Member Info for JoeyDiamond

https://www.nature.com/articles/s41586-021-03324-6#article-info

New peer reviewed nature article on mrna vaccines. Expect more mutations and vaccines will need to be updated to counter virus evolution.

'Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines1–4. Eight weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection5,6. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors5–8. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.'

Oh nos you said the word imminent :)

https://www.medrxiv.org/content/10.1101/2021.02.04.21251134v1

There is the trial design and some of the headline information on Budesonide.

Yes just read the email looks really good to me.

Sharing your experience of using SNG001 at home and how easy it was to do should be a big positive. I also like the activ-2 and the potential the treatment can be nicked by the USA :)

More vaccine vaccine vaccine.

I remember with this drug that there was a whistleblower Dr who claims it is mutagenic. No doubt powerful antiviral but has some 'baggage' it needs to sort out I suspect.

budesonide reduced relative risk of requiring urgent care or hospitalisation by 90% in 28-day study period sounds good. However we need some more data as 'urgent care' may just mean someone calling 111. The results wouldn't look as great if it said -

budesonide reduced relative risk of calling 111 by 90% in 28-day study period.

So need a breakdown of this data of who actually went to hospital or who went to walk in centre/called 111. I couldnt see it.

The other issue is the trial wasn't blinded and was an open label trial so the patients and researcher knew they were taking the drug or on SOC. They were then asked to fill out a questionnaire to get results. This obviously will influence results.

To clarify I should say this was based on human lung-only mice (LoM) :)

Thanks Borsaci06. This is Mercks new antiviral, probably SNGs biggest 'competitor'

This is an in vivo study, ie how the drug performs in the human lung and results looks to be very good at early stage. So looks like a real deal. However the surprise in this study is what could be the cause of such stellar results.

'Notably, numerous interferon-stimulated genes (ISGs) and inflammatory cytokine genes, including pro-inflammatory cytokines genes IL6, CXCL8 (IL-8), CXCL10(IP-10), TNF, and CCL5 (RANTES) were potently induced in infected lung tissue (Supplementary Tables 1 and 2). We also observed dramatic upregulation of IFNB1, IFNL1, IFNL2, and IFNL3 expression (>1,000 fold for all) at 2 days post-exposure, suggesting that these cytokines play a key role in the antiviral response to SARS-CoV-2 (Supplementary Tables 1 and 2). Gene set enrichment analysis (GSEA) showed over 840 gene pathways significantly upregulated (p<0.05) including response to type 1 interferon (p=0.0011), response to virus (p=0.0010), innate immune response (p=0.0010), cytokine mediated signaling (p=0.0010), cytokine production (p=0.0010)'

We observed robust induction of IFNB1 expression during acute infection followed by a decline in expression. Interestingly, an analysis of post-mortem COVID-19 patient lungs5 did not reveal increased IFNB1 expression and it has been shown in vitro that its expression is blocked during SARS-CoV infection31,32. These results suggest that in human lung tissue IFNB1 expression is induced during acute SARS-CoV-2 infection. While this study was not designed to evaluate the effect of type I IFN on SARS-CoV-2 replication in vivo, in vitro studies and in vivo mousestudies showed that type I IFN treatment restricts SARS-CoV-2 replication7,33.

The data I have seen is not from a site like simplywallstreet its from a very good source, I would need permission to divulge anything further.

Some members of the reddit board can confirm the findings.

'He also alluded to a key challenge in the administration of antivirals, which is portability. Access is a profound challenge in primary care for the delivery of antivirals, and that is one of the issues we have to resolve.'

This sentence refers to antivirals in general and the issue of portability ie using them at home or primary care settings. Not directed at SNG directly per se. No point having an efficacious treatment that can't be used at home by the patient. We have seen this in the USA very little takeup of mAbs treatments for primary care/home use.

Portability is an issue for the majority of mAbs treatments as they require trained medical staff on site and require IV plus very expensive. Hence not very suitable :0

SNG001 is portable, the home trial has proven this which Richard and Stephen have alluded to. Box gets delivered to your door with instructions and a zoom call or phone call if required by a nurse.

People are looking at this in the wrong light IMO, Lord Winston and Lord Bethell are indirectly highlighting an advantage of SNG over other treatments.

Who knows how they will play the price but at this stage any significant retraces are a gift for people to buy in.

Over 50% of stock is now in II hands and this number is slowly increasing.

I dont need to tell people the ramifications if E484K mutation variants takes hold in the UK and spreads over the coming months.

Elderly people who took the AZN vaccine will have zero protection for mild/moderate and very likely little protection vs severe disease.

10% efficacy in a trial population with an average age of 31. Will likely be zero effect for the elderly population.

Doc the data they are looking at is comparing the over 80s in the UK where at least 80% have been vaccinated (1 dose) vs younger under 80 populations in the UK without the vaccine. So the Israel vaccination uptake has no bearing on this graph.

We should be seeing some signs of falling cases rates in the over 80s vs under 80s in the UK. Sadly not yet. This is in contrast to Israels data hence the speculation as to the cause.

https://public.tableau.com/profile/helix6052#!/vizhome/SGTFDashboard/SGTFDashboard

https://twitter.com/alexbolze/status/1357831725225660416

USA virus surveillance efforts, a website tracking B117 (UK variant) spread. We can see from the tracking this variant is increasing in prevalence/spread. Using UK as an example there is a good chance it will become the main variant in USA in a few months if trend remains constant.

Good thread on the likely scenario in the USA in the near future

https://twitter.com/DrEricDing/status/1357570672860495872

Yes good point HarChris could well be the variant is having more impact than thought.

The UK started vaccine rollout 10 days before Israel, just odd no signs of vaccine effect yet.

https://twitter.com/ChrisGiles_/status/1358016395276136450

https://twitter.com/DFisman/status/1358020864701329408

You may remember the good news from Israel and the charts showing the Phizer vaccine having an affect in reducing cases in the elderly population. They have checked the UK data and there has been no vaccine effect in the elderly population as of yet.

Questions
Possibly just a delayed effect? In a few more weeks we may seen some vaccine effect?
AZN vaccine doesnt work as well as Phizer?
AZN vaccine not effective for elderly people? There is not enough clinical trial data to prove it does work hence most non UK countries banning it for over 55s/65s
Delayed dose strategy an issue?

Defo one to keep an eye on.

https://jamanetwork.com/journals/jama/fullarticle/2773058

Here is a paper co-written by Dr Fauci back in November outlining plans for early therapy.

Quote
'Several antivirals approved or in development for other viral infections, such as HIV, hepatitis C virus, and ebolaviruses, are under investigation for early treatment of COVID-19. These investigations have not yet yielded clinically actionable results; however, many trials are ongoing. Examples of antivirals in trials for early treatment of COVID-19 are MK-4482 (EIDD-2801), an orally bioavailable ribonucleoside inhibitor that was originally developed for influenza (NCT04575597); SNG001, a nebulized formulation of interferon-ß1a developed for viral infections in patients with chronic obstructive pulmonary disease (NCT04385095); and camostat mesylate, a serine protease inhibitor approved for treatment of chronic pancreatitis and postoperative reflux esophagitis (NCT04353284).

So these are the 3 that are in his and colleagues minds.