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

I think the original of this was on social media and might have been posted on this thread already.

Musings of an anonymous, pissed off virologist
  • Finally, and here’s the kicker: having developed a remarkable two-dose vaccine, that is extraordinarily effective, ADMINISTER IT TO MILLIONS OF PEOPLE – BUT DELAY THE SECOND DOSE. Generating a pool of hosts with just the right amount of neutralizing antibody to apply selection pressure, but also maintain sufficient levels of partially antibody-resistant virus to allow onward transmission is key here. We might not achieve this shortly after the first dose, but if we let immunity wane for a little while, say 4 to 12 weeks, we just might hit the sweet spot.
Of course, I don’t know if the above would be successful, but that’s what I’d try if I wanted to generate vaccine-resistant SARS-CoV-2 variants.
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https://www.virology.ws/2021/01/05/musings-of-an-anonymous-pissed-off-virologist/

By posting it on his blog as a guest post, I assume that Vincent Racaniello supports the message.
 
Amw66 said:
https://www.theguardian.com/world/2...ort-uk-delay-of-vaccines-second-dose-says-who

WHO not impressed by second dose delay either
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It is additionally curious given the interim data published in The Lancet for the AZ vaccine found no difference in efficacy for <6 weeks vs >6 weeks.

I suspect the decision to delay for 12 weeks was based on the data in the UK for the AstraZeneca data which showed that the ~12 weeks group had higher antibody titres.
Ignoring the cherry-picking aspect of this analysis, and the fact that it was only shown for the AZ vaccine, the analysis seems to be under the mistaken impression that antibody titre is the same as efficacy. A 12 week gap makes the second dose a 'booster', whereas a 2-4 week gap leads to increased likelihood of making strongly neutralising antibodies, due to the kinetics of B-cell maturation in germinal centres.

So they are emphasising quantity over quality in three different ways!
(1. single dose vs double dose means more people vaccinated in short term. 2. They're assuming that a 12 week gap will lead to higher antibody titre and 3. Use of the lower-efficacy AZ vaccine means more people can be vaccinated in the short term due to cost and supply limitations)
 
I expect there's vigilant monitoring of side effects going on but

1) are they also being categorised and analysed to see if there are certain side effects turning up more frequently in certain groups, be that age or disease like autoimmunity?

2) since it's not likely all groups were well represented in the trials, is anybody tracking how well different groups develop immunity after vaccination?

Not that I expect anyone is going to look at how pwME react to the vaccines, that would be too much to hope for...

Apologies if questions have already been answered, unable to keep up with this thread.
 
This is all true, of course. There have been no randomised controlled trials into whether a Pfizer prime and Ox/AZ boost works, or vice versa. And, traditionally, in medical science, if you haven’t got an RCT showing that your drug regimen works, then you haven’t got any evidence that it works.

But I want to argue that this sort of thinking doesn’t work in emergency situations like the one we’re in. More than that: it’s been a repeated problem throughout the pandemic that we have relied on this “we have the evidence/we don’t have the evidence” binary, meaning that we have moved slowly, waiting for rock-solid confirmation; but moving faster, making decisions on imperfect information, would have saved a lot of lives.
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https://unherd.com/2021/01/amid-covid-crisis-we-cant-wait-for-perfect-data/
 
Umbilical cord mesenchymal stem cells for COVID‐19 acute respiratory distress syndrome: A double‐blind, phase 1/2a, randomized controlled trial. Giacomo Lanzoni et al. Stem Cells Transl Med (2021)
Acute respiratory distress syndrome (ARDS) in COVID‐19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti‐inflammatory effects and could yield beneficial effects in COVID‐19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical cord mesenchymal stem cell (UC‐MSC) infusions in subjects with COVID‐19 ARDS. A double‐blind, phase 1/2a, randomized, controlled trial was performed. Randomization and stratification by ARDS severity was used to foster balance among groups. All subjects were analyzed under intention to treat design. Twenty‐four subjects were randomized 1:1 to either UC‐MSC treatment (n = 12) or the control group (n = 12). Subjects in the UC‐MSC treatment group received two intravenous infusions (at day 0 and 3) of 100 ± 20 × 106UC‐MSCs; controls received two infusions of vehicle solution. Both groups received best standard of care. Primary endpoint was safety (adverse events [AEs]) within 6 hours; cardiac arrest or death within 24 hours postinfusion). Secondary endpoints included patient survival at 31 days after the first infusion and time to recovery. No difference was observed between groups in infusion‐associated AEs. No serious adverse events (SAEs) were observed related to UC‐MSC infusions. UC‐MSC infusions in COVID‐19 ARDS were found to be safe. Inflammatory cytokines were significantly decreased in UC‐MSC‐treated subjects at day 6. Treatment was associated with significantly improved patient survival (91% vs 42%, P = .015), SAE‐free survival (P = .008), and time to recovery (P = .03). UC‐MSC infusions are safe and could be beneficial in treating subjects with COVID‐19 ARDS.
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Scienmag: University Of Miami Leads Groundbreaking Trial For COVID-19 Treatment
 
Kalliope said:
NIH News Releases NIH study uncovers blood vessel damage and inflammation in COVID-19 patient's brains but not infection

“We found that the brains of patients who contract infection from SARS-CoV-2 may be susceptible to microvascular blood vessel damage. Our results suggest that this may be caused by the body’s inflammatory response to the virus” said Avindra Nath, M.D., clinical director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We hope these results will help doctors understand the full spectrum of problems patients may suffer so that we can come up with better treatments.”

...
“We were completely surprised. Originally, we expected to see damage that is caused by a lack of oxygen. Instead, we saw multifocal areas of damage that is usually associated with strokes and neuroinflammatory diseases,” said Dr. Nath.

Finally, the researchers saw no signs of infection in the brain tissue samples even though they used several methods for detecting genetic material or proteins from SARS-CoV-2.

“So far, our results suggest that the damage we saw may not have been not caused by the SARS-CoV-2 virus directly infecting the brain,” said Dr. Nath. “In the future, we plan to study how COVID-19 harms the brain’s blood vessels and whether that produces some of the short- and long-term symptoms we see in patients.”
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NPR had an article about this study yesterday. How COVID-19 Attacks the Brain And May Cause Lasting Damage
 
Raynayd et al. COVID-19-related medical research: a metaresearch and critical appraisal
https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-020-01190-w
Since the beginning of the COVID-19 pandemic, the majority of research is composed by publications without original data. Peer-reviewed original articles with data showed a high risk of bias and included a limited number of patients
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More than half of all papers on COVID-19 did not include any data or analytics (comprising expert opinion pieces).. Original articles including patient data accounted for 713 (9.5%) of peer-reviewed studies. What a mess!
 
leokitten said:
Umbilical cord mesenchymal stem cells for COVID‐19 acute respiratory distress syndrome: A double‐blind, phase 1/2a, randomized controlled trial. Giacomo Lanzoni et al. Stem Cells Transl Med (2021)


Scienmag: University Of Miami Leads Groundbreaking Trial For COVID-19 Treatment
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The stem cell science blog 'The Niche' has published a post breaking down the results and limitations of the study...

"Overall this new small study is the most encouraging results we’ve seen on the cellular medicine for COVID-19 front, but there are good reasons for wanting a lot more data before coming to any conclusions."

https://ipscell.com/2021/01/small-umbilical-cord-stem-cell-covid-19-trial-efficacy/
 
TrixieStix said:
The stem cell science blog 'The Niche' has published a post breaking down the results and limitations of the study...

"Overall this new small study is the most encouraging results we’ve seen on the cellular medicine for COVID-19 front, but there are good reasons for wanting a lot more data before coming to any conclusions."

https://ipscell.com/2021/01/small-umbilical-cord-stem-cell-covid-19-trial-efficacy/
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The write-up is full of hype and bullshit (like the continuing reference to a cytokine storm that isn't there and guff about autoimmunity). I am also unclear how cells from an umbilical cord can be used without immediate graft rejection. But I am always ready to be proved wrong.
 
Jonathan Edwards said:
The write-up is full of hype and bullshit (like the continuing reference to a cytokine storm that isn't there and guff about autoimmunity). I am also unclear how cells from an umbilical cord can be used without immediate graft rejection. But I am always ready to be proved wrong.
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Am I correct in assuming your referring to the actual write up about the study results in 'Stem Cells Transitional Medicine' rather than the linked blog post by Paul Knoepfler in 'The Niche' given the post doesn't mention the study's claims about cytokine storms or autoimmunity?

Paul Knoepfler mentions the issue of 'rejection' of MSC stem cells (Mesenchymal Stem Cells) in a post from some months ago.....

"An issue concerning MSC treatments being studied for COVID-19 is that the cells are mostly allogeneic, meaning that they come from donors. Allogeneic cells may be rejected by the patient’s body because they are seen as foreign, resulting in getting attacked by the patient’s immune system. There is some debate as to whether stem-like cells such as MSCs may not trigger an immune response even in unmatched hosts, but this issue is still being studied. Allogeneic cells may also pose risks by having the potential to negatively impact the immune system."

https://ipscell.com/2020/08/review-of-4-cell-therapy-types-under-study-for-covid-19/

 
TrixieStix said:
Am I correct in assuming your referring to the actual write up about the study results in 'Stem Cells Transitional Medicine' rather than the linked blog post by Paul Knoepfler in 'The Niche' given the post doesn't mention the study's claims about cytokine storms or autoimmunity?
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I was reading the coverage in Science at the link that says Scienmag. If the author is quoted saying these things I would be pretty sceptical.

I have not kept up with what people are doing with stem cells recently but when I did this sort of thing was pretty much always pseudoscience. The main things unused stem cells are likely to do are tp produce an unwanted immune reaction - maybe with a real cytokine storm - and to clog up vessels by embolisation. They might conceivably have some magic power to put right somebody else's lungs but it would be extraordinarily serendipitous.
 
Snow Leopard said:
C Raina Macintyre discusses a range of vaccination roll-out approaches and discusses the importance of vaccine efficacy in controlling an epidemic.



See also, her recent manuscript:
https://www.medrxiv.org/content/10.1101/2020.12.15.20248278v2
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That was so interesting & informative thank you.

I notice they have approved the moderna vaccine in UK now, but it wont be here till spring, I'm quite worried about the lack of efficacy of AZ as so many more people will get that here
Moderna becomes third Covid vaccine approved in the UK - BBC News
 
According to the Swedish Medical Association's journal, legal action is being taken against a researcher in Sweden who is supected of having done long covid research without ethical approval.

(The researcher is not mentioned by name, but the details given in the article below have striking similarities to what has been discussed in this thread.)

Läkartidningen: Studier om långtidscovid åtalsanmäls
https://lakartidningen.se/aktuellt/nyheter/2021/01/studier-om-langtidscovid-atalsanmals/

Google Translate, English
Google Translate said:
The Board of Appeal for Ethical Review (ÖNEP) notifies a new case to the Public Prosecutor's Office. According to ÖNEP, there is a reasonable suspicion that a researcher has conducted studies on long-term covid without an ethical permit .[...]

It was after a feature in an TV program that ÖNEP began to look more closely at the current case. [...]

ÖNEP's decision states that the doctor himself rejects the information that he should have started a research study before he received an ethics permit.

He admits that he has sent out study packages with instructions, consent forms, questionnaires and sampling materials for, for example, urine samples, cheek scraping and blood sampling to patients. But no sensitive personal data has been collected and no biological material has been received or saved, according to the doctor. He also points out that he has now received permission from the Ethics Review Authority.

But according to ÖNEP, there is therefore a reasonable suspicion that the doctor conducted research without a permit. The Board of Appeal refers, among other things, to the fact that screenshots from the clinic's website show that the clinic recruited participants for the two studies - nine and eleven people, respectively - before the ethics permit was finally issued.

Violations of the Ethics Review Act can result in a fine or imprisonment for up to two years.
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Immune determinants of COVID-19 disease presentation and severity, Brodin, 2021
COVID-19, caused by SARS-CoV-2 infection, is mild to moderate in the majority of previously healthy individuals, but can cause life-threatening disease or persistent debilitating symptoms in some cases. The most important determinant of disease severity is age, with individuals over 65 years having the greatest risk of requiring intensive care, and men are more susceptible than women. In contrast to other respiratory viral infections, young children seem to be less severely affected. It is now clear that mild to severe acute infection is not the only outcome of COVID-19, and long-lasting symptoms are also possible. In contrast to severe acute COVID-19, such ‘long COVID’ is seemingly more likely in women than in men. Also, postinfectious hyperinflammatory disease has been described as an additional outcome after SARS-CoV-2 infection. Here I discuss our current understanding of the immunological determinants of COVID-19 disease presentation and severity and relate this to known immune-system differences between young and old people and between men and women, and other factors associated with different disease presentations and severity.
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https://www.nature.com/articles/s41591-020-01202-8

From the Long COVID section
This post-COVID syndrome bears resemblance to postinfectious syndromes that followed outbreaks of chikungunya18 and Ebola19, for example, and selected symptoms overlap with myalgic encephalomyelitis, a disease that is also often triggered by infection and immune activation20 and manifests as a dysregulated autonomic nervous system and perturbed immune parameters21. More research is needed to understand the pathogenesis of all of these postinfectious conditions, and long COVID offers a unique opportunity to perform such studies in larger numbers of individuals, all infected by the same virus during a limited time frame.
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