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Eric Topol
@EricTopol
Big jumps in science of Type 1 Interferon response to #COVID19 today
@ScienceMagazine
: auto-antibodies, genomic variants, together account for ~14% of critical/life-threatening covid patients
https://science.sciencemag.org/content/early/2020/09/23/science.abd4585
https://science.sciencemag.org/content/early/2020/09/23/science.abd4570
https://science.sciencemag.org/content/early/2020/09/23/science.abd4570
First paper- May explain why intravenous interferon 1 route may not work well. It does not exclude the efficacy of the nebuliser route. It lends support to the importance of interferon 1 's in the pathogenesis of seriously ill Covid-19 patients.
Gkb47 has answered the other 3 papers.
Eric is very highly regarded in the medical research/science field and when you see who follows him on twitter :) Dr Hahn for example.
This is huge news they now have evidence of people being more deficient in their immune response. Confirms what we non medical people suspected be the case.
Conclusion of the papers -
We report here that at least 10% of patients with life-threatening COVID-19 pneumonia have neutralizing auto-Abs against type I IFNs. With our accompanying description of patients with inborn errors of type I IFNs and life-threatening COVID-19 (18), this study highlights the crucial role of type I IFNs in protective immunity against SARS-CoV-2. These auto-Abs against type I IFNs were clinically silent until the patients were infected with SARS-CoV-2, which is a poor inducer of type I IFNs (28), suggesting that the small amounts of IFNs induced by the virus are important for protection against severe disease. The neutralizing auto-Abs against type I IFNs, like inborn errors of type I IFN production, tip the balance in favor of the virus, resulting in devastating disease, with insufficient, and even perhaps deleterious, innate and adaptive immune responses.
Our findings have direct clinical implications. First, SARS-CoV-2-infected patients can be screened to identify individuals with auto-Abs at risk of developing life-threatening pneumonia. Such patients recovering from life-threatening COVID-19 should also be excluded from donating convalescent plasma for ongoing clinical trial, or at least tested before their plasma donations are accepted (29). Second, this unexpected finding paves the way for therapeutic intervention, including plasmapheresis, monoclonal Abs depleting plasmablasts, and the specific inhibition of type I IFN-reactive B cells (30). Finally, in this patient group, early treatment with IFN-a is unlikely to be beneficial. However, treatment with injected or nebulized IFN-ß may have beneficial effects, as auto-Abs against IFN-ß appear to be rare in patients with auto-Abs against type I IFNs.
Staggering information there
1) Its possible to screen the patients to see who is suseptible to apply a therapy then we dose em with SNG001 fast.
2) IFN-A not beneficial unlike IFN-B. That seriously hammers our close competitor in Canada Betterlife.
3) Plasma being donated from these affected patients is a big no no. More pressure to come to the FDA for granting EUA and there is now an issue it can make you more ill!
It feels to me that the touch paper has been lit today...
Sir Jeremy Farrar, director of the Wellcome Trust and member of SAGE, has just tweeted about one of the studies mentioned in the Guardian article, https://twitter.com/JeremyFarrar/status/1309208351553847297?s=20 saying:
"The ability to control the initial infection through type I IFN may be so important in COVID and also many other acute viral infections - Flu, Dengue, Yellow Fever, Chik, and others."
The study is here https://science.sciencemag.org/content/early/2020/09/23/science.abd4570
Perhaps a good time to look back at https://www.synairgen.com/wp-content/uploads/2020/07/200720-Synairgen-data-readout-final-version.pdf
"injected or nebulised interferonB"......pretty obvious the choice will be nebulised owing to no or little side effects.
I think you are right. The scientific community now has its evidence.
Now from a big pharma view they have confirmation from independent unbiased sources IFN-B is key to treating many people with Covid-19. 14% of people who suffered with serious Covid in the study had these problematic genes.
Think of how many cases worldwide that is. So many people need an IFN-B drug thats now scientifically proven that is huge revenue.
Quite a few "may"s and "likely"s though so not "proven" but definitely worth investigating further while discounting other less likely treatments. Good to have a bit of excitement in these troubled times.
Excuse me for musing, but of 7.7 billion people worldwide, about 10% react badly to Covid-19 and Interferon works on 14% of those, so that is about 108 million people worldwide that will benefit from SNG001. That's before COPD treatments etc Seems like a good investment to me.
DYOR
Further information
Immunologist Jean-Laurent Casanova of the Rockefeller University suspects human genetics will end up explaining the majority of such serious cases, however, because the consortium has only looked for mutations in 13 of the 300-odd type 1 interferon-related genes so far – already a huge undertaking. Many other genes, including ones not related to interferon, could affect a person’s response to the virus.
So the 14% figure is likely to be very much higher. It gets to the point that the evidence could point to giving all patients a boost of IFN-B as the first stage drug.
Great posts tonight. Thank you.
Nice to see on twitter tonight amongst the Professors and senior scientists I follow that they are all retweeting/discussing these new findings. First time ive seen all these well regarded and professional people from mutliple fields getting excited over a paper at the same time.
Forget Synairgen and our shares for a minute, it does feel like here has been a genuine big step forward and breakthrough in the battle vs Covid-19. It deserves to be big news tomorrow and massive thanks to these super cool scientists.
In the short term, this research should make it much easier to argue for compassionate use of SNG001 specifically for those screening positive for the problem genes.
It also makes me wonder if this screening applied retrospectively to the patients in our trials might prove illuminating.
Further confirmation - if any were needed - that Synairgen has backed the right Interferon for the job
‘ It should guide diagnosis and treatment, since patients arriving at hospital and testing positive for auto-antibodies could undergo plasma exchange to remove those antibodies from their blood – potentially keeping them out of intensive care. Since the auto-antibodies spare one particular form of interferon – the beta form – these patients might also benefit from the experimental treatment inhaled interferon beta. ‘
Interferon Beta is the only effective interferons that work in this case !!!!!!!
Thanks Dave. What I find incredible is that on one is mentioning Synairgen anywhere in these articles. There are only references to studies involving inhaled interferon, so only relatively few people (i.e. scientists and shareholders) know who this is about. SNG need to raise profile as it helps commercialisation and puts pressure on government to move faster, imho
That's why they are working on a partnership. SNG are a small company with a massive product, just needs to right exposure.
It will come.
I wholeheartedly agree with the mass of posts expressing complete exacerbation at governments spending obscene sums on unproven medical solutions whilst seemingly ignoring the elephant in the room. We have been described as a ‘cult’ by some but when you do the research, apply reason and common sense this stacks up. The research released yesterday alludes to the ‘elephant’ - pretty much describes a large grey mammal with a trunk but again refuses to name him. It’s like the Emperors New Clothes so obvious but no one wants to see. Is it just me a wee tad frustrated!