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

If co-infections are so common though, it's more difficult to pinpoint an occuring death to Covid 19 (and not e.g. Influenza), isn't it?
 
Sasha said:
@Jonathan Edwards - is this likely to be a safe treatment, in the sense of the plasma (or antibodies or whatever, if anything, they're extracting from it) not carrying other infections?
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My understanding is that current methods for purifying Immunoglobulin (the useful antibodies) involve removing the great majority of infective particles. Also blood can be screened. Prions like BSE might be hard to exclude but they are not prevalent.

I doubt that co-infection of people recovered from COvid19 is a significant issue. And I don't think there is an issue about diagnosis. From what I hear the chest x-ray appearances of Covid19 are highly stereotypical.
 
I watched Andrew Como, Governor of New York propose that other USA states send a lot of ventilators to NY now. The state is short tens of thousands of ventilators.

And then Como said he would send the ventilators back to the states from which they came and send his hospital staff and along with them to help Los Angeles and other cities during their later surge or apex of hospitalized cases.

Hmm. I just wonder, and maybe @Jonathan Edwards you might add to this, that once you have a patient on a ventilator, he is on one typically for 3-6 weeks. Or will this be a new practice of: we'll give you a week on a ventilator, no more. There's the Italian one ventilator per two patients practice.

Getting those borrowed ventilators returned in time doesn't sound like something hospitals in other states would agree to. It's an idea though and Como has disaster experience. Details to be worked out?

New edit. French newscast of Covid ICU patients from Mulhouse area of eastern France being transferred via TGV to hospitals in the west of the country instead of helicopter. Also, some in eastern France airlifted to German (ventilators and ICU beds available).

So, maybe Governor Como should transfer patients out.
 
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large donner said:
Its the duty of every citizen to roll up their sleeve and take the vaccine. Vaccines are safe period.
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I can't tell whether you're joking or not.

We know vaccines can trigger autoimmune syndromes, Guillain Barre Syndrome and Immune Thrombocytopenic purpura in particular.

No mRNA based vaccine has yet been approved for use for humans, or even been tested in a large phase 3 trial.

I personally don't think the safety will be any worse than the older types of vaccines, but the efficacy may well be much poorer. Given the fact that the mRNA has to actually make it to the nucleus of cells, be transcribed and then somehow leave the cell - all while bypassing innate defences, until it is finally exposed to T-Cells and B-Cells...

A trial of lipid coated mRNA vaccine for rabies had didn't work when injected intramuscularly, as did other mRNA vaccine trials which found much poorer efficacy with that administration method. Guess what method the "first" Covid-19 vaccine made by Moderna and trialed by Kaiser Permanente is using - you guessed it, intramuscular injection. My hope therefore is in the academic research groups rather than commercial entities like Moderna, but that also means a longer time to production.
 
Stanford are one of the centers participating in the Remdesivir trial. According to this CNBC interview with the Stanford Medicine School Dean they are involved with two, one for severe and one for less severe.


Here is a Palo Alto Online newspaper report of a patient who participated and recovered. The story was published last Saturday, 21 March.
https://www.paloaltoonline.com/news...ks-a-clinical-trial-drug-was-her-saving-grace
Yeung-Arima was accepted into the randomized trial. For five days, she received intravenous treatments using the medication. Three days into her treatment, she began to feel better, she said. She finished her last dose on Thursday.

When she was released from the hospital on Friday, the hallway was empty and silent.
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This is also a nice personal piece about how Stanford is ramping up testing to 1000 tests a day in order to support other local hospitals. It required cooperation from a lot of folks to overcome shortages. California is way behind on testing, with a big backlog, and like other areas patients who suspect they have the disease still have trouble getting tested. Hopefully this work to ramp up will help the San Francisco Bay Area which has half of California's confirmed patients.
 
Here is some thing positive about COVID19. Scientists are coming together to help. Stanford has a list of projects they are working on.

COVID-19 Research at Stanford
Stanford Medicine scientists have launched dozens of research projects as part of the global response to COVID-19. Some aim to prevent, diagnose and treat the disease; others aim to understand how it spreads and how people’s immune systems respond to it.
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Below is a curated selection, including summaries, of the projects.
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https://med.stanford.edu/covid19/research.html

Some highlights I selected :

The Synder lab where some of the Stanford CFS Research Center team work has three projects listed. The first one is using multi-omics, something they are also doing for ME/CFS
Multi-omics assessment of individuals infected with COVID-19
Michael Snyder, PhD; Sam Yang, MD, FACEP; and Maya Kasowski, PhD

The Snyder group will collect biological samples from individuals ill with COVID-19 and those most at risk for the disease, observing and assessing levels of certain molecules involved in several biological pathways, including metabolism and immune function. The team will use this information to create “omics” profiles to look for potential molecular signatures of COVID-19 infection, as well as signs that an individual might have a strong adverse reaction to the virus.
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Tracking COVID-19 with wearables
Michael Snyder, PhD; Sam Yang, MD, FACEP and Megan Mahoney, MD

Snyder and his team will track biological parameters of individuals who are ill with COVID-19 or at risk for the disease using a smart watch. Their goal is to determine whether they can tell if the smart watch user is becoming ill based on measurements such as heart rate.
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Determining pathogenicity of various variants and strains of COVID-19
Michael Snyder, PhD and Ben Pinsky, MD, PhD

Snyder and his group plan to track different variants and strains of COVID-19 and quantitatively determine which ones correlate with different phenotypes, such as levels of pathogenicity. His team also plans to study the false negative rate of COVID-19, seeking to better understand how many people receive a false negative test result during early stages of the disease.
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There is also another therapeutic called Lambda that will be trialed in mild patients
Clinical trial of novel therapeutic for mild COVID-19 infection to prevent severe disease and reduce viral shedding
Upinder Singh, MD; Julie Parsonnet, MD; Jason Andrews, MD; Prasanna Jagannathan, MD; and other clinical collaborators

Singh’s team is conducting a trial of a novel therapeutic called Lambda, a broad-spectrum anti-viral compound that’s been given to more than 3,000 patients in clinical trials of hepatitis viruses, for efficacy in outpatients with mild COVID-19. In vitro and animal-model data suggest Lambda may also inhibit replication of respiratory viruses, such as the COVID-19 virus. The team plans to perform a phase 2 randomized controlled trial of Lambda among outpatients with mild COVID-19 to determine whether the drug reduces the duration of symptoms, viral shedding and the risk of hospitalization.
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Some other novel drugs being targeted for clinical trials
Develop proofs-of-concept for two novel COVID-19 drugs to begin clinical trials
Jeffrey Glenn, MD, PhD

Glenn is preparing two potential COVID-19 drugs for clinical trials: a lipid kinase inhibitor that could be used to combat COVID-19 and other viruses, and a locked nucleic acid, similar to one that he has successfully developed to target every known strain of the flu and that could potentially be used during any flu pandemic. Both of these drugs could treat multiple viruses and strains, have high barriers to resistance, and, in some cases, could be used in nonviral applications.
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There are a lot of posts on s4me about modelling. This project seems interesting.
Forecasting cases of COVID-19 in conjunction with public health policy
Nirav Shah, MD, MPH, and collaborators

A group of Bay Area technologists have created a website called COVIDACTNOW.org that provides forecasts of COVID-19 cases based on the implementation of actions, such as social distancing, to urge responsible action in real time. Endorsed by Shah, the website shows how adhering to these types of public health recommendations can affect if and when hospital bed capacity in a given state will run out.
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This is the projects website
https://covidactnow.org/

You can access the model on google sheets for those folks that are interested.
Code: 
https://docs.google.com/spreadsheets/d/1YEj4Vr6lG1jQ1R3LG6frijJYNynKcgTjzo2n0FsBwZA/edit#gid=1579455912

 
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Snow Leopard said:
I can't tell whether you're joking or not.

We know vaccines can trigger autoimmune syndromes, Guillain Barre Syndrome and Immune Thrombocytopenic purpura in particular.

No mRNA based vaccine has yet been approved for use for humans, or even been tested in a large phase 3 trial.

I personally don't think the safety will be any worse than the older types of vaccines, but the efficacy may well be much poorer.
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I don't understand, ask any credible scientist and they will tell you vaccines are safe that means they cant trigger autoimmune syndromes or any other
condition.

Thats official.
 
large donner said:
Thats official.
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Its also official that we have vaccine courts to provide compensation for damages.

Its also on scientific record that many vaccines have produced massive damage. Such vaccines are usually then recalled fairly quickly.

With vaccines its about relative risk. The diseases we vaccinate against are from somewhat to very dangerous. The risk of the disease is much, MUCH higher than the risk of the vaccine in specific individuals.

Official advice along the lines that vaccines are safe is a public health message. The risk of vaccine is much lower than the disease, or the vaccine is withdrawn.

There are also individuals who have had multiple severe reactions to vaccines. Such patients can no longer be vaccinated. Indeed, this is why the notion of herd immunity receives so much attention. For those few who cannot be vaccinated, usually with a damaged immune system that simply does not respond to the vaccine properly rather than an adverse reaction, others around them need to be vaccinated to protect them.

Vaccines are relatively safe, not absolutely safe. Every now and then a new vaccine is unsafe, and is recalled.

I wish we all had vaccination against measles decades earlier. I probably would not have ME , though this does not factor in possible genetic factors. In my case the most likely trigger was measles encephalitis. People look at death rates, but we also need to factor in disability rates. Vaccines can produce disability, but the diseases we vaccinate against can produce a much worse disability rate.

So again, unless you are a rare individual who should not be vaccinated, the risk of disease is much higher than the risk of the vaccine. Relative risk, not absolute risk. Those not being vaccinated have partial protection because others around them are vaccinated. Its a complex situation.
 
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shak8 said:
I watched Andrew Como, Governor of New York propose that other USA states send a lot of ventilators to NY now. The state is short tens of thousands of ventilators.

And then Como said he would send the ventilators back to the states from which they came and send his hospital staff and along with them to help Los Angeles and other cities during their later surge or apex of hospitalized cases.

Hmm. I just wonder, and maybe @Jonathan Edwards you might add to this, that once you have a patient on a ventilator, he is on one typically for 3-6 weeks. Or will this be a new practice of: we'll give you a week on a ventilator, no more. There's the Italian one ventilator per two patients practice.

Getting those borrowed ventilators returned in time doesn't sound like something hospitals in other states would agree to. It's an idea though and Como has disaster experience. Details to be worked out?

New edit. French newscast of Covid ICU patients from Mulhouse area of eastern France being transferred via TGV to hospitals in the west of the country instead of helicopter. Also, some in eastern France airlifted to German (ventilators and ICU beds available).

So, maybe Governor Como should transfer patients out.
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I heard him say that there is tons of equipment on the black market; and he (or some else in govt) contacted the black market, went to some hanger and stated there were tons upon tons of medical supplies.
 
shak8 said:
I watched Andrew Como, Governor of New York propose that other USA states send a lot of ventilators to NY now. The state is short tens of thousands of ventilators.

And then Como said he would send the ventilators back to the states from which they came and send his hospital staff and along with them to help Los Angeles and other cities during their later surge or apex of hospitalized cases.

Hmm. I just wonder, and maybe @Jonathan Edwards you might add to this, that once you have a patient on a ventilator, he is on one typically for 3-6 weeks. Or will this be a new practice of: we'll give you a week on a ventilator, no more. There's the Italian one ventilator per two patients practice.

Getting those borrowed ventilators returned in time doesn't sound like something hospitals in other states would agree to. It's an idea though and Como has disaster experience. Details to be worked out?

New edit. French newscast of Covid ICU patients from Mulhouse area of eastern France being transferred via TGV to hospitals in the west of the country instead of helicopter. Also, some in eastern France airlifted to German (ventilators and ICU beds available).

So, maybe Governor Como should transfer patients out.
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Update this morning 3/26 from Governor Como:

Average length of time a Covid-19 patient is on a ventilator is 11-21 days (normal patients use is 3-4 days average, according to him).
 
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Coincidental job opening in November 2019 researching bat innate immunity when exposed to "SARS-like" viruses at Wuhan institute of Virology...
link:https://translate.google.com/transl...341/201911/t20191118_5438006.html&prev=search

I don't think people can deny that there is always risk of contamination and infection for workers in virology labs. Nor that there were risks of transmission of the bat virus to humans eventually happening (regardless of how it actually happened) were known given the research interest.

"SARS How a Global epidemic was stopped" - WHO (2006)
https://apps.who.int/iris/bitstream/handle/10665/207501/9290612134_eng.pdf
Note page 236 "LABORATORY-ACQUIRED INFECTIONS IN CHINA", noting cases of laboratory-acquired infection by SARS-CoV.
 
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This was just posted in the other thread by Andy [mod note: that post was moved and now appears above], but:

The proximal origin of SARS-CoV-2
Kristian G. Andersen, Andrew Rambaut, W. Ian Lipkin, Edward C. Holmes & Robert F. Garry
https://www.nature.com/articles/s41591-020-0820-9

(Part 1: Natural selection in an animal host before zoonotic transfer)
Neither the bat betacoronaviruses nor the pangolin betacoronaviruses sampled thus far have polybasic cleavage sites. Although no animal coronavirus has been identified that is sufficiently similar to have served as the direct progenitor of SARS-CoV-2, the diversity of coronaviruses in bats and other species is massively undersampled.
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3. Selection during passage
Basic research involving passage of bat SARS-CoV-like coronaviruses in cell culture and/or animal models has been ongoing for many years in biosafety level 2 laboratories across the world27, and there are documented instances of laboratory escapes of SARS-CoV28. We must therefore examine the possibility of an inadvertent laboratory release of SARS-CoV-2.

In theory, it is possible that SARS-CoV-2 acquired RBD mutations (Fig. 1a) during adaptation to passage in cell culture, as has been observed in studies of SARS-CoV11. The finding of SARS-CoV-like coronaviruses from pangolins with nearly identical RBDs, however, provides a much stronger and more parsimonious explanation of how SARS-CoV-2 acquired these via recombination or mutation19.

The acquisition of both the polybasic cleavage site and predicted O-linked glycans also argues against culture-based scenarios. New polybasic cleavage sites have been observed only after prolonged passage of low-pathogenicity avian influenza virus in vitro or in vivo17. Furthermore, a hypothetical generation of SARS-CoV-2 by cell culture or animal passage would have required prior isolation of a progenitor virus with very high genetic similarity, which has not been described. Subsequent generation of a polybasic cleavage site would have then required repeated passage in cell culture or animals with ACE2 receptors similar to those of humans, but such work has also not previously been described. Finally, the generation of the predicted O-linked glycans is also unlikely to have occurred due to cell-culture passage, as such features suggest the involvement of an immune system18.
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