Phi for All Posted April 8, 2020 Posted April 8, 2020 ! Moderator Note Several posts with a focus on a conspiracy video have been hidden. We don't support the "watch the misinformation too" approach to science.
MatteasM Posted April 9, 2020 Posted April 9, 2020 Are there any theories of what exactly is happening after the Covid-19 virus enters the system and the mechanism by which it kills? I have only come across one reasonable theory on SSRN that discusses mast cell degranulation. https://ssrn.com/abstract=3566703 Almost all other scientific presentations seem to be data sets of symptoms and morbidities and genetic analysis of the virus and its receptors. Our medical establishment has nothing more than shots in the dark, hoping for a lucky hit. It seems that despite the trillions poured into setting up research superstructure, we are not even sure anymore if we should be using anti-parasite and/or antibiotic treatments to deal with a virus! Or even whether a mask will help or not? Where is the medical theory? Where are the old school immunologists?
Sciguy72 Posted April 9, 2020 Posted April 9, 2020 (edited) 4 hours ago, MatteasM said: Are there any theories of what exactly is happening after the Covid-19 virus enters the system and the mechanism by which it kills? I have only come across one reasonable theory on SSRN that discusses mast cell degranulation. https://ssrn.com/abstract=3566703 Almost all other scientific presentations seem to be data sets of symptoms and morbidities and genetic analysis of the virus and its receptors. Our medical establishment has nothing more than shots in the dark, hoping for a lucky hit. It seems that despite the trillions poured into setting up research superstructure, we are not even sure anymore if we should be using anti-parasite and/or antibiotic treatments to deal with a virus! Or even whether a mask will help or not? Where is the medical theory? Where are the old school immunologists? We looked at the early findings from Japan and had a small trial with ciclesonide, very effective if given early even presymptomatic benefited. The Chinese bought a large quantity and the S. Koreans are doing a study on its efficacy and potential as a treatment during later stage SARS2 infection (Pneumonitis). Unsure if there is much of the small molecule RNA inhibitor left out there, paediatrics should have a small amount on hand. Alvesco brand in NA. Debate now whether ventilation/intubation is doing more harm than good and looking at data for different antibiotic cocktails. Basically, treating for ARDS. Edit: It seems my correspondence here is being redacted by moderators and replaced with epic moderator diatribes. When people limit free exchange of information just to weight their own words it’s time to move on from the conversation. Good luck and stay safe. Edited April 9, 2020 by Sciguy72 Censoring information exchanges between medical professionals
CharonY Posted April 9, 2020 Posted April 9, 2020 There is some data out there, but typical molecular information are derived from animal models, rather than autopsies. It takes time to develop good animal or in vitro models and conduct the experiments. On top of that, creating targeted treatments based on biological information is really, really tricky, and takes even longer. Which is why medical research often skips the deeper biological parts at the beginning and focuses on outcomes instead. The ultimate reason is that biology is one of the most complex subjects out there and there is simply a ton we do not fully understand. Moreover, similar to the overall thrust of the post, more folks are interested in the applied bits. I.e. "treatment for the disease" is going to get more funds than "understanding the fundamentals of host-pathogen interactions", for example. While I may lament that from scientific and research interest point of view, I do see that the long-term research needs to take a seat on the back on this one. That being said, much of the pathophysiology is centered around the mechanisms related to adult respiratory stress syndromes (ARDS). The pattern is very similar to secondary haemophagocytic lymphohistocytosis and related hyperinflammation (or cytokine storm). One strategy is there to use cytokine-inhibition therapies, though they still remain to be tested.
MatteasM Posted April 9, 2020 Posted April 9, 2020 I think incidents like this point to the complete failure of the research system. To say that quick fixes will get more funds than slower more effective medical theory that will pinpoint exactly what needs to be done, is a disgusting comment on the state of things. To say that shots in the dark, are preferred to true science and a concerted intelligent effort, that this idiotic "pragmatism" encouraged by pharma companies and their collaborators, of lining up 392 drugs for trials without really understanding what is going on and what is gong to really help. I went through the paper evincing the link between mast cell degranulation and the coronavirus (https://ssrn.com/abstract=3566703) and noticed it was written by an unsponsored independent. I also noticed that it suggested a careful understanding of H4 antagonists, mast cell stabilizers, Tnf-alpha blockers etc to be used in conjunction. But what I see on the ground is the alchemy practiced by the pharma companies to turn their existing FDA "approved' drug portfolios into pots of gold. Sciguy72, your comment on ciclesonide just highlights what I am trying to say, while the paper calls for a reasoned approach to treat the Covid as an hyperallergenic response along with other factors indicated, all we have on the ground is a drug used for allergic rhinitis and asthma being tossed in to the list. While it echoes what the paper reasons, what if a complex combination of multiple drugs is needed? Good science and common sense dictates that understanding before action is far better than action before understanding. Almost six months into the outbreak and we are really no closer to a cure, decades after the SARS outbreak we are no closer to a vaccine, and when you say that they are looking at devising cytokine storm treatments, let me point out that this was the primary cause of death in the 1918 Spanish flu and also in the SARS epidemic. It has been 102 years and we have still not solution for the cytokine storm? More old people die of the cytokine storm in influenza related pneumonia each year than will die worldwide in the Covid massacre. When the solution appears, and it will sooner or later, you will find that our failings were not with the science but with the politics and money around it.
swansont Posted April 9, 2020 Posted April 9, 2020 18 hours ago, Sciguy72 said: Some info here, some is misinformation. You decide. ! Moderator Note No, that approach will not fly here, especially considering the consequences. 6 hours ago, Sciguy72 said: Edit: It seems my correspondence here is being redacted by moderators and replaced with epic moderator diatribes. When people limit free exchange of information just to weight their own words it’s time to move on from the conversation. Good luck and stay safe. ! Moderator Note "Free exchange" of information that is known to be wrong does not advance a conversation.
Phi for All Posted April 9, 2020 Posted April 9, 2020 7 hours ago, Sciguy72 said: Edit: It seems my correspondence here is being redacted by moderators and replaced with epic moderator diatribes. When people limit free exchange of information just to weight their own words it’s time to move on from the conversation. Good luck and stay safe. ! Moderator Note Thanks for understanding and moving on from this site. A piece of advice I'm pretty sure you'll ignore? If you truly want to help, you should stop acting like you work for a troll farm. Your posts are laden with conspiracy and misinformation, and your further claims of medical professionalism are untrustworthy. Best of luck elsewhere!
MigL Posted April 9, 2020 Posted April 9, 2020 For those of us ( like me ) who are not up to speed on Virology, this thread, from another forum I frequent, seems t be a good beginner tutorial... https://www.airliners.net/forum/viewtopic.php?f=11&t=1443947 Perhaps CharonY can have a look at it, and answer any questions we noobs might have. ( or make any corrections as needed ) 3
drumbo Posted April 9, 2020 Posted April 9, 2020 Hi all, I'm looking for any research or insights related to a couple of questions I have about covid-19. If a person with flu-like symptoms dies and tests positive for both flu and covid-19 viruses, how can we tell if the death should be blamed on covid-19? The flu virus infection may have resulted in death without the covid-19 virus infection, and the covid-19 virus infection may have not resulted in death without the flu virus infection. Furthermore, what percentage of covid-19 infected patients are also infected with a flu virus? If you need clarification please let me know. 1
CharonY Posted April 9, 2020 Posted April 9, 2020 3 hours ago, MigL said: For those of us ( like me ) who are not up to speed on Virology, this thread, from another forum I frequent, seems t be a good beginner tutorial... https://www.airliners.net/forum/viewtopic.php?f=11&t=1443947 Perhaps CharonY can have a look at it, and answer any questions we noobs might have. ( or make any corrections as needed ) Took a look at the first posts and they look very good. Certainly more effort were put into them than I would realistically do. Don't think I would have anything to contribute (unless there are specific questions that went unanswered and I happen to have read something about it or have general molecular biological knowledge that applies). 3 hours ago, drumbo said: I have about covid-19. If a person with flu-like symptoms dies and tests positive for both flu and covid-19 viruses, how can we tell if the death should be blamed on covid-19? I don't think that there there is a database that would try to deconvolute that information. Given the current situation folks are probably more likely to be tested for COVID-19 than for influenza, meaning that after a positive I suspect that this would take precedence. There are case reports with co-infections reported in small studies (e.g. individual clinics) but I am not aware of large-scale surveys. Within hospitals the cases detected with co-infections were fairly low (but rarely quantified in detail). 1
Danijel Gorupec Posted April 9, 2020 Posted April 9, 2020 26 minutes ago, CharonY said: I don't think that there there is a database that would try to deconvolute that information. Given the current situation folks are probably more likely to be tested for COVID-19 than for influenza, meaning that after a positive I suspect that this would take precedence. There are case reports with co-infections reported in small studies (e.g. individual clinics) but I am not aware of large-scale surveys. Within hospitals the cases detected with co-infections were fairly low (but rarely quantified in detail). What is your personal option.... would it be worth investigating whether flu+covid co-infection affects the outcome? And more importantly, what hinders such investigations? Are novice scientists discouraged to interfere / without ideas / need more time / have more interesting thing to do / or just afraid? I ask because it seems like an ideal job for young recruits.
zapatos Posted April 9, 2020 Posted April 9, 2020 4 minutes ago, Danijel Gorupec said: What is your personal option.... would it be worth investigating whether flu+covid co-infection affects the outcome? I would be shocked if having the flu while fighting COVID-19 did not affect the outcome.
drumbo Posted April 9, 2020 Posted April 9, 2020 29 minutes ago, CharonY said: Within hospitals the cases detected with co-infections were fairly low (but rarely quantified in detail). Thanks for the reply. I've found this article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30211-7/fulltext that reports in Wuhan Jinyintan Hospital (Jan 1-20, 2020) out of 78 covid-19 patients with pneumonia 0 of them were co-infected with the other viruses that were tested for. They tested for nine respiratory pathogens and influenza A and B. But take a look at this article from the Qingdao Women and Children’s Hospital https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3550013 . Among covid-19 patients in Qingdao, 24 (80.00%) of them had IgM antibodies against at least one respiratory pathogen, whereas only one (2.60%) of the patients in Wuhan had positive results for serum IgM antibody detection ( P <0.0001). The most common respiratory pathogens detected in Qingdao covid-19 patients were influenza virus A (60.00%) and influenza virus B (53.30%), followed by mycoplasma pneumoniae (23.30%) and legionella pneumophila (20.00%). And take a look at this article out of Iran https://www.preprints.org/manuscript/202003.0291/v1. They selected 4 patients who presented with pneumonia symptoms and were suspicious for covid-19 and referred them to the intended centers for covid-19 diagnosis and management of Shiraz University of Medical Sciences in the south of Iran. All 4 of them were diagnosed with co-infection of covid-19 and influenza virus. It seems like the patients in Wuhan had much lower rates of co-infection than patients outside of Wuhan, and that co-infection is very common outside of Wuhan. How can we explain this?
CharonY Posted April 9, 2020 Posted April 9, 2020 13 minutes ago, zapatos said: I would be shocked if having the flu while fighting COVID-19 did not affect the outcome. As mentioned there are only few reports, mostly on cases with positive outcomes. One by Ding et al. (2020) J Med Vir has not found any more severe clinical indicators. The numbers of co-infection are based on small sample sizes and depending on how the cohorts are built (e.g. severity of symptoms) the outcome may be biased.
drumbo Posted April 9, 2020 Posted April 9, 2020 14 minutes ago, CharonY said: As mentioned there are only few reports, mostly on cases with positive outcomes. One by Ding et al. (2020) J Med Vir has not found any more severe clinical indicators. The numbers of co-infection are based on small sample sizes and depending on how the cohorts are built (e.g. severity of symptoms) the outcome may be biased. I would like to see more data related to covid-19 and influenza virus co-infection in the US. Can anyone find anything? If it is true that co-infection does not result in more severe symptoms then co-infection numbers cannot be biased due building cohorts by selecting patients with pneumonia symptoms. And vice-versa, if the cohorts are biased due building cohorts by selecting patients with pneumonia symptoms then co-infection does result in more severe symptoms.
CharonY Posted April 9, 2020 Posted April 9, 2020 56 minutes ago, drumbo said: I would like to see more data related to covid-19 and influenza virus co-infection in the US. Can anyone find anything? If it is true that co-infection does not result in more severe symptoms then co-infection numbers cannot be biased due building cohorts by selecting patients with pneumonia symptoms. It is unclear as a) we do not know whether or in which patients influenza may result in different clinical manifestations b) studies are local with small sample sets which makes it difficult to build representative cohorts c) we do not know whether there is a relationship in infection process regardless of clinical outcome. That all being said, there is a paper (but I cannot quite recall the authors) which indicated that the influenza cases went down as COVID-19 went up in Wuhan. I do not recall the precise dates of the patients, so not sure whether it coincided with the shutdown. Edit: And did not come across any studies in the US yet.
Ismail Posted April 9, 2020 Posted April 9, 2020 I noticed that self-testing is very hard to get in many parts of the world. Why is this so? I was still troubled by this question when numbers of cases in my country doubled but thankfully they are doing a good job in handling it but I’m afraid that the numbers might be artificial numbers. So I thought of a device and wrote all the specifications of the device and I have not found a single scientist that could develop the device. please who can help?
Strange Posted April 9, 2020 Posted April 9, 2020 8 minutes ago, Ismail said: I noticed that self-testing is very hard to get in many parts of the world. Why is this so? I was still troubled by this question when numbers of cases in my country doubled but thankfully they are doing a good job in handling it but I’m afraid that the numbers might be artificial numbers. So I thought of a device and wrote all the specifications of the device and I have not found a single scientist that could develop the device. How does your test work? Are you detecting viral genes? Or antibodies? What is the sensitivity? What s the accuracy?
Sensei Posted April 10, 2020 Posted April 10, 2020 https://erj.ersjournals.com/content/early/2020/03/26/13993003.00688-2020 "Smokers and individuals with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus. "
CharonY Posted April 10, 2020 Posted April 10, 2020 21 hours ago, Ismail said: I noticed that self-testing is very hard to get in many parts of the world. Why is this so? Most tests require isolation of RNA. It is a bit difficult and requires a lab (not to mention the subsequent RT-PCR). Antibody based assays are coming but are not optimized yet, and most (that I know of) require lab conditions to yield accurate results. To make it possible for accurate (diagnostic) self testing, they need to be highly optimized and error proof. That takes time and is not a priority, considering that other tests are running low in many areas. I should add that there are lateral flow immunoassays, but they alone are not good for diagnosis of ongoing infections as the immunoresponse is not fully characterized yet. I.e. they may be good if there was a strong response, but a negative test will have uncertainties associated with it. Fundamentally self-tests are also prone to user errors, even with simple tests, which is why even well-established tests (e.g. pregnancy tests) usually require additional confirmation. Here, the uncertainty is higher.
CharonY Posted April 11, 2020 Posted April 11, 2020 On 4/9/2020 at 10:03 AM, Danijel Gorupec said: What is your personal option.... would it be worth investigating whether flu+covid co-infection affects the outcome? And more importantly, what hinders such investigations? Are novice scientists discouraged to interfere / without ideas / need more time / have more interesting thing to do / or just afraid? I ask because it seems like an ideal job for young recruits. For the first part, it is certainly of interest to some, as a number of folks have collected the existing data. For the second, the issue is probably urgency. The data would need to be collected in situations that are currently overburdened and there are only limited capabilities to do additional testing. Once the situation winds down (as it has in China) I am sure folks will try to collect more data in general and figure out the relevance of co-morbidities. At the same time, folks are actually collecting as much data as they can. And again, often it means more work for medical staff as they need to collect the data, code it appropriately on top of the work they need to do. As with all research it often boils down to expected impact, available personnel and funding. Though for the latter, there is a lot of money injected into everything COVID-19 related. 1
Kartazion Posted April 11, 2020 Posted April 11, 2020 On 3/22/2020 at 8:21 AM, CharonY said: There is an antibody based test (several actually) but not sure how well it works and whether they are put to test yet. So far all reinfections are suspected to be failure in tests. There is no strong evidence that folks get sick again (for now). Here's some news about it. coronavirus-may-reactivate-in-cured-patients-korean-cdc-says
CharonY Posted April 11, 2020 Posted April 11, 2020 That is not a case of reinfection (or at least that is not the assumption). Rather it is likely that the titer slipped below detection limit and then increased above in the specimen. This is especially likely when the levels hover near the limit of detection.
Ismail Posted April 11, 2020 Posted April 11, 2020 18 hours ago, CharonY said: Most tests require isolation of RNA. It is a bit difficult and requires a lab (not to mention the subsequent RT-PCR). Antibody based assays are coming but are not optimized yet, and most (that I know of) require lab conditions to yield accurate results. To make it possible for accurate (diagnostic) self testing, they need to be highly optimized and error proof. That takes time and is not a priority, considering that other tests are running low in many areas. I should add that there are lateral flow immunoassays, but they alone are not good for diagnosis of ongoing infections as the immunoresponse is not fully characterized yet. I.e. they may be good if there was a strong response, but a negative test will have uncertainties associated with it. Fundamentally self-tests are also prone to user errors, even with simple tests, which is why even well-established tests (e.g. pregnancy tests) usually require additional confirmation. Here, the uncertainty is higher. I do agree but with what I have in mind, Lab Investigation is definitely necessary and required for effectiveness but self-testing is the way to go for areas with dense population like countries in Africa.
Kartazion Posted April 11, 2020 Posted April 11, 2020 11 hours ago, CharonY said: That is not a case of reinfection (or at least that is not the assumption). Rather it is likely that the titer slipped below detection limit and then increased above in the specimen. This is especially likely when the levels hover near the limit of detection. Ok. And I read this Coronavirus found in air samples from up to 13 feet from patients. Can we catch the virus from the air?
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