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

Snow Leopard · Jun 18, 2020

Michiel Tack said: ↑

A lot of people on Twitter are frustrated that the dexamethasone researchers have sent out their press release without releasing their results to fellow scientists, for example in a preprint. I think COVID-19 has shown the importance of post-publication peer review.
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Yes, it's certainly cause for skepticism.

Andy · Jun 18, 2020

In a major U-turn, the UK is ditching the way its current coronavirus-tracing app works and shifting to a model based on technology provided by Apple and Google.

The move comes the day after the BBC revealed that a former Apple executive, Simon Thompson, was taking charge of the late-running project.

The Apple-Google design has been promoted as being more privacy-focused.

However, it means epidemiologists will have access to less data.
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https://www.bbc.co.uk/news/technology-53095336

Mithriel · Jun 18, 2020

It bugs me that the BBC says UK when it was only going to be used in England. On a par with their ME work.

Sean · Jun 18, 2020

The COVID tracing app put out by our government has been a flop. Nowhere enough people downloaded it, there was problems getting to work from the start and it still doesn't work very well, and I think only one contact has been traced by it.

The government has been very quiet about it since the initial hype at its release.

Wits_End · Jun 19, 2020

I didn't follow this through, but I noticed in passing by the local shop this afternoon that the Daily Mail had a front-page headline which implied that a deficiency of Vitamin D seemed to be associated with poor Covid-19 outcomes. Anyone know any more?

Once again, I can't believe I'm quoting the DM, but they do seem to have produced one or two good articles

Ebb Tide · Jun 19, 2020

Towards the bottom of this BBC article Vitamin D is mentioned (haven't read it properly yet):

"Meanwhile, work by Queen Mary University of London has suggested heart disease and vitamin D levels do not explain the increased risk of coronavirus in black, Asian and minority ethnic people.

Both had been suggested as potential explanations for the greater risk in some groups."

https://www.bbc.co.uk/news/health-53097676

MeSci · Jun 19, 2020

Wits_End said: ↑

This article from the Washington Post is wide-ranging:

http://www.msn.com/en-gb/news/coron...ill-others/ar-BB15C7Wx?li=BBoPRmx&ocid=ASUDHP
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Well, I am over 60, have hypertension and have Type A Rhesus Positive blood. I also have ME.

Type A blood is supposed to give "a 50 percent higher risk of needing oxygen or a ventilator" in covid-19 patients in Italy and Spain.

I haven't had any breathing problems, but do have occasional pains in my chest. This has been the case for several days at least.

Also had apparent gout in one toe, referred to earlier.

So who knows...?

ladycatlover · Jun 19, 2020

There's some interesting stuff about a possible new breath test arrived in my inbox from ProMED Mail today.

[2] South Africa: rapid point of service breath tests, trials pending
Date: Mon 15 Jun 2020
Source: The Scientist [edited]
<https://tinyurl.com/y9ajsnkj>

In Hillbrow, a suburb of Johannesburg, South Africa, researchers are
gearing up to start a trial to assess a rapid breath test for COVID-19
to deliver results on-site in less than 5 minutes. If successful, the
test would offer the advantages of being non-invasive, easy to use,
and appropriate in settings other than hospitals.

"We believe that breath is potentially a powerful medium in detecting
certain diseases early," says Mohammed Majam, the head of medical
technologies at Ezintsha, an academic policy and research unit of the
health sciences faculty at the University of the Witwatersrand (Wits).
"We are evaluating if this is the same for a virus like [SARS-CoV-2].
Our body responds immediately to the virus metabolically, and in the
process, unique gases are produced. These gases are a signature of the
virus and a breath test would be able to capture that," Majam, who
previously worked on the evaluation of HIV self-tests for the World
Health Organization in South Africa, tells The Scientist.

The investigators are waiting on approval from regulatory authorities
to begin the test and work out the logistics of importing it into
South Africa, as many tests suppliers have been affected by lockdown
regulations. If all moves ahead, the scientists will use a sensitive,
handheld device fitted with disposable nanosensors that pick up gases
in a normal exhaled breath. For the phase 1 study, breath samples will
be collected from 60 adults with positively confirmed COVID-19 and 90
negative controls. Ezintsha is assessing the product and the
developer, US-based Canary Health Technologies, would commercialize
it.

A cloud-based pattern-recognition technology will determine if a
COVID-19 breath pattern can be established with accuracy. "This study
at Wits will confirm the expected metabolic fingerprint of COVID-19
disease in the breath based on our assessment of the impact of
COVID-19 on human body," Raj Reddy, the chief executive officer of
Canary and inventor of the technology, tells The Scientist.
SARS-CoV-2, the virus that causes COVID-19, can initiate oxidative
stress by a similar mechanism observed in other viral pneumonias,
according to Reddy, with the production of highly reactive nitrogen
oxide species. "This would in turn enhance the concentration of
alkanes and oxygenated compounds that are exhaled from the breath. A
larger load of distinctive biomarker molecules would eventually result
in higher sensor response for patients with COVID-19 disease as
compared to COVID-19 negative individuals," says Reddy. "Our
differentially reactive sensor system is expected to generate a
distinct pattern that can discriminate between people with COVID-19
disease and those without."

Scientists will then use the breath patterns to measure the
sensitivity and specificity of the test when compared to a standard
PCR-based diagnostic. Majam says he believes the test is very safe, as
the disposable sensor prevents COVID-19 infected breath from touching
the inside of the main device that is used to transmit the data to the
cloud for analysis. The machine is disinfected between uses. "Any
rapid test that could be used to identify infected individuals during
this pandemic, especially those who are asymptomatic, is very
important, says Burtram Fielding, a molecular biologist at the
University of Western Cape who has been working on coronaviruses since
2003.

Diagnostic tests modeled around the same type of technology for asthma
and lung disease are globally in use. The typical problems with these
types of tests are that they are not very specific or sensitive,
Fielding says. "This means that it could register false positives --
someone tests positive, but is not infected -- and false
negatives--someone tests negative, but is indeed infected," Fielding
tells The Scientist. The latter, he says, is of much greater concern
as an infected person could spread the disease not knowing that they
are positive. False positives could also be due to the test detecting
the same biomarkers for other, less-dangerous coronaviruses or other
types of viruses altogether.

As with all other rapid tests, this could make a good screening tool
if the sensitivity and specificity are high enough, Fielding says.
Used as a screening test, individuals testing positive could at least
be isolated while they are tested by the confirmatory RT-PCR test,
which is the gold standard. "Unless the clinical trial shows very high
sensitivity and specificity, this would not be a very useful test
during the epidemic of a virus with such a high infective rate," he
says.

In May [2020], researchers at Ben-Gurion University of the Negev in
Israel announced they had developed a COVID-19 electro-optical test of
nose, throat, or breath samples that looks for signs of the virus's
presence itself and gives results in less than one minute. This
product would cost approximately USD 50. Current PCR tests range
between USD 45 and USD 70. "We believe we will be able to produce the
tests at a significantly lower cost," says Majam.

Canary Health is discussing plans to conduct clinical trials on the
device in the United Kingdom and the US, but a trial planned in Hong
Kong won't go ahead now that there are very few COVID-19 cases,
according to Anna Wang, Canary's senior vice president for corporate
affairs.

"We will seek accelerated regulatory approval in South Africa as soon
as they are confident of the performance, [and we hope] to have this
test on the market before the end of 2020," Wang says.

[byline: Munyaradzi Makoni]

--
communicated by:
ProMED-mail
<promed@promedmail.org>

[We usually do not post pre-phase 1 trials as many a good idea doesn't
pass through phase 1 to phase 2, or from phase 2 to phase 3. But this
struck me as a fascinating approach should it prove to be successful
after a rigorous case control study protocol. As mentioned above and
in prior posts, the need for point of care rapid testing is in great
demand, especially in Africa where border crossings are points where
passage of trucks carrying needed supplies and products are often
delayed at the crossing for days or even 1-2 weeks awaiting PCR test
results. In addition, international and domestic travel might benefit
greatly by a rapid point of care test.

A picture of the device is available at the source URL above. -
Mod.MPP

HealthMap/ProMED map of South Africa:
<http://healthmap.org/promed/p/179>]
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Anna H · Jun 19, 2020

https://www.svt.se/nyheter/inrikes/svart-sjuka-covidpatienter-behandlas-med-kortison

Severely ill covid patients are treated with cortisone in several large hospitals

Google translated:
The drug dexamethasone can save severely ill covid patients, according to a new British study. SVT's review shows that several large Swedish hospitals are already using the drug or similar preparations.
This week, the first seriously ill covid patients at Sahlgrenska University Hospital in Gothenburg were treated with corticosteroid dexamethasone (cortisone). A drug that has been rewritten worldwide in recent days as a result of a yet unpublished British study - which has shown that it can reduce the mortality rate of seriously ill covid patients.

- There are several patients with us who have received it after this study came. I think you will start using this at most clinics in the country, ”says Magnus Gisslén, an infectious doctor at Sahlgrenska.

Examined thousands of patients
But it is too early to assess the effect the treatment has had on patients at Sahlgrenska, according to him.

- It's very difficult to judge. For the individual patient you can only guess, you have to look at larger groups.

This is exactly what the researchers at Oxford University have done. More than 2,000 patients with covid-19 were treated with dexamethasone for ten days, then their disease status was compared with another group of more than 4,000 covid patients who received regular care.

The mortality rate for respiratory care patients decreased by one-third for those receiving dexamethasone compared to the other patients, according to the researchers.

The Swedish Medicines Agency gave green light
The WHO called the study a "scientific breakthrough" and in the UK it was decided to immediately start treating covid patients with dexamethasone, which is a relatively inexpensive and readily available drug. In Sweden, the Swedish Medicines Agency has provided green light for doctors to use the drug.

SVT Nyheter has been in contact with several of the university hospitals. They have all used dexamethasone or similar drugs in the treatment of patients with covid-19 (see fact box).

- It is a well-used drug that you have good control over. I think that seriously ill patients can already be treated today, said Anders Sönnerborg, professor of infectious diseases at the Karolinska Institute, in Aktuellt earlier this week.
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wastwater · Jun 21, 2020

COVID-19 –associated Diffuse Leukoencephalopathy and Microhemorrhages

https://pubs.rsna.org/doi/10.1148/radiol.2020202040

wastwater · Jun 21, 2020

https://www.jns-journal.com/article/S0022-510X(20)30282-3/fulltext
COVID-19-associated delayed posthypoxic necrotizing leukoencephalopathy

MeSci · Jun 21, 2020

MeSci said: ↑

Had he had gout before? Were his eyes like this? https://www.express.co.uk/life-styl...date-uk-news-symptoms-red-eyes-conjunctivitis
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In case you didn't see this question, I'm tagging you: @ukxmrv

ladycatlover · Jun 21, 2020

Winning by a nose: the dogs being trained to detect signs of Covid-19

In the battle against the virus, we have an unlikely ally. Already used to detect drugs and weapons, dogs are now being trained to sniff out when humans have the virus. Tim Lewis meets the trainers and their hounds
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Wits_End · Jun 22, 2020

Vitamin D, BAME patients, and a possible link?

http://www.msn.com/en-gb/news/newsm...hit-harder/ar-BB15NuzM?li=AAnZ9Ug&ocid=ASUDHP

Strange where you find these stories during the pandemic ...

rvallee · Jun 22, 2020

Decoding SARS-CoV-2 Hijacking of Host Mitochondria in Pathogenesis of COVID-19

https://journals.physiology.org/doi/abs/10.1152/ajpcell.00224.2020

Due to ongoing pandemic around the world, the mechanisms underlying the SARS-CoV-2 induced COVID-19 are subject to intense investigation. Based on available data for the SARS-CoV-1 virus, we suggest how CoV-2 localization of RNA transcripts in mitochondria hijacks the host cell's mitochondrial function to viral advantage. Besides viral RNA transcripts, RNA also localizes to mitochondria. SARS-CoV-2 may manipulate mitochondrial function indirectly, first by ACE2 regulation of mitochondrial function, and once it enters the host cell, ORFS such as ORF-9b can directly manipulate mitochondrial function to evade host cell immunity and facilitate virus replication and COVID-19 disease. Manipulations of host mitochondria by viral ORFs can release mitochondrial DNA (mtDNA) in the cytoplasm and activate mtDNA induced inflammasome and suppress innate and adaptive immunity. We argue that a decline in ACE2 function in aged individuals, coupled with the age-associated decline in mitochondrial functions resulting in chronic metabolic disorders like diabetes or cancer, may make the host more vulnerable to infection and health complications to mortality. These observations suggest that distinct localization of viral RNA and proteins in mitochondria must play essential roles in SARS-CoV-2 pathogenesis. Understanding the mechanisms underlying virus communication with host mitochondria may provide critical insights into COVID-19 pathologies. An investigation into the SARS-CoV-2 hijacking of mitochondria should lead to novel approaches to prevent and treat COVID-19.
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JaneL · Jun 22, 2020

Would anyone like to share their thoughts on the usefulness and/or ethics of using human challenge studies to study COVID-19? (For those who aren’t aware: human challenge studies involve the deliberate infection of healthy volunteers). I was a bit alarmed to learn that WHO appears to be endorsing their use in a recent document entitled “Key criteria for the ethical acceptability of COVID-19 human challenge studies”:

https://apps.who.int/iris/bitstream...2019-nCoV-Ethics_criteria-2020.1-eng.pdf?ua=1

I also came across this article:

Human COVID-19 vaccine trials are unnecessary, uninformative, and unethical
By William A. Haseltine

William A. Haseltine, a scientist, biotech entrepreneur, and infectious diseases expert, is Chair and President of the global think tank Access Health Information.
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My first reaction was that the advocates of such “human challenge studies” had gone so mad with panic that they had forgotten the history and horrors of medical experimentation on humans. But on closer inspection, I saw that they included some of the world’s most respected vaccine researchers and medical ethicists, and even the World Health Organization.
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Caveats notwithstanding, the rush to develop a COVID-19 vaccine that will definitively end the loss of life and stop the economic devastation has already produced more than 100 candidates, all in very early stages of development. With so many pharmaceutical companies and governments scrambling to get some skin in the game, each day seems to bring announcements of new programmes, most of them unaccompanied by supporting data.

But deliberately infecting volunteers with SARS-CoV-2 to test the efficacy of vaccine candidates is unnecessary, uninformative, and unethical.
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The article then goes on to explain precisely why deliberately infecting volunteers with SARS-CoV-2 is unnecessary, uninformative, and unethical. I hope he is correct that this approach is uninformative (?). But mostly I hope that the overwhelming majority of people in the research community share the view that these challenge studies are unethical and that they won’t be permitted to go ahead...

https://www.stabroeknews.com/2020/06/09/features/project-syndicate/human-covid-19-vaccine-trials-are-unnecessary-uninformative-and-unethical/

Snow Leopard · Jun 23, 2020

JaneL said: ↑

The article then goes on to explain precisely why deliberately infecting volunteers with SARS-CoV-2 is unnecessary, uninformative, and unethical. I hope he is correct that this approach is uninformative (?). But mostly I hope that the overwhelming majority of people in the research community share the view that these challenge studies are unethical and that they won’t be permitted to go ahead...
Click to expand...

There are only two ways to test the real-world efficacy of vaccines, a naturalistic randomised controlled study where you recruit a large population (tens of thousands of people) but only vaccinate half of them, and hope that many of them will be exposed to the infection. The other is to deliberately expose a much smaller number of people who have been vaccinated. The latter is the only choice to test effiacy in regions which means to control the spread of the infection are mostly successful.

Both have ethical issues. In the end, it is all about informed consent.

JaneL · Jun 23, 2020

Snow Leopard said: ↑

There are only two ways to test the real-world efficacy of vaccines, a naturalistic randomised controlled study where you recruit a large population (tens of thousands of people) but only vaccinate half of them, and hope that many of them will be exposed to the infection. The other is to deliberately expose a much smaller number of people who have been vaccinated. The latter is the only choice to test effiacy in regions which means to control the spread of the infection are mostly successful.

Both have ethical issues. In the end, it is all about informed consent.
Click to expand...

Thanks @Snow Leopard. So am I correct in my understanding that you disagree with the author of the article that the second type of study is “uninformative”? This is what he says in relation to that:

Challenge studies are also uninformative. To the best of my knowledge, all current protocols for vaccine trials envisage enrolling only young, healthy adults. This is understandable from a recruitment perspective, but COVID-19 morbidity and mortality are highest among the elderly, who have a plethora of underlying chronic diseases.

Numerous studies have shown that vaccines that are effective among the young can fail in older populations – sometimes completely. Our bodies’ ability to respond to most, if not all, vaccines declines precipitously with age. Are today’s COVID-19 vaccine developers seriously entertaining the idea of trials that use a live virus in this vulnerable population?
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Snow Leopard · Jun 23, 2020

JaneL said: ↑

Thanks @Snow Leopard. So am I correct in my understanding that you disagree with the author of the article that the second type of study is “uninformative”? This is what he says in relation to that:
Click to expand...

His argument about elderly individuals is a non-sequitur.

The reason why we have to test vaccines directly, is because seroconversion/antibody titres is not enough evidence to show the vaccine actually works. This is doubly so for SARS-2 vaccines, which are testing a variety of new and unproven vaccine technologies (that utilise genetic engineering), none of which is guaranteed. Whether you test in young people or elderly people is irrelevant on this point, since it is not antibody titres that we are interested in, but whether the antibodies actually neutralise the virus. It is true that elderly populations are less likely to seroconvert, but this is not specific to any vaccine and this doesn't discount the fact that the goal of vaccine efficacy is to achieve herd immunity - so that elderly people aren't exposed in the first place. Once we know the induced antibodies are effective at stopping infection in young volunteers, elderly participants don't have to be exposed to the virus for us to generalise whether the vaccine is likely to be effective - measurement of seroconversion would be sufficient.

Secondly, exposing volunteers speeds up the development process considerably, compared to a 3 month naturalistic exposure trial, and hence could save far more lives overall if the vaccine is able to be approved sooner!

Finally, he mentions that Australia, NZ, Taiwan etc have controlled the virus - this is true, but we can't hold the virus at bay forever without ongoing severe travel restrictions. For things to go back to normal, we need an effective vaccine.

Trish · Jun 24, 2020

The Guardian newspaper, UK:
https://www.theguardian.com/world/2...l&CMP=GTUK_email&utm_campaign=GuardianTodayUK
Covid-19 vaccine may not work for at-risk older people, say scientists

A vaccine against Covid-19 may not work well in older people who are most at risk of becoming seriously ill and dying from the disease, say scientists, which may mean immunising others around them, such as children.

Prof Peter Openshaw, from Imperial, one of the members of the UK’s Sage scientific advisory sub-group Nervtag, told the House of Lords science and technology committee it was this week considering a paper on targeting different groups in the population with vaccines.
[...]
Arne Akbar, professor of immunology at UCL and president of the British Society of Immunology, said scientists needed to work out what goes wrong with the immune system as people get older.

“One thing that’s apparent, even in healthy older people, is that there’s more inflammation all around the body. We need to understand where that inflammation is coming from,” he said. “And this baseline inflammation in older people is linked to frailty and many negative outcomes as we get older. And this seems to be exacerbated when you get a severe infection like Covid-19.
[...]
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