Covid, Phase II. Commonsense is the order of the day. | Page 89 | Vital Football

Covid, Phase II. Commonsense is the order of the day.

Part III

Symptomless transmission
The issue of asymptomatic transmission - and ministers’ lack of knowledge of it - has been cited by Mr Johnson almost every time he is asked about why Covid was able to spread in the UK.
It is a narrative that has gone largely unchallenged, yet some scientists on Sage did try to raise the alarm.
On Jan 28 Sage noted that “there is limited evidence of asymptomatic transmission, but early indications imply some is occurring”.
Then on Feb 21 last year the Italian village of Vo’Euganeo near Venice went into quarantine after the country’s first recorded death from Covid, and almost all of its residents were tested for the virus.
Around 40 per cent of those who tested positive were asymptomatic, strongly suggesting asymptomatic transmission was occurring.
Members of Sage were so struck by the findings that they raised them with the Chief Scientific Adviser, Sir Patrick Vallance, and with Prof Ferguson, only for their concerns to be dismissed.
One scientific adviser said: “Neil Ferguson’s response was that it doesn’t really make that much difference to the models, which seemed a bit strange, because it certainly made a bloody big difference.”
Tests on passengers on the Diamond Princess cruise ship in Japan, where hundreds of people became infected and were quarantined, including Britons as seen in the video below, also raised questions in February about whether the virus was being transmitted asymptomatically.



The European Centre for Disease Prevention and Control recommended that the new virus be treated like Middle East Respiratory Syndrome, telling health bodies such infections “may be asymptomatic” and should be diagnosed with polymerase chain reaction (PCR) tests.
The centre said the virus could potentially be transmitted through “aerosols” - in other words breath - and stressed the importance of contact tracing in order “to implement timely control measures like isolation or quarantine as appropriate”.
It turned out to be good advice, but at their Jan 28 meeting Sage decided to disregard the European centre's recommendation and instead said the Department of Health and Social Care should “use existing planning assumptions for an influenza pandemic to develop a reasonable worst case for [Covid-19] in the UK”.
It meant that government departments followed the pandemic response set out by Exercise Cygnus, effectively flicking a switch that turned on the policy of mitigation rather than prevention.
As one scientific adviser put it: “Flu becomes a metaphor for ‘it's an uncontrolled surge and you can't contain it any more’.”
Worst-case scenarios
By late February predictions of up to 500,000 deaths were making headlines, but even this was not the worst-case scenario presented to ministers.
“We were told early on, when we weren’t sure of the mortality rate, that there could be 830,000 deaths over a seven-week period,” said one Cabinet source.
“The normal death rate is 600,000 per year and we were having conversations about whether we were going to have to live with that figure going up to 700,000 deaths a year if this became endemic.”



Ministers could be forgiven for casting a sceptical eye over startling predictions; in 2005, for example, Prof Ferguson warned that bird flu could kill 200million people worldwide, when the true death toll turned out to be fewer than 300.
“In public Matt Hancock and others were saying we were well prepared because we had dealt with similar things before,” said one senior MP, “but privately they were saying they didn’t think it was going to come here in any major way.”
Another source said: “We were being told there could be 830,000 deaths and at the same time we were being told that if we locked down too tightly and too quickly we would push the second wave to Christmas where it would be even worse, so you can see how difficult the decisions were.”



Secrecy was also the order of the day in those first months. Mr Hunt said: “If Sage’s advice to ministers had been published contemporaneously it would have effectively been peer-reviewed straight away and we probably would have come to the conclusion we ultimately did come to much sooner.”
But outside Sage’s meetings, the wider scientific community had no idea of the course that was being followed. The idea of flu being the main pandemic threat is so ingrained in Government that the Sage sub-groups responsible for modelling and behaviour - SPI-M and SPI-B - contain the word influenza in their names, as Scientific Pandemic Influenza groups.
In mid-March, Sir Patrick spoke of the need “to build up some degree of herd immunity” which would mean that “probably 60 per cent” of the population would have to get the virus.
One health source said: “He was talking about herd immunity because that’s what you do with flu. What’s been forgotten in all of this is that herd immunity was what Sage wanted at the beginning.”
One senior MP said: “They definitely had a view early on that allowing it to spread to build up immunity was necessary. They were saying privately ‘this is going to be like chickenpox, we are probably all going to have to get this’.”
Sir Patrick later denied herd immunity had ever been the preferred policy of Sage, and it was never taken up by the Government.
The political dimension
What of the allegation that the Government was too distracted by politics to realise the danger of coronavirus?
Covid was initially seen as largely a matter for the Foreign Office and the Department of Health, with confirmed cases on British soil remaining in double figures throughout February, with no confirmed deaths.
Downing Street was fully focused on implementing the manifesto plans that had earned Boris Johnson an 80-seat majority less than a month earlier.
Brexit finally happened on Jan 31, and after that the talk was of levelling up. Mr Johnson was also plotting a reshuffle which was to take place on Feb 13, and included the unexpected resignation of Sajid Javid as chancellor.
One member of Mr Johnson’s team said: “Maybe with hindsight the Prime Minister and his team know they should have delved deeper into this at an earlier stage. But everyone can be a professor of hindsight and there was nothing in those early days to suggest where we were going to end up.”
 
Role of Sage to be reviewed over fears scientists hold too much power

Panel that set the course for some of the pandemic’s most controversial policies may hold ‘too much sway’ over ministers

By Gordon Rayner, Associate Editor 15 March 2021 • 8:00pm


Chris Whitty, left, and Sir Patrick Vallance, whose advice has heavily influenced government policy during the pandemic


The role of the Scientific Advisory Group for Emergencies (Sage) is likely to be reviewed when the Covid pandemic is over, government sources have said.
A future independent inquiry into the handling of coronavirus is expected to scrutinise Sage and consider whether such a monolithic body should hold so much power. Members of Sage have themselves expressed concern that the group holds too much sway over ministerial thinking and prevents alternative views being given equal weight.
One possibility is that the Government sets up a so-called “red team” structure to challenge and check Sage’s advice and the evidence behind it. Ministers could also demand more say over membership of the largely autonomous body, which changes with almost every meeting depending on who is invited by Sir Patrick Vallance, the Chief Scientific Adviser.
Matt Hancock, the Health Secretary, has made it clear during the pandemic that Sage’s role is kept “under review”. Formed under the last Labour government, Sage had, until the Covid crisis, been a largely obscure committee of scientists that was convened a handful of times each year. It was first called into action to advise on the 2009 swine flu pandemic, and went on to advise the Government on the 2014 Ebola outbreak, the 2016 zika virus outbreak and the 2018 Salisbury poisonings.
In 2019, Sage met just once, to discuss the feared collapse of the Toddbrook Reservoir dam in Derbyshire. However, over the course of 2020, it met 74 times.
The first of those meetings took place on Jan 22, a fortnight after reports of a cluster of illnesses in China being identified as a new strain of coronavirus first appeared in the UK press. During Sage’s “precautionary meeting on Wuhan Coronavirus”, the attendees set the course for many government policies that were later criticised.
The minutes of that meeting note that the Sage sub-committee on New and Emerging Respiratory Virus Threats (Nervtag) “does not advise port of entry screening, irrespective of the current limited understanding of the epidemiology”. Temperature checks on people arriving in the UK and other forms of screening were “unlikely to be of value”, the scientists decided.
The scientists agreed to review their response if there was “a severe confirmed case in the UK”, adding: “Sage is unable to say at this stage whether it might be required to reconvene.”
Six days later, they did reconvene, with Covid spreading at an alarming rate in China, and they continued to meet at least once a week for the rest of the year.
Ministers admit: we ‘bowed to Sage’ too often
Government insiders have admitted that they “bowed to” Sage too often, rather than appointing a so-called “red team” to challenge its advice.
Sage’s official remit is to provide Cabinet Office Briefing Room (Cobra) meetings with “coherent, coordinated advice and to interpret complex or uncertain scientific evidence in non-technical language”.
The Sage representative at Cobra meetings is Sir Patrick Vallance, the Chief Scientific Adviser, who is often accompanied by Chris Whitty, the Chief Medical Officer.
The two men also decide who attends each meeting, inviting experts from different fields depending on the nature of the emergency. Until the Covid crisis, participants’ names were not divulged, but Sage agreed that the exceptional nature of Covid warranted greater transparency.
To date, 87 experts have attended the Sage meetings at various times. They include the two deputy chief medical officers, Jonathan Van-Tam and Jenny Harries; Dido Harding, head of NHS Test and Trace; Neil Ferguson, the Imperial College modelling expert who became known as “professor lockdown” before stepping down for breaking lockdown rules; Sir Ian Diamond, the national statistician, and Dr David Halpern, head of the Cabinet’s Behavioural Insights Team, or “nudge unit”.
Others work in the fields of epidemiology, vaccines, data, tropical medicines and other disciplines.
More than 20 institutions are represented among the membership of Sage, which meets in a conference room at the Department for Business, Energy and Industrial Strategy in central London.
Around 20 government officials attend meetings on an ad hoc basis to report back to ministers on what has been discussed. They have in the past year included Dominic Cummings, the prime minister’s former chief adviser, and representatives from almost every Whitehall department.
 
This seems sensible because as most of us know scientists are curious creatures and are just as interested in'what if's to drive their research before eventually gathering data to support their theories, if things look promising. . They do not worry about failing they just move on to the next theory / hypothesis. A learning experience. That is the nature of their profession and associated research and development, which if I recall is about 30% success in general and 70% throwaway. .Not failure as such but accepted dead end, no end product reaearch. And of course common sense and practicalities rarely seem to get applied to their decision making. Someone else needs to try to do that side of the equation. I am generalising of course but that is the underlying nature of the scientific way initially..
 

Walthamstow wanderer

Vital Football Hero
Staff member
It is of course, just advice , at the end of the day . Maybe a more measured advice , but in this case , not a more informed advice .
Everyone was Damned , no matter what they did ..... or didn’t .... do .
In My Opinion , of course .
 
Walthy elements of arrogance has always worried me, the 'I am clever and I know know best syndrome'.
I would definitely have looked at the areas in the world who have more knowledge about dealing with SARS related issues such as South Korea and how they manage and apply logic to these situations and control things. I have never seen the merits of re-inventing the wheel and it seems our country took on the mantle of 'we know best'...hence 125k deaths,,,but what do I know?
 
It is not a vaccine if it requires annual booster shots. It's a recurring revenue stream for big pharma. I can't stand the misuse of words like this for the benefit of sales.
 
Now Britain’s genome-busters use Covid success to target superbugs
The sequencing infrastructure used on coronavirus is set to be repurposed to tackle a ‘silent pandemic’ of antibiotic resistance, Tom Whipple writes

Tom Whipple, Science Editor
Sunday March 21 2021, 6.00pm, The Times
China
Science

Scientists sequencing coronavirus genomes at COVID-19 Genomics UK, at the Wellcome Sanger Institute near Cambridge
DYLAN MARTINEZ/REUTERS
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Britain’s world-leading coronavirus sequencing infrastructure can be repurposed to help to tackle the “silent pandemic” of antibiotic resistance, scientists have said, as the government predicted superbugs could cause 20 million deaths a year worldwide by 2050.
Last week the integrated review of security and foreign policy identified the evolution of drug-resistant microbes as a critical strategic threat alongside the rise of China and Russia.
“Antimicrobial resistance remains a long-term challenge to human health,” it said. “On current trends, global deaths related to antimicrobial resistance will rise from 700,000 to 20 million per year by 2050.” The development of antibiotics has stalled at the same time as their overuse has encouraged the evolution of strains of bacteria that can evade them.
Scientists believe that routinely decoding the genomes of infectious bacteria, in the way that has been shown possible during the coronavirus pandemic, will be a vital tool in controlling the spread of drug-resistant strains until new antibiotics can be found.

“Sequencing is here to stay now in the country. It’s an important legacy, and we have to plan how to use it wisely,” Professor Sharon Peacock, from the University of Cambridge, said.

Peacock was instrumental in setting up Britain’s sequencing network for coronavirus. Since the start of the pandemic she and her colleagues have taken about 10 per cent of positive tests and derived their entire genome.
This has enabled them to track the evolution of the virus, trace the origins of outbreaks and also spot the UK variant. She said that when the Covid-19 response winds down the infrastructure, which has sequenced more than 200,000 genomes, had clear applications in treating and preventing outbreaks of drug-resistant bacteria.

Sequencing would allow scientists to spot drug-resistant bacteria, which are expected to cause 20 million deaths a year by 2050, more quickly
DYLAN MARTINEZ/REUTERS
Tuberculosis patients already have their infection sequenced, meaning doctors can know far quicker and easier if it is resistant. If other infections were treated in the same way there would be no need to waste time with drugs on bacteria whose genome would tell us they have evolved resistance. “It would mean treating somebody with the right drug at the right time,” Peacock said.
The real benefits may come in public health, however. Through sequencing it is possible to trace the source of specific outbreaks. It is also possible to pick up resistant bacteria before they would have been otherwise spotted.



“The list of bacteria that you’re thinking about for antibiotic resistance ranges from E. coli at one end to gonorrhoea at the other,” Peacock said. “It’s a really broad spectrum, but we want to really get a handle on the frequency of resistance, and the types of resistance in what bacteria.”
She thinks that some of the kinds of surveillance used during the pandemic, including of waste water, could help to identify and isolate outbreaks rapidly. “If you can get the information early enough, you can stop them.” Before the pandemic many microbiologists had argued that genetics could be an important public health tool. Peacock said that the past year had proven that to be the case and that work was under way to ensure that what has been built will remain part of health infrastructure.
“We have never applied sequencing to a single organism in this way. It’s unprecedented in terms of scale and has allowed us to really understand the evolution of an important pathogen in minute detail,” she said.
“But we can’t go backwards now. Now that we’ve got the technology, we will apply it much more widely.”
 
Delaying the first lockdown may have inadvertently saved more lives than it cost

A Cambridge expert argues that countries who locked down early just delayed part of their first wave, resulting in higher overall mortality

By Henry Bodkin, Health and Science Correspondent 21 March 2021 • 8:00pm


An almost deserted Central Line train in London during one of England's three national lockdowns, with legal restrictions introduced regarding travel and socialising Credit: Dominic Lipinski/PA Wire


Delaying the first lockdown may have inadvertently saved more lives than it cost, according to a new analysis.
Prime Minister Boris Johnson has been heavily criticised for only imposing the national restrictions on March 23 last year, at least nine days after he knew that the NHS would not be able to cope if coronavirus was allowed to rampage unchecked.
A number of scientists and opposition politicians have claimed that delaying the decision caused tens of thousands of unnecessary deaths.
However, a University of Cambridge expert now argues that countries who locked down early effectively delayed part of their first wave to the winter, resulting in higher overall mortality.
Dr Raghib Ali, a senior clinical research associate at the university’s MRC Epidemiology Unit, said Britain’s relatively late lockdown meant more people were infected in the spring, when underlying pressure on the NHS was relatively light, meaning they were protected by antibodies come winter, when the service traditionally struggles to cope.
Writing for The Telegraph, he saidin the absence of a vaccine, lockdowns postpone infections, rather than prevent them, and suggests that March and April was a better period in which to catch the virus.
Many of the claims that Britain’s late lockdown exacerbated the death toll have been made using the statistical models that urged the measure in the first place.
By contrast, Dr Ali compared the UK to European countries with similar populations, age structures, seasons and healthcare systems.
While Norway and Finland, which locked down a week before the UK have both had small first and second wave death tolls, these are exceptions, according to Dr Ali, also a professor public health at New York University.
“What happened in many other countries in Europe who also locked down (and closed their borders) at the same time is that they did have very small first waves in spring 2020 but this was followed by much larger second waves in autumn/winter 2021 (and now into spring 2021, too)”, he writes.

“And this has happened despite second and third lockdowns in many of these countries as people understandably struggled to maintain compliance with restrictions for months on end.”
He adds: “But based on current trends it seems likely that many of these countries that we thought were doing well due to their early lockdowns and small first waves will end up having higher excess mortality than the UK, including Czechia, Poland, Portugal, and many others.”
Dr Ali also argues that closing borders has emerged to be a key intervention in controlling the virus, and points out that Sage (the Scientific Advisory Group for Emergencies) opposed the policy last year.
However, he concludes that even if ministers had ignored the body’s advice and closed the borders last March, it would have been too late.
"The point is that getting the timing of lockdowns right is not straightforward, especially when you have to balance their very significant harms against their benefit, and there really is not good evidence that an earlier lockdown would have saved lives,” he said.
 
An mRNA vaccine for cancer immunotherapy

by American Chemical Society




Messenger RNA (mRNA) vaccines to prevent COVID-19 have made headlines around the world recently, but scientists have also been working on mRNA vaccines to treat or prevent other diseases, including some forms of cancer. Now, researchers reporting in ACS' Nano Letters have developed a hydrogel that, when injected into mice with melanoma, slowly released RNA nanovaccines that shrank tumors and kept them from metastasizing.

Cancer immunotherapy vaccines work similarly to mRNA vaccines for COVID-19, except they activate the immune system to attack tumors instead of a virus. These vaccines contain mRNA that encodes proteins made specifically by tumor cells. When the mRNA enters antigen-presenting cells, they begin making the tumor protein and displaying it on their surfaces, triggering other immune cells to seek and destroy tumors that also make this protein. However, mRNA is an unstable molecule that is quickly degraded by enzymes in the body. For cancer immunotherapy, researchers have tried using nanoparticles to protect and deliver mRNA, but they are typically cleared from the body within 1-2 days after injection. Guangjun Nie, Hai Wang and colleagues wanted to develop a hydrogel that, when injected under the skin, would slowly release mRNA nanoparticles, along with an adjuvant—a molecule that helps activate the immune system.

To develop their system, the researchers used ovalbumin (a protein found in chicken egg whites) as a model antigen. The team mixed ovalbumin mRNA and an adjuvant with other compounds to form a hydrogel. When injected under the skin of mice with melanoma tumors engineered to express ovalbumin, the hydrogel slowly released mRNA and adjuvant nanoparticles over a 30-day period. The mRNA vaccine activated T cells and stimulated antibody production, causing tumors to shrink in the treated mice. Also, in contrast to untreated mice, the vaccinated mice did not show any metastasis to the lung.

These results demonstrate that the hydrogel has great potential for achieving long-lasting and efficient cancer immunotherapy with only a single treatment, the researchers say.
 
The silver cloud..?

After a global disaster of this magnitude, how better could all these people who have died be better honoured by the World than this calamity and destruction and death be the reason we could cure cancer?

The whole of medical science after this ends, must get behind this next effort:


mRNA Vaccines Could Vanquish Covid Today, Cancer Tomorrow

The best news about the mRNA shots from BioNTech and Moderna is that the same technique could also defeat many other diseases.
By
Andreas Kluth

9 January 2021, 06:00 GMT



Fighting viruses is just the start.

Photographer: Chris Jackson/AFP via Getty Images

Andreas Kluth is a columnist for Bloomberg Opinion. He was previously editor in chief of Handelsblatt Global and a writer for the Economist. He's the author of "Hannibal and Me."


The night is darkest just before dawn, they say. Dark it certainly is right now. The more contagious variants of SARS-CoV-2 coming out of the U.K. and South Africa will make the pandemic worse before mass vaccination can make it better.



But take another look at some of these new vaccines. And then contemplate the dawn to come — not just its first rays in the coming months but also the bright light of future years and decades. It looks increasingly plausible that the same weapons we’ll use to defeat Covid-19 can also vanquish even grimmer reapers — including cancer, which kills almost 10 million people a year.


The most promising Covid vaccines use nucleic acids called messenger RNA, or mRNA. One vaccine comes from the German firm BioNTech SE and its U.S. partner Pfizer Inc. The other is from the U.S. company Moderna Inc. (its original spelling was ModeRNA, its ticker is MRNA). Another is on the way from CureVac NV, also based in Germany.



Ordinary vaccines tend to be inactivated or weakened viruses which, when injected into the body, stimulate an immune response that can later protect against the live pathogen. But the process of making such vaccines requires various chemicals and cell cultures. This takes time and provides opportunities for contamination.


mRNA vaccines don’t have these problems. They instruct the body itself to make the offending proteins — in this case, the ones that wrap around the viral RNA of SARS-CoV-2. The immune system then homes in on these antigens, practicing for the day when the same proteins show up with the coronavirus attached.
Therein lies mRNA’s bigger promise: It can tell our cells to make whatever protein we want. That includes the antigens of many other diseases besides Covid-19.


In its day-to-day function, mRNA takes instructions from its molecular cousin, the DNA in our cell nuclei. Stretches of the genome are copied, which the mRNA carries into the cytoplasm, where little cellular factories called ribosomes use the information to churn out proteins.

BioNTech and Moderna shortcut this process, by skipping the whole fiddly business in the nucleus with the DNA. Instead, they first figure out what protein they want — for example, a spike on the coat around a virus. Then they look at the sequence of amino acids that makes this protein. From that they derive the precise instructions the mRNA must give.

This process can be relatively fast, which is why it took less than a year to make the vaccines, a pace previously unimaginable. It’s also genetically safe — mRNA can’t go back into the nucleus and accidentally insert genes into our DNA.
Opinion. Data. More Data.


Researchers since the 1970s have had a hunch that you can use this technique to fight all sorts of maladies. But as usual in science, you need huge amounts of money, time and patience to sort out all the intermediary problems. After a decade of enthusiasm, mRNA became academically unfashionable in the 1990s. Progress seemed halting. The main obstacle was that injecting mRNA into animals often caused fatal inflammation.

Enter Katalin Kariko — a Hungarian scientist who immigrated to the U.S. in the 1980s and has heroically devoted her entire career to mRNA, through its ups and downs. In the 1990s, she lost her funding, was demoted, had her salary cut and suffered other setbacks. But she stuck with it. And then, after battling cancer herself, she made the crucial breakthrough.
In the 2000s, she and her research partner realized that swapping out uridine, one of mRNA’s “letters,” avoided causing inflammation without otherwise compromising the code. The mice stayed alive.

Her study was read by a scientist at Stanford University, Derrick Rossi, who later co-founded Moderna. It also came to the attention of Ugur Sahin and Ozlem Tureci, two oncologists who are husband and wife and co-founded BioNTech. They licensed Kariko’s technology and hired her. From the start, they were most interested in curing cancer.
Today’s weapons against cancer will one day seem as primitive an idea as flint axes in a surgery room. To kill a malignant tumor, you generally zap it with radiation or chemicals, damaging lots of other tissue in the process.



The better way to fight cancer, Sahin and Tureci realized, is to treat each tumor as genetically unique and to train the immune systems of individual patients against that specific enemy. A perfect job for mRNA. You find the antigen, get its fingerprint, reverse-engineer the cellular instructions to target the culprit and let the body do the rest.

Take a look at the pipelines of Moderna and BioNTech. They include drug trials for treating cancers of the breast, prostate, skin, pancreas, brain, lung and other tissues, as well as vaccines against everything from influenza to Zika and rabies. The prospects appear good.
Progress, admittedly, has been slow. Part of the explanation Sahin and Tureci give is that investors in this sector must put up oodles of capital and then wait for more than a decade, first for the trials, then for regulatory approvals. In the past, too few were in the mood.
Covid-19, fingers crossed, may turbo-charge all these processes. The pandemic has led to a grand debut of mRNA vaccines and their definitive proof of concept. Already, there are murmurs about a Nobel Prize for Kariko. Henceforth, mRNA will have no problems getting money, attention or enthusiasm — from investors, regulators and policymakers.
That doesn’t mean the last stretch will be easy. But in this dark hour, it’s permissible to bask in the light that’s dawning.
 
Excellent news/article....probably be too late for many though great for many others
Yes, these things always come to late for some, I was first alerted to it when I was scouring the earth for emerging treatments for my wife, she did go into a trail, which at first appeared to work, but sadly the trail was too late - and there you see the catch 22, your bodies immune system is so compromised by the time they let you enter a trail (my wife's was just six patients) that it's often too late as your body can't cope, as is what happened with her. The other five (who I lost touch with all got pushed into remission), so we need to change our protocol i.e. if you are diagnosed with probable unsurvivable cancer, then you should be able to enter trials, as at the end it's simply too late, the other thing is the horrendous hoops that the EU's ' do no harm approach' extends trials to ridiculous lengths when what you should be is science-led - do that and new drugs/treatments would/could happen in half the average 10 years it takes now.
 
Yes Ex that is the current way of thinking ...so risk averse when you are crying out for any sort of chance of a remission or extending life. I bet you would have signed anything to get your good wife into the trial foregoing any sort of right to claim and agreeing non compensation clauses
 
Pfizer Begins Human Trials of New Pill to Treat Coronavirus

Robert Langreth 17 hrs ago




https://www.msn.com/en-us/news/world/suez-canal-snarled-by-giant-ship-choking-key-trade-oil-route/ar-BB1eTAFz

(Bloomberg) -- Pfizer Inc. said it has begun human safety testing of a new pill to treat the coronavirus that could be used at the first sign of illness.

If it succeeds in trials, the pill could be prescribed early in an infection to block viral replication before patients get very sick. The drug binds to an enzyme called a protease to keep the virus from replicating. Protease-inhibiting medicines have been successful in treating other types of viruses, include HIV and Hepatitis C.

“Given the way that SARS-CoV-2 is mutating and the continued global impact of Covid-19, it appears likely that it will be critical to have access to therapeutic options both now and beyond the pandemic,” said Mikael Dolsten, Pfizer’s Chief Scientific Officer, in a statement.

In an interview, Dolsten said no unexpected problems had been seen in the study so far and that it could generate results within weeks.
The new protease inhibitor is the second such medicine Pfizer has brought into human trials to treat Covid-19. Pfizer is testing another given intravenously to hospitalized virus patients.

Shares of Pfizer were down 1.3% to $35.55 at 12:36 p.m. in New York. Over the past year, the stock has climbed 32%.

Easy-to-use treatments are lacking for early-stage Covid-19 patients. While antibody therapies from Eli Lilly & Co. and Regeneron Pharmaceuticals Inc. are authorized in the U.S. for Covid patients who haven’t yet been hospitalized but are at high risk of developing severe symptoms, they must be infused in the hospital or at a doctor’s office.

That has created logistical challenges that have limited their use. Other therapies are intended for sicker people: Gilead Sciences Inc.’s antiviral drug remdesivir must be infused over several days and is approved only for hospitalized patients.
Among major drugmakers, Merck & Co. has one of the few coronavirus pills that is far along in human testing. Its experimental antiviral drug molnupiravir works by a different mechanism than the Pfizer drug and is in late-stage human trials. Merck is developing its drug in collaboration with Ridgeback Biotherapeutics LP.

Combined Trial
If everything continues to go well, Pfizer could begin a much larger combined phase 2-phase 3 trial early in the second quarter, Dolsten said, potentially allowing it to apply for emergency-use authorization from the Food and Drug Administration by the end of this year, depending on how the pandemic evolves.
The drug is likely to be given twice a day for about five days, he said.

“This is really a potential game changer,” Dolsten said.

While initial efficacy testing will focus on people with early infections, Pfizer also plans to explore whether the drug works to protect healthy people who have been exposed to the coronavirus, such as family members or roommates who live with someone who got sick.

Dolsten said Pfizer’s oral protease inhibitor, code-named PF-07321332, had a number of potential advantages. In lab tests, it worked against many coronaviruses, including the original SARS virus and MERS. Additionally, the coronavirus protease doesn’t mutate much, which means the therapy is likely to work equally well against numerous variant strains, he said.

In theory, the protease inhibitor could also be combined with other antiviral drugs, such as the one Merck is developing, Dolsten said.
Pfizer said it plans to share more data on the compound at the American Chemical Society meeting on April 6.
 
As I said right from the beginning of this thing, my most likely route to this disaster is their 'wet markets' which are truly horrific....The Wu-Han Chinese simply do not know what good hygiene is in these places..


Exclusive: WHO Covid-19 origins report says lab leak 'extremely unlikely'

Leaked report says virus most probably jumped from bats into farmed animals, before spreading to humans

By Paul Nuki, Global Health Security Editor and Sarah Newey, Global Health Security Correspondent 29 March 2021 • 10:20am


The WHO team travelled to Wuhan to investigate the origins of the coronavirus pandemic


The long awaited World Health Organization report on the origins of Sars-Cov-2 has concluded that a leak from a laboratory, while possible, is “extremely unlikely”.

Instead, the virus was most likely to have been passed from bats via an “intermediate animal host” to humans before sparking an “explosive outbreak” in Wuhan in December 2019, it says.

The Telegraph has obtained a copy of the report, which has been repeatedly delayed but was sent to all WHO member states on Sunday evening.
The 123 page document presents detailed studies of morbidity, cases, pharmacy records, food samples and genetic sequencing from in and around Wuhan in late 2019, “to better understand how the virus might have been introduced and started”.

It finds no firm evidence to distract from the already established idea that the pandemic started in Wuhan in or around December 2019, and that the Huanan wet market either sparked or “amplified” the outbreak.
The authors, a team of 34 Chinese and international scientists, say it remains “possible” the virus entered Wuhan through frozen food, imported from another area of China or even from overseas - although there is scant evidence to support this in the report or its annexes.

“While there is some evidence for possible reintroduction of Sars-CoV-2 through handling of imported contaminated frozen products in China since the initial pandemic wave, this would be extraordinary in 2019 where the virus was not widely circulating,” the report says.

The Huanan seafood market in Wuhan, China, which was linked to an early cluster of cases. The WHO team visited the site during a visit to the city in February Credit: OEL CELIS / AFP
A widely held local conspiracy theory that the virus was introduced to Wuhan through the World Military Games - held from 18 to 27 October 2019 - is also all but ruled out, with no cases found by Chinese or international scientists to have related to it.
“The joint team’s assessment of likelihood of each possible pathway was as follows,” the report reads. “Direct zoonotic spillover is considered to be a possible-to-likely pathway; introduction through an intermediate host is considered to be a likely to very likely pathway; introduction through cold/ food chain products is considered a possible pathway; introduction through a laboratory incident was considered to be an extremely unlikely pathway.”
The authors call for further investigation by the Chinese authorities in many areas and make a firm point about the need for more historic data from China’s blood banks.
“Given the outstanding questions and the potential for limited clusters that would not be detected through the studies done so far, access to systematically collected historic samples including routinely stored blood bank samples would be of great added value for the origins studies,” it says.
While most experts expected inconclusive findings - establishing the origins of diseases usually takes years, if not decades - the lack of a “smoking gun” is likely to fuel international tensions.
Critics point to the team’s heavy reliance on Chinese data for its initial conclusions, while others say the great bulk of that data suggests the virus emerged in the country anyway.
“We’ve got real concerns about the methodology and the process that went into that report, including the fact that the government in Beijing apparently helped to write it,” US Secretary of State Antony Blinken said in a CNN interview that was recorded before the report was released.
China rejected that criticism yesterday. “The US has been speaking out on the report. By doing this, isn’t the US trying to exert political pressure on the members of the WHO expert group?” asked Foreign Ministry spokesperson Zhao Lijian.
“When will [the US] invite WHO experts to visit the US and to conduct work to trace the source? When will it open the Fort Detrick [laboratory] for international experts to tour?” he added.

Members of the WHO-led team arrive at the Wuhan Institute of Virology in February Credit: REUTERS/Thomas Peter
On the controversial possibility of a leak from a laboratory, the report says: “Although rare, laboratory accidents do happen, and different laboratories around the world are working with bat [coronaviruses].
“When working in particular with virus cultures, but also with animal inoculations or clinical samples, humans could become infected in laboratories with limited biosafety, poor laboratory management practice, or following negligence.”
However, it then adds: “There is no record of viruses closely related to Sars-CoV-2 in any laboratory before December 2019, or genomes that in combination could provide a Sars-CoV-2 genome… and therefore the risk of accidental culturing Sars-CoV-2 in the [Wuhan] laboratory is extremely low”.
“The Wuhan CDC lab which moved on 2 December 2019 reported no disruptions or incidents caused by the move. They also reported no storage nor laboratory activities on CoVs or other bat viruses preceding the outbreak”.
The report lays out the following four scenarios, giving the evidence for and against each as follows:
Direct spillover event: ‘likely’
This theory explored the possibility Sars-Cov-2 jumped directly from the animal reservoir, most likely bats, to humans. This hypothesis was deemed “likely”.
Arguments in favour:
  • The majority of emerging diseases - including previously identified coronaviruses - originate in animals and there is a long history of coronaviruses lurking in bats, which harbour “the highest proportion” of potential zoonotic viruses of any mammal.
  • There is also “strong evidence” that Sars - which emerged in China in 2003 - jumped from bats, particularly the Rhinolophus species. And antibodies to bat coronaviruses have been identified in humans with close contact with the flying mammals.
  • In terms of Covid-19, viruses with a “high genetic similarity to Sars-Cov-2” have been detected in Rhinolophus bats sampled in 2013 in China and Japan, in 2020 in Thailand and in 2010 in Cambodia.
  • The report notes other possible animal reservoirs: though the virus’ ability to bind to the ACE2 cells of the Malayan pangolin is “not optimal” (this is how the virus enters human cells), two distinct types of Sars-Cov-2 related coronaviruses have been detected in the endangered species; and mink appear “highly susceptible”, meaning researchers “cannot rule out” the possibility they were the primary source.

Arguments against:
  • Despite the closest genetic relationship with Sars-Cov-2 coming from bats, detailed analysis found “evidence for several decades of evolutionary space between the viruses”, suggesting it did not jump straight from bats to humans.
  • While full genomes sequenced from bats are rare, few have the critical ACE2 binding properties and samples tend to be “genetically still quite distinct from Sars-CoV-2”.
  • There are also concerns that the focus on bats may be “spurious”. There are far fewer samples from other species, and those identified in Cambodia, Japan and Thailand may be a “confirmation of this potential bias”, as the studies were published after the pandemic began.
  • Researchers found “no evidence” that transmission of Sars-Cov-2 took place as a result of the consumption of bat and wild animal meat.
  • The report suggests the discovery mink are highly susceptible to the virus raises the potential that other mustelids could be the original disease reservoir - especially because humans come into contact with bats or pangolins less commonly than with livestock or farmed wildlife.
The report suggests studies tracing the supply chains of Wuhan markets has provided “credible leads” to follow, and argues that “surveys should be expanded to include other countries, guided by knowledge on ecology and smuggling routes”.
 
Virus jumped from animal reservoir, to animal host, to humans: ‘very likely’
This is the idea that Sars-Cov-2 spread from the original reservoir to another animal, or “spillover host”, before jumping to humans. The virus may or may not have changed to better target humans during this chain.
This hypothesis was considered “very likely” - the most probable explanation examined.
Arguments in favour:
  • The closest related viruses have been detected in bats - but the “evolutionary distance” suggests there is a “missing link” in the transmission chain.
  • As highly similar viruses have been found in pangolins, too, it is possible there was some “cross species transmission” at some point.
  • But again, the considerable difference suggests another animal was involved in the chain, especially because bats and pangolins are “infrequently in contact with humans”.
  • It is known that an “amplifying host” has been involved in the spread of emerging pathogens including Mers, influenza and henipaviruses.
  • The report points to high density farming as a good place for the emergence of “complex transmission pathways that may be difficult to unravel”: farmed animals such as mink are susceptible to Sars-Cov-2; in “many places across the world” there are substantial networks of interconnected farms rearing both wild and domesticated animals; humans regularly come into contact with animals in these locations; there is a greater year-round transmission potential, whereas virus seasonality needs to be considered in the direct spillover theory.
Arguments against:
  • While Sars-Cov-2 has been found in a growing number of animals, genetic and epidemiological studies suggest infections were introduced from humans, not vice versa.
  • Analysis of new Covid-19 cases in China throughout 2020 shows “no evidence of repeated introduction” of the early strains from Sars-Cov-2 from animals to humans.
  • A wide range of domestic and wild animals have been tested to date, but there is “no genetic or serological evidence” that they harbour the Sars-Cov-2 or a related coronavirus.
  • Screening of farmed wildlife has been “limited”, but conclusive evidence is lacking.

The report calls for increased sampling of animal populations with a “further geographic range”, as studies of the supply chain of markets in Wuhan have found no evidence that infected animals were present.
However, existing work has offered “meaningful” clues for where to look next: there was evidence, for example, that supply chains are linked to wildlife farms in provinces with a higher prevalence of Sars-Cov-2 related coronaviruses.
The report also suggests “animal products from areas outside southeast Asia where more distantly related [Sars-Cov-2 related coronaviruses] circulate should not be disregarded”.
Virus emerged via frozen food products: ‘possible’
This theory looked at whether cold or food chain products and their containers were a potential route for Sars-Cov-2 to enter the human population, which is considered “possible”.
The report is careful to note that there is a distinction between the contamination of cold chain products leading to secondary outbreaks, and the potential for such products to act as the “entry pathway” for the origins of the pandemic in 2019.
Arguments in favour:
  • Frozen food items are commonly sold at markets, including the Huanan market initially linked to an early cluster of cases.
  • Since the “near-elimination” of the coronavirus in China, screening programmes have traced some new outbreaks to “imported frozen products” throughout 2020, showing this is possible. Live virus was isolated from the outer package of these products in Qingdao, for example, and coronaviruses can persist in frozen conditions.
  • Food outbreaks are also commonly associated with enteric viruses (the most common cause of gastroenteritis globally), which can trigger outbreaks that are geographically dispersed and difficult to detect.
  • Most evidence for this is found through sewage or contaminated water for irrigation - and Sars-Cov-2 nucleic acids have been found in sewage. Some literature suggests the virus could have been circulating in Spain and Italy earlier than December 2019.
  • Hamster infection experiments found the oral route, from contaminated foodstuffs, could lead to Sars-Cov-2 infections.
Arguments against:
  • There is “no conclusive evidence” for foodborne transmission of Sars-Cov-2, while the probability of a cold-chain contamination from the animal reservoir is “very low”.
  • There is evidence that the virus was reintroduced via imported contaminated frozen products in China, but “this would be extraordinary in 2019 where the virus was not widely circulating”, the report says. Most virus found in cold-chain products were in “low concentrations”.
  • Industrial food production has stringent hygiene standards and is regularly audited.
  • It is also not clear what the infection route would be, the report notes, and there is no evidence that any of the animals tested were infected.
  • The risk of foodborne transmission is “very low” compared to respiratory transmission.
The report suggests that case-control studies of outbreaks where products in the cold chain tested positive would be “useful”, and screening of leftover frozen cold chain products is needed if they are still available.
It adds that, if there are “credible links” to products that came from outside China, where there is evidence for the circulation of Sars-Cov-2 before the end of 2019, they need to be followed up.

A laboratory-related incident: ‘extremely unlikely’
This is the controversial theory that the pandemic emerged via an incident in the lab. The report does not consider the deliberate release or bioengineering of Sars-Cov-2, with the latter having been “ruled out by other scientists following analyses of the genome”.
Instead, the team looked at whether a staff member was accidentally infected through working with relevant viruses. This possibility has been deemed “extremely unlikely”.
Arguments in favour:
  • Accidents in the lab are rare, but they do happen, and there are institutions across the world working with bat coronaviruses.
  • When scientists are working with virus cultures in particular, but also with animal inoculations or clinical samples, humans can be infected - if the lab has limited biosafety, poor management practices or negligence is involved.
  • The closest known coronavirus strain - RaTG13, which is 96.2 per cent related to Sars-Cov-2 - was detected in bat anal swabs that have been sequenced at the Wuhan Insitute of Virology.
  • The Wuhan Centre for Disease Control lab moved to a new location close to the Huanan market, linked to an early cluster of cases, on 2 December 2019. The report notes that “such moves can be disruptive for the operations of any laboratory”.
Arguments against:
  • Though there has been some speculation about the presence of the ACE2 receptor binding and a furin-cleavage site in Sars-Cov-2, which makes the virus so good at infecting humans, both these characteristics have been found in animal viruses.
  • There is also “no record of viruses closely related to Sars-CoV-2 in any laboratory before December 2019, or genomes that in combination could provide a Sars-CoV-2 genome”.
  • In reference to the idea that the virus was cultured accidentally, the report says “there is also “no evidence of circulation of Sars-CoV-2 among people globally” and the surveillance system in place means “the risk of accidental culturing Sars-CoV-2 in the laboratory is extremely low”.
  • It adds that the three labs in Wuhan working with coronavirus diagnostics or coronaviruses isolation and vaccine development all had “high quality biosafety level (BSL3 or 4) facilities that were well-managed”.
  • The labs also have a staff health monitoring programme, and there were no reports of Covid-19 compatible respiratory illnesses in the weeks or months before the virus was detected in December 2019. Antibody testing also found “no serological evidence of infection in workers”.
  • The report adds that the Wuhan CDC reported “no disruptions or incidents caused by the move” on December 2, and “no storage nor laboratory activities on [coronaviruses] or other bat viruses preceding the outbreak.”
There are few recommendations following this section, with the team deeming a laboratory origin of the pandemic “extremely unlikely”.
The report does, though, suggest “regular administrative and internal review of high-level biosafety laboratories worldwide”, and calls for new evidence supplied about possible leaks to be followed up.
 

Nick Real Deal

Vital Football Legend
The Astra Zenica vaccine gives 82% protection after both doses. The Pfizer 91 %. The Astra jab has caused blood clots although only a minute % , the Pfizer has not.

I'm not sure 82 % is good enough, it means roughly 1 in 5 vaccinated are still vulnerable although the threat of death might be lessened.

Its looking like Pfizer is the way to go. Of course I had the Astra !!
 

Nick Real Deal

Vital Football Legend
So Astra is now not recommended for younger people due to blood clots. A potentially deadly side effect although rare.
I can understand why the vaccine was rushed through the approval stage but it highlights the dangers of cutting corners.
 
So Astra is now not recommended for younger people due to blood clots. A potentially deadly side effect although rare.
I can understand why the vaccine was rushed through the approval stage but it highlights the dangers of cutting corners.
It didn't cut corners; the blood clot issue is less than the chances of happening than if you were on the pill. the percentage is so small, that no trial, ever, was likely to come across it.
 

meee93

Vital Champions League
The Astra Zenica vaccine gives 82% protection after both doses. The Pfizer 91 %. The Astra jab has caused blood clots although only a minute % , the Pfizer has not.

I'm not sure 82 % is good enough, it means roughly 1 in 5 vaccinated are still vulnerable although the threat of death might be lessened.

Its looking like Pfizer is the way to go. Of course I had the Astra !!
Protection % is not the same as death prevention %. The first effectively shows how likely you are to not get symptoms. So you can have a situation where the vaccine efficacy is lower in a certain vaccine but fewer people die compared to the other.

In all likelihood, we would be happy to get mild Covid every now and then if it meant that we were less likely to actually die (similarly to the flu). ie. If the other 9% of people with a vaccine with 91% efficacy all died, then you would prefer a vaccine with 82% efficacy if those 18% were less likely to die.

I do not know what the data suggests for the vaccines that you mention, but just thought it was an important aspect to highlight.