Don't blame your lack of ability to control yourself thus getting banned, then lying about it, on other people. That's all on you baby. #BeBetter
COVID-19 Pandemic: Transmissions, Deaths, Treatments, Vaccines, Interventions and More...
- Thread starter Richie O
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Don't blame your lack of ability to control yourself thus getting banned, then lying about it, on other people. That's all on you baby. #BeBetter
Yes it’s BS..not even close to be truthful
$12 billion in damage too....its not based on any science and no reputable medical organization would publish it
yet its out there and being retweeted for all to see like its fact....yeah the guy comes on the tv and tells you what to think..the sheep buy it...those who question are ahead of the game
yet its out there and being retweeted for all to see like its fact....yeah the guy comes on the tv and tells you what to think..the sheep buy it...those who question are ahead of the game
Except when you quote fake news sources for answers every day. You're not even actually playing the game. It's more like you're the kid playing Trivial Pursuit with a group of parents and adults who make up questions you'll know the answers to so you feel like you belong. But you don't actually belong at that particular adult table.
what does this have to do with the study. Its complete garbage and politically motivated, that its being spread throughout twitter as if true is more proof that the coronavirus is completely political at this point.
Hope this isn’t serious.
www.statnews.com
AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction in participant in the U.K.
AstraZeneca's Covid-19 vaccine study has been put on hold due to a suspected adverse reaction in participant in the U.K.
www.statnews.com
I’m aware that there is a lot of fake news these days but on what basis do you claim this is fake news??
not to mention the $12 billion in costs is totally made up based on no records of hospitalizations....these guys will peddle their fear on Anderson Cooper tonight, perhaps the believers can emerge from their basements and be brave enough to turn the television sets on...but wear your masks you may not know if a Karen is peering into your window ready to report you to the pandemic authorities
This is why we do phase III trials, although trial halts are not that unusual in the vaccine world - no need for major concern at this point. What is unusual is 7 billion people following clinical trials.Hope this isn’t serious.
AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction in participant in the U.K.
AstraZeneca's Covid-19 vaccine study has been put on hold due to a suspected adverse reaction in participant in the U.K.
Ha, agree. Hopefully it’s nothing, but hate to see any delays at this point.
Have been struggling with the Oak Ridge paper (that the Medium article above is based on) and another paper by a couple of prominent cardiologists, which just came out in the journal Circulation (by the American Heart Association), which seems somewhat complementary, but somewhat contradictory to the Oak Ridge one. And on top of that, there's a recent commentary in JAMA, by some Dutch doctors, saying the "cytokine storm" (over-inflammation reaction from the immune system), which many have said is key to the death spiral in many patients, doesn't really occur in COVID patients, which kind of supports the Oak Ridge paper, but is not in complete agreement with the Circulation paper (although they weren't investigating the inflammatory part of the system). Clearly, there's still some confusion out there amongst the medical experts on what exactly is going on with COVID, especially at the cellular level and how that impacts macro-level patient outcomes.
I think what the Oak Ridge folks are saying is that there is an incredibly complex cascade of effects once the virus enters both lung and vascular endothelial cells, via the ACE2 (angiotensin converting enzymes) pathway, eventually leading to wild swings in the RAS system (renin-angiotensin system), which induce similar effects in the related bradykinin system, leading to "bradykinin storms" featuring massive buildup of bradykinin in the body, leading to many of COVID's deadly effects. At one point, they do say, “the pathology of Covid-19 is likely the result of Bradykinin Storms rather than cytokine storms,” which had been previously identified in Covid-19 patients, but that “the two may be intricately linked.” They also mention that this can lead to increased production of hyaluronic acid (HLA, a molecule that can trap 1000X its weight in water) in the lungs. forming a "hydrogel," and according to the paper, once this happens, “it’s like trying to breathe through Jell-O.”
The Circulation paper makes the case that while COVID is obviously a respiratory disease, at its heart (pun intended) it's more of a microvascular disease: "We propose that severe COVID-19 is a microvascular disease in which coronavirus infection activates endothelial cells, triggering exocytosis, a rapid vascular response that drives microvascular inflammation and thrombosis." This paper goes through a ton of clinical data on progression of the disease, especially in blood vessel epithelial cells, host to countless ACE2 receptors, and talks about how that can lead to the "cytokine storms" and ARDS (acute respiratory distress syndrome), but due to the underlying vascular issues. I would imagine "bradykinin storms" which are part of the vascular system would be consistent with their research (it's just not a detail they looked into, I think).
The Dutch paper was aimed specifically at trying to measure cytokines for patients in the "cytokine storm" phase of severe COVID disease, but their findings were that they didn't really see highly elevated levels of cytokines. As per the authors, "The results from this study show that COVID-19 is not characterized by a cytokine storm....the severe disease observed in critically ill COVID-19 patients is therefore not explained by strongly elevated levels of inflammatory proteins in the blood. This means that critically ill COVID-19 patients likely will not benefit from specific anti-cytokine therapies." Obviously, there are all kinds of systemic effects leading to serious illness and death in many COVID patients, but maybe those aren't driven by a cytokine storm.
I'll admit confusion here. Might be time to "phone a friend," lol. Maybe one of our medical/immunology folks can help make more sense of this (and correct any major errors I might have above). @LETSGORU91 @93RUDoc @RUfubar @UMRU?
A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm
Gene expression analysis reveals a novel, integrated molecular mechanism for much of the pathogenesis of COVID-19 that provides therapeutic intervention points that can be addressed with existing approved pharmaceuticals.elifesciences.org
Does the COVID-19 cytokine storm exist? - Research may have an impact on the chances of success of a specific treatment
4 September 2020www.radboudumc.nl
Not a one-size-fits-all disease. Not all have typical cytokine release syndrome or storm. Differing immune responses give different disease trajectories and implications for treatment. The immune system seems to be confused and not only is there different storms at different times but different other tornadoes and cyclones are coming in all different times. These are the gurus out of Yale who have defined 3 phenotypes of disease
Longitudinal analyses reveal immunological misfiring in severe COVID-19 - Nature
A longitudinal analysis of immune responses in patients with moderate or severe COVID-19 identifies a maladapted immune response profile linked to severe disease.www.nature.com
Perfect timing. Today's In the Pipeline blog by Derek Lowe is all about the bradykinin hypothesis. He acknowledged this is not his area of expertise, but his perspective was that it was certainly plausible. He does have a ton of expertise, though in drug discovery and development, so he has a nice write-up of potential pharmaceuticals (mostly existing ones) to address this biological cascade at different key points.
AAAS
blogs.sciencemag.org
Also, here's a very early paper (April) which an MD friend of mine on FB posted, which first mentioned both bradykinins and cytokines. Wish I understood this stuff more, lol.
https://www.preprints.org/manuscrip...nu7uM6uXjRb6wDA5AOx-RAeP8qH_zg9P49SjUOumKO2BM
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Politics thats how
Someone can always twist data for their intended narrative to send the Karens into a frenzy today
There have been roughly 900k cases in the United States since the end of Sturgis (8/16) so we are to believe that over 1 in 4 cases in the last 3.5 weeks came from one event/site, and in spite of that, we've seen a steady decrease in 7dma of daily new cases anyway?
Lets actually believe this study for a minute for giggles..where is the superspread of hospitalizations and deaths
One death tied so far
One death tied so far
Hard to believe this one completely. Cases in South Dakota, which one would think would be hardest hit, have only gone up by 6000 since the rally - find it really hard to believe that nearly 25% of the 1.1MM case increase in the US from 8/7 to 9/2 were due to this rally. Holding the rally without much distancing/masking was dumb and irresponsible and likely led to tens of thousands of cases, but 263,000 just sounds high like a significant overestimate of cases resulting from it, to me, especially given the methodology used. Just my two cents - would like to see what some other epidemiologists say about the model used by the authors.
Edit: just to be clear, they may be right and my "assessment" may be wrong. The case increases from 8/7 (start of the rally) to 9/2 (study end date) in SD and all of its neighboring states total up to 58,000: 6000 in SD, 6000 in ND, 19,000 in IA, 16,000 in MN, 7000 in NE, 3000 in MT, and 1000 in WY.
I don't think anyone is saying anywhere near all of those cases are from Sturgis, although on the other hand, roughly 72% of the attendees appear to have been from outside of this 6-state SD area (based on cellphone pings) and COVID rates did go up in many of the counties with large numbers of attendees.
My issue isn't with the attempt to determine the number of infections stemming from this, but is more that there really isn't much actual "data" of actual contact A being infected leading to contacts B-L being infected for many transmission chains. The entire exercise is a modeling exercise. I would have felt much better if they published ranges of potential infections, denoting the likely high uncertainty range around the 266K infected number.
My gut still tells me their number is probably at least 2X too high but this is where we need other experts in the epidemiology field to weigh in and I'm sure some will. Regardless of the number, I'm sure it's still pretty high and the event never should have been allowed, especially with the reports of very little distancing/masking at both indoor and outdoor events and bars, restaurants, etc.
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You would have to believe 19% from August 2nd to September 2nd.
I mostly agree but most of the population including the workers are not from South Dakota.
I am waiting for the spike from the 4th of July celebration in South Dakota from the open air outdoor event with no masks..oh wait nevermind
It happens all the time. People getting excited about early good reports is fools gold.Hope this isn’t serious.
AstraZeneca Covid-19 vaccine study put on hold due to suspected adverse reaction in participant in the U.K.
AstraZeneca's Covid-19 vaccine study has been put on hold due to a suspected adverse reaction in participant in the U.K.
Most Sturgis visitors aren't from South Dakota. So to say that event is responsible isn't accurate.
Just saw this on Twitter. I wonder how often this happens in trials, doesn’t sound ideal.
I edited my post to add some more details - still think it's high, but need to hear more from other experts...
Below is what the Times said...sounds like the system is working as it's supposed to and the investigation needs to look into whether the serious adverse event (reportedly spinal inflammation) was vaccine related or not. Most vaccines have rare serious side effects (usually less than 1 in 1 million people), so if it's vaccine related, it could be an issue, but most of the time it's simple coincidence, as it's hard not to have a few out of 30K people in a trial not getting sick. In longer trials for chronic conditions (not vaccines usually, i.e., for things like diabetes or high blood pressure), there are often patients who die and those have to be closely compared for the treatment and the placebo groups.
https://www.nytimes.com/2020/09/08/health/coronavirus-astrazeneca-vaccine-safety.html
A person familiar with the situation, who spoke on the condition of anonymity, said that the participant who experienced the suspected adverse reaction had been enrolled in a Phase 2/3 trial based in the United Kingdom. The individual also said that a volunteer in the U.K. trial had received a diagnosis of transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections. However, the timing of this diagnosis, and whether it was directly linked to AstraZeneca’s vaccine, is still unknown.
Transverse myelitis can result from a number of causes that set off the body’s inflammatory responses, including viral infections, said Dr. Gabriella Garcia, a neurologist at Yale New Haven Hospital. But, she added, the condition is often treatable with steroids.
AstraZeneca declined to comment on the location of the participant and did not confirm the diagnosis of transverse myelitis. “The event is being investigated by an independent committee, and it is too early to conclude the specific diagnosis,” the company said. Some said the company’s halt was evidence that the process was working as it should.
“At this stage, we don’t know if the events that triggered the hold are related to vaccination,” said Dr. Luciana Borio, who oversaw public health preparedness for the National Security Council under Mr. Trump and who was acting chief scientist at the F.D.A. under President Barack Obama. “But it is important for them to be thoroughly investigated.”
As an aside, most clinical trials of non-vaccines fail due to efficacy (57%) with only 17% failing due to safety (22% for commercial reasons). I haven't found similar data for vaccines, but I know from my work in the field that vaccines fail at an even lower rate for safety issues, although almost all vaccines have minor to moderate side effects (injection pain, mild fever, headaches, etc.), since they're affecting one's immune system on purpose and the body responds to the "invader" as it should.
Publication of Drug Failures in Late-Stage Clinical Development
This study assesses factors associated with regulatory approval or reasons for failure of investigational therapeutics in phase 3 or pivotal trials and rates of publication of trial results.
jamanetwork.com
They really try to latch on to anything to fit into their narrative 🗿
Another great update on the vaccine landscape by Derek Lowe today in his In The Pipeline blog in Science Translational Medicine. He's done several updates on individual vaccines over the past month or two, but this is his first comprehensive update in almost two months. He does a very nice job going through all the various vaccine categories and candidates in each category, with significant focus on the 9 in phase III and others already in early clinical trials. The NY Times also has a nice vaccine tracker, which is visually better organized than Lowe's effort and it contains a nice overview of the vaccine development process, but it's not nearly as detailed around the science of the vaccines. Lowe also has embedded links to all of his more in-depth blogs on individual vaccines and animal/human results to date.
Science | AAAS
Coronavirus Vaccine Tracker (Published 2022)
A look at all the vaccines that have reached trials in humans.www.nytimes.com
I'm not going to try to repeat the discussions in either link, other than to say that we're really getting down to brass tacks soon, with the pivotal phase III trial results likely only about 2 months away and while I'm optimistic we'll have an approved vaccine by the end of the year (been saying that since April), I think people talking about approvals by the end of October are kidding themselves, given how much data are being generated and how much there will be to review prior to approval. I have listed the 10 vaccines in phase III, below for easy reference and all of them have had reasonably good safety profiles and implied efficacy (prompting good immune responses), so far, meaning no major red flags, but obviously in smaller phase II trials w/o any data on conferring immunity yet.
Keep in mind that all of the vaccines in phase II or III right now will require an initial shot and then a booster shot (typically a month later) to achieve optimal immunity, with the exception of the J&J (Janssen) vaccine which is looking at a single shot. Some of the vaccines that are a few months behind the frontrunners, like Novavax and the Merck/Themis vaccine are looking at single shots and possibly greater immunity levels. Also, remember that the FDA is saying a vaccine is "effective" if it can "prevent disease or decrease its severity in at least 50% of people who are vaccinated," so it's possible efficacy will look similar to the flu vaccine (although most experts expect much greater than 50% protection).
In addition, here are a few more interesting links on some key issues for these vaccines. The first one is another Lowe blog entry, this time on what exactly "cold chain" means for vaccine stability, supply chains, and availability, especially in the 3rd world. The 2nd one is also a Lowe blog, on what can sound like a mundane topic, but it really isn't, as it's on things like ensuring there are enough glass vials or silica-coated vials for billions of doses and ensuring that the vials used are gas tight (a key for stability), which is no trivial task. I've done a lot of work in both of these areas over the years for new pharmaceuticals and they're not as "sexy" as the actual product, but if mishandled, they can derail an entire product launch.
- Moderna's mRNA vaccine; no mRNA vaccine has ever been approved before; requires -20C cold chain (freezers)
- Pfizer/BioNTech's mRNA vaccine - requires -70C cold chain for stability of the formulation (dry ice storage typically - probably not a huge issue in first world countries, but a major issue elsewhere)
- Astra Zeneca/Oxford's chimp adenovirus viral vector vaccine (only 1 vvv has been approved - Merck's Ebola vaccine)
- CanSino's human adenovirus viral vector vaccine; human adenoviruses might have pre-existing immunity issues
- J&J's human adenovirus viral vector vaccine (using an obscure human virus, hoping to avoid the pre-existing immunity issues); this one starts phase III any day now, so I included it.
- Russia's Gamaleya Institute's human adenovirus viral vector vaccine (already "approved" in Russia - a PR stunt)
- There are three Chinese vaccines using "old school" deactivated actual coronavirus (most vaccines in use today use this approach, but it's much harder to scale and often less potent, but it works usually); two of these also have "emergency use approvals" without phase III data, which is just dumb.
- The last one is an oddball. It's a trial of the existing Bacillus Calmette-Guerin vaccine for tuberculosis in Australia.
Science | AAAS
Science | AAAS
Lastly, we should talk at least a bit about rumors of premature approvals or emergency use without appropriately vetted safety and efficacy data. Clearly, there is immense pressure to get some great vaccines out there as quickly as possible without cutting important corners (as there should be with lives at stake every day). My sincere hope is that this should be a moot point if the scientists at Warp Speed, NIH, FDA, etc. are making the decisions and I liked what I've heard from both Fauci and Slaoui (Warp Speed scientific lead) lately with regard to them not cutting corners to meet any artificial deadline (election day, for example) - if something is safe and effective by then, great, but if it's not, we wait for that day. The only thing I could see happening "early" is a potential "emergency use authorization" for early use in highly vulnerable people (health care workers in locations with outbreaks). I simply can't imagine this being "approved" for the public before full data on safety and efficacy are available from phase III trials. It would simply be monumentally stupid - and there's no way many would participate. We're not Russia or China.
Science | AAAS
www.sciencemag.org
Top Adviser To Operation Warp Speed Calls An October Vaccine 'Extremely Unlikely'
Dr. Moncef Slaoui, chief adviser to the administration's effort to develop a COVID-19 vaccine, said having a vaccine by next month was "not impossible." But a longer timetable appears more likely.www.npr.org
Edit: I liked reading that the Pfizer and Merck CEO's both came out and said their companies simply won't consider filing for approval for a vaccine without having completed a successful phase III trial. That is excellent news for vaccine safety and efficacy.
https://www.livemint.com/news/world...gulatory-nod-for-vaccines-11599147880530.html
Liked seeing seven more BioPharma CEOs joining the Pfizer and Merck CEOs in their pledge guaranteeing their "commitment to developing and testing potential vaccines for COVID-19 in accordance with high ethical standards and sound scientific principles." This was basically done to preempt concerns that politics might muddy the waters of the approval process in the US. Smart move to get out ahead of the issue. As I said the other day, I'd like to see every politician muzzled on this topic, so we can see what the science and the lead scientists say.
https://www.businesswire.com/news/home/20200908005282/en/Biopharma-Leaders-Unite-Stand-Science
Thought this was a nice graphical summary of the status of the 5 major vaccines that might be approved by the end of the year, worldwide. Shows AZ/Oxford was in the lead - will be interesting to see how long the "pause" is (assuming it's not a major issue stemming from the vaccine; if it is, there could be a more significant delay or even a need for a larger trial to fully assess safety). The other potential issue is that if there were truly a problem with the AZ/Oxford vaccine, it could be related to using an adenovirus vector for delivery - and the J&J/CanSino vaccines also use adenovirus vectors.
Who is they? I posted because I thought it was interesting. I don’t agree with all their findings. Perhaps if you didn’t have a pre-existing narrative you can look at things with a different lens.
‘You mean the one hour event that drew 7500 people .. with some of the more sensible people wearing masks versus 250,000 over a long weekend ?
https://www.google.com/amp/s/www.nytimes.com/2020/09/08/health/covid-masks-immunity.amp.html
Interesting, and somewhat intuitive, theory — in some of my many rebuttals to the anti-maskers here (who have no argument above the teenage-type response: someone is telling me to do it, so I won’t do it), I’ve wondered if masks played a role in the improved statistical outcomes of COVID cases since March by reducing load transfer. Immunity from micro-loads would be a major benefit.
Interesting, and somewhat intuitive, theory — in some of my many rebuttals to the anti-maskers here (who have no argument above the teenage-type response: someone is telling me to do it, so I won’t do it), I’ve wondered if masks played a role in the improved statistical outcomes of COVID cases since March by reducing load transfer. Immunity from micro-loads would be a major benefit.
From what I read, a major concern about Sturgis was that the indoor bars and restaurants in the town were open without restrictions / masks.
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