Your reports are an example par excellence of how all science should be reported to the public - and to other scientists. Congratulations on nailing it!
From antivirals to boosters, a singular obsession with hospitalization/death reduction misses the chance to understand the full benefits of any intervention. A study announced in March seems really promising in this regard. I’m just going to copy and paste from a post I did a couple weeks ago:
Mucosal vaccine study announced, with $57 million funding
An international research consortium is picking up the agonizingly slow pace on nasal spray vaccines that might provide even better protection against coronaviruses at the point of entry in the nasal passages and upper respiratory system. This would be an amazing development towards restoring true freedom in Covidlandia.
In the challenge trial, volunteers will first receive either a dose of an investigational vaccine designed to provide mucosal coronavirus immunity or placebo before being intentionally exposed to a calibrated dose of SARS-CoV-2.
"With controlled human infection studies, scientists have the participants on site for approximately two weeks, they know the dose of the challenge virus, and they can take a lot of samples, frequently, from mucosal areas — in other words from saliva, from nasal swabs and so on — so they can get really good insights into what is going on."
Awesome. Many thanks to the intrepid volunteers signing up to get intentionally dosed with coronaviruses. I admit I’m just cautiously optimistic though. Nasal vaccines for other illnesses like influenza have not been game changers. But we’ll take any incremental benefit.
Do we know what variant the fall ‘24 boosters will target? Or will we continue to use the’23 boosters this fall? Will the recommendation be for everyone to receive another fall booster or just certain groups?
Your clarity and logic in writing, as well as admitting what you do not know and listing who helps you have convinced this old retired primary care doc of your value. Thank you, keep up the good work.
Wonderful! Can you tackle any oral treatments for covid at some point? Are any in the pipeline? Any further studies of Paxlovid? Thanks! The oral from Japan has been "fast tracked" for over a year, with crickets and the one from Gilead was pulled for no symptom relief, but Paxlovid doesn't show symptom relief either. Our tools seem kind of scant to me.
Thanks so much for your work. I am 68 and fully vaxed and boosted, all Pfizer. May have had Covid early 2020, but not sure since there wasn’t any testing. I’m planning to get another vax now.
Is there any compelling reason to get Novavax this time?
On one hand, this is exciting news. On the other hand, the pharmaceutical industry, WHO, FDA, CDC, etc. have lost a lot of trust and simply declaring it "safe and effective" is not enough.
Do we have enough data yet to understand if the mRNA vaccine’s side effects might be caused by the plasmid or dna fragments in the vaccine that shouldn't be there?
What is a reasonable timeline for mucosal vaccines (if at least one of the ones on your chart were effective) to be available in the US? And is there any preliminary data to suggest that it actually might decrease transmission well? Thanks!
@YLE: Continued efforts to find the holy grail of vaccines shouldn’t be denigrated, but I/we contend that for this particular coronavirus, the efforts will necessarily require the efforts to be upgraded vaccine versions for a long long time. It appears that this virus eludes our best efforts thus far. Credible repurposed therapeutics are being “left on the table”. There are those that address invasiveness at the ACE2 gateway for entry, viral replication, dissemination and especially targets. In our concepts of therapeutic intervention, it’s the host’s immune antibody response and the ultimate targets that promote multisystemic inflammation that need to be addressed. Those targets appear to be the a7nAChRs whose diminution and immune-based dysfunctions with COVID19 are pro-inflammatory. Restoring a7R function with an immune modulator enables a return to their normal anti-inflammatory functions, a critical feature in the host cytokine response. These and other biological and immune mechanisms are slowly being clarified and we believe form the basis for a therapeutic intervention shown to have such efficacy in the laboratory,
Additionally, the issues of Long COVID/PASC/PCC appear to have relevance with the S-protein antigen mirror image in the form of an anti-idiotypic antibody also causing a lingering systemic inflammation as outlined in this reference by the same group of a7nAChR experts.
We would suggest that the a7nAChRs are not unlike magnets and their ubiquitous presence throughout the human host, intimately connected to mitochondria may account for many of the multisystems signs and symptoms as the viral immune response proceeds unchecked. The only current therapeutic is really a single dart in the entire sequence. It addresses replication after the virus’ S-protein has found the ACE2 receptors for entry, but its benefits are designed for mild-mod, non-hospital COVID19 cases within the first 5 days of symptoms (as aptly demonstrated by Pfizer’s cartoon commercials), after which the benefits for protecting against hospitalization or aggressive intervention have decline. A specific immune modulator, anti-inflammatory, and nitric oxide donor that can enhance tissue oxygenation will mitigate signs and symptoms rapidly. Clinically, even after the arrival of multiple SARS-Cov2 variants such rapid onset and consistent benefits, have been demonstrated. Ready availability, inexpensive, no adverse reactions and with consistent and durable effects were evident after a few dozen therapies for advanced post-COVID afflicted inpatients and subsequent for ~2,500 outpatient COVID19 victims with varying stages of the disorder. Sadly, the original mission of the Cure Drug Repurposing Collaboratory a consortium, conceived by the FDA, NIH, NCATS, CDC, C-Path, and I.D.S.A. for repurposed drug discovery has had a drastically altered course when it reverted to data mining from large clinical databases searching for that acorn in the forest soil. The most recent data came from several hundred thousand hospital and clinic records of COVID19 treated patients. According to that labor intensive and expense exercise, the top 2 drugs prescribed for COVID19 were………#1 NaCl IV. and #2 O2 by face mask. Seriously. No filters whatsoever. Credible repurposed therapeutics used in real world clinical practices have much value as candidates and there is no need for such extravagance and illogical data-mining in my/our opinion and others. A substack describing any efforts for such therpeutics, esp repurposed ones is sorely needed. The need for a 2-prong approach for COVID19 and subsequent pandemic virus is quite evident to me.
thanks for this info! I was (am) really hoping that mucosal vaccines will prove more effective against infection. The oral/intranasal vaccine for bordetella bronchoseptica (canine) proved much better than injectable in veterinary medicine. My pipe dream for now......
A couple of quick comments on intranasal vaccines and antibodies. I recall that intranasal flu vaccine works better in children and are not any better than shots. Wonder if we will see the same with COVID. Also seems to remember that the mucous Ab contracted sooner and does elicit humoral/cellular immunity as well. (I'll try to look that up.) Since Ab contraction is normal after either vaccines or infection, we ultimately depend on humoral/cellular immunity.
Your reports are an example par excellence of how all science should be reported to the public - and to other scientists. Congratulations on nailing it!
Superb, as always! I want to give particular compliments to the YLE team for the excellent, easy to read, graphs.
Glad to hear so many irons in the fire.
From antivirals to boosters, a singular obsession with hospitalization/death reduction misses the chance to understand the full benefits of any intervention. A study announced in March seems really promising in this regard. I’m just going to copy and paste from a post I did a couple weeks ago:
Mucosal vaccine study announced, with $57 million funding
An international research consortium is picking up the agonizingly slow pace on nasal spray vaccines that might provide even better protection against coronaviruses at the point of entry in the nasal passages and upper respiratory system. This would be an amazing development towards restoring true freedom in Covidlandia.
In the challenge trial, volunteers will first receive either a dose of an investigational vaccine designed to provide mucosal coronavirus immunity or placebo before being intentionally exposed to a calibrated dose of SARS-CoV-2.
"With controlled human infection studies, scientists have the participants on site for approximately two weeks, they know the dose of the challenge virus, and they can take a lot of samples, frequently, from mucosal areas — in other words from saliva, from nasal swabs and so on — so they can get really good insights into what is going on."
Awesome. Many thanks to the intrepid volunteers signing up to get intentionally dosed with coronaviruses. I admit I’m just cautiously optimistic though. Nasal vaccines for other illnesses like influenza have not been game changers. But we’ll take any incremental benefit.
Thanks for the update. Too bad we don't have a House of Representatives that makes science and public health a priority.
Thank you! Great summary of a difficult topic.
Do we know what variant the fall ‘24 boosters will target? Or will we continue to use the’23 boosters this fall? Will the recommendation be for everyone to receive another fall booster or just certain groups?
Your clarity and logic in writing, as well as admitting what you do not know and listing who helps you have convinced this old retired primary care doc of your value. Thank you, keep up the good work.
Wonderful! Can you tackle any oral treatments for covid at some point? Are any in the pipeline? Any further studies of Paxlovid? Thanks! The oral from Japan has been "fast tracked" for over a year, with crickets and the one from Gilead was pulled for no symptom relief, but Paxlovid doesn't show symptom relief either. Our tools seem kind of scant to me.
Thanks so much for your work. I am 68 and fully vaxed and boosted, all Pfizer. May have had Covid early 2020, but not sure since there wasn’t any testing. I’m planning to get another vax now.
Is there any compelling reason to get Novavax this time?
Excellent - thank you so much as always for a great explanation of a complex topic
As always, Thank You! I rely on your expertise and information.
On one hand, this is exciting news. On the other hand, the pharmaceutical industry, WHO, FDA, CDC, etc. have lost a lot of trust and simply declaring it "safe and effective" is not enough.
Do we have enough data yet to understand if the mRNA vaccine’s side effects might be caused by the plasmid or dna fragments in the vaccine that shouldn't be there?
What is a reasonable timeline for mucosal vaccines (if at least one of the ones on your chart were effective) to be available in the US? And is there any preliminary data to suggest that it actually might decrease transmission well? Thanks!
@YLE: Continued efforts to find the holy grail of vaccines shouldn’t be denigrated, but I/we contend that for this particular coronavirus, the efforts will necessarily require the efforts to be upgraded vaccine versions for a long long time. It appears that this virus eludes our best efforts thus far. Credible repurposed therapeutics are being “left on the table”. There are those that address invasiveness at the ACE2 gateway for entry, viral replication, dissemination and especially targets. In our concepts of therapeutic intervention, it’s the host’s immune antibody response and the ultimate targets that promote multisystemic inflammation that need to be addressed. Those targets appear to be the a7nAChRs whose diminution and immune-based dysfunctions with COVID19 are pro-inflammatory. Restoring a7R function with an immune modulator enables a return to their normal anti-inflammatory functions, a critical feature in the host cytokine response. These and other biological and immune mechanisms are slowly being clarified and we believe form the basis for a therapeutic intervention shown to have such efficacy in the laboratory,
Ref:https://doi.org/10.1016/j.jneuroim.2023.578244.
Additionally, the issues of Long COVID/PASC/PCC appear to have relevance with the S-protein antigen mirror image in the form of an anti-idiotypic antibody also causing a lingering systemic inflammation as outlined in this reference by the same group of a7nAChR experts.
Ref:https://doi.org/10.1016/j.biocel.2024.106519
We would suggest that the a7nAChRs are not unlike magnets and their ubiquitous presence throughout the human host, intimately connected to mitochondria may account for many of the multisystems signs and symptoms as the viral immune response proceeds unchecked. The only current therapeutic is really a single dart in the entire sequence. It addresses replication after the virus’ S-protein has found the ACE2 receptors for entry, but its benefits are designed for mild-mod, non-hospital COVID19 cases within the first 5 days of symptoms (as aptly demonstrated by Pfizer’s cartoon commercials), after which the benefits for protecting against hospitalization or aggressive intervention have decline. A specific immune modulator, anti-inflammatory, and nitric oxide donor that can enhance tissue oxygenation will mitigate signs and symptoms rapidly. Clinically, even after the arrival of multiple SARS-Cov2 variants such rapid onset and consistent benefits, have been demonstrated. Ready availability, inexpensive, no adverse reactions and with consistent and durable effects were evident after a few dozen therapies for advanced post-COVID afflicted inpatients and subsequent for ~2,500 outpatient COVID19 victims with varying stages of the disorder. Sadly, the original mission of the Cure Drug Repurposing Collaboratory a consortium, conceived by the FDA, NIH, NCATS, CDC, C-Path, and I.D.S.A. for repurposed drug discovery has had a drastically altered course when it reverted to data mining from large clinical databases searching for that acorn in the forest soil. The most recent data came from several hundred thousand hospital and clinic records of COVID19 treated patients. According to that labor intensive and expense exercise, the top 2 drugs prescribed for COVID19 were………#1 NaCl IV. and #2 O2 by face mask. Seriously. No filters whatsoever. Credible repurposed therapeutics used in real world clinical practices have much value as candidates and there is no need for such extravagance and illogical data-mining in my/our opinion and others. A substack describing any efforts for such therpeutics, esp repurposed ones is sorely needed. The need for a 2-prong approach for COVID19 and subsequent pandemic virus is quite evident to me.
thanks for this info! I was (am) really hoping that mucosal vaccines will prove more effective against infection. The oral/intranasal vaccine for bordetella bronchoseptica (canine) proved much better than injectable in veterinary medicine. My pipe dream for now......
A couple of quick comments on intranasal vaccines and antibodies. I recall that intranasal flu vaccine works better in children and are not any better than shots. Wonder if we will see the same with COVID. Also seems to remember that the mucous Ab contracted sooner and does elicit humoral/cellular immunity as well. (I'll try to look that up.) Since Ab contraction is normal after either vaccines or infection, we ultimately depend on humoral/cellular immunity.