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

Landmark coronavirus study to trial inhaled Imperial and Oxford vaccines
UKRI and NIHR funded researchers at Imperial College London are set to begin trials to assess the safety and effectiveness of two of the UK’s coronavirus vaccines in development, when inhaled into the lungs.

Clinical study
Researchers at Imperial College London funded by UKRI and the NIHR through the COVID-19 rapid response call are set to begin trials to assess the safety and effectiveness of two of the UK’s coronavirus vaccines in development, when inhaled into the lungs.

The clinical team will compare COVID-19 vaccine candidates being developed by both Imperial College London and Oxford University, delivering the vaccines directly to the respiratory tract of human volunteers, by inhalation through the mouth.

The research, led by Dr Chris Chiu, head of the Imperial Network for Vaccine Research, aims to assess the safety and efficacy of administering the vaccines as airborne droplets inhaled by a volunteer, rather than an injection into muscle.

The hope is that directly targeting the cells lining the airways – the typical point of infection for respiratory viruses – may induce a more effective immune response against the SARS-CoV-2 virus.

This could potentially accelerate the development of effective vaccines against COVID-19 by exploring additional delivery methods and targets.

Dr Chris Chiu, from the Department of Infectious Disease, who will lead the project, said: “We have evidence that delivering influenza vaccines via a nasal spray can protect people against flu as well as help to reduce the transmission of the disease. We are keen to explore if this may also be the case for SARS-CoV-2 and whether delivering COVID-19 vaccines to the respiratory tract is safe and produces an effective immune response.”

Dr Chiu added: “The current pandemic is caused by a respiratory virus which primarily infects people through the cells lining the nose, throat and lungs. These surfaces are specialised and produce a different immune response to the rest of the body, so it is critical we explore whether targeting the airways directly can provide an effective response compared to a vaccine injected into muscle.”

Vaccine delivery
Currently, clinical trials are being carried out to assess the safety and efficacy of multiple COVID-19 vaccines delivered by intramuscular injection: these include Oxford’s ChAdOx1 nCoV-19, as well as Imperial’s saRNA vaccine platform, which are both in clinical trials.

But scientists are keen to explore the potential for vaccines to be delivered to the respiratory tract. Here they could induce a localised, and potentially more specialised, immune response. It is unclear how this compares to the systemic immune response induced by injected vaccines.

Dr Chiu will work with Imperial’s Professor Robin Shattock and Oxford’s Professor Sarah Gilbert to assess the vaccines by delivering them to a small group of healthy volunteers as an aerosol – similar to how inhaled asthma medications are delivered.

A total of 30 people are expected to be recruited to the trials. For each vaccine, researchers will assess three dose levels (low, medium and high dose) with three volunteers per group (18 in total), followed by an additional six in each group at the best dose (12 total).

In addition to blood and nasal sample analyses, volunteers will undergo bronchoscopy to obtain samples from deeper within the lungs and monitor the effects in the lower respiratory tract.

Volunteers will receive aerosolised vaccines through a nebulizer, which will deliver the vaccine as airborne droplets through a mouthpiece. With direct vaccine administration to the respiratory tract, based on previous studies, lower doses may be required than by intramuscular injections to induce protective responses.

In addition to blood being analysed for the presence of neutralising antibodies (Immunoglobulin G, or IgG) and T cells, which fight the virus and protect against re-infection, the team will analyse nasal samples for the presence of specialised antibodies found in the nose and throat, called IgA, which would indicate a more specialised and localised immune response to the virus.
Click to expand...

https://mrc.ukri.org/news/browse/la...ines/?utm_medium=email&utm_source=govdelivery
 
With regards to inhaled vaccinations, I note that the nasal Influenza vaccine has inferior efficacy compared to the intramuscular vaccine.

Despite all the claims that there is no mucosal immunity induced by intramuscular immunisation, this is simply not true, IgA was induced by the moderna vaccine for example and IgG play a key role in the respiratory mucosa. It is the gut which has less protection from intramuscular immunisation, but this basically means a few days of asymptomatic infection in the gut until significant class-switching and lymphocyte migration to the gut occurs. The intramuscular polio vaccination is enough to prevent serious symptoms in the gut for example.

With regards to the adenovirus vector and mRNA vaccines, since there is no exposure to the spike protein until after the vector has infected the cell and the DNA or RNA has been transcribed, the dosages need to be much larger than a live influenza nasal vaccine or intramuscular immunisations. This increased dosage requirement could lead to poor efficacy or increase risk of side effects.
 
Wits_End said:
people who are going around using their mask as a chin hammock now.
Click to expand...

You see them on the TV news all the time. I scream at them, but of course they can't hear me since they're on TV and I'm in my bedroom. But just as bad are the ones whose noses aren't covered, and whose mouths are covered but not well (you can see their upper lip). I noticed an awful lot of that with people complaining about how they couldn't get a test for their kids. I haven't used a mask yet, since I haven't been out of caravan/car/house/garden.

I'm shocked that while we're (in England) told to wear masks in public transport and in shops and hairdressers etc that we haven't had any public service adverts telling people how to put masks on and off (very important!!!), and how important it is to cover nose as well as mouth. They should at least put out some joke about how "leaving yer nose out is like leaving yer bits out of yer underwear"? People don't understand how masks work - it's important to educate them.
 
Can Corona be exhaled through the nose?

So assuming a Corona+ person isn't sneezing, can they spread it when they don't talk?

I see the nose-free version in public transport and thought about mentioning it to them. But if I make them talk back to me I might put myself more at risk..
 
Leila said:
Can Corona be exhaled through the nose?

So assuming a Corona+ person isn't sneezing, can they spread it when they don't talk?

I see the nose-free version in public transport and thought about mentioning it to them. But if I make them talk back to me I might put myself more at risk..
Click to expand...

My guess would be that the virus is not expelled from the nose except when sneezing. But if someone is infected they will almost certainly tough their nose and then wipe virus of the rails and seat handles.
 
Remember Russia's Sputnik V vaccine? Summary data for phase I and II testing were published in The Lancet. Now other researchers have published an open letter to those authors, also referenced in Nature. Some of the questions they ask are fairly standard, but I'm bothered by the finding of duplicate data points. This is very unlikely to occur by chance, and often shows up in cases of fraud.

Their call for access to raw data is reasonable, but I would bet against them getting it.
 
anciendaze said:
Remember Russia's Sputnik V vaccine? Summary data for phase I and II testing were published in The Lancet. Now other researchers have published an open letter to those authors, also referenced in Nature. Some of the questions they ask are fairly standard, but I'm bothered by the finding of duplicate data points. This is very unlikely to occur by chance, and often shows up in cases of fraud.
Click to expand...

There were lots of problems with the methodology of the Sputnik V vaccine trial. The data presentation was far poorer than the similar Chinese (Sinovac) adenovirus vector based vaccine trial. I don't know why it was published in The Lancet...

In particular, the Chinese study tested participants for adenovirus-5 antibodies and then performed analyses to see whether this would reduce the performance of vaccine - and indeed they found that prior adenovirus antibodies did lead to significantly lower spike-RBD antibodies.

The Russian study also used an adenovirus-5 based vector, but seemingly, they decided not to utilise this additional test. Likewise, the lack of randomisation on the crossover was another sloppy omission.
 
Kalliope said:
The Scientist - The Immune Hallmarks of Severe COVID-19 by Katarina Zimmer

Researchers are trying to make sense of immune systems gone haywire and develop biomarkers to predict who will become the sickest from a coronavirus infection.
Click to expand...

The usual hype around cytokines.

I liked the response by Manu who likened it to a “cytokine breeze”. Fortunately there was mention of studies that found that patients who died, did not have elevated cytokines compared to those who lived.

The impaired interferon response early in the infection probably does play a role (allowing the virus to gain a strong foothold), but it is not the whole story. Notably, this hypothesis predates COVID19.

It seems strange that many researchers are hyper focused on lymphocytes and immune signalling without considering the overall physiological picture - the diminished clearance of immune complexes and the role of the vascular system, especially given the risk factors (high blood pressure) and the known role of the spike protein interacting with factors that affect the regulation of blood flow, such as ACE2, heparan sulfate etc.
 
I can't remember the details, so many things have come and gone over the years, but it was suggested that blood thinners could be useful for ME.

There have also been studies which have found problems with the lining of blood vessels and suggestions that a vasculitis could account for some of the symptoms. I have strange blistering which appears on my fingertips and other symptoms in my nails and fingers that are suggestive of vasculitis.

Any research into these things for covid could give insight into ME
 
According to a study at Danderyd's hospital in Sweden, four out of five people keep their SARS-CoV-2 antibodies for at least four months.

Danderyds Sjukhus: Fyra av fem behåller antikroppar mot SARS-CoV-2
https://www.mynewsdesk.com/se/dande...-behaaller-antikroppar-mot-sars-cov-2-3035673

Google Translate, English
Press release Google Translate said:
This spring, samples were collected from 2,149 employees at Danderyd Hospital, where 19 percent were shown to have antibodies to SARS-CoV-2 (COVID-19). Phase 2 of the study has now been carried out, where 92 percent of the group have given blood samples again. The results show that of the 405 who had antibodies in the spring, 82 percent still have measurable levels after at least four months. [...]

- We see that the duration of antibodies is linked to certain symptoms such as difficulty breathing and fever. [...]

Now the COMMUNITY study continues and next, the memory of the T cells and the neutralizing ability of the antibodies will be examined. Among other things, study participants with low and high antibody levels, respectively, will be compared with a group that has been highly exposed at work and at home, but still has not developed antibodies.

- By continuing to follow this group, and also analyze the antibodies' ability to neutralize the virus, we will get further information about how the immune system reacts in the long term and in the long run also how a vaccine can create long-term immunity, says Sophia Hober, professor of molecular biotechnology at KTH.

- It will be very interesting to get information about whether the T cells' memory can be linked to exposure, symptoms or different antibody levels. As we still do not have a comprehensive picture of the immunity of COVID-19, we want to continue to follow this unique group and we plan ongoing sampling for at least one year to come, says Charlotte Thålin. [...]
Click to expand...
 
An interesting new tack:

Scientists find Covid-19 weakness which could be beaten with small molecule anti-viral drugs

http://www.msn.com/en-gb/news/newsl...iral-drugs/ar-BB19h6DM?li=AAnZ9Ug&ocid=ASUDHP

An international team from Bristol University believe they have found a “druggable” pocket within a Sars-CoV-2 sample which could be a potential pandemic "game-changer".

The scientists hope the discovery could lead to small molecule, anti-viral medicines being developed to shut down and eliminate the virus before it enters human cells.
Click to expand...
 
Last edited:
Wits_End said:
An interesting new tack:

Scientists find Covid-19 weakness which could be beaten with small molecule anti-viral drugs

http://www.msn.com/en-gb/news/newsl...iral-drugs/ar-BB19h6DM?li=AAnZ9Ug&ocid=ASUDHP
Click to expand...

https://science.sciencemag.org/content/early/2020/09/18/science.abd3255

I usually reserve a bit of extra skepticism on research about omega-6 fatty acids...

They speculate that it stabilises the spike protein conformation, but do not provide any conclusive evidence. The "pocket" also seems to be a part of most other human coronaviruses too.

It will be years before this could lead to approved treatments and by then, I'd hope that we'd already have a vaccine by then...
 
You must log in or register to reply here.
Back
Top Bottom