The biology of coronavirus COVID-19 - including research and treatments

Snow Leopard said:
To put it as an obscure analogy: you need to make two trips and your vehicle choices are a Ferrari Portofino and a Morris Marina.

These people are therefore arguing that one trip in a Morris Marina, the second trip in a Ferrari is cheaper than two trips in a Ferrari. Plus you still have the enjoyable experience of one trip in a Ferrari, rather than two mediocre trips in a Morris Marina, with risk of not getting to your destination on the second trip due to unreliability.
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Is this a means of boosting the astra zeneca efficiency and extending age ranges of trial group?

I was wondering how you monitor side effects etc if you use 2 completely different types ?

It also seemed a bit strange to me that if ackower initial dose boosted efficacy that a 2 lower dose option was not tested ?

Musings of a sleep deprived parent may not stack up at this time in the morning though !
 
Amw66 said:
Is this a means of boosting the astra zeneca efficiency and extending age ranges of trial group?
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Or providing some relevance for an inferior product, take your pick...

Amw66 said:
I was wondering how you monitor side effects etc if you use 2 completely different types ?
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If there is a no-covid-vaccination control group, then you monitor as usual, with any conclusions only being generalisable for the combination protocol, not the individual vaccines. If they don't have such a control group, then it is indeed cause for concern.
 
  • sC5b9 plasma levels are elevated in children with SARS-CoV-2 infection, even if they have minimal symptoms of COVID-19.

  • A high proportion of children with SARS-CoV-2 infection met clinical criteria for TMA.
https://ashpublications.org/bloodad...nce-of-thrombotic-microangiopathy-in-children

Regarding sC5b9 and ME/CFS, there is a report of a patient who for the duration of the illness had increased levels of sC5b9. When the patient recovered, levels normalized. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028106/
 
NY Magazine: We Had the Vaccine the Whole Time
By David Wallace-Wells

...None of the scientists I spoke to for this story were at all surprised by either outcome — all said they expected the vaccines were safe and effective all along. Which has made a number of them wonder whether, in the future, at least, we might find a way to do things differently — without even thinking in terms of trade-offs. Rethinking our approach to vaccine development, they told me, could mean moving faster without moving any more recklessly. A layperson might look at the 2020 timelines and question whether, in the case of an onrushing pandemic, a lengthy Phase III trial — which tests for efficacy — is necessary. But the scientists I spoke to about the way this pandemic may reshape future vaccine development were more focused on how to accelerate or skip Phase I, which tests for safety. More precisely, they thought it would be possible to do all the research, development, preclinical testing, and Phase I trials for new viral pandemics before those new viruses had even emerged — to have those vaccines sitting on the shelf and ready to go when they did. They also thought it was possible to do this for nearly the entire universe of potential future viral pandemics — at least 90 percent of them, one of them told me, and likely more.
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Curious about @Snow Leopard 's thoughts on this.
 
Michelle said:
NY Magazine: We Had the Vaccine the Whole Time
By David Wallace-Wells



Curious about @Snow Leopard 's thoughts on this.
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The vaccine did exist the almost whole time - as soon as the virus was sequenced the mRNA vaccines can be created right away.
The preclinical studies and all trial phases were heavily overlapped. Dose discovery was mixed with initial efficacy and side effects in "phase 1/2" trials for example.

https://en.wikipedia.org/wiki/Phases_of_clinical_research

If sequencing data was released sooner and vaccine developers started work sooner, this could have saved maybe a month. But all of this requires substantial investment, without any knowledge that there would even be a worldwide pandemic - this is what held back vaccines for SARS-1.

The biggest difficulties in terms of time was ramping up the scale of production and rapid recruitment for phase 3 trials. Before this pandemic, that knowledge and capacity did not exist. But given the billions of dollars that governments have thrown at a wide variety of vaccines, along with commercial investment, it is possible that this process, in terms of future pandemics could occur maybe 2 months sooner. Phase 3 trials also require significant follow up time to monitor both safety and efficacy.

So we're still looking at around 6 months from the point at which it is known that there is a global pandemic to the point at which a safe and effective vaccine is first approved. In historical terms this would be considered very impressive!

But I think there is too much focus on vaccines as the saviour, when there are other lessons to be learned. A number of countries have shown that vaccines are not necessary to eliminate community transmission of the virus.
 
Snow Leopard said:
The vaccine did exist the almost whole time - as soon as the virus was sequenced the mRNA vaccines can be created right away.
The preclinical studies and all trial phases were heavily overlapped. Dose discovery was mixed with initial efficacy and side effects in "phase 1/2" trials for example.

https://en.wikipedia.org/wiki/Phases_of_clinical_research

If sequencing data was released sooner and vaccine developers started work sooner, this could have saved maybe a month. But all of this requires substantial investment, without any knowledge that there would even be a worldwide pandemic - this is what held back vaccines for SARS-1.

The biggest difficulties in terms of time was ramping up the scale of production and rapid recruitment for phase 3 trials. Before this pandemic, that knowledge and capacity did not exist. But given the billions of dollars that governments have thrown at a wide variety of vaccines, along with commercial investment, it is possible that this process, in terms of future pandemics could occur maybe 2 months sooner. Phase 3 trials also require significant follow up time to monitor both safety and efficacy.

So we're still looking at around 6 months from the point at which it is known that there is a global pandemic to the point at which a safe and effective vaccine is first approved. In historical terms this would be considered very impressive!

But I think there is too much focus on vaccines as the saviour, when there are other lessons to be learned. A number of countries have shown that vaccines are not necessary to eliminate community transmission of the virus.
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Yea, I was day dreaming about this; the bit where you have the amino acid sequence, for the virus spike protein, to identifying the genetic (RNA) code for that protein (the vaccine in essence) seems really quick - maybe two weeks? Since I don't know the underlying science I'm wowed by it e.g. how do you identify which bit of the virus's genome codes for that protein? Mind you how do you identify the spike protein ---

I assume though that this technology cannot be applied as easily/quickly to all virus's e.g. I'm not aware of an AIDs vaccine--- happy to be proved wrong though!
 
Moved post
This is a Royal Society of Medicine Webinar
https://www.rsm.ac.uk/resources/rsm-live/
For health professionals, by health professionals.

This webinar series is dedicated to give healthcare workers on the frontlines, regular and easy-to-access updates from healthcare leaders on COVID-19.

Chaired by leading experts, these webinars will discuss different topics and challenges that healthcare workers, leaders and the public are facing, and how we are responding.
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Food for thought?

Episode 54: One year on, what have we learned?


Date: Thursday 10 December 2020
Time: 12:30pm - 1:15pm GMT
Dear Sir/Madam,

A year on from the first recorded cases of COVID-19, Professor Tim Spector joins us this afternoon to discuss how the virus has spread through the UK, and the success of the measures put in place to suppress it.

Lead scientist on the ZOE COVID Symptom Study app, Professor Spector has spent the year tracking the virus using symptom data inputted by 4.5m people across the country.

Using insights from the ‘largest community monitoring of COVID in the world’, Professor Spector will speak about the impact of national lockdowns, firebreaks, and the tier system.

He will also tell RSM President Professor Roger Kirby about his predictions for the vaccine roll-out, and whether we can expect a third wave in the new year.

As usual, there will be plenty of opportunities for Q&A during this webinar. We invite you to submit your questions when you register or during the live broadcast.

Join in the conversation online using #RSMLive
Follow us on Twitter: @RoySocMed
Guest speaker
Professor Tim Spector OBE
Lead Scientist, ZOE COVID Symptom Study app, Professor of Genetic Epidemiology and Director of the TwinsUK Registry at King's College London

Free to watch on Zoom. Register now to join live today at 12:30pm GMT.

Reply-To: rsm.replies@rsm.ac.uk
Head of Department
TimSpector1.jpg
Professor Tim Spector
MB MSc MD FRCP
Tim Spector is a Professor of Genetic Epidemiology and Director of the TwinsUK Registry at Kings College, London.

He trained originally in rheumatology and epidemiology. In 1992 he moved into genetic epidemiology and founded the UK Twins Registry, of 13,000 twins, which is the richest collection of genotypic and phenotypic information worldwide.

He is past President of the International Society of Twin Studies and directs the European Twin Registry Consortium (Discotwin) and collaborates with over 120 centres worldwide.

He has demonstrated the genetic basis of a wide range of common complex traits, many previously thought to be mainly due to ageing and environment. Through genetic association studies (GWAS), his group have found over 500 novel gene loci in over 50 disease areas.

He has published over 800 research articles and is ranked as being in the top 1% of the world’s most published scientists by Reuters. He held a prestigious European Research Council senior investigator award in epigenetics and is a NIHR Senior Investigator.

His current work focuses on omics and the microbiome and directs the crowdfunded British Gut microbiome project.

Together with an international team of leading scientists including researchers from King’s College London, Massachusetts General Hospital, Tufts University, Stanford University and nutritional science company ZOE he is conducting the largest scientific nutrition research project, showing that individual responses to the same foods are unique, even between identical twins. You can find more on https://joinzoe.com/

He is a prolific writer with several popular science books and a regular blog, focusing on genetics, epigenetics and most recently microbiome and diet (The Diet Myth).

He is in demand as a public speaker and features regularly in the media.

For more information visit Professor Tim Spector's research profile.
 
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I haven't watched this myself so far:

RSM COVID-19 Series | Episode 54: One year on, what have we learned?

Royal Society of Medicine
Royal Society of Medicine
7.38K subscribers


SUBSCRIBE
Recorded on Thursday 10 December 2020, as part of the Royal Society of Medicine's COVID-19 Series. A year on from the first recorded cases of COVID-19, Lead scientist on the ZOE COVID Symptom Study app, Professor Tim Spector has spent the year tracking the virus using symptom data inputted by 4.5m people across the country. Taking insights from the ‘largest community monitoring of COVID in the world’, Professor Spector joined RSM President Professor Roger Kirby to speak about the impact of national lockdowns, firebreaks, and the tier system. He also shared with us his predictions for the vaccine roll-out, and whether we can expect a third wave in the new year. The RSM COVID-19 Series is for health professionals, by health professionals; a series of talks dedicated to give healthcare workers on the frontline, regular and easy-to-access updates from healthcare leaders on COVID-19. Learn more about all our webinars here: https://rsm.ac/2UDvcsg Join in the conversation online using #RSMLive Consider making a donation to the RSM: www.rsm.ac/donation All views expressed in this webinar are of the speakers themselves and not of the RSM.
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I had big hopes for this vaccine (the UQ "molecular clamp" stabilised subunit vaccine). But I didn't know how they had engineered the "clamp" using a HIV GP41 glycoprotein fragment of sufficient length to be recognised by T-cell receptors.

https://www.theage.com.au/national/...t-options-do-we-now-have-20201211-p56mlj.html

The key point is that they did anticipate such a risk, which is why they tested for it. The question is why did it proceed so far knowing this risk?

Given the importance of accurate HIV test diagnostics around the world, they've decided not to continue with development of this iteration of the "molecular clamp".
 
Genetic mechanisms of critical illness in Covid-19
Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs).

We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 × 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 × 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 × 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 ×× 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19.

Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice.
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https://www.nature.com/articles/s41586-020-03065-y
 
Interesting to see low expression of interferon receptor. Prof Holgate's team in S'hampton had good results using inhaled interferon to reduce length and severity of illness. They had developed it to help those with severe asthma/COPD, originally. He mentioned it in his talk.
 
This is a pretty cool study that showcases what GWAS studies like DecodeME can do - though the authors had the advantage of knowing that there are strong genetic factors influencing severity of viral illnesses.

Amongst the authors are DecodeME's Dr Veronique Vitart and @Chris Ponting. Veronique has kindly written a blog about the study that will come out on Monday.
 
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