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

A vaccine against the spike protein made the virus more dangerous in animal tests.

 

Yes I heard something about that. It may not be relevant but a finding like that in an animal system might prevent development. If it is true then it begins to look as if making a vaccine might be as hard as for HIV. Maybe we have to factor in the possibility that you cannot make a vaccine against this thing.

 

Wow! As easy as that!

 

The key factor is the delivery mechanism. The RNA has so somehow make it inside the cell intact, then migrate to the nucleus, be transcribed into viral proteins and then the viral proteins have to make it outside the cell to be detected by the immune system. Most of the time this process fails, but in principle (quite a few animal models and a few human studies), it can work just enough for seroconversion to occur.

Rogue RNA simply doesn't survive outside the cell and has little chance of being internalised, so traditionally these sorts of vaccines simply didn't work.

The key innovations are "nanotechnology" based (hey, that was my major at UNI! ). So there are various technologies that involve novel lipid/polymer/dendrimer coatings that allow the RNA to survive in tact and to enter the cell via endocytosis.
Some details on the technology:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/

The second key is how and where it is delivered into the body. Evidence in humans shows that delivery using a needle and into the muscle results in poor immunity - most likely because the RNA never manages to undergo the process I described above. Efficacy is increased by targeting the lymph and high velocity fluid 'jet' injection. The latter likely improves efficacy since it spreads out the payload over a larger area.

There are DNA vaccines that work in much the same way, DNA is more stable, but it still has the other disadvantages described above, and there is additional risk of the viral genes being incorporated into the genome.

The vaccine that @Jonathan Edwards was talking about is not strictly a DNA vaccine, but a recombinant viral-vector vaccine. The typical example is a an Adenovirus (which is a double stranded DNA virus) which has been engineered with recombinant technology to include proteins from other pathogens. Do note however, that these additional proteins won't actually be incorporated in the virion (complete virus particle) as some sort of hybrid virus. This vaccine also has the risk of genome incorporation.
As far as I know, this type of vaccine has only had widespread use (albeit in an experimental sense) to control Ebola virus. I personally doubt this type of vaccine will be approved for universal vaccination due to the additional risks compared to conventional vaccines.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994731/

The other key type is engineering bacteria to produce the viral proteins using recombinant technology. The downside to this is they might not fold in quite the same way as in a human cell and hence the resulting antibodies that are developed upon exposure might not work as well.

Compared to traditional vaccines, all of these have a key advantage, namely the basic technology can be re-purposed to pretty much any pathogen (so long as we know the genetic sequence), in a matter of weeks.

 

I saw that China was working on this type of vaccine for covid, in the same vein as the ebola vaccine you mention.

https://statnano.com/news/67536/China’s-First-Coronavirus-Vaccine-Delivered-for-Human-Trials

The search also led me to this vaccine theory, which seems a far way off and I didn't quite understand.

https://news.northeastern.edu/2020/...lp-us-get-closer-to-a-treatment-for-covid-19/

 

Can COVID-19 cause long-term lung damage?
At this early stage of the pandemic there is no evidence to show that permanent or long-term lung damage is a common consequence of infection. A report from Hong Kong suggests short-term declines in lung function among those recovering from COVID-19.


An electron microscope image for the SARS-CoV-2 virus (in orange) emerging from a cell (grey) that had been cultured in the lab. (NIAID-RML)
A recent report by Dr. Keith Mortman of George Washington University Hospital, circulated widely in the media, provides a graphic description of the extensive damage to the lung caused by COVID-19 in otherwise healthy patients.

However, these reports describe currently ill or newly recovered victims of the disease. It is still too soon to know whether the damage caused by the infection is permanent or long-term.

 

https://twitter.com/user/status/1244501818601689088

 

Thank you very much for the explanation; hopefully, they can deliver RNA vaccines in the near future. Interesting that it's been used (successfully?) for Ebola; maybe the seriousness of the current situation will mean that some countries will try an RNA vaccine.

Based on a very brief glance, I noticed references to tuberculosis; looks like they have potential for difficult to treat pathogens.

 

Interesting report about testing a drug which is inhaled to deliver IFN-B to the lungs to increase the antiviral activity. Phase 2 Trials in asthma have been encouraging.
https://www.southampton.ac.uk/news/2020/03/covid19-drugs-trial.page

Apologies if this has already been mentioned, have not read much of this thread.

Stephen Holgate is one of the 3 founders of the drug development Company involved.

 

Not sure if this March 27 article about Australian researchers studying the TB vaccine, as an immune booster has been posted.

If it's effective, it might buy time while a specific vaccine, or vaccines are developed for COVID-19.

"Healthcare workers trial TB vaccine for coronavirus protection"
https://www1.racgp.org.au/newsgp/clinical/healthcare-workers-to-trial-tuberculosis-vaccine-f

ETA: Anyone have any comments? @Sean @Jonathan Edwards @Snow Leopard ?

If we've all already had this vaccine many years ago, might a repeat help? Act as a booster, if that's the thinking here? Thank you.

 

@dave30th

Has anyone else noticed how the narrative has switched to how people have died WITH coronavirus instead of FROM coronavirus.

I have noticed this via a number of outlets and in the media.

They are two massively different things.

https://www.bbc.co.uk/news/uk-52101040

 

I thought that was reasonably clear from the outset, at least from BBC reports.

 

@dave30th

Matching like for like figures country to country is certainly not clear when there is the option to jump between terms.

Also it makes seasonal like for like figures of "unexpected deaths" an unreliable data set.

I have literally just seen live on the BBC news channel the total number of people who have died OF the virus whilst I am making this post.

Thats 3 constantly changing terms that mean drastically different things.


At the same time we are being told that one can be unsymtonmatic and still test positive and may only ever be a carrier.....
Exactly what does it mean if one dies with stage 4 lung cancer, COPD and then also tests positive for coronavirus?

Where are the OF, FROM, and WITH like for like data sets with each term fully defined for China, Italy the US the UK Spain and all underlying medical conditions shown for each patient etc?

Bloody hell theres a fourth term now just as I am still making this post right from goverment.....

https://news.sky.com/story/coronavi...-after-testing-positive-for-covid-19-11966273

https://www.telegraph.co.uk/global-...-19-news-updates-cases-deaths-flights-latest/

So thats...

Died of..

Died from....

Died with....

Died after testing positive....

 

"Is There a Role for Tissue Plasminogen Activator (tPA) as a Novel Treatment for Refractory COVID-19 Associated Acute Respiratory Distress Syndrome (ARDS)?"

https://journals.lww.com/jtrauma/Ci...e_for_Tissue_Plasminogen_Activator.97967.aspx

This article says it's Open Access. I couldn't. Hope others can. (Apologies if this is already posted.)

 

From the web page you linked

Click the PDF symbol near the top on the left.

 

Thank you!

 

2 dogs and 2 cats infected by their owners in different countries.

It can jump from humans to pets. Nobody can predict what will happen.

Will it spread through pet populations?

 

Most proteases / inhibitors like this are weak antivirals at best, generally used to enhance a primary therapy.

 

It looks as if the idea is to mitigate diffuse intravascular coagulation and fibrin obstruction to alveoli as part of ARDS. Reasonably sensible but with undoubted risks of haemorrhage.