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

Eight new projects will explore how the virus spreads in schoolchildren, healthcare workers, in medical settings, on surfaces in public spaces, and in strictly-Orthodox Jewish communities.

Funded by UK Research and Innovation (UKRI) and the National Institute for Health Research (NIHR), these new research projects on coronavirus transmission, which have been awarded a total of £5.3 million, will help inform policy decisions about COVID-19, including infection prevention strategies and containment measures.

Children appear to be less likely to test positive for coronavirus (SARS-CoV-2) infection than adults and their symptoms are generally milder. More data are needed to fully understand the role children play in transmitting the virus and help schools operate safely.
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https://www.ukri.org/news/5-million-for-new-research-projects-investigating-how-coronavirus-spreads/
 
Coronavirus: Oxford University to resume vaccine trial after pause

Trials of a Covid-19 vaccine being developed by AstraZeneca and Oxford University will resume after being paused due to a reported side effect in a patient in the UK.

On Tuesday, AstraZeneca said the studies were being paused while it investigated whether the adverse reaction was linked with the vaccine.

But on Saturday, the university said it had been deemed safe to continue.

Health Secretary Matt Hancock welcomed the news that the trials would resume.

"This pause shows we will always put safety first. We will back our scientists to deliver an effective vaccine as soon as safely possible," he added.

The university said in a statement that it was "expected" that "some participants will become unwell" in large trials such as this one.

It added that the studies could now resume following the recommendations of an independent safety review committee and the UK regulator, the Medicines and Healthcare Products Regulatory Agency.
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https://www.bbc.co.uk/news/uk-54132066
 
I am a big fan of Hilda Bastian's vaccine updates, she seems to know far more than any other commentator about the details.

https://absolutelymaybe.plos.org/20...is-put-on-hold-covid-19-vaccine-race-month-9/

Sisyphus said:
Do you think the trial should have been halted permanently?
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The problem is the communication and timeframe. They haven't done in-depth investigation. They're pretending like they've checked and disproven the link with the vaccination, when they've simply accepted that this may be a rare side effect.

A reminder that the AstraZeneca vaccine had the highest rate of adverse effects (fever and similar) https://www.wired.com/story/covid-19-vaccines-with-minor-side-effects-could-still-be-pretty-bad/
Which are a consequence of the high doses compared to typical (approved) vaccines- I'd speculate and suggest this increases the risk of the rare autoimmune consequences.

In animal models of autoimmune illness that use "Freund's adjuvant" (typically a bacterial antigen with some sort of oil based adjuvant), the high rate of inducing autoimmune illness is simply a consequence of the high doses they use (roughly 20-100 times the dose/per body weight as immunisations in humans). (note these studies aren't safety trials, they are deliberately inducing autoimmune illness for study of the immune system)
 
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Coronavirus: Monoclonal antibodies to begin UK trial

A new antibody treatment is to be trialled on Covid-19 patients in UK hospitals.

Monoclonal antibodies, which are potent, laboratory-made antibodies, will be given to about 2,000 people to see if they are effective against coronavirus.

It forms part of the UK Recovery Trial, which found that a cheap steroid called dexamethasone could save lives.

The first patients will be given the new drugs in the coming weeks.

Prof Martin Landray from the University of Oxford, who is co-leading the Recovery Trial, said: “This is the first type of treatment that's targeted for this specific virus.

“There are lots of good reasons for thinking it might well be effective - stopping the virus from reproducing, stopping the virus from causing damage, improving survival for patients.

“We need to know, and the way to know is to do the trials that will tell us whether that hope turns into reality.”

What are monoclonal antibodies?
Antibodies could be described as the "warriors" of the immune system.

When coronavirus infects your body, antibodies attach to the spikes of the virus, blocking it from entering your cells.

But we produce many different types of antibodies - the most potent are called neutralising antibodies.

So scientists "sieve" through them to find the one that’s best at sticking to the spike.

The chosen antibody is multiplied in the lab, and produced in huge quantities.

This is then given to patients, immediately boosting their immune response.

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https://www.bbc.co.uk/news/health-54120753
 
The Recovery Trial is also looking at azithromycin, a commonly used antibiotic, and tocilizumab, an anti-inflammatory treatment.
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I thought antibiotics were only effective against bacteria, not viruses.
 
RECOVERY trial will evaluate REGN-COV2 investigational antibody cocktail in the UK

One of the world’s largest efforts to find effective COVID-19 treatments will evaluate the impact of REGN-COV2 on mortality, hospital stays, and the need for ventilation.

The University of Oxford and its partner Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that RECOVERY (Randomised Evaluation of COVid-19 thERapY), one of the world’s largest randomised clinical trials of potential COVID-19 treatments, will evaluate Regeneron’s investigational anti-viral antibody cocktail, REGN-COV2.

The Phase 3 open-label trial in patients hospitalised with COVID-19 will compare the effects of adding REGN-COV2 to the usual standard-of-care versus standard-of-care on its own.
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https://www.ukri.org/news/recovery-...-investigational-antibody-cocktail-in-the-uk/
 
A tiny monoclonal antibody blocks SARS-CoV-2 in animal models. A journal preproof is available. This is not a normal complete human antibody, only one particular domain from the variable heavy chain.

The mention of a tiny antibody naturally makes me think of the nanobodies that occur in species like lamas and alpacas. This, however, is an artificial molecule discovered by searching a huge library of potential human antibodies using the virus spike protein as "bait". It binds to the spike, but not to human cells, which is encouraging in terms of potential side effects.
 
9/14/2020

Tiny Antibody Component Highly Effective Against COVID-19
https://www.upmc.com/media/news/091420-mellors-dimitrov-covid-ab8

University of Pittsburgh Schools of Health Sciences

The researchers report today in the journal Cell that Ab8 is highly effective in preventing and treating SARS-CoV-2 infection in mice and hamsters. Its tiny size not only increases its potential for diffusion in tissues to better neutralize the virus, but also makes it possible to administer the drug by alternative routes, including inhalation. Importantly, it does not bind to human cells—a good sign that it won’t have negative side-effects in people.
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At very low concentrations, Ab8 completely blocked the virus from entering cells. With those results in hand, Ralph Baric, Ph.D., and his UNC colleagues tested Ab8 at varying concentrations in mice using a modified version of SARS-CoV-2 . Even at the lowest dose, Ab8 decreased by 10-fold the amount of infectious virus in those mice compared to their untreated counterparts.
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[ETA: Same research @anciendaze posted about above.]
 
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Interesting.

I wonder how long it persists in the blood?

Would it be used as a preventative (eg medical staff treating infected) as well as a treatment of infected?

Could whole populations receive it and could it help eradicate the virus???

A lot might ride on side effects and it’s effective life.
 
This is interesting
. . . an immunization through a spiky Band-Aid-like patch and overcomes the need for needles and refrigeration, the researchers are “thinking outside the box” when it comes to how Ab8 could be administered. Its small size might allow it to be given as an inhaled drug or intradermally, rather than intravenously through an IV drip, like most monoclonal antibodies currently in development.
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Keela Too said:
Interesting.

I wonder how long it persists in the blood?

Would it be used as a preventative (eg medical staff treating infected) as well as a treatment of infected?

Could whole populations receive it and could it help eradicate the virus???

A lot might ride on side effects and it’s effective life.
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Good questions. I think my biggest question is how long it would take for it to get approval for use in humans. I believe it's only been used in mice and hamsters so far. If it takes as long as a vaccine trial, the pandemic might be largely over by the time it gets approved. It might be that they accelerate the approval of treatments, as opposed to preventatives (like vaccines), because the risks have to be weighed differently between something given to all healthy people and something given only to people who are already ill.
 
Covid-19 Hyperinflammation and Post-Covid-19 Illness May Be Rooted in Mast Cell Activation Syndrome
One-fifth of Covid-19 patients suffer a severely symptomatic, hyperinflammatory course, but specific causes remain unclear. Mast cells (MCs) are activated by SARS-CoV-2. Though only recently recognized, MC activation syndrome (MCAS), usually due to acquired MC clonality, is a chronic multisystem disorder with inflammatory and allergic themes and estimated prevalence of 17%. We describe a novel conjecture explaining how MCAS might cause propensity for severe acute Covid-19 infection and chronic post-Covid-19 illnesses. Observations of Covid-19 illness in patients with/without MCAS, set against our extensive clinical experience with MCAS. The prevalence of MCAS is concordant with the prevalence of severe cases within the Covid-19-infected population. Much of Covid-19's hyperinflammation is concordant with manners of inflammation which MC activation can drive. Drugs with activity against MCs or their mediators have been preliminarily observed helpful in Covid-19 patients. None of our treated MCAS patients who have endured Covid-19 infection have suffered severe courses of the infection, let alone mortality. Hyperinflammatory cytokine storms in many severely symptomatic Covid-19 patients may be rooted in aberrant response to SARS-CoV-2 by the dysfunctional MCs of MCAS rather than normal response by normal MCs. If provable, our conjecture has significant therapeutic and prognostic implications.
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Open access pre-proof PDF, https://www.ijidonline.com/article/S1201-9712(20)30732-3/pdf
 
Just a comment about Ab8. Even if this does not provide long-term immunity, it could still be effective in stopping outbreaks, which is an important part of epidemic control. While this has not undergone any testing in humans, it has been tested against a library of human proteins, and it bound to none of these. This is encouraging. If this were our only weapon against SARS-CoV-2, the time required for human testing would be a problem. This could still become available by the middle of 2021. So could a number of other measures, which would end the crisis phase of COVID-19.

SARS-CoV-2 will be around for a long time, but it doesn't have bring civilization to a halt.
 
Keela Too said:
Interesting.

I wonder how long it persists in the blood?

Would it be used as a preventative (eg medical staff treating infected) as well as a treatment of infected?

Could whole populations receive it and could it help eradicate the virus???

A lot might ride on side effects and it’s effective life.
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The molecule seems to be just one Ig domain, being what is n=known as Vh (variable domain of heavy chain).
That many well mean that it is small enough to be lost in urine so the half life may be quite short - a day or two maybe. IgG is around 20 days.

A potential problem is that the specific binding sequence may itself be immunogenic - generating anti-idiotype that would neutralise any further doses after the first couple of weeks.

Clever mini-antibodies have been developed over a couple of decades but so far, as far as I know, all the licensed antibodies (i.e. proven useful) are full structure. A mini-antibody does not have all the clever signalling equipment attached that facilitates an immune response.

Mini-antibodies might be good for controlling severe viraemia over a 24 period. I am not sure how much conclusion to draw from a ten fold reduction in viral load in mice. That may be under optimal conditions and to clear a virus you need to do much better than that - maybe a millionfold reduction.
 
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