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Medical Science for Treatment of Covid-19 Medical Science for Treatment of Covid-19

07-22-2020 , 01:32 AM
I think there should be a thread on 2+2 for discussion of the developing medical science for the treatment of Covid-19. Existing threads are mostly concerned with the politics and management of the pandemic. Please limit your discussion here to the developing medical science for the treatment of the Covid-19 disease.

Here are two videos to get things started.

Dr. Yo on the Dr. Drew Show



Dr. Patterson on the Dr. Been Show



PairTheBoard
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07-22-2020 , 05:24 AM
https://www.thelancet.com/journals/l...604-4/fulltext

https://www.statnews.com/2020/07/20/...id-19-vaccine/

"A Covid-19 vaccine being developed by Oxford University and the drug giant AstraZeneca generated an immune response in a study of roughly 1,000 patients, according to interim results published Monday.

The data, published in the medical journal the Lancet, also show that the vaccine caused side effects, including fever, headaches, muscle aches, and injection site reactions, in about 60% of patients. All of the side effects were deemed mild or moderate, and all resolved themselves over the course of the study.

While the Oxford-AstraZeneca vaccine, known as AZD1222, has moved most rapidly into larger-scale studies of any major contender — and AstraZeneca has said that billions of doses could be manufactured — the new data represent the first glimpse researchers have gotten at its efficacy. They show a relatively safe vaccine — though side effects were greater than for a meningitis vaccine, to which it was compared — that engages the immune system to fight the virus. AstraZeneca said that, because of the results, it is likely that future studies will test giving patients two doses of the vaccine."
Medical Science for Treatment of Covid-19 Quote
07-22-2020 , 04:04 PM
Some Vaccine basics for background information:

Vaccines are like a training course for the immune system. They prepare the body to fight disease without exposing it to disease symptoms.

When foreign invaders such as bacteria or*viruses*enter the body, immune cells called lymphocytes respond by producing antibodies, which are protein molecules. These antibodies fight the invader known as an antigen and protect against further infection. According to the Centers for Disease Control and Prevention (CDC), a healthy individual can produce millions of antibodies a day, fighting infection so efficiently that people never even know they were exposed to an antigen.

Unfortunately, the first time the body faces a particular*invader, it can take several days to ramp up this antibody response. For really nasty antigens like the measles virus or whooping cough bacteria, a few days is too long. The infection can spread and kill the person before the immune system can fight back.

That's where*vaccines*come in. According to the Children's Hospital of Philadelphia Vaccine Education Center, vaccines are made of dead or weakened antigens. They can't cause an infection, but the immune system still sees them as an enemy and produces antibodies in response. After the threat has passed, many of the antibodies will break down, but immune cells called memory cells remain in the body. When the body encounters that antigen again, the memory cells produce antibodies fast and strike down the invader before it's too late.

Vaccines also work on a community level. Some people can't be vaccinated, either because they are too young, or because their immune systems are too weak, according to the CDC. But if everyone around them is vaccinated, unvaccinated people are protected by something called*herd immunity. In other words, they're unlikely to even come in contact with the disease, so they probably won't get sick. When it comes to vaccines, sometimes it can pay to follow the crowd.

Above purloined from Live Science website.
**********************

Below is a link to a good video on vaccines and how they work:



how-do-vaccines-work#

Last edited by Zeno; 07-22-2020 at 04:07 PM. Reason: Typos
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07-22-2020 , 04:19 PM
+1 on the idea of the thread.
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07-22-2020 , 05:05 PM
I didn't find the Dr. Drew youtube to be very helpful.
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07-22-2020 , 05:14 PM
Quote:
Originally Posted by Howard Treesong
I didn't find the Dr. Drew youtube to be very helpful.
You did not foresee this?

I also didn't find it helpful, but it did help that I knew not to watch it.
Medical Science for Treatment of Covid-19 Quote
07-22-2020 , 09:23 PM
Quote:
Originally Posted by BrianTheMick2
You did not foresee this?

I also didn't find it helpful, but it did help that I knew not to watch it.

I watched it against my better judgment.

BTM 1
HT 0
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07-22-2020 , 11:09 PM
It’s only the first inning......
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07-23-2020 , 02:47 AM
This video is from April 1, 2020. Dr. Ho is highly respected for his years of research in HIV. He was on the Rachel Maddow show July 22 where he described progress his group has made with neutralizing monoclonal antibodies derived from people having recovered from Covid. He says the most potent ones they've developed come from people who had the most severe illnesses from Covid.

On Neutralizing Monoclonal Antibodies




PairTheBoard
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07-24-2020 , 09:34 AM
Dr David Ho on Rachel Maddow show July 22, 2020



Here is a link to the Nature article with abstract
and link to the PDF file of the paper Dr Ho mentions
on Maddow's show above.

https://www.nature.com/articles/s41586-020-2571-7


PairTheBoard
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07-24-2020 , 09:47 AM
That was a slow softball for Howard
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07-24-2020 , 09:59 AM
LOL. I'll read the paper.
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07-24-2020 , 10:38 AM
Every time I watch a news clip like that, I find that it raises many more questions than it answers. Here, the message is that researchers have isolated 19 potent antibodies, nine of which are exquisitely potent. Questions: would any one of these alone neutralize the virus? What is the development path for these to become treatments or vaccines, as the case may be? What's Ho's assessment as to how likely it is that these are useful and practical research/development avenues?

I'll stay away from characterizing Maddow's narrative. Thanks, PTB, interesting.
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07-24-2020 , 09:19 PM





In any case, I believe it will be endemic, vaccine or not. It won't be eradicated like smallpox and polio but will insread bug us like the flu and the other coronaviruses that do infect humans.

Last edited by MacOneDouble; 07-24-2020 at 09:24 PM.
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07-24-2020 , 09:51 PM
Obviously right, with a respiratory virus spreading throughout the world like wildfire. You'd have to vaccinate 60 percent or more of the growing world's population to eradicate it. It will succeed.
Medical Science for Treatment of Covid-19 Quote
07-24-2020 , 10:47 PM
Quote:
Originally Posted by MacOneDouble





In any case, I believe it will be endemic, vaccine or not. It won't be eradicated like smallpox and polio but will insread bug us like the flu and the other coronaviruses that do infect humans.


Nice post, Mac. He's watchable: the right level of depth for laymen.
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07-25-2020 , 01:39 AM
I don't know what the medical community thinks of this theory but it would be bad if it was proved true.

https://gh.bmj.com/content/5/6/e002564

Quote:
In this paper we discuss a hypothesis that prior viral infections—either by SARS-CoV-2 or different strains of coronaviruses, or potentially even other respiratory viruses—may predispose to more severe forms of COVID-19, following a secondary infection with SARS-CoV-2.
The proposed mechanism is called "antibody-dependent enhancement (ADE), sustained by prior exposure to SARS-CoV-2 or other viruses/coronaviruses."

The idea is that non-neutralizing or subneutralizing antibodies, or even fully neutralizing antibodies (for other corona viruses?) may actually foul up the immune response to a second infection of Cov-Sars-2. Thus setting off the cytokyne storm. Evidently this ADE effect is a known thing for other viruses.

From what I gather, if this is true then you only want antibodies that are fully neutralizing for Sars-Cov-2. The idea is that's what makes transfusion therapy work. It might also explain why Dr. Ho found the most potent mab-antibodies he produced were from patients who recovered from the most severe form of the disease. Maybe that's where fully neutralizing antibodies get produced.

A lot of speculation here. But it's a warning that vaccines should be fully tested for safety before being widely used.


PairTheBoard
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07-25-2020 , 04:57 AM
Synairgen press release of results for it's Inhaled Interferon-beta treatment of Covid-19. (See MacOneDouble's video post above).

https://www.synairgen.com/wp-content...9-patients.pdf


Several experts react to the Synairgen press release.

https://www.sciencemediacentre.org/e...d-19-patients/

Quote:
Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine (LSTHM), said:

“This announcement is a requirement of stock market rules rather than a proper, even preliminary, scientific report. It does suggest that this new inhaled treatment of a drug that has been used in an injectable form for many years in multiple sclerosis, giving moderate symptomatic benefit in that condition.

“The primary outcome of this phase II study (as described in the trial protocol) was stated to be an ordered scale for clinical improvement from a minimum of 0 (patient is well) to a maximum of 8 (death), which is similar to that used for other clinical trials in COVID-19. It was intended to be measured over the 14 days during which a patient received treatment.

“The press release relates to this outcome but may not be quite what was the outcome defined in the protocol. The company state ‘The odds of developing severe disease (e.g. requiring ventilation or resulting in death) during the treatment period (day 1 to day 16) were significantly reduced by 79% for patients receiving SNG001 compared to patients who received placebo (OR 0.21 [95% CI 0.04-0.97]; p=0.046).’

“The treatment is targeted at those in a very early stage of their clinical disease in that they had to be within 24 hours of their positive test for the SARS-CoV-2 virus. It was intended that patients could be treated at home as well as in hospital, but the press release only refers to hospitalised patients. It is not clear whether the reported data are a sub-group or whether they did not recruit sufficient patients to be treated at home. The intended number was 400, but this report is based on 101 patients.

“It is clear that this seems to be a promising treatment for the early stages of COVID-19 but should definitely be regarded as preliminary – it is a phase II study, though it has some aspects of a phase III trial in that it considers clinical outcomes and is randomised with a placebo control. From this point of view the study has definite strengths.

“It is sad that stock market rules seem to militate against proper scientific release of at least a preprint of a scientific paper. It is also not clear whether a data monitoring committee was involved in advising release of the data publicly. The adage that says “beware of small studies claiming large benefits” should be borne in mind here. There are reasons to believe it could well be an effective treatment, but these results, while encouraging, should not be taken to mean that the treatment is so dramatic that everyone should be given it. There is a need for many more patients to be recruited and for any adverse effects to be carefully evaluated. Thrombotic microangiopathy was a rare but severe coagulation complication associated with an injectable form of the drug, and, given the coagulation problems associated with COVID-19, great care will be needed to ensure that such problems do not occur with the inhaled form of the drug.”

PairTheBoard
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07-25-2020 , 07:03 AM
Well, pretty much everything is in the preliminary phase. Generally, that means don't get your hopes up on your favorite.
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07-25-2020 , 08:46 AM
From the link to experts' opinions on the Synairgen Interferon-b trial
https://www.sciencemediacentre.org/e...d-19-patients/

Quote:
Dr Penny Ward, Visiting Professor in Pharmaceutical Medicine at King’s College London and Chair of the Education and Standards Committee of the Faculty of Pharmaceutical Medicine, said:

"Baseline features of each arm demonstrated that the proportion of patients with diabetes was three times higher in the placebo arm (9/50, 18%) than among those taking interferon (3/48, 6.3%). There was also an imbalance in the proportion of patients with cardiovascular disease between those taking placebo (8/50, 16%)and those taking interferon (5/48; 10.4%). These differences could have affected the outcome, although at a press conference today the company commented that the analysis was adjusted for baseline risk factors."
How could they possibly adjust for that? Why didn't they even those things out to begin with?

In the Dr. John Campbell video (2nd one in MacOneDouble's post) he has this the other way around with the worse comorbidities in the drug arm. At about 16:40 of the video.

Furthermore, in Synairgen's PR there's this
https://www.synairgen.com/wp-content...9-patients.pdf

Quote:
Patient groups were evenly matched in terms of average age (56.5 years for placebo and 57.8 years for SNG001), comorbidities and average duration of COVID-19 symptoms prior to enrolment (9.8 days for placebo and 9.6 days for SNG001).

PairTheBoard
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07-25-2020 , 09:35 AM
On the Interferon-beta trial, the patients with comorbidities would have been by far the ones most likely to progress to severe status. Also, diabetes and heart disease are probably by far the two most likely comorbidities. Then if Dr. Penny Ward has it right that for these two comorbidities there were 17 out of 50 for placebo compared to 8 out of 50 for the drug, better than a 2-1 ratio, that's a huge skewing bias in the Synairgen report that the drug produced a 79% reduction in progression to severity. The real p-value is more like one for improving from an expected 50% reduction to 79%. If the actual number of such patients who progressed to severity was something like 5 and 1, all coming out of the 17 and 8 with comorbidities, the p-value would have to be almost worthless.


PairTheBoard
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07-25-2020 , 10:11 AM
i'm very skeptical on synairgen, primarily because this is a press release with some significant analysis gaps.
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07-25-2020 , 11:58 AM
Scientists claim enzyme nsp16 produced by Sars-Cov-2 virus turns off the immune response of infected cells. Interferon mentioned.

https://bgr.com/2020/07/25/coronavir...me-camouflage/

Quote:
Scientists identified an enzyme called nsp16 that the virus produces and then uses to modify its RNA cap. Once the virus binds to cells, it uses its RNA to instruct those cells to mass-produce thousands of virus copies. The cell is destroyed in the process and the new copies can infect other cells. The immune system would block some of them and would destroy infected cells as well. This ongoing battle happens at the cellular level, and it’s a critical process that affects the recovery of patients.

PairTheBoard
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07-26-2020 , 09:21 AM
Easy to follow Dr. Been presentation of results from new German study for how the coronavirus is working at the cellular level. The study concludes that blockers of the CCR1 and CCR5 receptors are indicated for treatment. Also, the immune system responds differently in the nasal area (where it first infects) than in the lungs. In the lungs the immune system produces much more chemokines telling normal cells to suicide.





PairTheBoard
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07-27-2020 , 05:53 PM
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