SARS-CoVID-2/ CoVID-19/ CoronaVirus: Information Only from Well Informed Members

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First ~10 minutes on vaccine development. A few highlights: Moderna mRNA vaccine on track for 30,000 subject phase III trial beginning the first week of July. The Oxford vaccine is on more or less the same schedule, and by the end of the summer 4-5 vaccines could be there. November-December projection for positive efficacy results. At risk manufacturing should produce 100 million doses by then, and several hundred million by the beginning of 2021. Durability of response is a central concern now. Natural coronavirus immune protection often lasts less than a year.
 
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Dr. Evil is right, there are things not known about the immune response to SARS-COv-2. The reason to be optimistic, however, is that researchers have identified things called CD4+ memory T-cells in patients who have had Covid-19 (and also earlier in SARS patients), which would usually suggest that immunity will be somewhat long lasting. It is possible that people might need to re-vaccinate every few years.

https://www.medrxiv.org/content/10.1101/2020.04.17.20061440v1.full.pdf

The next link is an explanation of some of this in less technical terms. Unfortunately, immunology is ridiculously complicated.

https://blogs.sciencemag.org/pipeli...-the-human-immune-response-to-the-coronavirus

With that said, some people in ICUs show signs of "immune exhaustion" which may be why they ended up there.

https://www.frontiersin.org/articles/10.3389/fimmu.2020.00827/full

There is a thing called immune senescence. Regular exercise is known to delay it. By the way, one of the reasons HIV is so persistent and refractory to vaccine development is that virus actually INFECTS the CD4+ T-cells! So it is able to evade the immune system pretty much forever.

Cornonaviruses fortunately do not have any superpowers quite like that, and they don't seem to mutate very rapidly at the most antigenic places (in contrast to, say, influenza viruses).
 
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This came out today. Another drug that might actually work in severely ill Covid-19 patients. This result us VERY preliminary but it certainly justifies a decent clinical trial, which they indicate is being organized. This study was not a true clinical trial per se, it was an off-label observational study. This drug is FDA approved for lymphoma. But.... it costs $14,000 per month!!!

Inhibition of Bruton tyrosine kinase in patients with severe COVID-19

Mark Roschewski et al.

Science Immunology 05 Jun 2020:

Abstract
Patients with severe COVID-19 have a hyperinflammatory immune response suggestive of macrophage activation. Bruton tyrosine kinase (BTK) regulates macrophage signaling and activation. Acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing oxygen requirements at baseline. Over a 10-14 day treatment course, acalabrutinib improved oxygenation in a majority of patients, often within 1-3 days, and had no discernable toxicity. Measures of inflammation – C-reactive protein and IL-6 – normalized quickly in most patients, as did lymphopenia, in correlation with improved oxygenation. At the end of acalabrutinib treatment, 8/11 (72.7%) patients in the supplemental oxygen cohort had been discharged on room air, and 4/8 (50%) patients in the mechanical ventilation cohort had been successfully extubated, with 2/8 (25%) discharged on room air. Ex vivo analysis revealed significantly elevated BTK activity, as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers. These results suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial.
 
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A misleading statement according to many epidemiologists and infectious disease experts asked to comment on this statement, as well as a few peer-reviewed studies. But the person from the WHO did say it. Presymptomatic is not necessarily the same as asymptomatic, and this statement was not accompanied by release of any data. As we have seen, data transparency is essential.

From Forbes....

"While the comments drew questions from experts on Twitter, it may simply be an issue of semantics, with Dr. Isaac Bogoch and Dr. Allan Detsky of the University of Toronto previously pointing out the misuse of the term "asymptomatic" when referring to "presymptomatic" patients.


While asymptomatic people never show signs of the coronavirus, presymptomatic people exhibit no signs of contracting the disease for the first few days before experiencing the classic symptoms.


Dr. Ashish K. Jha, director at the Harvard Global Health Institute, tweeted out the distinction and noted that the agency "should be clearer in communication, also noting that some models "suggest 40-60% of spread is from people when they didn't have symptoms."
 
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Here is a peer-reviewed article on this Takkyu. Annals of Internal Medicine

Prevalence of Asymptomatic SARS-CoV-2 Infection


A Narrative Review
Daniel P. Oran, AMEric J. Topol, MD


Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world since the first cases of coronavirus disease 2019 (COVID-19) were observed in December 2019 in Wuhan, China. It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing pandemic, but their relative number and effect have been uncertain. The authors sought to review and synthesize the available evidence on asymptomatic SARS-CoV-2 infection. Asymptomatic persons seem to account for approximately 40% to 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography. Because of the high risk for silent spread by asymptomatic persons, it is imperative that testing programs include those without symptoms. To supplement conventional diagnostic testing, which is constrained by capacity, cost, and its one-off nature, innovative tactics for public health surveillance, such as crowd-sourcing digital wearable data and monitoring sewage sludge, might be helpful.


Key SummaryPoints
The likelihood that approximately 40% to 45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.


Asymptomatic persons can transmit SARS-CoV-2 to others for an extended period, perhaps longer than 14 days.


The absence of COVID-19 symptoms in persons infected with SARS-CoV-2 might not necessarily imply an absence of harm. More research is needed to determine the significance of subclinical lung changes visible on computed tomography scans.


The focus of testing programs for SARS-CoV-2 should be substantially broadened to include persons who do not have symptoms of COVID-19.
 
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Thanks Baal. Really helpful (including the Annals of Internal Medicine article).

Just from my own observations it didn't make sense. I was almost ready to go back to playing table tennis. *sigh*
 
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Thanks Baal. Really helpful (including the Annals of Internal Medicine article).

Just from my own observations it didn't make sense. I was almost ready to go back to playing table tennis. *sigh*

They just walked it back. Look for the press report.
 
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The WHO lady was responding to a question, said something quite dumb, maybe because she has little experience handling a press conference (?). And it set off a tsunami. The annoying thing is, it took me all of about three minutes of searching to find papers that show the current consensus -- that people without symptoms can transmit Covid-19. If you are presymptomatic you dont have symptoms.

Too much science and health journalism is done by people who dont have appropriate backgrounds or the minimal ability to do a quick literature search. As for the WHO, Ihave no idea what kinds of people rise up the ranks of the organization. About all I saw about this person is she is an epidemiologist. So by definition she knows more than I do about this, but she kind of screwed up this time. Nobody is perfect.

I'm just hazarding a guess --pure speculation but based on my experience -- that a lot of mid-level scientists and field workers are good, and the higher up you go in organizations like the WHO the less the people's talents lie in science. Again, just a general comment on how the world works. Anthony Fauci and the NIH in general is a notable exception and the institute directors there have to be good scientists and are expected to maintain active research programs.
 
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Baal is on the money as usual. Asymptomatic people -- meaning people who feel and seem healthy -- can be contagious. That's an established fact. It's probably the single most important reason why we have a pandemic. But leave it to the World Health Organization to make it seem debatable. Unlike certain related questions (what fraction of cases come from asymptomatic transmission, at what point in the disease course are people most infectious, etc.), it's not.
 
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By the way, this may be overly alarmist, but for me a scary part is that we don't know what long term consequences of people who have had relatively mild cases may emerge later. Covid-19 hasn't been around long enough to really know what happens to recovered people 1, 2, 5 years down the road. Hopefully nothing much. But we dont know. Based on SARS, we can predict that people who had more severe Covid-19 will have reduced pulmonary function and chronic fatigue for quite a long time (more than a year).
 
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A great place to get a list of Covid-19 clinical trials for about everything, drugs, vaccines, etc.. is

https://Covid-trials.org

I counted 66 different trials for vaccines worldwide at different stages. It includes some trials of BCG which is not specifically a Covid-19 vaccine. A bunch of monoclonal antibodies (not all against SARS-CoV-2 proteins), A bunch of drugs.

People are working hard to find things for this. Some of these therapies are bound to be helpful.

You can click on trial and find where they are at in the process, see the trial design, endpoints, etc.

If you look closely some of the listings are duplicate because each place where part of a trial is going on are listed separately, and a .ot of trials are mu.ti-center. The Jansen and Johson and Johnson vaccine just mentioned is included.
 
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Metaxa, do you have a question about this link you posted?

If you look at the rules of this thread, if you are posting, it has to be a question that you have for Baal, Rain, Dr Evil or Passifid. Those four can post information or content and answer questions. If you asked a question and it was answered, a comment about the information presented is sometimes okay. However, since I don't see a question in your post, I am removing your post until you can clarify the purpose of your post. I am also posting the rules of the thread as presented in the Original Post of this thread.

So, I just want this to be clear. I closed the last 2 threads on the Novel CoronaVirus Pandemic as it seemed that each, at some point went off into unsubstantiated territory. Nevertheless, with this global crisis, I still feel, having useful information on the subject available to our members will be valuable.

So, we are going to try something different here.

The rules of this thread are not the rules of most threads.

Baal, RainNeverEver, Dr Evil, and Passifid will be the well informed members or "Experts" on the thread since they all have science and medical related backgrounds. They can post as they see fit to provide information and to answer questions.

Other members can ask questions but cannot simply post thoughts, opinions, answers.

I will HEAVILY MODERATE the thread so that, if a member, unaware of the rules for this thread, posts content rather than a question, I will delete and inform that member of the special rules for this thread.

Thank you for you understanding and cooperation in this endeavor. I am looking forward to seeing how this thread turns out.
 
Metaxa, do you have a question about this link you posted?

If you look at the rules of this thread, if you are posting, it has to be a question that you have for Baal, Rain, Dr Evil or Passifid. Those four can post information or content and answer questions. If you asked a question and it was answered, a comment about the information presented is sometimes okay. However, since I don't see a question in your post, I am removing your post until you can clarify the purpose of your post. I am also posting the rules of the thread as presented in the Original Post of this thread.

Apologies.


The link was about testing on people who are apparently starting next month.
The question could have been:
Isn't this much faster than expected if they are still experimenting everywhere?


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Here is an answer to Metaxa's question.

A few vaccines have reached the point where various clinical trials have started. The technologies for developing vaccines are constantly advancing, and SARS-CoV-2 seems to offer lots of ways to approach vaccine development (or neutralizing antibodies). Also some groups were anticipating that a pandemic like this was inevitable. Regeneron (a biotech/pharma company in Califirnia), for example created a unit for this a few years ago and even included coronaviruses as something they were prepared to tackle, and they now have an antibody cocktail going into trials. (That is not a vaccine, but I just mention it to indicate that people have been thinking about this for awhile). Having thousands and thousands of people die in six months is highly motivating, and of course there is money to be made.

It remains the case, however, that Phase 3 clinical trials for a vaccine take quite a long time and need LOTS of people. It takes longer than trials for a drug or an antibody. I explained why earlier in this thread.

Some of the vaccines in development (Moderna) are using very new technologies, others are using more traditional methods. Odds are very high we will have several, eventually. Hard to predict exactly when (certainly hard for me anyway).

Another point worth noting in response to Metaxa, the vaccine he mentioned uses an Adenoviral vector developed by Janssen Pharmaceuticals in Belgium (who were bought by Johnson and Johnson) to introduce viral proteins into human cells and hopefully generate an immune response. This is the same method that is being used by a Chinese group that Rainever mentioned earlier in this thread who are also doing a trial now. Because it is a relatively new method, safety issues will probably be scrutinized a bit more closely by regulatory agencies. Moderna will introduce RNA into cells to do the same thing. And some groups, for example in the UK, are betting on vaccines made from recombinant proteins (a bit more old-fashioned by tried and true).
 
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New study in Proceedings of the National Academy of Scince of the USA.

Identifying airborne transmission as the dominant route for the spread of COVID-19
Renyi Zhang, Yixin Li, Annie L. Zhang, Yuan Wang, and Mario J. Molina


Significance
We have elucidated the transmission pathways of coronavirus disease 2019 (COVID-19) by analyzing the trend and mitigation measures in the three epicenters. Our results show that the airborne transmission route is highly virulent and dominant for the spread of COVID-19. The mitigation measures are discernable from the trends of the pandemic. Our analysis reveals that the difference with and without mandated face covering represents the determinant in shaping the trends of the pandemic. This protective measure significantly reduces the number of infections. Other mitigation measures, such as social distancing implemented in the United States, are insufficient by themselves in protecting the public. Our work also highlights the necessity that sound science is essential in decision-making for the current and future public health pandemics.


Abstract
Various mitigation measures have been implemented to fight the coronavirus disease 2019 (COVID-19) pandemic, including widely adopted social distancing and mandated face covering. However, assessing the effectiveness of those intervention practices hinges on the understanding of virus transmission, which remains uncertain. Here we show that airborne transmission is highly virulent and represents the dominant route to spread the disease. By analyzing the trend and mitigation measures in Wuhan, China, Italy, and New York City, from January 23 to May 9, 2020, we illustrate that the impacts of mitigation measures are discernable from the trends of the pandemic. Our analysis reveals that the difference with and without mandated face covering represents the determinant in shaping the pandemic trends in the three epicenters. This protective measure alone significantly reduced the number of infections, that is, by over 78,000 in Italy from April 6 to May 9 and over 66,000 in New York City from April 17 to May 9. Other mitigation measures, such as social distancing implemented in the United States, are insufficient by themselves in protecting the public. We conclude that wearing of face masks in public corresponds to the most effective means to prevent interhuman transmission, and this inexpensive practice, in conjunction with simultaneous social distancing, quarantine, and contact tracing, represents the most likely fighting opportunity to stop the COVID-19 pandemic. Our work also highlights the fact that sound science is essential in decision-making for the current and future public health pandemics.
 
Here is an answer to Metaxa's question.

A few vaccines have reached the point where various clinical trials have started. The technologies for developing vaccines are constantly advancing, and SARS-CoV-2 seems to offer lots of ways to approach vaccine development (or neutralizing antibodies). Also some groups were anticipating that a pandemic like this was inevitable. Regeneron (a biotech/pharma company in Califirnia), for example created a unit for this a few years ago and even included coronaviruses as something they were prepared to tackle, and they now have an antibody cocktail going into trials. (That is not a vaccine, but I just mention it to indicate that people have been thinking about this for awhile). Having thousands and thousands of people die in six months is highly motivating, and of course there is money to be made.

It remains the case, however, that Phase 3 clinical trials for a vaccine take quite a long time and need LOTS of people. It takes longer than trials for a drug or an antibody. I explained why earlier in this thread.

Some of the vaccines in development (Moderna) are using very new technologies, others are using more traditional methods. Odds are very high we will have several, eventually. Hard to predict exactly when (certainly hard for me anyway).

Another point worth noting in response to Metaxa, the vaccine he mentioned uses an Adenoviral vector developed by Janssen Pharmaceuticals in Belgium (who were bought by Johnson and Johnson) to introduce viral proteins into human cells and hopefully generate an immune response. This is the same method that is being used by a Chinese group that Rainever mentioned earlier in this thread who are also doing a trial now. Because it is a relatively new method, safety issues will probably be scrutinized a bit more closely by regulatory agencies. Moderna will introduce RNA into cells to do the same thing. And some groups, for example in the UK, are betting on vaccines made from recombinant proteins (a bit more old-fashioned by tried and true).

Great explanation Baal, like always!
Thank you very much [emoji1360]


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OK, bringing this really bizarre chapter to a close, the Food and Drug Administration (FDA) has revoked its emergency use authorization for hydroxychloroquine in Covid-19. The FDA has now concluded that “it is no longer reasonable to believe that oral formulations of HCQ and CQ may be effective in treating COVID-19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks.”

https://www.fda.gov/news-events/pre...s-emergency-use-authorization-chloroquine-and
 
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