Coronavirus

[Mr._Clark]

Here's a recent "final report" concerning Remsdesivir. It seems to be at least somewhat effect:

>>>Results
A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).<<<

https://www.nejm.org/doi/full/10.1056/NEJMoa2007764

 

[Mr._Clark]

I believe masks help, but even N95 masks are certainly not 100% effective:

>>>The next day I got a call that I had also tested positive for Covid-19. I should have expected that news, because the night before I had lit a pumpkin-scented candle but didn’t realize until later that I hadn’t smelled its fragrance.

I was extremely scared. But I was also angry. I was angry at my school for not following state recommendations to keep students home and use remote learning, at my doctor for downplaying the increasing threat of the virus, at my family members and friends who brushed off my concerns, and even angry at myself for creating a false sense of security that using an N95 mask, an air purifier, and a plexiglass shield in my classroom would keep me safe.

I was angry, and still am, that the response to a worldwide pandemic has become so deeply politicized in the U.S. and that even though I took every precaution, it still wasn’t enough. I began taking nebulizer treatments four times a day to keep my lungs clear and began taking zinc and vitamin D.<<<

I worked hard to protect myself from Covid-19 and the flu. Yet I got both — at the same time

During the time when I felt the worst, anxiety compounded my physical symptoms. I wondered every time I fell asleep if I would wake up wheezing or unable to breathe.

www.statnews.com

 

[Mr._Clark]

It looks like we're close to starting vaccine distribution.

United Airlines charters flights to distribute Pfizer’s COVID-19 vaccine

United Airlines on Friday commenced charter flights to send doses of Pfizer and BioNTech’s COVID-19 vaccine candidate to prepare for distribution, according to a report by The Wall Stree…

thehill.com

 

[Dude#1279435]

I believe masks help, but even N95 masks are certainly not 100% effective:

I think masks work better in the spreading of it but no evidence in preventing the wearer from getting it. Common sense says to me if it does even that little bit you wear one.

 

[highfigh]

Should be against the rules of the forum to speak that much truth.

my standing questions are and have been:
when did America cease being the greatest country on earth (warts and all)
what was the seminal event that caused its fall from greatness
what period of time are we trying to return to?

How does "The US depends on China for far too much manufacturing and if they stop, our economy could grind to a halt" show World domination? Many store shelves are empty and whole aisles have been removed- it's not only so the stores aren't buying merchandise, it's because the merchandise hasn't been available. Sure, Amazon can sell it but they aren't the ones stocking everything on that site. Electronics distributors have had a hard time getting equipment and they're suffering for it because that industry didn't seem to have considered the possibility of a massive slowdown.

The US must have something people from other countries want- otherwise, they wouldn't continue to come here.

That said, millions of people who were born here enter adulthood without being able to read, do basic math, get a decent job/enough food or house themselves. The fact that many poor immigrants can succeed in all of these areas is a problem. The last sentence isn't anti-immigration, it's anti 'let people fail and do nothing about it'.

 

[Mr._Clark]

I think masks work better in the spreading of it but no evidence in preventing the wearer from getting it. Common sense says to me if it does even that little bit you wear one.

"no evidence in preventing the wearer from getting it"

Not true. There is evidence masks protect the wearer:

>>>Another study highlighted by the CDC found that among 1,000 people contact-traced in Thailand, those who reported always wearing a mask during high-risk exposures had a greater than 70% reduced risk of becoming infected compared with those who didn't wear masks under those circumstances.<<<

Wear Masks To Protect Yourself From The Coronavirus, Not Only Others, CDC Stresses

The public health agency had previously emphasized that masks protect other people from viruses you might expel. The new advice gives a less altruistic reason to wear face coverings.

www.npr.org

 

[Old Onkyo]

How does "The US depends on China for far too much manufacturing and if they stop, our economy could grind to a halt" show World domination? Many store shelves are empty and whole aisles have been removed- it's not only so the stores aren't buying merchandise, it's because the merchandise hasn't been available. Sure, Amazon can sell it but they aren't the ones stocking everything on that site. Electronics distributors have had a hard time getting equipment and they're suffering for it because that industry didn't seem to have considered the possibility of a massive slowdown.

The US must have something people from other countries want- otherwise, they wouldn't continue to come here.

That said, millions of people who were born here enter adulthood without being able to read, do basic math, get a decent job/enough food or house themselves. The fact that many poor immigrants can succeed in all of these areas is a problem. The last sentence isn't anti-immigration, it's anti 'let people fail and do nothing about it'.

you didn’t answer the questions.Try again billy.

 

[Mr._Clark]

you didn’t answer the questions.Try again billy.

There's a thread devoted to this topic. Please post in that thread.

 

[Dude#1279435]

"no evidence in preventing the wearer from getting it"

Not true. There is evidence masks protect the wearer:

>>>Another study highlighted by the CDC found that among 1,000 people contact-traced in Thailand, those who reported always wearing a mask during high-risk exposures had a greater than 70% reduced risk of becoming infected compared with those who didn't wear masks under those circumstances.<<<

Wear Masks To Protect Yourself From The Coronavirus, Not Only Others, CDC Stresses

The public health agency had previously emphasized that masks protect other people from viruses you might expel. The new advice gives a less altruistic reason to wear face coverings.

www.npr.org

It does. Great then.

 

[Swerd]

https://www.cnbc.com/2020/11/26/astrazeneca-oxford-defend-vaccine-trials-after-questions-raised-in-us.html

You've got to love this. So some subjects in the Oxford-Astrazeneca trial were accidentally given half doses of the vaccine, and the smaller does increased efficacy to ~90% from 62%. And, of course, the mob goes on the attack for this lack of rigor, when it looks to me like good news. The manufacturing capacity should go twice as far if a half-dose is actually better. I still think I'd rather have an mRNA vaccine myself, but considering the manufacturing and distribution problems with the mRNA products, this is probably good news for most of the world where distribution is more challenging.

Clinical trials are all about careful adherence to treatment protocols that were written out in detail prior to initiating the trial. In AstraZeneca's trial, fewer than 2,800 people were accidentally given half doses of the vaccine on their first shot. In the USA, the FDA would automatically rule out data from those people because their primary vaccinations resulted from a protocol deviation. I don't know what happens in the UK.

It is possible for AZ to file an amendment of their protocol with the FDA, and once the FDA approves that amendment, they could request that the results from those <2,800 people be included in the final analysis. The FDA might accept that considering the emergency nature of Covid-19. However, I can think of many examples in the past where the FDA said tough luck about that accidental dose change, the results from those people must be excluded in the final analysis.

You may believe this is "the mob going on the attack for this lack of rigor". But in clinical trials for drugs in the USA, the FDA is all about rigor, procedure, and above all, statistical validity. To outside viewers who aren't acquainted with this, it may seem unreasonably compulsive. I once thought that myself. But after 20 years of experience with this approach, I see how necessary it is. AZ's mistake has delayed using their vaccine, at least in the USA.

 

[Irvrobinson]

The mob I was talking about were the press and the science skeptics. Many anti-vaxers seem to be chomping at the bit for evidence that the science is somehow flawed.

 

[Swerd]

Hopefully this will prove to be an effective treatment:

>>>Because TNF-alpha and IFN-gamma are produced during COVID-19 and cause inflammatory cell death, the investigators questioned whether these cytokines were responsible for the clinical manifestations and deadly effects of the disease. They found that the TNF-alpha and IFN-gamma combination triggered tissue damage and inflammation that mirror the symptoms of COVID-19 along with rapid death.

Neutralizing antibodies against TNF-alpha and IFN-gamma are currently used to treat inflammatory diseases in the clinic. The investigators found that treatment with these antibodies protected mice from death associated with SARS-CoV-2 infection, sepsis, HLH and cytokine shock.

"The findings link inflammatory cell death induced by TNF-alpha and IFN-gamma to COVID-19," Kanneganti said. "The results also suggest that therapies that target this cytokine combination are candidates for rapid clinical trials for treatment of not only COVID-19, but several other often fatal disorders associated with cytokine storm."<<<

In the lab, scientists identify possible COVID-19 treatment

Immunologists have determined the process driving life-threatening inflammation, lung damage and organ failure in patients with COVID-19, sepsis and other inflammatory disorders suggesting possible treatment using existing drugs.

www.sciencedaily.com

Interesting. The results with Tumor Necrosis Factor-alpha (TNF-α) and Interferon-gamma (IFN-λ) are similar to the earlier findings with antibodies directed against the Interleukin-6 receptor (IL-6R). Humanized monoclonal antibodies against the IL-6R (Tocilizumab, Acetmra by Hoffman-LaRoche) are already licensed for use against rheumatoid arthritis (RA), are being tested now in Covid-19 patients.

Antibodies against TNF-α (Adalimumab, Humira by Abbvie) are also approved for use a host of autoimmune diseases including RA. Abbvie would be just delighted to sell more of their overpriced product.

I'm not aware of a monoclonal antibody against IFN-λ that is approved for clinical use. There is one, Fontolizumab, but it never advanced beyond Phase 2 clinical trials for use in treating RA.

 

[Swerd]

The mob I was talking about were the press and the science skeptics. Many anti-vaxers seem to be chomping at the bit for evidence that the science is somehow flawed.

Agreed.

One of the more prominent science skeptics is the soon-to-be former president.

I doubt if most anti-vaxers read or understand the science about vaccines. This is definitely true about those that I've met.

 

[Swerd]

I dunno, immunology isn't my field, but isn't it very weird that a smaller dose results in greater efficacy? I'm having trouble getting past that.

It has long been conventional wisdom in drug therapy that more is more and less is less. One of the major goals of clinical trials is to find what the maximum drug dose is that can be tolerated by patients. This is mostly true for drugs that are synthetic small molecules. They are foreign chemicals that have biological activity. They usually inhibit the activity of one or several enzyme(s). And they are inactivated and removed from circulation by the liver or the kidney.

If you plot a dose response curve (dose on the horizontal axis, and some pharmaceutical effect on the vertical axis) with these types of drugs, they usually result in a sigmoid curve, such as one of these, below. Once you reach a maximum dose, the response reaches a plateau.

In the last 20-30 years the biotech industry has mainly been investigating biological molecules as disease treatments. These can be both small (for example Vitamins A or D), and large molecules (proteins, cytokines, enzymes, all of which are gene products). Because these agents naturally occur in the body, there are existing natural mechanisms to inactive and remove them from circulation, and limit the extent of their biological signal. They result in a bell-shaped dose response curve (examples below), where there is an optimum dose. In contrast, non-naturally ocurring drugs and their sigmoid dose response curves (above), reveal a maximum dose. With vaccines, I believe they may have bell-shaped dose response curves, and not sigmoid curves.

 

[Dude#1279435]

Just for the sake of counter argument. Some have said the cost/benefit of a downward economy isn't worth it. So...

--what if we did nothing and relied on herd immunity?
--how many more projected deaths?
--hospital infrastructure overflow?
--the cost on business with so much sick turnover?

Any studies into that? My impression was you'd have to reach 60% to reach herd and even then there's no guarantee it would work. You'd have hospitals sending people home, and I'm assuming temp workers employed would be mile high. I don't know how the business numbers would play out though. I'm assuming it would be one huge mess. Worth a thought though.

 

[Trell]

Drugs hyped as coronavirus treatment linked to psychiatric disorders, says EU agency

EU’s drug regulator issues warning about chloroquine and a related compound, hydroxychloroquine.

www.politico.eu

 

[Swerd]

We have a worldwide pandemic of a virulent and novel virus. Infection has a higher mortality rate than influenza, and we are still learning about it's long-term effects in survivors. Is it worth the cost to develop vaccines and immunize people worldwide? Or is it too costly compared to the economic damage from failing to respond? I'm not sure where you intend to go with this. Is this a straw man argument, or are you for real?

Just for the sake of counter argument. Some have said the cost/benefit of a downward economy isn't worth it. So...

Any studies into that? My impression was you'd have to reach 60% to reach herd and even then there's no guarantee it would work. You'd have hospitals sending people home, and I'm assuming temp workers employed would be mile high. I don't know how the business numbers would play out though. I'm assuming it would be one huge mess. Worth a thought though.

--what if we did nothing and relied on herd immunity?

First of all, herd immunity has recently become a buzz word for ignoring vaccines and letting the chips fall where they may. Here's a better definition:

Herd immunity is a form of indirect protection from infectious disease that occurs when a sufficient percentage of a population has become immune to an infection, whether through vaccination or previous infections, thereby reducing the likelihood of infection for individuals who lack immunity.​

With that definition in mind, it is clear that many infectious viral diseases never reached 'herd immunity' without the aid of large scale vaccination. Small Pox, measles, mumps, rubella, chicken pox, polio, just to name a few were all world-wide causes of disease and death for centuries or longer, until vaccines were developed.

Assuming that we can achieve herd immunity after 60% of humans have been exposed to Covid-19, and recovered is probably a very large underestimation. At present, we do not know how many people must be vaccinated before the virus infection is checked. Measles, a virus with similar contagiousness, requires somewhere between 92-95% of the population to be immunized before herd immunity can work. I've read that Covid-19 is estimated to require 60-75% to reach herd immunity, but that is simply a guestimation. At present, no one knows what that value is. If we don't know what the herd immunity threshold is for Covid-19, how can we discuss it inteligently?

--how many more projected deaths?

In the USA, we've had somewhere between 250,000 and 400,000 deaths from SARS-CoV-2. How many deaths are too many?

--hospital infrastructure overflow?
--the cost on business with so much sick turnover?

These last two questions aren't really worth discussing. In case I haven't made myself clear enough, I'll say it directly:

• We cannot afford to ignore the Corona virus pandemic while doing nothing, hoping it will be effective.
• The hospital infrastructure has been underfunded for a long time. Spending now to increase this will have long-term benefits. Why avoid that?
• The pharmaceutical industry, both in the USA and worldwide, has long made vaccines the unwanted orphan of drug development. They don't provide enough profit to warrant serious interest. That has already changed because of Covid-19. Now, AstraZeneca, Pfizer, Moderna, Johnson & Johnson, among many others in the US, Europe, India, Russia, & China, have fallen all over themselves to be the first to produce a safe & effective vaccine. The very large investment from this will have long-term benefits, both financially, and to the world's overall health.

I think it's a no-brainer. Get the vaccines ASAP!

 

[davidscott]

Just for the sake of counter argument. Some have said the cost/benefit of a downward economy isn't worth it. So...

--what if we did nothing and relied on herd immunity?
--how many more projected deaths?
--hospital infrastructure overflow?
--the cost on business with so much sick turnover?

Any studies into that? My impression was you'd have to reach 60% to reach herd and even then there's no guarantee it would work. You'd have hospitals sending people home, and I'm assuming temp workers employed would be mile high. I don't know how the business numbers would play out though. I'm assuming it would be one huge mess. Worth a thought though.

My niece works at a north Texas hospital now and told me that they have already converted 2 units to covid cases and might have to add a 3rd. Both her parents (my sister and brother in law) have just been released after spending some time in the ICU. So I think the deaths and hospitalizations go way up for older people in particular. And the staff is overloaded. We hopefully only have a few months for a vaccine so my thought is to keep trying to slow the spread. If masks help even a little why do people still refuse the wear them? And social distance?

 

[Dude#1279435]

Is it worth the cost to develop vaccines and immunize people worldwide? Or is it too costly compared to the economic damage from failing to respond? I'm not sure where you intend to go with this. Is this a straw man argument, or are you for real?

I'm playing devil's advocate for that side that claims the sooner we get to herd immunity the sooner we'll be out of it. My gut says it doesn't work that way and social distancing has always been something gov't has used through history. Not the other way around like some claim. Sure you can look at the total deaths compared to the overall population and say it's no big deal. But if the hospitals don't have the infrastructure to deal with the mass outbreak without intervention than I assume the death count is much higher. Whatever that total is. In fact, you can only guess and it isn't worth contemplating.

 

[Trell]

Is it worth the cost to develop vaccines and immunize people worldwide? Or is it too costly compared to the economic damage from failing to respond? I'm not sure where you intend to go with this. Is this a straw man argument, or are you for real?

I'm playing devil's advocate for that side that claims the sooner we get to herd immunity the sooner we'll be out of it. My gut says it doesn't work that way and social distancing has always been something gov't has used through history. Not the other way around like some claim. Sure you can look at the total deaths compared to the overall population and say it's no big deal. But if the hospitals don't have the infrastructure to deal with the mass outbreak without intervention than I assume the death count is much higher. Whatever that total is. In fact, you can only guess and it isn't worth contemplating.

Achieving herd immunity without an effective vaccine will cause many deaths and many survivors appears to have long term debilitating effects from the infection. Perhaps you can play somewhere else?