Coronavirus Sars-CoV-2/Covid-19 Megathread

[Zanza]

For reference, Germany considers harsher measures while hitting 100 7 day average.

It only considers though. Basically we went back to the restrictions from 14 days ago. Merkel wanted more, but the state prime ministers refused (so far). Her power is waning, close to being a lame duck.

But then they allowed travelling to Mallorca again. WTF.

[viper37]

2 schools have been closed in my home town due to covid-variants infecting staff and students.  So far, the spread seems to have been noticed very early, but nonetheless, globally in the county, cases are ticking up

The variant has not been specified, but I'm guessing it's the UK one.  And I'll bet it comes from student sports. If it's a teacher that visited friends/family in Montreal, I don't know who he/she is or where he/she is, but I'm going him to find him/her and kill him/her.

That was fast...
It is now 30 cases, mostly in my immediate area, 14 schools shutdown including one where no cases have been found but many teachers have to self isolate for 10 days so there's no teachers left available

[The Larch]

Apparently the FDA is not very convinced of the data from the AZ vaccine trials. I hope it gets solved eventually, as it only seems to concern how updated some of the data is.

US agency questions AstraZeneca's Covid vaccine trial data
UK drug firm may have provided incomplete view of efficacy data from US trial, says safety monitor

AstraZeneca may have provided an incomplete view of efficacy data on its Covid-19 vaccine from a large-scale trial in the United States, a US health agency has said, in a fresh setback for the drug.

The concerns throw into question whether the British pharmaceutical firm can seek US emergency use authorisation for the vaccine in the coming weeks as planned, and come just one day after interim data from the trial had shown better-than-expected results.

The vaccine developed with Oxford University was 79% effective in preventing symptomatic illness in the large trial that also took place in Chile and Peru, according to the data. It was also 100% effective against severe or critical forms of the disease and hospitalisation and posed no increased risk of blood clots.

The Data and Safety Monitoring Board (DSMB), an independent committee overseeing the trial, has "expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data", the USNational Institute of Allergy and Infectious Diseases (NIAID) said in a statement.

NIAID is headed by the US infectious diseases expert Dr Anthony Fauci and is part of the National Institutes of Health.

"We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible," it said, adding that the DSMB had informed AstraZeneca of its concerns.

AstraZeneca did not immediately respond to a request for comment.

Authorisation and guidelines for use of the vaccine in the US will be determined after thorough review of the data by independent advisory committees, the NIAID statement added.

Hailed as a milestone in the fight against the pandemic when it emerged as a vaccine contender last year, the AstraZeneca shot has since been dogged by doubts over its efficacy, dosing regimen and possible side-effects.

More than a dozen European countries halted use of the vaccine this month after reports linked it to a rare blood-clotting disorder in a very small number of people.

Germany and France resumed inoculations after the EU's drug regulator said last week it was safe, but an opinion poll on Monday showed Europeans remained sceptical about its safety.

Fauci, who also serves as the chief medical adviser to the US president said on Monday the US trial found no indication of the rare blood clots.

Before the blood clot concerns, there were also separate late-stage studies that had raised questions about its dosing regimen and the lack of data about its efficacy for elderly people.

The latest data, which has yet to be reviewed by independent researchers, was based on 141 infections among 32,449 participants. Analysts had also noted AstraZeneca's achievement of producing strong trial data against a backdrop of more infectious variants spreading in the US and other countries.

The AstraZeneca vaccine, which is already widely used outside the US, is seen as crucial in tackling the spread of ovid-19 across the world because it is easier and cheaper to transport than rival shots.

It has been granted conditional marketing or emergency-use authorisation in more than 70 countries. Many countries are relying heavily on it to end the pandemic, and several leaders have taken the shot to boost confidence in the vaccine including South Korea's president, Moon Jae-in, who received it on Tuesday.

The treatment has also been at the centre of a growing conflict between Brussels and London over so-called vaccine nationalism after a string of supply setbacks in Europe.

[Tamas]

The Hungarian state media's handling of the pandemic has really crossed into criminality.

Yesterday alone 600+ new people were admitted to hospitals, 252 new covid deaths (which is round about the  daily average of all deaths in the country during normal times. What did the state TV do? They zero in on the fact that during the weekends there are less tests done so, as clockwork, on Tuesday morning you get far less new cases than the rest of the week, and that's the only thing they mention: "Yesterday the number of infections fell to half"

[Tamas]

Incidentally, Hungary is making a good case for strict lockdowns. A year ago there were barely any cases yet when they went into a lockdown pretty much on level of the eventual English one, and the first wave was kept fairly minor, especially compared to nightmares like Italy.

The 2nd wave had far were restrictions and hit much stronger. Restrictions for the first wave were introduced way too late (2 weeks ago) and they are quite lax. There are lots of excuses that let most shops and all shopping centres to remain open, and the populace seem only to have mildly changed daily routines. The only significant step has been to close schools. The result is that according to more and more reports (never official ones as the official communication is basically the "this is fine" meme"). hospitals are at the brink and non-covid care is already at near-complete halt.

[Sheilbh]

From another NYT piece - because the description by this board is pretty vague:

In a highly unusual statement released after midnight, the National Institute of Allergy and Infectious Diseases said that the data and safety monitoring board, an independent panel of medical experts under the National Institutes of Health that has been helping to oversee AstraZeneca's U.S. trial, had notified government agencies and AstraZeneca late Monday that it was "concerned" by information the company had released that morning.

The institute urged AstraZeneca to work with the monitoring board "to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible."

AstraZeneca did not immediately return a request for comment early Tuesday.

In a news release on Monday announcing the results of the U.S. trial, the company said that the vaccine it developed with the University of Oxford was 79 percent effective against Covid-19, higher than observed in previous trials, and completely prevented the worst outcomes from the disease. The long-anticipated results were seen as encouraging global confidence in the vaccine, which was shaken this month when more than a dozen countries, mostly in Europe, temporarily suspended the shot's use over concerns about possible rare side effects.

In recent days, the monitoring board's analysis was delayed several times because the board had to ask for revised reports from those handling trial data on behalf of the company, according to a person familiar with the matter who was not authorized to discuss it publicly.

Companies sponsoring drug or vaccine trials typically wait for the monitoring board to run analyses and conclude that the study has yielded an answer before they announce trial results. During the trial, an unblinded statistical analysis group that is walled off from the company acts as an intermediary to handle data requests and many other interactions with the monitoring board.

Company executives are blinded to the results of the study until the monitoring board reports their study data back to them. The monitoring board ultimately conveyed the results of the study to AstraZeneca in a meeting over the weekend, leading to the company's announcement Monday morning.

An AstraZeneca spokeswoman, whom the company declined to name, said last week that it was "completely incorrect" that the trial data had formatting problems or had not been submitted to the monitoring board in a clean fashion.

"As is often the case," the spokeswoman said, monitoring boards "can request new or clarifying analyses of data from the trial. This would enable them to ensure the robustness of their determinations."

Dr. Eric Topol, a clinical trials expert at Scripps Research in San Diego, said it was "highly irregular" to see such a public display of friction between a monitoring board and a study sponsor, which are typically in close concordance.

"I've never seen anything like this," he said in an interview after the institute's statement was released. "It's so, so troubling."

AstraZeneca's relationship with the U.S. authorities has been fraught since last year, when senior health officials believed the company was not being forthright about the design of its clinical trials, its results and safety issues. That skepticism carried over to last week, when senior officials at a number of federal health agencies grew suspicious about why AstraZeneca had not announced data from its U.S. study.

That U.S. trial, which involved more than 32,000 participants, was the largest test of its kind for the shot. The results AstraZeneca released on Monday were from an interim look at the data after 141 Covid-19 cases had turned up among volunteers.

The company did not disclose how up-to-date the data are. If the analysis was conducted on data from a month or two ago, it is possible that a more current look would present a different picture of the vaccine's effectiveness and safety. The company has said it will provide the Food and Drug Administration with a more comprehensive, recent set of data than what it disclosed on Monday. Although no clinical trial is large enough to rule out extremely rare side effects, AstraZeneca reported that its study had turned up no serious safety issues.

Given that the statement is highly unusual - it seems weird how vague the detail is and it seems to relate to data formatting/not updating data in the last month during analysis I'm not sure. At best it feels like they're possibly a bit pissed off that AZ jumped the gun (but then other officials were apparently suspicious about the lack of statements). Very weird - and given that it will probably be too late to be used in the US market it would be helpful if it was exported instead. There's some speculation that it might have been a severe case in the dosed group - but that's speculation and it's not clear if that happened after the cut-off date in the protocol, or if it relates to a variant where we know the vaccines are less effective. From looking around apparently it's not uncommon for the DSMB to disagree with investigators on interpreting trial data but it's normally dealt with in private and releasing a public statement is pretty unprecedented.

[Tamas]

For sure there has been too much bruhaha around AZ for EVERYTHING to be fine with it. I suspect it's the weakest and/or riskiest of the Western vaccine options. But also I am resigned to the fact it will be the one I'll be jabbed with.

[Sheilbh]

For sure there has been too much bruhaha around AZ for EVERYTHING to be fine with it. I suspect it's the weakest and/or riskiest of the Western vaccine options. But also I am resigned to the fact it will be the one I'll be jabbed with.

I've no doubt the trials have been mishandled and this may be because the trials and data is, I think, run by Oxford academics who have experience producing vaccines and managed by AZ who've never made a vaccine before - so I wonder if that's part of it.

But I don't think there's any real reason to think it's weaker or riskier than any of the other options. The analysis of the real world data in Scotland of over 1 million people (healthcare workers and the elderly) seem to indiciate it's mildly more effective than the Pfizer vaccine. I think they're all very effective (I remember in the summer when 60% effectiveness was something to hope for ) and very safe. While I'm not entirely conspiracy minded on this, I find it striking that there is so much bruhaha about the non-profit option

[Zanza]

I get the impression that the company should review its regulatory documentation processes. You would expect a pharma giant like AZ to be on top of this.

[garbon]

I get the impression that the company should review its regulatory documentation processes. You would expect a pharma giant like AZ to be on top of this.

I mean it isn't like the regulatory bodies all follow same rules or even consistently apply their frameworks. It isn't unusual in a standard drug lifecyle to have hiccups when say FDA suddenly decides it wants more trial data or more robust analysis.

[Sheilbh]

I get the impression that the company should review its regulatory documentation processes. You would expect a pharma giant like AZ to be on top of this.

You could be right - my suspicion is this is more about regulatory engagement. I don't know about the US or medical regulation, but in the area I work in with European regulators you normally want to have contacts and a relationship with the regulator. You try to build a profile with the regulator because the same information will be viewed differently if they think you're dodgy or hiding stuff or have never heard of you than if they think you're basically one of the good guys who they know.

This issue in particular - which seems to be a data query - is one that I think if you had a decent relationship with the regulator would be dealt with in private. Making it public seems to me more suggestive of relationship breakdown/issues than document issues. Normally you can get information about how it's going and what you need to do to fix it, before the regulator's making public statements.

As I say that could be totally wrong - and in the US it may be more arm's length and neutral.

[The Larch]

The FDA is notoriously punctilious when approving new drugs, and even the largest pharmaceutical companies whiff it sometimes, these developments are not *that* strange. What might be happening now is that what used to be done behind closed doors (the asking for new studies, the raising of doubts about the data, etc.) or with only the industry paying attention is now being made public at every single step.

[Sheilbh]

Yeah - totally unrelated but How To Survive A Plague is a really goood documentary that I strongly recommend if you get a chance. And it's fascinating how much the activists focus on the FDA and its process being part of the problem in responding to AIDS because they were so punctilious as you say. It's just really interesting because activists in the late 80s/early 90s were basically demanding the right to have clinical trials and for the FDA to not treat potentially life-saving treatments in the same way as they treat a nasal spray for congestion. I think the AIDS crisis led to a lot of reforms at the FDA but I could be wrong.

And there's definitely something about us all paying attention But I think it's more likely this is something normally done in private rather than us just noticing, given Eric Topol's comments about it being highly unusual - I saw another expert saying this stuff happens in private a lot but for it to happen in public is in his view "unprecedented".

But the statement's so vague all we can do is speculate which is unfortunate.

Edit: Incidentally from the amazing Kai Kupfershmidt:

As far as I can parse this:
Results yesterday were interim analysis based on data with cut-off point February 17.
More up to date data is coming in form of the primary analysis within 48 hours and should not look all that different...
Let's wait and see...

AZ's statement:

The numbers published yesterday were based on a pre-specified interim analysis with a data cut-off of 17 February.

We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis. We are now completing the validation of the statistical analysis.

We will immediately engage with the independent data safety monitoring board (DSMB) to share our primary analysis with the most up to date efficacy data. We intend to issue results of the primary analysis within 48 hours.

[The Larch]

A big factor in all Covid related drug approvals is the fact that it's a new disease for which there are no benchmarks for, and I guess that makes regulators extra anxious about how to validate results and give new drugs the final ok (in fact all these drugs are being approved employing emergency protocols, a drug for an existing disease would follow an even more stirngent protocol). If regulators are cautious by definition (and they must be cautious with something as sensitive as drugs), this kind of scenario exacerbates that.

[Sheilbh]

Yeah and you wonder if it was a mistake. From a purely UK perspective it was probably the right decision to stop the Merck deal due to risks of it mainly being manufactured in the US/fears around Trump. From a global perspective it might have been better if it was being produced by a company with lots of experience in vaccines who would probably have had a smoother ride through the regulators because of experience and possibly have had less issue upscaling production which has been a huge issue for AZ everywhere. But maybe not - maybe the same issues would have happened because the data/trial structure problem was on the Oxford side and maybe they would have more production but it wouldn't be globally distributed so would be 90% in the US right now a bit like Moderna.

Edit: Incidentally with lockdown and vaccines it looks like the UK second wave is more or less over - 7 day rolling average of deaths has fallen below the 5 year average for the first time since the summer