BBO Discussion Forums: Coronavirus - BBO Discussion Forums

Jump to content

  • 56 Pages +
  • « First
  • 49
  • 50
  • 51
  • 52
  • 53
  • Last »
  • You cannot start a new topic
  • You cannot reply to this topic

Coronavirus Those who ignore history are doomed to repeat it

#1001 User is offline   thepossum 

  • PipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 1,006
  • Joined: 2018-July-04
  • Gender:Male
  • Location:Australia

Posted 2020-November-24, 05:37

View Postcherdano, on 2020-November-24, 04:01, said:

Last weeks I was here to tell you that the 94% figures or thereabouts by Pfizer and Moderna were as good as they sounded.
This week I am here to tell that that the 90% for the half-dose/full-dose regimen by the Oxford vaccine might not be as good as it sounds.
It's based on a small sample size - just two infections in that group. It's biased due to hypothesis selection - while it's not difficult for experts to come up with a posteriori explanations for the better success of this regimen, they would just as easily have been able to explain if it had been less successful.

Still, the 90% could hold up. They also state this regimen leads to fewer PCR-positive participants (regardless of symptoms) - important for reducing transmission. And they had Zero severe cases in either treatment group.
I also wonder whether they could support plausibility of the effectiveness of the half/full regimen by comparing the antibody levels a few weeks after the booster dose.


I did say it was up for review and it was only one regimen, and its only interim results, and I only put it up for interest, and I'm sick of all the media beatups and BS. This is serious stuff reduced to a stupid PR marketing game with politcs and all sorts thrown in for the last 10 months. I actuallyput up a serious article for once

You have shares in Moderna and Pfizer or something Cherdano? :)

What I am actually interested in, is the very small number of cases from such large trials - all of them - and the nature of the analysis and trust in the results. Will be interesting to read all the final studies. And I was also interested that give or take the issues you mention they are all in similar ballparks :)

But bearing in mind the point you raise about different groups (and the small numbers) is it reasonable for me to ask a question what it would/could mean in relation to the two regimens and the overall combined result. I appreciate it may not be appropriate to disucss at that level at this stage
0

#1002 User is offline   cherdano 

  • 5555
  • PipPipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 9,311
  • Joined: 2003-September-04
  • Gender:Male

Posted 2020-November-24, 07:46

View Postthepossum, on 2020-November-24, 05:37, said:

You have shares in Moderna and Pfizer or something Cherdano? :)

No, just waiting for the right time to buy AstraZeneca stocks after their stock has taken enough for a hit :D
The easiest way to count losers is to line up the people who talk about loser count, and count them. -Kieran Dyke
0

#1003 User is offline   Winstonm 

  • PipPipPipPipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 15,252
  • Joined: 2005-January-08
  • Gender:Male
  • Location:Tulsa, Oklahoma
  • Interests:Art, music

Posted 2020-November-24, 13:45

As for the U.S.? You can fix a lot of problems - you can't fix stupid.



Quote

Dr. Thomas Benzoni, an emergency medicine physician in Des Moines, Iowa, is experiencing many of the same things Molina is — some of which he blames on individuals who don't believe that the virus is real. "It's maddening that people could do something about it and choose not to. It's like if you have an infection and don't take the antibiotics. It doesn't make sense," he says. "And the warped logic that I'm seeing used. ... In the old days, that would warrant you an antipsychotic and a psych bed."

For doctors like Benzoni, those who believe the virus is a hoax or avoid things like personal protective gear are a direct threat. "We're immersed in it. So my colleagues will keep getting sick, and a number of them will unfortunately die," Benzoni says. "It's already happening around the nation and it's just going to be happening more in the Midwest because that's the choice the Midwest has made."





Flyover Country has become Trump Die Over Country. How stupid is that?
"Injustice anywhere is a threat to justice everywhere." Black Lives Matter.
0

#1004 User is offline   cherdano 

  • 5555
  • PipPipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 9,311
  • Joined: 2003-September-04
  • Gender:Male

Posted 2020-November-25, 04:32

View PostWinstonm, on 2020-November-24, 13:45, said:


(...)

Flyover Country has become Trump Die Over Country. How stupid is that?


Iowa has three Biden states as neighbours, Minnesota, Wisconsin, Illinois.

7-day rolling averages of cases/day per 100,000, changes since last week:
Iowa 114 -12%
Minnosota 119 -3%
Wisconsin 109 -10%
Illinois 85 -8%

7-day rolling average of deaths/day per 100,000:
Iowa 0.93 +21%
Minnesota 0.92 +38%
Wisconsin 1 +9%
Illinois 1.05 +41%

(Source: Washington post, https://www.washingt...guide-box-1-1-1 )

I would urge everyone to be more cautious in drawing political conclusions from the current trend of the pandemic in the US, in particular as the basic pattern holds exactly the same in the UK:
- 1st wave: hotspots were rich cities with lots of international travel
- 2nd wave: hotspots are poorer regions/cities, even down to the neighborhood level

Obviously the current response by many governors of US states looks terrible. But so did the response by Cuomo and de Blasio in March.

And here is an article about the high level of personal responsibility displayed by young New Yorkers throughout this pandemic: https://www.thecut.c...e-covid-19.html Would that have made headlines/social media clicks if it had been about truckers in Wyoming?
(Yes, I am generalising with no basis to do so. But so are all the reports about covid-deniers in red states causing a resurgence.)
The easiest way to count losers is to line up the people who talk about loser count, and count them. -Kieran Dyke
2

#1005 User is offline   johnu 

  • PipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 3,952
  • Joined: 2008-September-10
  • Gender:Male

Posted 2020-November-26, 04:24

fter Admitting Mistake, AstraZeneca Faces Difficult Questions About Its Vaccine

AstraZeneca denies that its researchers got their degrees at Trump University :lol: Seriously, this puts a large dent in the release timetable for this vaccine.
0

#1006 User is offline   Winstonm 

  • PipPipPipPipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 15,252
  • Joined: 2005-January-08
  • Gender:Male
  • Location:Tulsa, Oklahoma
  • Interests:Art, music

Posted 2020-November-26, 11:12

View Postcherdano, on 2020-November-25, 04:32, said:

Iowa has three Biden states as neighbours, Minnesota, Wisconsin, Illinois.

7-day rolling averages of cases/day per 100,000, changes since last week:
Iowa 114 -12%
Minnosota 119 -3%
Wisconsin 109 -10%
Illinois 85 -8%

7-day rolling average of deaths/day per 100,000:
Iowa 0.93 +21%
Minnesota 0.92 +38%
Wisconsin 1 +9%
Illinois 1.05 +41%

(Source: Washington post, https://www.washingt...guide-box-1-1-1 )

I would urge everyone to be more cautious in drawing political conclusions from the current trend of the pandemic in the US, in particular as the basic pattern holds exactly the same in the UK:
- 1st wave: hotspots were rich cities with lots of international travel
- 2nd wave: hotspots are poorer regions/cities, even down to the neighborhood level

Obviously the current response by many governors of US states looks terrible. But so did the response by Cuomo and de Blasio in March.

And here is an article about the high level of personal responsibility displayed by young New Yorkers throughout this pandemic: https://www.thecut.c...e-covid-19.html Would that have made headlines/social media clicks if it had been about truckers in Wyoming?
(Yes, I am generalising with no basis to do so. But so are all the reports about covid-deniers in red states causing a resurgence.)


Denying the reality of the virus is not a political problem but an information-source problem. That the virus is again rapidly spreading is an everyone problem.
"Injustice anywhere is a threat to justice everywhere." Black Lives Matter.
0

#1007 User is offline   cherdano 

  • 5555
  • PipPipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 9,311
  • Joined: 2003-September-04
  • Gender:Male

Posted 2020-November-26, 16:12

And here, my friend, is why you should never trade in individual stocks:

Quote

With AstraZeneca’s shares declining on Monday, company executives held several private conference calls with industry analysts in which they disclosed details that were not in the public announcement, including how the Covid-19 cases broke down across different groups. Such disclosures to analysts are not uncommon in the industry, but they often generate criticism about why the details were not shared with the public.

(From fter Admitting Mistake, AstraZeneca Faces Difficult Questions About Its Vaccine)
The easiest way to count losers is to line up the people who talk about loser count, and count them. -Kieran Dyke
0

#1008 User is offline   thepossum 

  • PipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 1,006
  • Joined: 2018-July-04
  • Gender:Male
  • Location:Australia

Posted 2020-November-26, 17:33

View Postcherdano, on 2020-November-26, 16:12, said:

And here, my friend, is why you should never trade in individual stocks:

(From fter Admitting Mistake, AstraZeneca Faces Difficult Questions About Its Vaccine)


Unless you know what you are doing. Looking at their share price over the years it looks an excellent candidate for trading :)

And I believe there are professional traders who spend much of their time trading and being expert in some individual stocks

What I am finding interesting (having forgotten my original reading of the trial protocol and design) is whether a mistake has been dressed up as a treatment regimen - but at least if it was a mistake they knew enough about the mistake for it still to be useful :)
0

#1009 User is offline   barmar 

  • PipPipPipPipPipPipPipPipPipPipPipPip
  • Group: Admin
  • Posts: 20,455
  • Joined: 2004-August-21
  • Gender:Male

Posted 2020-November-26, 17:48

View PostWinstonm, on 2020-November-26, 11:12, said:

Denying the reality of the virus is not a political problem but an information-source problem. That the virus is again rapidly spreading is an everyone problem.

That would be true if there weren't such a strong correlation between political leanings and belief in the virus. Many people these days get their information from politically biased sources.

#1010 User is online   y66 

  • PipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 5,490
  • Joined: 2006-February-24

Posted 2020-December-02, 12:35

Joe Weisenthal at Bloomberg said:

This, from @elashton, explains how the UK managed to approve the Pfizer vaccine even before the US did. They've been reviewing the data on a rolling basis as it was collected, and not waiting for one big submission.

https://bloomberg.co...navirus-vaccine

Quote

The U.K.’s Medicines and Healthcare Products Regulatory Agency, like the European Medicines Agency, has been using a so-called rolling review process that lets officials monitor trial data as they arrive, rather than waiting for a full submission after a study is completed. BioNTech is awaiting a decision from the FDA in the middle of December, around the same time as it expects a ruling from the EU regulator, Chief Medical Officer Ozlem Tureci said in a press conference.

Ahead of the FDA’s scheduled Dec. 10 meeting to review the vaccine, agency staff members are going over the raw clinical trial data and checking Pfizer’s calculations as well as reviewing information on the manufacturing process. The agency’s regular approval process can take anywhere from six to 10 months for most drugs and vaccines.

“The amount of data submitted to the FDA includes thousands of pages of technical information that must be divided up and reviewed by experts from different disciplines,” an FDA spokesperson said in an emailed statement.

If you lose all hope, you can always find it again -- Richard Ford in The Sportswriter
0

#1011 User is online   y66 

  • PipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 5,490
  • Joined: 2006-February-24

Posted 2020-December-03, 15:53

NYT has a calculator that U.S. residents can use to determine their place in line for a covid vaccine.

Quote

A vaccine may be around the corner, but how long will it be until you get the shot? Health officials are considering vaccine timelines that give some Americans priority over others. If you’re a healthy American, you may wait many months for your turn.

To put this in perspective, we worked with the Surgo Foundation and Ariadne Labs using their vaccine tool to calculate the number of people who will need a vaccine in each state and county — and where you might fit in that line.

If you lose all hope, you can always find it again -- Richard Ford in The Sportswriter
0

#1012 User is online   y66 

  • PipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 5,490
  • Joined: 2006-February-24

Posted 2020-December-06, 10:17

Via Tyler Cowen: New CRISPR-based COVID-19 test uses smartphone cameras to spot virus RNA

Quote

Scientists at UC Berkeley and Gladstone Institutes have developed a new CRISPR-based COVID-19 diagnostic test that, with the help of a smartphone camera, can provide a positive or negative result in 15 to 30 minutes. Unlike many other tests that are available, this test also gives an estimate of viral load, or the number of virus particles in a sample, which can help doctors monitor the progression of a COVID-19 infection and estimate how contagious a patient might be.

“Monitoring the course of a patient’s infection could help health care professionals estimate the stage of infection and predict, in real time, how long is likely needed for recovery and how long the individual should quarantine,” said Daniel Fletcher, a professor of bioengineering at Berkeley and one of the leaders of the study…

The new diagnostic test takes advantage of the CRISPR Cas13 protein, which directly binds and cleaves RNA segments. This eliminates the DNA conversion and amplification steps and greatly reduces the time needed to complete the analysis.

“One reason we’re excited about CRISPR-based diagnostics is the potential for quick, accurate results at the point of need,” [Jennifer] Doudna said. “This is especially helpful in places with limited access to testing or when frequent, rapid testing is needed. It could eliminate a lot of the bottlenecks we’ve seen with COVID-19.”

In the test, CRISPR Cas13 proteins are “programmed” to recognize segments of SARS-CoV-2 viral RNA and then combined with a probe that becomes fluorescent when cleaved. When the Cas13 proteins are activated by the viral RNA, they start to cleave the fluorescent probe. With the help of a handheld device, the resulting fluorescence can be measured by the smartphone camera. The rate at which the fluorescence becomes brighter is related to the number of virus particles in the sample.

Posted Image
In the diagnostic test, a patient sample is mixed with CRISPR Cas13 proteins (purple) and molecular probes (green) which fluoresce, or light up, when cut. When coronavirus RNA is present in the sample, it prompts the CRISPR proteins to snip the molecular probes, causing the whole sample to emit light. This fluorescence can be detected with a cell phone camera. (Image courtesy Science at Cal)
If you lose all hope, you can always find it again -- Richard Ford in The Sportswriter
1

#1013 User is offline   barmar 

  • PipPipPipPipPipPipPipPipPipPipPipPip
  • Group: Admin
  • Posts: 20,455
  • Joined: 2004-August-21
  • Gender:Male

Posted 2020-December-06, 13:53

View Posty66, on 2020-December-03, 15:53, said:

NYT has a calculator that U.S. residents can use to determine their place in line for a covid vaccine.

I could barely find myself at the end of that long line.

#1014 User is online   y66 

  • PipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 5,490
  • Joined: 2006-February-24

Posted 2020-December-06, 19:35

Bojan Pancevski at WSJ said:

Sweden’s Covid-19 experiment is over.

After a late autumn surge in infections led to rising hospitalizations and deaths, the government has abandoned its attempt—unique among Western nations—to combat the pandemic through voluntary measures.

Like other Europeans, Swedes are now heading into the winter facing restrictions ranging from a ban on large gatherings to curbs on alcohol sales and school closures—all aimed at preventing the country’s health system from being swamped by patients and capping what is already among the highest per capita death tolls in the world.

The clampdown, which started last month, put an end to a hands-off approach that had made the Scandinavian nation a prime example in the often heated global debate between opponents and champions of pandemic lockdowns.

Admirers of the Swedish way as far as the U.S. hailed its benefit to the economy and its respect for fundamental freedoms. Critics called it a gamble with human lives, especially those of the most vulnerable. With its shift in strategy, the government is now siding with those advocating at least some mandatory restrictions.

When the pathogen swept across Europe in March, Sweden broke with much of the continent and opted not to impose mask-wearing and left known avenues of viral transmission such as bars and nightclubs open, leaving it to citizens to take their own precautions.

As late as last month, Swedes enjoyed mass sporting and cultural events and health-care officials insisted that the voluntary measures were enough to spare the country the resurgence in infections that was sweeping Europe.

Weeks later, with total Covid-19-related deaths reaching almost 700 per million inhabitants, infections growing exponentially and hospital wards filling up, the government made a U-turn.

In an emotional televised address on Nov. 22, Prime Minister Stefan Löfven pleaded with Swedes to cancel all nonessential meetings and announced a ban on gatherings of more than eight people, which triggered the closure of cinemas and other entertainment venues. Starting Monday, high schools will be closed.

“Authorities chose a strategy totally different to the rest of Europe, and because of it the country has suffered a lot in the first wave,” said Piotr Nowak, a physician working with Covid-19 patients at the Karolinska University Hospital in Stockholm. “We have no idea how they failed to predict the second wave.”

Last week Sweden’s total coronavirus death count crossed 7,000. Neighboring Denmark, Finland and Norway, all similar-sized countries, have recorded since the start of the pandemic 878, 415 and 354 deaths respectively. For the first time since World War II, Sweden’s neighbors have closed their borders with the country.

“We don’t like to say that Sweden has been the black sheep, but it has been the different sheep,” said Vivikka Richt, spokeswoman of the Finnish health ministry.

Dr. Nowak said medical personnel had never shared the optimism of the country’s public-health agency about so-called herd immunity—population-wide resistance to a pathogen acquired through gradual exposure—and had repeatedly warned that the virus couldn’t be controlled with voluntary measures alone.

One reason Sweden stuck to its approach for so long despite the warning signs is the high degree of independence and authority enjoyed by the health agency and other similar state bodies under Swedish law.

The public face of the country’s pandemic strategy was Anders Tegnell, Sweden’s chief epidemiologist.

Dr. Tegnell declined to be interviewed this week, but in earlier conversations with The Wall Street Journal and other media he said lockdowns were unsustainable and unnecessary. His agency has continued to discourage mask-wearing just as the European Center for Disease Prevention and Control, a European Union agency whose headquarters are located near Dr. Tegnell’s office in Stockholm, recommends wearing them.

In recent months, Dr. Tegnell predicted that Swedes would gradually build immunity to the virus through controlled exposure, that vaccines would take longer than expected to develop, and that death rates across the West would converge.

Instead, the West’s first coronavirus vaccine was authorized in Britain last week, Sweden’s death rate remains an outlier among its neighbors, and Dr. Tegnell acknowledged in late November that the new surge in infections showed there was “no sign” of herd immunity in the country.

Meanwhile, Sweden’s laissez-faire pandemic strategy has failed to deliver the economic benefits its proponents had predicted. In the first half of the year, Sweden’s gross domestic product fell by 8.5% and unemployment is projected to rise to nearly 10% in the beginning of 2021, according to the central bank and several economic institutes.

Businesses such as restaurants, hotels and retail outfits are facing a wave of closures; unlike in the rest of Europe, where governments coupled restrictions with generous stimulus, Swedish authorities have offered comparatively less support to businesses since they didn’t impose closures.

“This is worse than a lockdown and it has been a catastrophic year for everyone in the business: They haven’t closed us so they don’t give us any substantial support, yet they say to people ‘don’t go to restaurants’,” said Jonas Hamlund, who was forced to close one of his two restaurants in the coastal city of Sundsvall, laying off 30 people.

Fear of the virus and the government’s advice to avoid social interactions have weighed on domestic demand, damaging business and investor confidence, said Lars Calmfors, an economist and member of the Royal Swedish Academy of Sciences.

“Countries that had mandatory restrictions have done better than us,” he added.

In Stockholm, Anna Lallerstedt runs a chain of three popular restaurants that was started by her parents in the 1980s. Last month she closed two of them, shedding nearly 100 jobs. She says she fears that her last restaurant, now employing just over 10 people, might also be at risk with the current surge expected to peak around the Christmas season, which traditionally brings substantial revenues.

“Maybe we should have had masks earlier,” Ms. Lallerstedt said.

Mr. Löfven’s intervention amounted to a demotion for Dr. Tegnell, who has de facto ceded control of the government’s pandemic effort. But some scientists said the failed experiment had shaken confidence in authorities and experts in a country with a long tradition of respecting both.

An Ipsos poll found in November that 82% of responses are worried about the pandemic burden on hospitals, while 44% said authorities didn’t take sufficient measures, up from 31% in October. Dr. Tegnell remains popular, however, with a majority still supporting him.

“The spread of the disease is increasing in Stockholm and we have a very, very serious situation right now,” said Björn Eriksson, Health and Hospitals Director for the Stockholm region, the country’s most populous area.

Mr. Eriksson said that the capital’s health-care professions were struggling with the patient load and that the pandemic was putting a strain on the system that could only be eased by more restrictive measures.

“We like to think of ourselves as being very rational and pragmatic,” Mr. Calmfors, the economist, said. Yet for months, he added, authorities persisted in their approach despite mounting evidence that it was failing. “I can’t recognize my country anymore.”

If you lose all hope, you can always find it again -- Richard Ford in The Sportswriter
1

#1015 User is offline   johnu 

  • PipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 3,952
  • Joined: 2008-September-10
  • Gender:Male

Posted 2020-December-07, 05:01

For those not living in the USA, this is what is going on in Red States.

Gala uproar, deputy dragged, anti-mask doctor: News from around our 50 states

Quote

Wyoming
Casper: A state Department of Health official involved in Wyoming’s response to the coronavirus questioned the legitimacy of the pandemic and described a forthcoming vaccine as a biological weapon at a recent event. The “so-called pandemic” and efforts to develop a vaccine are plots by Russia and China to spread communism worldwide, department readiness and countermeasures manager Igor Shepherd said at the Nov. 10 event held by the group Keep Colorado Free and Open. Shepherd was introduced as and talked about being a Wyoming Department of Health employee.


Quote

Even so, Wyoming officials including Gov. Mark Gordon, who at a recent news conference called people not taking the virus seriously “knuckleheads,” declined to comment. Shepherd has worked for the health department since 2013 and has been a part of the state’s team responding to COVID-19, though not in a leadership role, department spokeswoman Kim Deti said.

0

#1016 User is online   y66 

  • PipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 5,490
  • Joined: 2006-February-24

Posted 2020-December-12, 21:15

From How Pfizer Delivered a Covid Vaccine in Record Time: Crazy Deadlines, a Pushy CEO by Jared S. Hopkins at WSJ:

Quote

Pfizer Inc. was months from proving its Covid-19 vaccine would even work when Chief Executive Albert Bourla got into a tense WebEx debate with his head of manufacturing.

It was a warm day in June and Pfizer was racing to develop a radical new vaccine based on a technology that had never been approved before. Mr. Bourla and his team were so optimistic they had committed hundreds of millions of dollars to build a global manufacturing network.

Mr. Bourla, speaking from his suburban New York home during one of Pfizer’s twice-weekly meetings on the project, told the team he wanted them to increase commercial production at least 10-fold.

“Why can’t we make more and why can’t we make it sooner?” Mr. Bourla demanded.

Mike McDermott, who oversees Pfizer’s global manufacturing network, pushed back. His team already was working furiously, he said.

"What we’re doing already is a miracle,” he said he told Mr. Bourla. “You’re asking for too much.”

Even for jaded pharmaceutical scientists, what happened next was little short of miraculous. U.S. health regulators Friday night authorized the Covid-19 vaccine developed by Pfizer and its German partner BioNTech SE. The shot is already in U.K. use and will be the first given in the U.S., capping the fastest vaccine development ever in the West.

How the drugmakers pulled off the feat, cutting the typical time from more than 10 years to under one, partly stems from their bet on the gene-based technology.

As the inside story shows, it was also the product of demanding leadership, which bordered on the unreasonable. From urging vaccine researchers to move fast to pressing the manufacturing staff to ramp up, Mr. Bourla pushed employees to go beyond even their own ambitious goals to meet Covid-19’s challenge.

Pfizer couldn’t meet every target set by its chief executive. Mr. Bourla wanted the vaccine done by October and as many as 100 million doses by year’s close, enough for 50 million people. Instead about half that will be produced.

Yet the company, which has spent more than $2 billion on the effort, achieved more, faster, than outside experts and even its employees thought possible. In a series of interviews over more than seven months, senior Pfizer executives and other managers shed new light on how the vaccine project took shape.

Early in the pandemic, U.S. health officials cautioned the first vaccines wouldn’t be ready until 2021. Pfizer’s vaccine researchers initially forecast the middle of next year at the earliest.

Previously, the quickest vaccine development program was the four years it took to make the mumps vaccine, licensed in 1967. After getting Mr. Bourla’s go-ahead, Pfizer researchers figured they could shorten the timeline to a year, give or take.

Crucial to what they considered an ambitious forecast: the unproven gene-based technology honed by BioNTech, a small biotech company based in Mainz, Germany, already in partnership with the big drugmaker to develop a flu shot.

BioNTech wanted to make vaccines out of messenger RNA, or mRNA, the molecules that carry genetic instructions telling cells what proteins to make.

The German company’s researchers thought they could use the genetic sequence of the coronavirus, which had recently been published, to synthesize mRNA that would instruct cells to make a harmless version of the spike protein that protrudes from the surface of the virus.

The defanged spike proteins would prompt a person’s immune system to produce antibodies that could fight off the real virus.

Unlike the months it takes to cultivate a vaccine in test tubes, designing an mRNA vaccine would be quick. BioNTech simply plugged the genetic code for the spike protein into its software. On Jan. 25, BioNTech Chief Executive Ugur Sahin designed 10 candidates himself.

The company’s researchers would create 10 more different potential coronavirus vaccines for a total of 20, each slightly different in the event one design worked better and more safely than the others.

But BioNTech, founded in 2008 and with just 1,000 employees when the pandemic hit, needed a big partner to manufacture the vaccines for human trials and potentially for people around the world.

Many in pharma were skeptical of mRNA, which had been long in the making but never the basis for an approved product. Dr. Jansen, known in the industry for helping develop Merck & Co’s cervical-cancer shot Gardasil, saw promise, in large part because mRNA vaccines appeared to produce stronger immune responses than older shots.

“This is a disaster, and it’s getting worse,” Dr. Jansen told Dr. Sahin. “Happy to work with you.”

Mr. Bourla gave his go-ahead a week later, at one of Pfizer’s first leadership meetings on the program. When vaccine researchers at a follow-up meeting in mid-March forecast a coronavirus vaccine in the middle of 2021, Mr. Bourla spoke up.

“Sorry, this will not work,” he said. “People are dying.”

Mr. Bourla demanded a vaccine by October, when it looked like a second wave of the pandemic would be peaking.

Growing up in Greece, Mr. Bourla never envisioned a career running one of the world’s biggest drugmakers. He trained to be a veterinarian. At Pfizer, Mr. Bourla gained a reputation for his friendliness and achievements, brightly chatting up colleagues and rescuing troubled products. He took the helm of Pfizer in 2019.

“I’m a true believer that people, they don’t really know their limits,” Mr. Bourla said in an interview. “And usually, they have the tendency to underestimate what they can produce.”

Pfizer’s leadership held hour-long meetings Mondays and Thursdays on the vaccine program. The WebEx calls lacked a formal agenda so that discussions could flow freely. Dr. Jansen and the two dozen other colleagues who joined grew accustomed to Mr. Bourla urging fast progress.

Pfizer and BioNTech researchers collaborating via video sought to narrow down the number of vaccine candidates from 20. In test tubes, they examined various doses and looked for molecular signs of effectiveness and safety. BioNTech also tested the candidates in mice.

The whittling was especially tough, because mRNA vaccines weren’t tried-and-true commodities. Researchers wanted to collect as much data as they could to inform their judgments. They also had to move fast.

Vaccines normally are tested in three stages, with the first test on a limited number of people to ensure they are safe. To save time, the researchers took unorthodox steps. In April, they filed their plans for testing a candidate with regulators, but the paperwork was littered with holes for data they would need to fill in. Pfizer also combined the second and third stages. And then they decided they should test more than one version of the vaccine. The company sent the U.S. Food and Drug Administration updated batches of data almost daily.

By April 12, the scientists eliminated 16 candidates. They didn’t know how to choose among the remaining four. Normally, researchers would take years and finish animal testing before injecting any doses into a human. Pfizer didn’t have that kind of time. It still tested the vaccines in monkeys, but simultaneously with humans. “We needed speed, and with speed, you have to rethink how you normally go,” said Dr. Jansen, who leads a team of 650.

On April 23, they started trying the four candidates on a small number of human volunteers in Germany. Within two days of getting two of the shots, some subjects developed fevers and chills, signs the vaccines wouldn’t be well tolerated.

The companies went ahead with testing the other two experimental vaccines in the U.S. One directed cells to produce a partial-spike protein, while the other generated a full-spike protein. Researchers tested different doses and determined either version would require two shots to deliver maximum immunity.

On Sunday, June 7, researchers emailed Dr. Jansen the first results from the early-stage trial of the first vaccine candidate. Dr. Jansen, preparing a presentation in her Manhattan apartment, brightened.

The findings showed the experimental shot produced an antibody response in study subjects, a good sign it could protect against Covid-19.

“Really, really encouraging,” she replied to the researchers by email. “When can I see the next data?”

Pfizer announced the full findings July 1. The second, or full-spike, candidate wouldn’t finish its own study for a few weeks. Without that data, the companies weren’t sure which of the two to take into the large, final trial that regulators would use to determine whether to authorize the shot or not.

Most of the results didn’t arrive until July 23, the day before Pfizer told the FDA it would name a candidate.

Like its cousin, the second candidate also generated a strong immune response. Yet subjects reported fewer cases of fevers and chills than the first vaccine candidate, so it was considered more tolerable.

The choice was tough because the candidates were so close, Pfizer officials said. On July 24, Pfizer and BioNTech agreed to go with the second vaccine candidate.

“I started to relax a little bit, which I haven’t really done since the beginning of all of this,” Dr. Jansen recalled a week later. “It is just a major, major, major decision to make.”

As the researchers zeroed in on a vaccine selection, Pfizer’s manufacturing team geared up to make the shots with BioNTech. Given the urgent need for a vaccine, the companies planned to make supplies for testing, but also to begin making vaccines for real-world use even before the final study finished.

One problem: Pfizer didn’t have the equipment to make an mRNA vaccine, a new and different manufacturing process.

To assemble its mRNA production network, Pfizer used its own money and didn’t take any from the federal government. Executives said they didn’t want to give agencies outside the FDA more leverage over the design of the trials.

Rival Moderna, which took funding from a division of the U.S. Department of Health and Human Services, suffered a three-week delay in completing its own mRNA trial after federal officials there asked the company to slow down enrollment to boost the racial and ethnic diversity of study subjects.

Starting in March, Mr. McDermott spent $500 million to buy and design equipment, more than double what he budgeted. Pfizer retrofitted an Andover, Mass., plant to make the mRNA, and assigned a St. Louis factory to make the raw materials for the shots. Numerous times it returned to suppliers or contractors to increase orders.

Instead of making mRNA in giant steel tanks, which would add months, Pfizer used disposable bags. Each fits at least 500,000 doses.

In April, the company began buying machines the size of a single-car garage that play a crucial role in production. These formulation machines deposit the mRNA vaccine in the fatty, or lipid, envelope that carries it to a cellular target. Without the safe passage, the vaccine breaks down during the journey.

Pfizer bought seven of the machines, each costing $200 million, destined for company plants in Puurs, Belgium, and Kalamazoo, Mich. It takes about a week to make a batch of doses, which then undergo two weeks of testing. The finished product is stored at subzero temperatures to stay stable and potent.

Mr. McDermott and his team took steps to maximize output. Companies typically put one vaccine dose in a single vial so a nurse doesn’t need to draw out and measure how much to inject. Pfizer went with vials capable of holding multiple doses, because filling them was faster.

Demands for doses kept increasing, sometimes frustrating Mr. McDermott. He was a 30-year industry veteran who became part of Pfizer in 2009, and has years of experience making vaccines such as the pneumonia shot Prevnar. A hands-on engineer, he likes crawling under the machinery for a look.

Then on June 30, regulators in the U.S. and Europe said they wanted the late-stage trials to have far more subjects than initially anticipated—30,000 rather than 8,000.

That meant Pfizer and BioNTech would have to make triple the dose supplies it had planned—within weeks. And Mr. McDermott’s vaccine-research counterparts hadn’t settled on a final candidate, which meant the company would have to make materials for two candidates.

“It was like, ’Oh, my God, we can’t do this,’ ” Mr. McDermott said, recalling his reaction.

Within a day, he and one of his deputies, Kevin Nepveux, got a call from their Belgian plant. Engineers would speed up preparation of filling lines to make more trial doses. They also figured out how to squeeze another formulation machine into the facility, helping make commercial doses six months earlier.

It wouldn’t be cheap. Mr. McDermott, working out of his New Jersey home office, rang up Pfizer Chief Financial Officer Frank D’Amelio. “I got an idea, and I need $10 million. Is it an issue?” Mr. McDermott said.

“Just do it,” Mr. D’Amelio said.

Pfizer wasn’t sure how long doses would last in a refrigerator before expiring, and the company didn’t have time to conduct studies to figure it out. Manufacturing staff decided to play it safe and ship the supplies at subarctic temperatures.

In April, Pfizer started working with contractors to create a container to keep the shots cold. The suitcase-size box could hold nearly 5,000 doses. To test it, the company ferried containers on hundreds of trips around the world, visiting Dubai, Africa, and even the doorsteps of Pfizer employees.

Mr. Nepveux’s grown son was visiting his parents’ New Jersey home when a package arrived. “When it got delivered, he thought it was some kind of fancy beer cooler,” Mr. Nepveux said.

Just before the July 4 weekend, Mr. McDermott’s team showed off the container to colleagues. The team was excited because of the quick turnaround. Then came Mr. Bourla’s reaction.

“What in the hell is CVS going to do with 5,000 doses?” he said. Pharmacies run by CVS Health Corp. and doctor’s offices, he said, would need to receive fewer doses.

Mr. McDermott’s team went back to the drawing board. Pfizer now plans to release a 25-vial, or 125-dose, package next year.

The decision to go ahead with the second vaccine candidate, made at the end of the month, was another shock. While colleagues on the call cheered the milestone, Mr. McDermott did some math in his head and groaned.

His team had anticipated the first candidate would be the choice. The second one required a larger dosage, which meant fewer shots could be packed in a vial.

By that point, Pfizer was targeting as many as 100 million doses for 2020. Mr. McDermott asked whether they could toggle back to 80 million. Mr. Bourla wouldn’t relent. “Find a way,” he said.

The late-stage trial, cleared to start on July 27, began quickly. Within hours, the first four healthy volunteers received injections at the University of Rochester Medical Center in upstate New York.

Evaluating whether the experimental shot protected against Covid-19 meant finding people for the trials in places where a study subject had a good chance of getting exposed. Then researchers could see if they developed symptoms or not, and whether they had taken the vaccine or placebo.

The company deployed mathematical models that crunched infection rates down to ZIP Codes, to identify hot spots.

Researchers hoped the seriousness of the disease would encourage people to sign up. Some 20,000 enrolled through August. By the end of the month, however, enrollment had veered off track.

There were two problems. People weren’t signing up in target areas as fast as the companies expected. And the mathematical models weren’t doing a good job at predicting virus hot spots more than a few weeks out.

The virus had shifted to other places by the time subjects had joined the pivotal study and taken both shots. Due to local efforts to curb the pandemic, infection rates were falling in places like New York and Washington state where researchers had been recruiting.

“It is like a puzzle, and the puzzle is changing,” Dr. Jansen said.

Dr. Jansen convened researchers and computer scientists on Sept. 1 to review the virus’s behavior and make changes to the trial.

Within days, researchers stopped enrolling patients at certain sites, including in New York City. They upped the recruitment goals in emerging hot spots such as Argentina. They also expanded the trial by 14,000 subjects to increase the odds of exposure.

Still, by early October, fewer subjects than expected had become sick. Pfizer scientists were perplexed. Perhaps study subjects were taking precautions to stay healthy, such as wearing masks and social distancing, the researchers theorized. Maybe the FDA-authorized tests Pfizer was using to confirm cases weren’t accurate, Dr. Jansen said.

Pfizer stopped processing test results and asked the FDA to permit use of a different test. The FDA, meanwhile, wanted Pfizer to wait until 64 subjects became sick before taking its first peek, rather than just 32, as the company had planned.

By the time the two sides struck an agreement in early November, the issue was moot: 94 people had become sick, triggering a preliminary review that found the vaccine was more than 90% effective and looking safe.

Mr. Bourla learned the results Sunday afternoon. When he gave the findings to senior company officials on a call, Mr. Bourla said people jumped up from their chairs.

To get a head start building up supplies, in mid-August the company began producing doses at its Belgium factory that could go immediately into use should any country give clearance.

By the end of September, the company had set aside 1.5 million doses to be frozen and ready to ship.

Yet most of Pfizer’s manufacturing network wouldn’t be ready for making shots until October. Installing, testing and certifying the machines made supplies correctly took weeks, culminating in engineering runs in September.

Looking for workarounds, Mr. McDermott tweaked the production process in a way he figured would add 5 million more doses a week. But in the end, despite making enough mRNA for 100 million doses, Pfizer and its partners incurred a three-week delay securing enough raw materials to make the lipid nanoparticle that wraps around the vaccine. On Nov. 9, Pfizer disclosed it would make 50 million doses this year, half what Mr. Bourla wanted.

Still, the chief executive is looking on the bright side. “I always try to shoot for the stars, because I know that even if you miss it, you will land somewhere in the moon,” he said. “But right now it looks like we landed, more or less, in the stars.”

If you lose all hope, you can always find it again -- Richard Ford in The Sportswriter
0

#1017 User is offline   johnu 

  • PipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 3,952
  • Joined: 2008-September-10
  • Gender:Male

Posted 2020-December-17, 15:28

Why are the US Trump Virus cases, hospitalizations and deaths skyrocketing out of control???

One reason is this:

Emails show former Trump health appointee advocated herd immunity strategy

Quote

In a July 27 email to CDC director Robert Redfield, Alexander said the country “essentially took off the battlefield the most potent weapon we had...younger healthy people, children, teens, young people who we needed to fastly [sic] infect themselves, spread it around, develop immunity, and help stop the spread.”


Herd "Mentality" (sic) is the Manchurian President's way of describing this. One of the stupidest and criminally insane ideas I've ever come across. Maybe the Grifter in Chief believed that only Democrats could get infected by the Trump Virus.
0

#1018 User is offline   barmar 

  • PipPipPipPipPipPipPipPipPipPipPipPip
  • Group: Admin
  • Posts: 20,455
  • Joined: 2004-August-21
  • Gender:Male

Posted 2020-December-18, 09:52

View Postjohnu, on 2020-December-17, 15:28, said:

Why are the US Trump Virus cases, hospitalizations and deaths skyrocketing out of control???

One reason is this:

Emails show former Trump health appointee advocated herd immunity strategy

You omitted the quotes that say that his recommendations were never adopted as HHS policy.

#1019 User is offline   hrothgar 

  • PipPipPipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 14,892
  • Joined: 2003-February-13
  • Gender:Male
  • Location:Natick, MA
  • Interests:Travel
    Cooking
    Brewing
    Hiking

Posted 2020-December-18, 10:20

View Postbarmar, on 2020-December-18, 09:52, said:

You omitted the quotes that say that his recommendations were never adopted as HHS policy.


Never adopted as official HHS policy.

However, if you look at HHS's actual behaviour and incompetence its entire consistent with a herd immunity policy
Alderaan delenda est
0

#1020 User is offline   awm 

  • PipPipPipPipPipPipPipPipPip
  • Group: Advanced Members
  • Posts: 8,151
  • Joined: 2005-February-09
  • Gender:Male
  • Location:Zurich, Switzerland

Posted 2020-December-18, 10:26

View Posthrothgar, on 2020-December-18, 10:20, said:

Never adopted as official HHS policy.

However, if you look at HHS's actual behaviour and incompetence its entire consistent with a herd immunity policy


One of the many messed up things about the Trump administration is a lack of official policies (as well as a lack of official appointees to a lot of positions). This perhaps helps to shield the administration from congressional or legal oversight, but it doesn't really make things better. Still, it's effectively a significant expansion of presidential power and it will be interesting to see if Biden continues this particular Trump tradition (especially if he is met with unified opposition from Senate Republicans).

As far as Covid goes, there really isn't a centralized US government response. This more or less leaves state governors to their own devices, and it will be interesting to see how states perform relative to each other as well as how much things change when Biden takes over next month.
Adam W. Meyerson
a.k.a. Appeal Without Merit
0

Share this topic:


  • 56 Pages +
  • « First
  • 49
  • 50
  • 51
  • 52
  • 53
  • Last »
  • You cannot start a new topic
  • You cannot reply to this topic

2 User(s) are reading this topic
0 members, 2 guests, 0 anonymous users

  1. Google