in ICU's before Covid. Release of chemicals in massive amounts causing massive inflammation. Inhalation breathing treatments greatly reduced the inflammatory response and kept many out of the hospital. Those who were hospitalized were usually past the massive viral replication phase and into the cytokine release phase but were not given high enough doses of steroids and the less effective steroids to boot.
Part of the whole problem to begin with is that "what happens in ICUs, stays in ICUs." Regardless, there are no studies showing cytokine storm in severe Covid-19 - cytokines are low. Citations and reviews in my linked TASD 1 post. As for steroid efficacy, it is what would be expected in severe lung injury, so I agree that hospitalization is too late to intervene. However, PCRs of lungs in autopsy show the virus RNA still present in lungs up to death
"Thus, the presence of viral RNA was only detected in less than 25% of the human serum samples, whereas all had multiple positive nasal swabs for SARS-CoV-2. Notably, we found viral RNA not only in lungs, but also in heart and kidney of deceased COVID-19 patients."
This may still be past the replication phase, as a new lung-slice ex vivo infection model study shows that RNA accumulates after replication stops
"At the second phase (48-96 h), while infectious virus production rapidly 17 decreases (Fig. 2A), viral RNA continues to accumulate"
If you look at the "example patient" in supplemental figure 8 of Goa, et al., BAL is SARS-CoV-2 positive on day 27.
So viral RNA is still everywhere, flooding lungs with viral proteins responsible for sabotaging HPV and causing hypoxia. This isn't a story about the immune system causing damage.
"CRP is a type I acute phase response protein synthetized in the liver and regulated by the pro-inflammatory cytokines IL-6, IL-1, and TNF-" . . . In other words, cytokines can result in markedly elevated CRP and high CRP can indicate high cytokines. My own experience of COVID during the summer of 2020 (probably the first Wuhan strain or close to it): four weeks post onset of COVID= sky high CRP of over 73 mg/l. but no symptoms of bacterial infection or other likely alternate cause. Eight months later when I retested, it was only about 1 mg/l. Even though cytokines weren't specifically tested, it was a strong possibility that they were the cause of the dramatically elevated CRP, with COVID the only realistic explanation.
Sure, but that would be consistent with persistent high inflammation in the post-injury healing phase. It isn't an after-image of a "storm" because CRP has such a short half-life, so no CRP from acute infection would still be around. Post-acute persistent high inflammation is consistent with vascular injury or inflammation cascades that take a while to settle down, akin to a short-tern-chronic inflammatory disease. It does not affirm the cytokine storm myth.
The presence of RNA is not at all indicative of replicable virions. PCRs will pick up fragments for an extended period and are meaningless. We basically had a Plandemic of PCR tests, not a virus!
Including in Australia, April 2020 - September 2021, 38 million tests but only 100,000 cases and 1,300 deaths? What was going on with the other 37.9 million tests in that time, that they were "pandemic"-ing like our tests were? I think the virus is a pretty important ingredient.
Another take that seems more reasonable:
https://popularrationalism.substack.com/p/missed-bacterial-pneumonia-cases
Most cases are generated in waves. It doesn't matter if the base false positivity rate is 100% "when prevalence is low" because positives when prevalence are low are not even a rounding error of total positives. PCR works fine.
The case against bacterial infections driving deaths is simple. People hospitalized for "Covid-19" were given antibiotics aggressively, to no benefit, and screened for bacterial infections aggressively, with very low positivity rates. So bacteria aren't important here. https://unglossed.substack.com/p/the-myth-of-secondary-infection-in
The actual results reported by Gao, et al. don't dispute this. First, ICU patients are being screened for bacterial infections. So nothing is being "missed," it is looked for aggressively. There is only a marginal increase in mortality for ICU patients that experience said infections. The bulk of deaths are therefore unrelated to bacterial infections.
And so he quotes:
"They concluded: 'These data suggest mortality associated with severe SARS-CoV-2 pneumonia is more often associated with respiratory failure that increases the risk of unresolving VAP and is less frequently associated with multiple-organ dysfunction.'"
Note that "that increases the risk of unresolving VAP" *doesn't mean* the "risk of unresolving VAP" is relevant to mortality, vs. "respiratory failure" qua respiratory failure. If VAP were the driver, the text would say as much. Instead the text is just stringing spurious associations together in absence of a real message. The virus killed via respiratory failure.
It seems very hard to get to the truth, or is it the case that so many are interested in muddying the waters?
https://peterhalligan.substack.com/p/denis-rancourt-there-was-no-c19-respiratory
Rancourt is quoted all the time, best I can tell he doesn’t actually have anything to say.
I don’t remember where I used the phrase but the analogy is that a picture of a man watering his garden does not prove rain is not real. The “no pandemic” theorists just like to show pictures they found of men watering gardens. Maybe spring 2020 death spikes were care protocols. These are drop in the bucket to later recorded Covid deaths.
Another interesting speculation about suddenly:
https://geoffpain.substack.com/p/atrial-fibrillation-is-the-most-common
However, this article suggests to me that there are multiple mechanisms relating to vaccinations and suddenly: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166549/pdf/pone.0283988.pdf
I've seen a few other people covering this, and so I finally decided to look at the paper. Just as you stated, it seems entirely confusing how they got their results.
For instance, when considering VAP did they differentiate pneumonia from SARS-COV2 vs VAP? The methods suggest that at least 48 hours on a ventilator with bacterial culturing were used to suggest a VAP episode:
". By definition, VAP was considered to be an incident pneumonia that was diagnosed by a BAL performed after at least 48 hours of mechanical ventilation (39); only VAP episodes that were adjudicated to be due to bacteria were included in the analysis. "
They don't provide any evidence of what bacteria they cultured, and the study does not appear to use SARS-COV2 ICU patients without ventilation as a frame of reference (the 190 included appeared to have had SARS-COV2-related pneumonia, although one can argue that the design of SCRIPT would inherently focus only on pneumonia so this group should be assumed to not be included).
So I'm struggling to see how they were able to fully differentiate SARS-COV2 pneumonia from VAP, but I suppose that's an issue with any VAP study. They also don't indicate specific timepoints for when BAL samples were collected, just stating they did "serial collection".
I tried skimming through the supplemental section but it doesn't seem to indicate the number of BAL samples collected. This sentence in the methods makes it seem as if they only collected samples at the time of a suspected episode of pneumonia, but does that mean they continued to take samples throughout the course of the infection:
"ICU physicians at NMH routinely obtain bronchoscopic or non-bronchoscopic BAL samples
from mechanically ventilated patients whenever pneumonia is suspected (47)."
Given that all of the correlations made by their software are dependent upon the data they provide it, I would assume that there's an inherent bias in these results that should be taken into great account.
I think the last thing I noticed so far is that they never mentioned anything related to actual quantitation of cytokine profiles. Their limitations actually mentions that they did not quantitate any inflammatory biomarkers, but rather it appears that they are making assumptions about a "cytokine storm" with respect to the transitions into worse groups. This would seem like a non-answer for anything for or against the cytokine storm argument. It just looks like they didn't take any approach at all and are just making qualitative assumptions.
I haven't spent more time with this paper but it seems like so much was left up to how the AI interpreted the results that I can't help but consider this a fishing expedition.
Everyone has to be in ICU for "severe pneumonia and respiratory failure" before they can qualify for VAP. "VAP" can only be a panel-positive BAL >48 after already being on ventilator (p1 of Supp 1); maybe this included some persistent infections for the 252 patients with bacterial pneumonia but overall it's probably accurate for infections "associated" with ventilator.
We already have studies showing that cytokines are relatively crickets-ville during severe infections and ICU, from back in 2020. And not one study supporting the myth with actual measurement of cytokines, just assumption quoting assumption. I put quote-marks around the claim in the title because what this study is, is the one that is saying the thing that is already true, and people are listening to it. Is it adding the most impressive new results? I think they're ok - enough to refute the author's own attempt to twist the conclusion regarding VAP.
For cytokine storm, (lack of) multi-organ failure as a proxy is entirely fair. It would be nice to have the raw data. They must have had access to neurological, renal, and shock metrics in order for the ML to incorporate those into states. Either way the ones that involve those have few patient-days.
I probably should have clarified more, but I was not feeling well today. Or maybe it's my lack of general coherence?
So I generally took the set-up for the study to include anyone who was put on ventilators, so those within the SARS-COV2 pneumonia group were also on ventilators. The issue becomes how they determine that VAP is occurring. The criteria of 48 hrs post-intubation plus a positive bacterial culture from a BAL sample acts more as a confirmatory test, as in they had to suspect VAP which led to collection of another BAL sample. The language appears to suggest that unless they suspect this on/off case of VAP they didn't collect additional BAL samples. If that's the case I'm curious how they determined who should be considered for BAL sample for VAP.
Also, Supplemental Figure 6 appears to be the only one to provide an outline of VAP incidences. It appears that they are associating it with a positive culture of methicillin-sensitive S. aureus. This appears to be the strain most-associated with VAP (strangely more than MRSA?)
With respect to cytokine storm, it's apparent that the language and use of the word "storm" is creating the same issues as "sin" for OAS. The researchers defined their assumption of cytokine storm with respect to multi-organ failure, and irrespective of how other studies define it as long as they lay out that it is cytokine storm based upon their definition. It does create issues that they didn't confirm this assumption with inflammatory biomarkers, and it adds issues if all of their correlations in their AI are based on BAL samples.
I think people are running away with the term "storm" in cytokine storm, and are applying to any indication of cytokine production or elevation. This is one of those issues of terms of art coming into common usage and being interpreted as something different than the intended definition, although the assumption with cytokine storm is that hyper-inflammation may lead to multi-organ failure.
I may do a bit of a write-up. I think your end assessment is correct in that the VAP deaths would have to be compared to non-VAP deaths, which aren't strikingly huge, but this is the only comparison that can be made as non-VAP but SARS-COV2 deaths are the baseline to work with. It'd be nice if they had non-intubated patients to compare with to see if intubation in general led to worse outcomes.
Ok right, forgot that was limited to ventilated + at least one BAL. So this is applying essentially a test-negative design within the nest of severe pneumonia + respiratory failure, they really were committed to the hypothesis.
I still don't see any reason to doubt the accuracy of the VAP designation. That seems to be taking a "what are they hiding" approach to the study's control groups, but the study isn't about the control groups, and we don't really care about them. Presumably for SARS-CoV-2 all VAP is true VAP, and you can compare them to VAP- to see that the authors' conclusions about the importance of VAP in SARS-CoV-2 are contrived, so you don't care about any details in the control VAP+ group.
Again, I am not very concerned with how rigorous their results are for cytokine storm. This is a headline-generator, which will force those who have voiced the prevailing narrative to show evidence supporting their narrative. They won't have any because it's just a big myth. So the big myth will get binned. Finally.
As it pertains to VAP diagnosis I don't have any issues. I suppose my main issue is figuring out how they determined an episode of VAP was occurring prior to the BAL sample. Some sort of symptom must have been present, in which case how did they differentiate symptoms of VAP from symptoms of SARS-COV2? Supplemental Figure 6 seems to suggest that "routine sampling" was more along the lines of "sample when suspected VAP". If it was routine, such as maybe every 3 days and they happened to catch VAP that would make sense, but given this sampling method I wonder if there's the chance they happened to miss some episodes of VAP. It also would suggest that the timing of VAP would not be accurate- we wouldn't know how long they had VAP.
Like you said, this probably wouldn't do much, but I suppose I just wanted to find holes so that I get a better understanding of the study as a whole.
I'll see what comes of the cytokine storm issue. A lot of my prior thoughts are being questioned so I'll see how things are playing out.
By chance, did you happen to look at the "spike in the brain" study?
https://www.biorxiv.org/content/10.1101/2023.04.04.535604v1.full
I looked at it a bit, but had to consider it from the context of that Alzheimer's study I looked at previously and didn't get back to it. I was curious if you had any thoughts.
"Some sort of symptom must have been present," as in respiratory distress. Why assume that distinguishing from SARS-CoV-2 comes first? In "Myth of secondary infection" which was built off of your links, it was shown that use of antibiotics was rampant for Covid-19 hospitalizations, and co-infections were looked for when they weren't there (low + rate) https://unglossed.substack.com/p/the-myth-of-secondary-infection-in
So in ICU they could easily have looked for infections without any special prompts.
NL63 is an ACE-2 binding ubiquitous coronavirus and they should have used that as a control, instead of flu HA. And then you could say "SARS-CoV-2 spike is doing something different from NL63" or "same as NL63," otherwise, who knows what it means... I found https://www.biorxiv.org/content/10.1101/2023.01.15.524078v1
RE E protein more interesting as a lead for the etiology of neuro symptoms and brain fog
But aren't we already starting from the assumption that the SARS-COV2 intubated patients are already in respiratory distress? My question in distinguishing is more to look at how they became aware of VAP. The language suggests that they did not do routine testing so they couldn't hit on it by chance, and Supplemental Figure 6J doesn't seem like coincidence to me. So I'm just curious because the BAL sampling seems to be used for the modeling constructed by CarpeDiem, so I was curious in knowing how they were timing these samplings, that's all. I never argued against antibiotic use, and the language suggests that the lack of VAP clearance wasn't due to negligence but due to unknown circumstances that made the clearance of bacteria more difficult in a subset of patients (which they did not elaborate on). All of this is related specifically to this SCRIPT endeavor. I wouldn't doubt that other hospitals may have conducted more routine assessments irrespective of any prompt for VAP, it just appears that in the case of this study the researchers were looking for things to suspect VAP. But all of this is based on the fact that more data is not provided, including the timeline of clinical assessment for more than just one patient, which is honestly annoying.
I wasn't too confident in the assessment of the brain study. I think the main issue in histology reporting is inferring that the presence of the antigen within a designated location is related to the pathology. I don't think they provide any behavioral or neurological changes in the autopsies they examined, and to find "spike in the brain" seems more incidental. I think the report relating to Alzheimer's that I covered seems to suggest that changes in brain pathology may occur by targeting of the vascular endothelial without needing to invade the brain, so I'm trying to discern if spike in any organ may just be a red herring for endothelial dysfunction that can explain those symptoms as well.
On a related subject, a paper was published suggesting that the S1 protein contains a nuclear localization signal and that the mRNA piggy backs on it.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9536038/
Thank you - that is already included in my spike knowledge map. It is a frustrating paper because Alpha, Delta, the Omicrons, all of them take away the P. Sattar et al. could have used any of these spikes as a control so the reader doesn't have to put their results in the "here's another could-be thing" file...
So, the virus caused lung damage, which we can infer because their O2sats got real low, but that was likely because they were denied any meds to treat the virus.
Then they were hooked up to ventilators and lots of them developed secondary infections which then killed them.
It that the real story?
Sorry late reply.
Er - it does not sound like you have read the post. The conclusion section:
The new paper by Gao, et al. supports dumping both the myth of cytokine storm and unresolved secondary infections in in-hospital deaths. These result from severe lung injury and hypoxia induced by ventilation-perfusion mismatch, as proposed in TASD and the review of Archer, et al.
Well, that is why I ask questions.
So, the virus causes lung damage if you don't treat it and that can cause you to die.
So, ignoring people until they turn purple was exactly the wrong thing to do.
These people have no idea what they're talking about. Look at CRP of severe covid sufferers, driven predominantly by IL-6, TNF-alpha, and IL-1ẞ. I experienced it first-hand. Thank God for colchicine.
Are you claiming that high levels of DAD do not cause high levels of CRP?
Do we have any data that correlates DAD levels with CRP levels?
This must be a bit of a joke, The cytokine storm is not real but covid is? Come on. How can anyone take this article seriously?
The ancient Egyptians did not have a concept for the tide, nor know where the water of the Nile came from, because both these things would have required observing the world beyond their lands.
I must remember that.
The ancient Egyptians did not have a concept of DAD or CRP because that would have required observing a world beyond their visability.
Off-topic but related.
Years ago, they were doing a study on ARDS (acute respiratory distress syndrome.) I don't know the difference with the SARS supposedly caused by the sars virus.
It was about high-dose intravenous vitamin c treatment.
Brian, do you know anything about this?
In particular, to your current knowledge, is it possible to stop viral replication by using megadoses of ascorbic acid or sodium ascorbate directly on the bloodstream?
One last question, if you don't mind. to your knowledge, is it possible to prevent the progression of the disease by the mechanism of preventing viral entry to non-infected cells?
Thhanks!
A lot of viruses can be stopped a lot of different ways. The thing to keep in perspective is that cells already have a huge toolkit here of virus-disabling genes, which every successful virus has evolved to counteract. Early versions of SARS-CoV-2 could be disabled by interferon and have cellular entry prevented by interferon-induced membrane proteins. P681H, in Alpha and Omicron spike proteins, gets around this limitation.
Yes, humans can probably add novel molecules tailored to specific viruses, like Paxlovid for the SARS-CoV-2 nsp5 protease, that stop replication (temporarily in that case). But how much benefit can we expect, should be tempered by understanding that we already make tons of antiviral molecules in our own cells.
Regarding vitamin C, maybe it stops coronaviruses, but for whatever reason evolution chose to drop it in bats and apes / humans. However, coronaviruses still thrive just fine in animals that can make their own vitamin C, so it doesn't seem like a magic bullet.
It is interesting that Ivermectin is also a protease inhibitor but also seems to bind to the N protein, and thus stop progeny virion assembly, but also seems to block the activity of the S protein in some cases.
It's really a numbers game. If you can cut the production of new virions by some percentage and prevent infection of cells by some percentage you are going to be OK.
Thank you.
The lungs were injured by the ventilators - hence the urgency to have more ventilators at the beginning of 2020
It was increased lung pressure and
oxygen toxicity that resulted in
Alveoli damage in 90%
Read my article
We breathe air not oxygen
And you’ll see lung physiology has no thing to do with oxygen and carbon dioxide gaseous exchange - and this gaseous belief retards medicine!
Research oxygen toxicity!
The lungs are hydrating the RBCs with salt water.
The oxygen red light monitoring is really just recording RBC hydration with light penetration
Dehydrated: contracted dense RBCs
Hydrated: plump bright RBCs
80% oxygenation is really 80% hydration or 20% dehydrated
Salt is the sponge
Water then follows
Reminds me of this study which got no attention attention in the media whatsoever:
Myocarditis is rare in COVID-19 autopsies: cardiovascular findings across 277 postmortem examinations
https://pubmed.ncbi.nlm.nih.gov/33132119/
Basically even in the sickest and most comorbid of patients who actually died from covid, true myocarditis was a factor in less than 2% of deaths, whereas cardiac clotting and inflammation was a factor in ~50% of deaths.
I take this to mean that spike protein is basically bad for you, whatever the source. 🤔
Spike protein is a bioweapon, "whatever the source", BUT it is vastly higher in the Vaxxed! There have been virtually NO myocarditis deaths among natural infections. Essentially all of them are from the shots.
Does it matter what you call it? High levels of inflammation and very elevated markers of inflammatory cytokines/chemokines are characteristics of the early variants of SARS-CoV-2.
The first autopsies on COVID deaths uniformly revealed major blood clotting (micro & macro clots) in the lungs, quite capable of being the cause of the severe hypoxia observed in those patients. They didn't even need secondary bacterial infections/pneumonia. They suffocated to death because of severely impaired perfusion from the blocked circulation.
The markers aren't "very elevated." The studies looking at the markers in 2020 just shows them "elevated," nothing that exceeds flu - and why shouldn't they be elevated when fighting an infection? This does not mean inflammation is causing the damage; and fails to affirm the myth of cytokine storm. The only "support" for the myth comes from the assumptions made in advance of evidence.
As reviewed here - https://unglossed.substack.com/i/101475744/the-myth-of-cytokine-storm
"Enthusiasm for the use of immunomodulatory approaches in COVID-19 seems to derive in large part from clinical experience with cytokine release syndrome (CRS), a term frequently interchanged with cytokine storm. In the 2016 study of CRS by Maude and colleagues […] the peak plasma IL-6 level in patients who developed CRS was approximately 10 000 pg/mL—almost 1000-fold higher than that reported in severe COVID-19. […]"
"Circulating cytokines in COVID-19 patients, at least early in their clinical course, did not show widespread elevation. Most COVID-19 patients had either no elevation or only mild increases in the major proinflammatory cytokines including TNF-α, IL-1α, IL-1β, IFN-ɣ, etc"
Microclotting was extensive in severe cases, but will I think be replaced by the HPV-suppression model proposed by Archer, et al. as the main explanation for hypoxia. Blood has to be sent to the non-ventilated lung tissue by suppressing the reflex that normally shuts it away; this is more critical for explaining the low blood oxygen. If you just have clotting but blood is shunted then you don't have hypoxia https://unglossed.substack.com/p/the-virus-and-hpv
Guess what causes micro clots in the alveoli
Oxygen toxicity and ventilators with too much pressure
They knew exactly what to do to increase deaths using ventilators
Oxygen toxicity and improper PEEP settings? Negative, even if intubation contributed to their deaths. Those folks who were improperly intubated early on were already hypoxic due to coagulopathy cascade induced by runaway complement hyperactivation. Look at the platelet-neutrophil axis.
Pathophysiological processes are associated with increased levels of hyperoxia-induced reactive O2 species (ROS) which may readily react with surrounding biological tissues, damaging lipids, proteins, and nucleic acids. Protective antioxidant defenses can become overwhelmed with ROS leading to oxidative stress. Activated alveolar capillary endothelium is characterized by increased adhesiveness causing accumulation of cell populations such as neutrophils, which are a source of ROS. Increased levels of ROS cause hyperpermeability, coagulopathy, and collagen deposition as well as other irreversible changes occurring within the alveolar space. In hyperoxia, multiple signaling pathways determine the pulmonary cellular response: apoptosis, necrosis, or repair. Understanding the effects of O2 administration is important to prevent inadvertent alveolar damage caused by hyperoxia in patients requiring supplemental oxygenation.
Source https://www.hindawi.com/journals/nrp/2011/260482/
You’ll need to read my Substack article
We breathe air not oxygen
To understand why oxygen is not part of our lung physiology
It’s the opposite of what our lungs are expecting
6. Conclusion
Oxygen, often used to treat hypoxemia in the clinical setting, 👉 is itself a triggering factor 👈 in HALI given that the exposure is sufficiently concentrated and of adequate duration.
The lung is a vulnerable target for oxidant-induced injury, initiating a cascade of protein signals that determine the cellular response. The alveolar epithelial and alveolar capillary endothelial surfaces are injured.
👇
Hyperpermeability, microthrombi (resulting from altered coagulation and fibrinolysis), collagen deposition, and fibrosis alter alveolar structure and function.
☝️
Understanding precise mechanisms of injury and pulmonary cellular responses to hyperoxia is essential evidence for expert practice.
Same source as above
https://www.hindawi.com/journals/nrp/2011/260482/
Or are "they" just stupid? Based on my acquaintances and friends who are MDs, I'd say ego and group think can explain the covid tragedy. The paper Brian is discussing here, a pile of turgid bombast, is unfortunately fairly typical in medical literature.
Cytokine storm is real and has been discussed in ICU's before Covid. Release of chemicals in massive amounts causing massive inflammation. Inhalation breathing treatments greatly reduced the inflammatory response and kept many out of the hospital. Those who were hospitalized were usually past the massive viral replication phase and into the cytokine release phase but were not given high enough doses of steroids and the less effective steroids to boot.
Right!
Part of the whole problem to begin with is that "what happens in ICUs, stays in ICUs." Regardless, there are no studies showing cytokine storm in severe Covid-19 - cytokines are low. Citations and reviews in my linked TASD 1 post. As for steroid efficacy, it is what would be expected in severe lung injury, so I agree that hospitalization is too late to intervene. However, PCRs of lungs in autopsy show the virus RNA still present in lungs up to death
https://www.medrxiv.org/content/10.1101/2023.03.29.23287591v1
"Thus, the presence of viral RNA was only detected in less than 25% of the human serum samples, whereas all had multiple positive nasal swabs for SARS-CoV-2. Notably, we found viral RNA not only in lungs, but also in heart and kidney of deceased COVID-19 patients."
This may still be past the replication phase, as a new lung-slice ex vivo infection model study shows that RNA accumulates after replication stops
https://www.biorxiv.org/content/10.1101/2023.04.18.537373v1
"At the second phase (48-96 h), while infectious virus production rapidly 17 decreases (Fig. 2A), viral RNA continues to accumulate"
If you look at the "example patient" in supplemental figure 8 of Goa, et al., BAL is SARS-CoV-2 positive on day 27.
So viral RNA is still everywhere, flooding lungs with viral proteins responsible for sabotaging HPV and causing hypoxia. This isn't a story about the immune system causing damage.
"CRP is a type I acute phase response protein synthetized in the liver and regulated by the pro-inflammatory cytokines IL-6, IL-1, and TNF-" . . . In other words, cytokines can result in markedly elevated CRP and high CRP can indicate high cytokines. My own experience of COVID during the summer of 2020 (probably the first Wuhan strain or close to it): four weeks post onset of COVID= sky high CRP of over 73 mg/l. but no symptoms of bacterial infection or other likely alternate cause. Eight months later when I retested, it was only about 1 mg/l. Even though cytokines weren't specifically tested, it was a strong possibility that they were the cause of the dramatically elevated CRP, with COVID the only realistic explanation.
Sure, but that would be consistent with persistent high inflammation in the post-injury healing phase. It isn't an after-image of a "storm" because CRP has such a short half-life, so no CRP from acute infection would still be around. Post-acute persistent high inflammation is consistent with vascular injury or inflammation cascades that take a while to settle down, akin to a short-tern-chronic inflammatory disease. It does not affirm the cytokine storm myth.
The presence of RNA is not at all indicative of replicable virions. PCRs will pick up fragments for an extended period and are meaningless. We basically had a Plandemic of PCR tests, not a virus!
Including in Australia, April 2020 - September 2021, 38 million tests but only 100,000 cases and 1,300 deaths? What was going on with the other 37.9 million tests in that time, that they were "pandemic"-ing like our tests were? I think the virus is a pretty important ingredient.