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By way of followup to the ibuprofen-related discussion ack on page 19 of the thread:

[url=https://www.nakedcapitalism.com/2020/04/coronavirus-research-done-too-fast-is-testing-publishing-safeguards-bad-science-is-getting-through.html]Coronavirus Research Done Too Fast Is Testing Publishing Safeguards, Bad Science Is Getting Through[/url] | naked capitalism
[quote]Nothing better illustrates how trusted institutions can make misinformed recommendations than the recent fiasco over ibuprofen.

The most common early symptom of COVID-19 is fever, and ibuprofen is one of the most widely used drugs in the world to treat fever. In a letter published in The Lancet Respiratory Medicine, European researchers raised concerns that ibuprofen use could worsen COVID-19 symptoms. The idea is that since ibuprofen increases the quantity of ACE2 in human cells – the protein that the coronavirus uses to enter lung cells – the virus could infect lung cells more easily if a person was on ibuprofen. This was not a study nor did it present sufficient experimental evidence; it was simply a theoretical concern based on a mechanism.

Three days after the letter was published, the French health minister tweeted a message urging people to avoid ibuprofen for coronavirus associated fever based on four “cited” cases of people getting sicker after taking ibuprofen. These cases were never published in a journal. The French Health Ministry followed this with a broad ban on treating COVID-19 fever with nonsteroidal anti-inflammatory drugs like ibuprofen. The WHO tweeted an essentially similar warning. The media followed with more case anecdotes, dubiously relating worsening early symptoms with ibuprofen use and referring to the letter as a “study,” adding to the confusion and fear.

The Lancet letter also hypothesized that two other drugs commonly used to treat hypertension and diabetes – ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) – could be problematic in people with COVID-19. However, the mechanism they put forward was incompletely described and neglected that a protein these drugs promote can be helpful in reducing inflammation and tissue damage in the lungs and heart.
[b]
The Response
[/b]
This letter to The Lancet slipped past the safeguards in research and institutional and media interpretation, but one of science’s oldest pastimes – definitively calling out the errors of others – reestablished patience and perspective.

Clinicians and scientists pushed back swiftly, supporting the use of ibuprofen in COVID-19 patients. The support was outlined in a published literature review. In response, the WHO quickly reversed its position on ibuprofen.

There was a similar rapid response to the statements about ARBs. Within days, three prominent cardiology groups, including the American Heart Association, released a joint statement urging practitioners not to discontinue ACE-I and ARBs in their patients.

The risk-benefit ratio is always a clinical factor for the use of any drug in any patient. But the risk must be more than theory for the use of a drug to be discontinued or any major policy change to be implemented.
[b]
Some Perspective
[/b]
As the coronavirus rampages across the U.S., it is incredibly important to know whether commonly used drugs like ibuprofen or ARBs are risky, neutral or of therapeutic potential. There are ways to find out quickly. Researchers can look for correlations between the use of ibuprofen or ARBs and more severe infections or deaths, for example. And standard clinical trials can, should and are being done. There are several studies currently underway testing the effect and risk of ARBs for COVID-19 patients. But until the science is finished, it is foolish and potentially dangerous to flee from tested clinically important drugs.[/quote]

[QUOTE=ewmayer;542380]By way of followup to the ibuprofen-related discussion ack on page 19 of the thread:

[URL="https://www.nakedcapitalism.com/2020/04/coronavirus-research-done-too-fast-is-testing-publishing-safeguards-bad-science-is-getting-through.html"]Coronavirus Research Done Too Fast Is Testing Publishing Safeguards, Bad Science Is Getting Through[/URL] | naked capitalism[/QUOTE]
Very happy to see the pushback on ACE-I since I've been taking one for well over 20 years, and my BP is well regulated.

Trump is playing a disgusting political game with our lives

-By The Denver Post Editorial Board

[URL]http://www.informationclearinghouse.info/55042.htm[/URL]
[QUOTE]President Donald Trump is treating life-saving medical equipment as emoluments he can dole out as favors to loyalists. It’s the worst imaginable form of corruption — playing political games with lives. For the good of this nation during what should be a time of unity, he must stop.

In just the latest example of his gross display, the president tweeted on Wednesday:

[CENTER] Will be immediately sending 100 Ventilators to Colorado at the request of Senator Gardner! [URL]https://t.co/Nj4EPxfZl6[/URL]
— Donald J. Trump (@realDonaldTrump) April 8, 2020
[/CENTER]

[U]Trump had only days before prevented Colorado Gov. Jared Polis from securing 500 ventilators from a private company, instead, taking the ventilators for the federal government.[/U] Polis sent a formal letter pleading for medical equipment, but the president took the time to make clear he was responding to a request from Gardner. We are left to believe that if Colorado didn’t have a Republican senator in office, our state would not be getting these 100 ventilators. How many ventilators would we be getting if we had a Republican governor and a second Republican senator? Would that indicate we had more Republican lives in our state worth saving for Trump and resources would start flowing? Should Utah be concerned that Sen. Mitt Romney voted to remove the president from office?

This behavior comes, of course, weeks after Trump informed states they would have to compete against one another in the procurement of medical supplies at a time of global shortages due to the coronavirus pandemic.[/QUOTE]

Re: Trump is playing a disgusting political game with our lives

Anyone who expected anything different from [i]Il Duce[/i] has their head stuck in the sand, or somewhere else the sun don't shine.

[QUOTE=Dr Sardonicus;542393]Anyone who expected anything different from [I]Il Duce[/I] has their head stuck in the sand, or somewhere else the sun don't shine.[/QUOTE]
No sh!t!

It still bears mentioning, if only as a futile gesture.

Trump is visited by three ghosts.

Early in the night, the ghost of FDR appears. When Trump asks him how he can make America great again, FDR replies: "Think only of the people, do not make laws based on hatred, bigotry, or with the thought of lining your own pockets."
Trump's face sours and he yells, "Fake news!"

A few hours later Trump is awakened by George Washington's ghost. Trump again asks, "How can I make America great again?" Washington says, "I would suggest that you never tell a lie."

This infuriates Trump.

At around 3:00 a.m. he is visited by the ghost of
Abraham Lincoln. Trump again asks how he can make America great again.

Lincoln replies, [SPOILER]"Go to the theater."[/SPOILER]

[QUOTE=kladner;542400]Trump is visited by three ghosts.

Early in the night, the ghost of FDR appears. When Trump asks him how he can make America great again, FDR replies: "Think only of the people, do not make laws based on hatred, bigotry, or with the thought of lining your own pockets."
Trump's face sours and he yells, "Fake news!"[/QUOTE]

FDR preaching against bigotry, [url=https://www.history.com/topics/world-war-ii/japanese-american-relocation]that's rich[/url].

Boris Johnson released from the hospital; expected to convalesce for a week. [url]https://www.bbc.com/news/uk-politics-52262012[/url]
His fiancee is expecting to give birth in two months and has been self isolating with symptoms but has not been tested.

Easter greetings from the Elbphilharmonie in Hamburg: An excerpt from Brahms' Sinfonie Nr. 1
[URL]https://www.ndr.de/kultur/musik/Ein-hoffnungsvoller-Gruss-in-die-Welt,ostern1236.html[/URL]
Just watch the video.

[QUOTE=Till;542428]Easter greetings from the Elbphilharmonie in Hamburg: An excerpt from Brahms' Sinfonie Nr. 1
[URL]https://www.ndr.de/kultur/musik/Ein-hoffnungsvoller-Gruss-in-die-Welt,ostern1236.html[/URL]
Just watch the video.[/QUOTE]
Amazing! I have seen remote ensembles of half a dozen, but an entire orchestra is a stunning accomplishment.

[QUOTE=CRGreathouse;542403]FDR preaching against bigotry, [url=https://www.history.com/topics/world-war-ii/japanese-american-relocation]that's rich[/url].[/QUOTE]Thanks in no small part to official policy approved by FDR, the good ol' USA didn't have a stellar record in taking in refugees trying to flee the Holocaust, either.

In addition, some prominent US citizens were viewed with gratitude by the Nazis. Charles Lindbergh, Henry Ford, GM Exec James Mooney, and IBM funder Thomas J. Watson were all awarded the Order of the Eagle for their "service to the Reich."

Henry Ford even got an "honorable mention" in [u]Mein Kampf[/u], thanks to his publication, [i]The Dearborn Independent[/i]. Ford has an additional distinction WRT the Reich. It is a standard, and by now perhaps trite cliche for cartoonists to portray tyrants as having a portrait of Hitler hanging in their offices. But one may ask, whose portrait adorned the wall of Adolph Hitler's office? Why, Henry Ford's! I heard this quite a few years ago, on a PBS program about the depression. An American correspondent was in Berlin in 1932 to interview the up-and-coming head of the Nazi Party. When he went to his office, he was surprised to see copies of [i]The Dearborn Independent[/i], both in English and in German translation, and a portrait of Henry Ford on the wall...

In a desperate attempt to bring things "back on topic," my visiting ghost would suggest that [i]Il Duce[/i] could improve America by volunteering Mike Pence, and himself, as human guinea pigs for [b]all[/b] the COVID-19 remedies being suggested. Starting with the one suggested by the Church of Bleach.

[QUOTE=Dr Sardonicus;542433]But one may ask, whose portrait adorned the wall of Adolph Hitler's office?[/QUOTE]I have been trying hard to keep my proo-freading [sic] instincts in check but this is not the first time I've seen der Führer's name spelled incorrectly here in recent days.

It is [B]Adolf[/B] Hitler.

[QUOTE=xilman;542435]I have been trying hard to keep my proo-freading [sic] instincts in check but this is not the first time I've seen der Führer's name spelled incorrectly here in recent days.

It is [B]Adolf[/B] Hitler.[/QUOTE]

Jawohl.

My text editor's stupid spell checker kept flagging "adolf." Being tired, I mindlessly appeased it.

I leave the spell checker on because I make so many typos, it is actually quite useful to me.

This particular problem is fixed. I have ordered it to accept the spelling "adolf." It has complied.

Re. whose-portrait-is-on-Adolf's-office-wall, my gues would've been a signed one of his good friend and colleague, [url=https://tvtropes.org/pmwiki/pmwiki.php/Recap/MontyPythonsFlyingCircusS1E12]Ron Vibbentrop[/url]. Or perhaps one of Bimmler.

[QUOTE=ewmayer;542450]Re. whose-portrait-is-on-Adolf's-office-wall, my gues would've been a signed one of his good friend and colleague, [url=https://tvtropes.org/pmwiki/pmwiki.php/Recap/MontyPythonsFlyingCircusS1E12]Ron Vibbentrop[/url]. Or perhaps one of Bimmler.[/QUOTE]You are confusing him with a certain Mr Hilter, the notorious baby biter.

Crooks and Liars in DC

[URL]https://talkingpointsmemo.com/edblog/more-details-on-airlifts-and-supply-seizures[/URL]
This has Kushner's bloody hand prints all over it.

[QUOTE]Here are a couple more details on [U]shipment seizures and inter-state bidding[/U] we’ve been discussing here in recent days. Both are interviews on this evening’s Newshour, flagged to me by TPM Reader [I]KM[/I].
Gov. J.B. Pritzker (D-IL) appeared to confirm one point that remained ambiguous from the [URL="https://talkingpointsmemo.com/edblog/you-need-to-look-at-this"]press conference last week[/URL] in which Rear Admiral Polowczyk explained the ‘Airbridge’ flights from China. According to Pritzker, the [U]US military planes airlift the PPE and other medical supplies to the US and then hand them over to the major medical supply distributors the White House taskforce is working with. That part was clear from the discussion April 2nd. What Pritzker confirmed is that the [B]states then have to bid against each other[/B] to purchase the supplies from those distributors.[/U]
[CENTER]
[/CENTER][INDENT] Gov [URL="https://twitter.com/GovPritzker?ref_src=twsrc%5Etfw"]@GovPritzker[/URL] confirms that the federal ‘Air Bridge’ flights from China, organized by the White House taskforce, are bringing PPE back from China which are then turned over to private companies. The states then have to bid against each other to purchase from those companies. [URL="https://t.co/QG62dWtQuc"]pic.twitter.com/QG62dWtQuc[/URL]
— Josh Marshall (@joshtpm) [URL="https://twitter.com/joshtpm/status/1247335425074696199?ref_src=twsrc%5Etfw"]April 7, 2020[/URL]
[/INDENT]The distributors are McKesson Corp., Owens & Minor, Cardinal Health, Medline Industries and Henry Schein. [/QUOTE]

[QUOTE=kladner;542566][URL]https://talkingpointsmemo.com/edblog/more-details-on-airlifts-and-supply-seizures[/URL][/QUOTE]
It's not clear to me which part you object to and on what basis. Government intrusion into a free market? Use of government owned planes instead of or in addition to the fleets of Fedex, DHL, UPS, et al? People paying for what they receive?
Do you prefer more than just pilots go to China, to seize the PPE without the prospect of anyone paying, fly it to the US, and give it away? Now that could be very bloody.

[QUOTE=kriesel;542571]It's not clear to me which part you object to and on what basis. Government intrusion into a free market? Use of government owned planes instead of or in addition to the fleets of Fedex, DHL, UPS, et al? People paying for what they receive?
Do you prefer more than just pilots go to China, to seize the PPE without the prospect of anyone paying, fly it to the US, and give it away? Now that could be very bloody.[/QUOTE]

If the federal gvmt has arranged to acquire the goods, why are they being turned over to private distributors? And why are states bidding at all, let alone against each other? Why isn't FEMA or similar simply distributing directly to hospitals as needed, cutting out the other steps?

Acquire -> hand off to private companies -> sell to states -> distribute from states to hospitals / locations in need. You don't see a problem here?

How about Acquire -> distribute to locations in need?

[QUOTE=VBCurtis;542580]How about Acquire -> distribute to locations in need?[/QUOTE]

That would be "Big Government". Can't have that -- where's the profit?

[QUOTE=VBCurtis;542580]How about Acquire -> distribute to locations in need?[/QUOTE]No. Then none of the politician's cronies can make money in order to give kickbacks to said politician. We can't have that. :devil:

Thanks, VBCurtis. You lay things out very directly. I didn't have it in me.

chalsall and retina: I share your gallows humor. It seems that there is nothing to stop the pillage. The corporatist powers see the real crash coming and are stripping the treasury down to a mountain of debt while people go without treatment, and caregivers go without protection.
[URL="https://www.dailykos.com/stories/2020/4/12/1936741/-FEMA-Was-Planning-to-Seize-Masks-Destined-for-States-Until-the-FBI-Found-Out-They-Were-Fake?utm_campaign=trending"]https://www.dailykos.com/stories/2020/4/12/1936741/-FEMA-Was-Planning-to-Seize-Masks-Destined-for-States-Until-the-FBI-Found-Out-They-Were-Fake?[/URL]
[QUOTE][CENTER]FEMA Was Planning to Seize Masks Destined for States --

Until the FBI Found Out They Were Fake[/CENTER]
[LEFT]A major California labor union that claimed to have discovered a stockpile of 39 million masks for health care workers fighting the coronavirus was duped in an elaborate scam uncovered by FBI investigators, according to a newspaper report Sunday. …
...................................[INDENT] [B]Investigators stumbled onto the scheme while looking into whether they could intercept the masks for the Federal Emergency Management Agency under the Defense Production Act, the U.S. attorney’s office said Friday.[/B]
The federal government has been quietly seizing supplies across the country as the outbreak spreads. But in this case, there was no warehouse, and there were no masks to seize, the Los Angeles Times reported. [emphasis added]
[/INDENT][/LEFT]
[/QUOTE]

Project Airbridge is to gain weeks by air freight compared to usual ocean freight, allowing a surge of more than the usual supply rate. The stuff that was shipped ocean freight is still coming. So right now while more is needed, more is coming; air and ocean in parallel for a few weeks.

UPS is flying the stuff as part of Airbridge. [URL]https://finance.yahoo.com/news/fema-project-airbridge-takes-flight-124510509.html[/URL]

Where's the graft? FEMA is just mobilizing the big fleets of air shippers and existing distributors that are better set up to handle such tasks than the government is.
FEDEX too. [URL]https://www.marketwatch.com/press-release/fedex-activates-project-airbridge-operation-expands-covid-19-relief-efforts-around-the-globe-2020-04-08[/URL]
And apparently the combined commercial cargo fleets are not enough, so capacity is being supplemented with military cargo planes.

The shippers take physical possession but are not the owners of the materials being moved.

"A handful of American health care distributors purchases the supplies, and the Federal Emergency Management Agency paid for the Shanghai-to-New York flight." The distributors are the ones buying the bulk shipments and are set up to break down bulk shipments to lot sizes suitable for individual hospitals and smaller trucks that can actually go to the hospital loading docks. Can't run an 18 wheeler everywhere, or cargo jet to the hospital receiving dock. [URL]https://www.npr.org/sections/coronavirus-live-updates/2020/03/29/823543513/project-airbridge-to-expedite-arrival-of-needed-supplies-white-house-says[/URL]

I don't see cutting distributors out of a vital flow and teaching the National Guard or other govenrment staff how to be distributors as a great alternative to using the distributors that are already up to speed.

This article mentions "giving" supplies to various destinations. That might have been accurate reporting, or might not.It implies government-purchased supplies. [URL]https://www.cbsnews.com/news/coronavirus-what-is-project-airbridge/[/URL]

FEMA page regarding supplies [URL]https://www.fema.gov/fema-supply-chain-task-force-leads-four[/URL]
"Additionally, in some cases, the federal government may purchase some of the supplies to be used to replenish the Strategic National Stockpile (SNS) or to provide to states with any identified and unmet needs."

Healthcare Distribution Alliance AIrbridge page [URL]https://www.hda.org/news/2020-03-29-hda-statement-on-project-airbridge-initiative[/URL]

NY Times article with conflicting statements on supplies handling. In a nutshell, FEMA is attempting fast rational rationing. [URL]https://www.nytimes.com/2020/04/06/us/politics/coronavirus-fema-medical-supplies.html[/URL]

Well...we all love [URL="https://www.youtube.com/watch?v=JSbT7JVNEU4"]George Carlin[/URL]...

Several MDs post about reopening for business and ending the shutdowns. [url]https://medium.com/@jbgeach/eight-reasons-to-end-the-lockdowns-as-soon-as-possible-b7bb0bc94f00[/url]

An Ancient Computer Language Is Slowing America’s Giant Stimulus

[URL]https://www.bloomberg.com/news/articles/2020-04-13/an-ancient-computer-language-is-slowing-america-s-giant-stimulus?srnd=technology-vp[/URL]
[QUOTE]The Covid-19 pandemic has exposed aging, inflexible computer systems at the heart of the U.S. economy -- and a shortage of experts to fix the problem. This is slowing the government’s effort to get billions of dollars in stimulus checks to millions of newly unemployed citizens.

The $2.2 trillion CARES Act passed in late March includes a $600 weekly increase in unemployment benefits. That money won’t reach anyone until state agencies update technology systems to reflect the law and handle the flood of new applications.

Oklahoma is trying to implement CARES as quickly as it can, but some claims are taking as long as two weeks to process because of a mainframe computer that runs on a 60-year-old programming language called COBOL.[/QUOTE]

HRW an Empire Tool? I'm Shocked, Shocked

[url]https://thegrayzone.com/2020/04/08/billionaire-human-rights-watch-sanctions-nicaragua-venezuela/[/url]

[QUOTE]Regime change-hungry HRW is proudly taking credit for crushing new US sanctions on Nicaragua while pushing to escalate Washington’s economic war on Venezuela. The Grayzone presents a deep dive into the “human rights” arm of US empire.
By Ben Norton

Human Rights Watch, the leading so-called rights organization in the United States, has actively lobbied for Washington to impose suffocating sanctions on leftist governments in Latin America. The group has even praised the Donald Trump administration for ramping up its aggressively destabilizing regime-change measures.

NGOs like Human Rights Watch (HRW) depict targeted sanctions as a more palatable alternative to military action, although these measures are widely recognized by international legal experts to be a form of economic warfare that have led to the deaths of many thousands of civilians, destroyed the livelihoods of countless people, and devastated entire nations’ economies.

As the coronavirus pandemic spread across the globe, HRW operatives took credit for new sanctions the Trump administration had imposed on Nicaragua’s democratically elected leftist government. Among those cheering on the escalation of economic warfare was HRW Australia development and outreach manager Stephanie McLennan, who chirped that the fresh round of sanctions were “great news!”

This is great news! US sanctions on #Nicaragua officials open door for accountability. In 2019, we recommended sanctions against two of the three named officials—Luis Alberto Pérez Olivas and Justo Pastor Urbina—after finding evidence of grave abuses. [url]https://t.co/f7zFdl2X22[/url]

— Stephanie McLennan (@StephMcLennan) March 17, 2020[/QUOTE]

Study: No One Could Have Seen Pandemic Coming Except People Capable of Reading

[URL]https://readersupportednews.org/opinion2/277-75/62406-study-no-one-could-have-seen-pandemic-coming-except-people-capable-of-reading[/URL]
Yes. I know that Bororwitz is at the New Yorker. There is an 'Go to original' link at the top of the page. I like to support leftist news aggregation sites, as folks here may have noticed. Reader Supported is pretty tame. Information Clearing House is more on the edge. I do not subscribe to, or endorse any of these views except explicitly. I like to spread diverse viewpoints, especially those which may be less enamored of the political mainstream views emanating from DC.
[QUOTE]No one could have seen the coronavirus pandemic coming except for people who are capable of reading, a new study indicates.

The study, published by the University of Minnesota, is highly critical of the current early-warning system for global pandemics, which requires that a person have the literacy necessary to read, comprehend, and digest a memo.
[/QUOTE]

[QUOTE=kladner;542724][URL]https://readersupportednews.org/opinion2/277-75/62406-study-no-one-could-have-seen-pandemic-coming-except-people-capable-of-reading[/URL][/QUOTE]

Whole lot of 20/20-hindsight running rampant in the MSM these days. I was pleasantly surprised to see none other than a Vox reporter try to provide some sobering perspective on the media's own role in the early days of what turned into a pandemic:

[url=https://www.vox.com/recode/2020/4/13/21214114/media-coronavirus-pandemic-coverage-cdc-should-you-wear-masks]What went wrong with the media’s coronavirus coverage?[/url] - Vox
[quote]While President Trump has been correctly pilloried for describing the coronavirus as less dangerous than the flu, that message was commonplace in mainstream media outlets throughout February. And journalists — including my colleagues at Vox — were dutifully repeating exhortations from public health officials not to wear masks for much of 2020.

As we head into the next phase of the pandemic, and as the stakes mount, it’s worth looking back to ask how the media could have done better as the virus broke out of China and headed to the US.

Why didn’t we see this coming sooner? And once we did, why didn’t we sound the alarm with more vigor?

If you read the stories from that period, not just the headlines, you’ll find that most of the information holding the pieces together comes from authoritative sources you’d want reporters to turn to: experts at institutions like the World Health Organization, the CDC, and academics with real domain knowledge.

The problem, in many cases, was that that information was wrong, or at least incomplete. Which raises the hard question for journalists scrutinizing our performance in recent months: How do we cover a story where neither we nor the experts we turn to know what isn’t yet known? And how do we warn Americans about the full range of potential risks in the world without ringing alarm bells so constantly that they’ll tune us out?

Let’s be clear: Journalists have been doing crucial reporting about what the US government got wrong as the pandemic advanced, and what US leaders could have done to prepare America. They provided analysis that put the news in context. And they have also provided important on-the-ground dispatches from places around the world that have been devastated by the disease — often at great personal risk — starting at its epicenter in Wuhan, China.

But when it came to grappling with a new disease they knew nothing about, journalists most often turned to experts and institutions for information, and relayed what those experts and institutions told them to their audience.

And given that the Covid-19 coronavirus is brand new, even the best-meaning experts and institutions gave conflicting information, some of which now has proven to be inaccurate or up for debate. That includes National Institute of Allergy and Infectious Diseases director Anthony Fauci, who is now the most trusted official in the federal government when it comes to the Covid-19 response, but as late as February was calling the risk from coronavirus “minuscule” and warning people to worry instead about “influenza outbreak, which is having its second wave.”

“There’s a line between doing aggressive reporting and kind of acting in the role of a public health agency,” Joe Kahn, the New York Times’s managing editor, told Recode. “And you never have a degree of complete certainty about the medical analysis, and the epidemiology.”

That degree of uncertainty is much larger when it comes to a new virus that moves around the world as quickly as a plane. It’s a problem that comes built into the reporting. Perhaps the only solution journalists have is to simply say: The experts we talked to aren’t sure, but they’re trying to find out.[/quote]
That collage of soothing MSM headlines in the Dan Bongino twitter thread linked near the bottom of the article is quite damning.

Re. Intel-community memos: POTUS gets a lot of memos, and premature panic can carry its own steep cost not just in terms of $ but in lives - as the MSM were frequently reminding us back then. How many very-scary-sounding "this could turn into a global pandemic" warnings has the world experienced in the last 100 years - heck, just in the last 50 we've had Swine Flu, Ebola, SARS and MERS, with Covid-19 the latest in the that series - and how many "panned out", pardon the pan-pun?

[QUOTE=ewmayer;542787]How many very-scary-sounding "this could turn into a global pandemic" warnings has the world experienced in the last 100 years - heck, just in the last 50 we've had Swine Flu, Ebola, SARS and MERS, with Covid-19 the latest in the that series - and how many "panned out", pardon the pan-pun?[/QUOTE]

This one. And the costs in not taking it appropriately seriously have been high.

I agree that risk management is all about balancing various probabilities, and the costs of optional actions. But perhaps the balancing should be more towards taking actions which might be safer, even if it they turn out to not have been necessary.

Take the summation of costs of the damage from this over the long term (read: 50 or 100 years or so), and compare that to the costs of faster (and better) action over the same time period.

Where do the economic curves cross? That's your optimization point (to greatly oversimply it -- I know humans aren't very good at collective long-term thinking yet).

[QUOTE=ewmayer;542787]Whole lot of 20/20-hindsight running rampant in the MSM these days. I was pleasantly surprised to see none other than a Vox reporter try to provide some sobering perspective on the media's own role in the early days of what turned into a pandemic:

[url=https://www.vox.com/recode/2020/4/13/21214114/media-coronavirus-pandemic-coverage-cdc-should-you-wear-masks]What went wrong with the media’s coronavirus coverage?[/url] - Vox[/QUOTE]

This New York Times reporter "Donald G. McNeil Jr." really was one of the few who saw where it could be headed. On Feb 27th he said: "Mentally prepare that you might need to stay home for a month, not being able to take the subway".

[url]https://www.nytimes.com/2020/02/27/podcasts/the-daily/coronavirus.html[/url]

A look at the years 2000, 2038, & 2100. And why disaster prevention success is misperceived by the general population.
[url]https://www.flashforwardpod.com/2020/04/14/doomsday-2000-2038-2100/[/url]

Let's get that second wave going...

[url=https://apnews.com/57f673f31fb343042e3806b9806e8f7d]Powerful GOP allies propel Trump effort to reopen economy[/url][quote]The push to revive the economy is being influenced and amplified by a potent alliance of big money business interests, religious freedom conservatives and small-government activists, some with direct dial to Trump. They are gaining currency as a counter-point to the health professionals who warn of potentially deadly consequences from easing coronavirus stay-home restrictions too soon.[/quote]

[QUOTE=Dr Sardonicus;542815][URL="https://apnews.com/57f673f31fb343042e3806b9806e8f7d"]Powerful GOP allies propel Trump effort to reopen economy[/URL][/QUOTE]
Hey everyone dies sometime. A lot of you folks are probably on your last legs anyway, or will be once we put you back to making money for us and you can't distance.

[QUOTE]I agree that risk management is all about balancing various probabilities, and the costs of optional actions. But perhaps the balancing should be more towards taking actions which might be safer, even if it they turn out to not have been necessary.[/QUOTE]Just to reinforce what chalsall said, we might look at SARS, MERS, etc. as dodging bullets. Four or five, or more have just nicked us, RECENTLY, as in the last 90 years. Got hit pretty bad just over a hundred years ago, and the machine gun has a [I]very[/I] long belt. Dodging may be tiresome, but remember 1918 when we really took a hit. Also, per chalsall, collective memory doesn't extend much past the last commercial break, but some folks have longer memories, AKA History. Finally, we don't know if the 50 caliber gun we've been dodging has something bigger and badder behind it; but given the longer history the odds of something worse are pretty strong.

[QUOTE=Uncwilly;542795]A look at the years 2000, 2038, & 2100. And why disaster prevention success is misperceived by the general population.
[URL]https://www.flashforwardpod.com/2020/04/14/doomsday-2000-2038-2100/[/URL][/QUOTE]Great link.

One that may have caught my former employer unaware is while we were finishing Y2K preparation, a large costly DEC Printserver 20 network printer ceased working in September 1999, possibly 9/9/99. It was by then old and superseded by newer faster printers in the department, so not a priority to solve. [url]https://www.wired.com/2011/09/0909090999-not-computer-problem/[/url]

Some forward thinking folks are already running into the Y10K problem. [URL]https://en.wikipedia.org/wiki/Year_10,000_problem[/URL]

[QUOTE=kladner;542835]Just to reinforce what chalsall said, we might look at SARS, MERS, etc. as dodging bullets. Four or five, or more have just nicked us, RECENTLY, as in the last 90 years. Got hit pretty bad just over a hundred years ago, and the machine gun has a [I]very[/I] long belt. Dodging may be tiresome, but remember 1918 when we really took a hit. Also, per chalsall, collective memory doesn't extend much past the last commercial break, but some folks have longer memories, AKA History. Finally, we don't know if the 50 caliber gun we've been dodging has something bigger and badder behind it; but given the longer history the odds of something worse are pretty strong.[/QUOTE]
There is also the pandemic I mentioned a few posts back, whose declaration as such was a long time a-comin'. I was [i]not[/i] referring to COVID-19.

[QUOTE=kladner;542835]Finally, we don't know if the 50 caliber gun we've been dodging has something bigger and badder behind it; but given the longer history the odds of something worse are pretty strong.[/QUOTE]

While there isn't sentience behind this kind of thing, it isn't to a virus's evolutionary advantage to kill its host (at least, not too quickly). Not to say there won't be a "bug" (no joke intended) which results in the elimination of both the virus and the hosts.

[QUOTE=Dr Sardonicus;542865]There is also the pandemic I mentioned a few posts back, whose declaration as such was a long time a-comin'. I was [I]not[/I] referring to COVID-19.[/QUOTE]
Oops. My bad. What was the intent?

Some rural areas near metropolises have high per capita Covid19 rates. My guess is due to shopping and commuting patterns. (It's not unusual for rural couples to have at least one city job with employment-related health insurance coverage. This is common on farms, for example; husband farms full time, wife works in a nearby city, perhaps in health care.) [URL]https://www.scientificamerican.com/article/map-reveals-hidden-u-s-hotspots-of-coronavirus-infection/[/URL]

Current state of knowledge summary on COVID19 treatment [URL]https://www.scientificamerican.com/article/heres-what-we-know-about-the-most-touted-drugs-tested-for-covid-19/[/URL]

Manufacturing antibodies [URL]https://www.globenewswire.com/news-release/2020/03/30/2008438/0/en/GigaGen-Initiates-Development-of-Recombinant-Polyclonal-Antibody-Therapy-for-COVID-19.html[/URL]

EIDD2801: [URL]https://finance.yahoo.com/news/ridgeback-biotherapeutics-drug-innovations-ventures-205900313.html[/URL]

[QUOTE=kriesel;542870]Some rural areas near metropolises have high per capita rates. My guess is due to shopping and commuting patterns.[/QUOTE]Andorra has a remarkably high per capita rate. Last I heard it was 33 deaths in a population of 77000.

My guess is due to shopping patterns.

[QUOTE=xilman;542873]Andorra has a remarkably high per capita rate. Last I heard it was 33 deaths in a population of 77000.

My guess is due to shopping patterns.[/QUOTE]Population density seems to be a factor. Andorra at 466 persons/sq mile, 180/sq km is quite high population density compared to American rural areas. Compare to say 19/sq mile [URL]https://en.wikipedia.org/wiki/Buffalo_County,_Wisconsin[/URL]
Looking at some of the 72 individual counties in Wisconsin, per capita rate increases with density.
Milwaukee County at 3800/sq mile has less than 1/5 the state's population but the majority of the state's Covid19 cases. Most counties have considerable local variation in population density; farmland is much less dense population than even villages and unincorporated settlement areas. Zoning laws formalize the population density variation even in rural areas. One side of a road might be a house per 2 acres, while the other side might be a house per 35 acres or more, for preservation of cropland. Due to nonlinearity, the higher density areas will determine the outcome.

[QUOTE=kriesel;542876]Population density seems to be a factor.[/QUOTE]True, but perhaps you are not aware of two significant characteristics of Andorra.

First, it is a tax haven where Spaniards traditionally hide their wealth.
Second, it attracts very large numbers of shoppers from both Spain and France because its low tax rates lead to much lower prices than are generally available in the surrounding countries. I've heard Andorra being described as being just one large supermarket.

[URL="https://www.bbc.co.uk/news/uk-england-beds-bucks-herts-52303859"]WWII vet raises >£15M[/URL]

Very impressive!

Nonetheless the NHS is such a big organization that that sum corresponds to less than £10 per employee. The NHS employs roughly 1.7M people. The annual budget is roughly 140 gigaquid, so £15M corresponds to about 1 hour's expenditure.

[QUOTE=kriesel;542876]Population density seems to be a factor. Andorra at 466 persons/sq mile, 180/sq km is quite high population density compared to American rural areas.[/QUOTE]There are two main factors involved with the spread of the virus:[LIST=1][*]How dense the population is.[*]How dense the population is.[/LIST]

[QUOTE=Uncwilly;542898]There are two main factors involved with the spread of the virus:[LIST=1][*]How dense the population is.[*]How dense the population is.[/LIST][/QUOTE]

No - especially in a non-open-borders context (e.g. islands like Iceland or 'hermit' states like North Korea), you also need to account for inital-seeding effects. An example:

[url=https://www.nature.com/articles/d41586-020-00502-w]Pick of the coronavirus papers: Ski buffs helped to seed coronavirus in Iceland[/url] | Nature
[quote]Holidaymakers returning from ski trips to the Alps helped to bring the coronavirus to Iceland.

In late January, Kari Stefansson at deCODE Genetics-Amgen in Reykjavik and his colleagues began testing for SARS-CoV-2 among Iceland residents at high risk of exposure to the virus, such as travellers to China (D. F. Gudbjartsson et al. N. Engl. J. Med. [url]http://doi.org/ggr6wx;[/url] 2020). Some 13% of the 9,199 people tested by early April were infected. The team sequenced viral RNA from people who tested positive and found that some of the strains had probably originated in Austria or Italy, which both have Alpine ski resorts.[/quote]
Tracing one of those links further back, it appears the initial seeding in Northern Italy involved close China links there among its famous garment and fashion industry, which in recent decades has both moved much production to China and also increasingly relied on cheap guest-worker labor from there. And on the ski-buff angle, I recall in 3rd week of February watching TV broadcasts from the [url=https://en.wikipedia.org/wiki/2019%E2%80%9320_Biathlon_World_Cup]2019-2020-season Biathlon World Cup[/url] in the South Tyrolean (officially Northern Italy since end of WW1, but still nearly 100% German-speaking) ski resort of Antholz/Anterselva, so that probably caused a significant spread across the then-still-open northern border to Austria proper.

In the US, the Washington-state regional outbreak has been traced back to a single initial returning traveler from Wuhan.

Again using my (admittedly imperfect) fissile-material analogy, population density is like % enrichment, but even a supercritical lump of U235 or Pu239 needs one or more "Initial seed" neutrons to start the chain reaction. Larger countries with open borders, that is of coures more less guaranteed, but the seeding aspect is still useful in explaining local outbreaks and hotspots.

[QUOTE=kladner;542869]Oops. My bad. What was the intent?[/QUOTE]
I was thinking of AIDS. WHO doesn't officially call it a pandemic, but a "global epidemic," so [i]my[/i] bad.

I have frequently seen it referred to as a "pandemic" in recent years, however. To date, it has killed something like 30 million people worldwide, and around 700,000 people in the US.

Fortunately, it has become relatively manageable. In the early years it was running rampant and had a high mortality rate. In the 1990's it was killing around 50,000 a year in the US. Now it's down to around 12,000.

[QUOTE=Uncwilly;542898]There are two main factors involved with the [B][COLOR="Red"]spread[/COLOR][/B] of the virus:[LIST=1][*]How dense the population is.[*]How dense the population is.[/LIST][/QUOTE]

[QUOTE=ewmayer;542902]No - especially in a non-open-borders context (e.g. islands like Iceland or 'hermit' states like North Korea), you also need to account for inital-seeding effects.[/QUOTE]I stand by my statement. The spread in any given population (of a given contagious substance) happens from a condition that starts it. So, however the population gets it initially, the spread is mainly a factor of the the 2 conditions that I stated. If it comes from Mohamed Lee eating the brains of sea cucumber or is delivery to Johan Garcia nasally by an alien UFO probe, the 2 conditions are the main factors of how it spread in that population, as opposed to a different population.

Your arguments support my point #2.

You make a good point, that AIDS [I]should[/I] be (or have been) considered a pandemic.

The 80s were the nightmare years in the Chicago gay community. Most of the friends of my age who contracted HIV probably did so around 1983, before it was really recognized or understood. Many of those friends succumbed. Only one that I know of from that era has survived. Bob was being treated early enough that he has permanent peripheral neuropathy in his legs from AZT. He lost his partner many years back. Whereas Bob is rigid in his medication schedule, Scott did not take his meds. Perhaps he had worse side effects. I can't remember now.

I attribute my escape to hangups and inhibitions which kept me from joining the bacchanalia around me wholeheartedly.

The theories that flew about then as to the cause of the illness in gay men included semi-plausible things like the use of poppers (Nitrate inhalants), and more far-fetched things like specific kinds of sex lubricants (mentholated "hot lube".)

I appreciate that you made that observation Dr S. It triggered a realization of how much I have discounted or buried the full impact of HIV/AIDS.

Please read a dictionary and don't trust your gut on pandemic vs. epidemic.
[url]https://www.medicinenet.com/script/main/art.asp?articlekey=4751[/url]
Or check the CDC
[url]https://www.cdc.gov/flu/pandemic-resources/basics/past-pandemics.html[/url]

[QUOTE=Uncwilly;542911]Please read a dictionary and don't trust your gut on pandemic vs. epidemic.
[URL]https://www.medicinenet.com/script/main/art.asp?articlekey=4751[/URL]
Or check the CDC
[URL]https://www.cdc.gov/flu/pandemic-resources/basics/past-pandemics.html[/URL][/QUOTE]
I don't think the links exclude HIV/AIDS. It may have been slower moving, or not immediately identified, but it is worldwide and had a very high death rate before drugs were developed to treat it. It still does for people without access to medication. Being called The Gay Plague greatly suppressed awareness and delayed research, especially in the US where Ronnie Raygun didn't give a tinker's damn about queers, except maybe for some of his Tinsel Town buddies.

The second link is specific to influenza and thereby implies that the only pandemics are from flu.

[QUOTE=Uncwilly;542911]Please read a dictionary and don't trust your gut on pandemic vs. epidemic.
[url]https://www.medicinenet.com/script/main/art.asp?articlekey=4751[/url]
Or check the CDC
[url]https://www.cdc.gov/flu/pandemic-resources/basics/past-pandemics.html[/url][/QUOTE]
Firstly, my basic point was, AIDS is definitely a serious disease. And it hadn't been mentioned in this discussion. I thought it merited a place.

IMO it was officially disregarded, at least in the USA, because of political/religious ideology, and so became much worse that it needed to.

In the late 1980's a book by San Francisco [i]Chronicle[/i] journalist Randy Shilts entitled [u]And the Band Played On[/u] had this theme. The jacket claimed, "the epidemic spread widely because the federal government put budget ahead of the nation's welfare; health authorities placed political expediency before the public health; and scientists were more often more concerned with international prestige than saving lives."

Does that sound familiar?

One public figure who distinguished himself during the Reagan Administration was US Surgeon General C. Everett Koop. He put his public-health duty above religious/political dogma.

Why you would wish to sidetrack my basic point by, apparently, trying to incite a squabble about dictionary definitions is beyond me.

But to address your hairsplitting objection:

I didn't "trust my gut." As I wrote in my post, I'd read AIDS being called a pandemic numerous times in recent years.

Want me to check the CDC? OK, how about this (my emphasis)? [url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5531a1.htm]The Global HIV/AIDS [b]Pandemic[/b], 2006[/url]

Or, how about the New England Journal of Medicine? [url=https://www.nejm.org/doi/full/10.1056/nejmp068074]The HIV–AIDS [b]Pandemic[/b] at 25[/url]

The WHO calls AIDS/HIV an epidemic.
[url]https://apps.who.int/iris/handle/10665/79079[/url]

And it is not listed here, where they still list smallpox (extinct), and MERS, and SARS (which are basically gone).
[url]https://www.who.int/emergencies/diseases/en/[/url]

[url=https://apnews.com/599338c54097ab68a1f2eda09c2d8a3b]China's virus death toll revised up sharply after review[/url][quote]BEIJING (AP) — China's official death toll from the coronavirus pandemic jumped sharply Friday as the hardest-hit city of Wuhan announced a major revision that added nearly 1,300 fatalities.

The new figures resulted from an in-depth review of deaths during a response that was chaotic in the early days. They raised the official toll in Wuhan by 50% to 3,869 deaths. While China has yet to update its national totals, the revised numbers push up China's total to 4,632 deaths from a previously reported 3,342.

The higher numbers are not a surprise — it is virtually impossible to get an accurate count when health systems are overwhelmed at the height of a crisis — and they confirm suspicions that many more people died than the official figures had showed.

The undercount stemmed from several factors, according to a notification issued by Wuhan's coronavirus response headquarters and published by the official Xinhua News Agency.

The reasons included the deaths of people at home because overwhelmed hospitals had no room for them, mistaken reporting by medical staff focused on saving lives, and deaths at a few medical institutions that weren't linked to the epidemic information network, it said.[/quote]

[QUOTE=Uncwilly;542931]And it is not listed here, where they still list smallpox (extinct), and MERS, and SARS (which are basically gone).
[URL]https://www.who.int/emergencies/diseases/en/[/URL][/QUOTE]Smallpox is eradicated, but not yet extinct, since the Russians and apparently the US are still holding samples. A test of some American samples before they were destroyed showed stored samples could be viable for ~60 years or more.
There is also the possibility that it could be recreated in a lab.
[url]https://en.wikipedia.org/wiki/Smallpox_virus_retention_debate[/url]
[url]https://www.ph.ucla.edu/epi/bioter/CDCracingsmallpoxgenome.html[/url]

In the plethora of online references about pandemics, [url=https://academic.oup.com/jid/article/200/7/1018/903237]this one[/url] got my attention because of one of the author's names, which I have emphasized in the biblio:

What Is a Pandemic?
David M. Morens, Gregory K. Folkers, [b]Anthony S. Fauci[/b]
The Journal of Infectious Diseases, Volume 200, Issue 7, 1 October 2009, Pages 1018–1021, [url]https://doi.org/10.1086/644537[/url]
Published: 01 October 2009

The article gives eight features of pandemics:

Wide geographic extension, Disease movement, High attack rates and explosiveness, Minimal population immunity, Novelty, Infectiousness, Contagiousness, and Severity

HIV/AIDS is listed under three of these: Wide geographic extension, Novelty (at the time of its emergence in the 1980's), and Severity.

[QUOTE=Uncwilly;542911]Please read a dictionary and don't trust your gut on pandemic vs. epidemic.[/QUOTE]

You want me to read a dictionary? Alrighty then!

My old Merriam-Webster unabridged defines an [i]epidemic[/i] as [quote]A rapidly spreading or widely prevalent attack of disease.[/quote] It defines the [i]adjective[/i] "pandemic" as [quote]Of or pertaining to all the people; vulgar; general; universal; specif., [i]Med[/i]., affecting the majority of people in a country or a number of countries; everywhere epidemic.[/quote]It then defines the [i]noun[/i] pandemic as "A pandemic disease."

I'm not sure even COVID-19 would qualify as affecting a [i]majority[/i] of people in any country, but it is certainly epidemic in many places at once, so close enough to "everywhere epidemic."

WHO categorizes HIV/AIDS as a "global epidemic." This seems to fit nicely with the description "everywhere epidemic" in the above dictionary definition of [i]pandemic[/i].

However, HIV/AIDS may no longer be as rapidly spreading in many areas as the term [i]epidemic[/i] usually connotes. It would seem to qualify, however, as "widely prevalent."

[QUOTE=Uncwilly;542898]There are two main factors involved with the spread of the virus:[LIST=1][*]How dense the population is.[*]How dense the population is.[/LIST][/QUOTE]

There is the population density, and the density of the skulls in the population. From what I see around me, the latter is quite dominant.

I see many people wearing masks. There appears to be a misconception. I believe they feel protected from COVID-19 if they wear them. Only an N95 rated mask can do that, supposedly. My sister works at the local hospital and must wear one on each of her 12-hour shifts. From what I gather, they are very tight-fitting making them uncomfortable to wear.

I have read articles in the past few weeks which indicate this virus may have gotten here as early as late November of 2019, in a slightly different form. I picked up a really nasty bug back in January. I had a low-grade fever for two weeks and coughed so much that I felt I had pulled every muscle in my abdomen. I feared I would actually crack a rib. They were extremely sore. After two doctor visits and two rounds of different antibiotics, I began to feel better. The recovery has been slow, and continues, even now. I am 64 and I am sure this plays a role.

Did I have COVID-19, or a close variant? Perhaps. The antibiotics would not have done anything for it, but it would have takes care of the other problems. This may have allowed me to recover on my own. All I really know is that I [U]do not[/U] want to catch it again.

Regarding your January experience, did you have head or body aches? Crazy-making headaches are frequently reported.
EDIT: From the front page of the Guardian:
[QUOTE]Andrew Cuomo criticized Trump after the president lashed out against the New York governor in a tweet. In response to Trump’s suggestion that Cuomo should “spend more time ‘doing’ and less time ‘complaining,’” the governor said, “If he’s sitting home watching TV, maybe he should get up and go to work.” Cuomo went on to offer some of his harshest criticism of Trump since the start of the current crisis.

Cuomo’s comments represented some of his harshest criticism of Trump since the start of the crisis. The Democratic governor has generally tried to avoid getting involved in fights with Trump to protect New York’s relationship with the federal government, but Cuomo said the president was asking to be thanked for merely doing his job. “This was your role as president,” Cuomo said.

Cuomo demanded more funding for states, as governors have received the bulk of responsibility for reopening. The governor said the federal government could not expect states to take on so many duties without giving them additional funding. “That is passing the buck without passing the bucks,” Cuomo said.[/QUOTE]

[QUOTE=kriesel;542952]Smallpox is eradicated, but not yet extinct, since the Russians and apparently the US are still holding samples. A test of some American samples before they were destroyed showed stored samples could be viable for ~60 years or more.
There is also the possibility that it could be recreated in a lab.[/QUOTE]Not a possibility so much as a certainty. The complete genome is on file.

[QUOTE=storm5510;542954]<snip>
I picked up a really nasty bug back in January. I had a low-grade fever for two weeks and coughed so much that I felt I had pulled every muscle in my abdomen. I feared I would actually crack a rib. They were extremely sore. After two doctor visits and two rounds of different antibiotics, I began to feel better. The recovery has been slow, and continues, even now. I am 64 and I am sure this plays a role.

Did I have COVID-19, or a close variant? Perhaps. The antibiotics would not have done anything for it, but it would have takes care of the other problems. This may have allowed me to recover on my own. All I really know is that I [U]do not[/U] want to catch it again.[/QUOTE]
I had a nasty cold this past winter, that began Christmas Eve with a sore throat. By Christmas Morning the sore throat had been joined by other symptoms: upper-respiratory congestion, runny nose, slight body aches, greatly impaired sense of taste, and the headachy, head-stuffed-with-wet-feathers, mentally zombified sensations I associate with having a low-grade fever.

My sense of taste was pretty much gone, but I could still experience the burn of my favorite hot sauce. (It's not nearly as hot as some, but at well over 11,000 Scoville units, it's hot enough to get most folks' attention. I've had colds that killed my sense of taste so dead, even a goodly dollop of that stuff didn't cause any sensation in my mouth or throat.)

Mucus dripping down my throat added a tickling sensation to the soreness, provoking some dry coughing. I fought back with highly mentholated cough drops, which I always keep on hand. They killed off the throat tickling well enough that I was able to sleep.

One night I experienced the unpleasant sensation of having one of my nostrils swell shut. After some time it would re-open, whereupon the [i]other[/i] nostril would swell shut. That grew old real quick. It also interfered with sleeping. At least I was glad my nostrils didn't [i]both[/i] swell shut at the same time!

Christmas dinner went out the window. My symptoms gradually abated over a week and a half or so -- a bit longer than the usual run of a week or less for colds. I was generally lacking in pep for quite some time after that. I was pretty much back to normal by Super Bowl Sunday.

Whatever it was, I know a [i]lot[/i] of people in my area had it around the same time. At least one of them had that persistent chest-racking dry cough, so couldn't sleep, and just wasn't recovering like most folks were. Finally, a pharmacist recommended an OTC long-acting cough suppressant, and that did the trick. It silenced the cough, allowing sleep, and recovery soon followed.

Sorry, I'm not buying the various "I had a nasty ___ last Nov/Dec and now I'm sure it was Covid-19" anecdotes. There were several nasty seasonal-flu strains that began circulating last Fall, and given the known high infectivity of the Covid-19-causing virus and attendant lethality in especially vulnerable subgoups (e.g. nursing-home patients), had the virus reached the US before February, there would have been mass outbreaks. Hello? NYC hospitals over the past month, anyone? So, please - before peddling "there's a reason they're called 'flu-like symptoms'" anecdotes and claiming Covid-19 - show us a reliable antibody test, either from you or the elderly relatives you infected and whse deaths you caused, confirming the claim. You think no one's ever been "sick and feeling like death" due to seasonal flu or any of the other cold-and-flu-season-typical bugs?

[QUOTE=ewmayer;542981]Sorry, I'm not buying the various "I had a nasty ___ last Nov/Dec and now I'm sure it was Covid-19" anecdotes. [.......]
You think no one's ever been "sick and feeling like death" due to seasonal flu or any of the other cold-and-flu-season-typical bugs?[/QUOTE]

This. :tu:
I've had a few otherwise-intelligent friends claim the same thing. Seems the human-nature "I was there first" brag draws stronger than actual evidence. Some of those very-same people that railed on folks for calling Covid "just a really bad flu, stop panicking" are now making the connection that a really bad flu must have been Covid.

[QUOTE=ewmayer;542981]Sorry, I'm not buying the various "I had a nasty ___ last Nov/Dec and now I'm sure it was Covid-19" anecdotes.
<snip>
You think no one's ever been "sick and feeling like death" due to seasonal flu or any of the other cold-and-flu-season-typical bugs?[/QUOTE]

Just to be clear: I don't think what I had was COVID-19. Like I said, whatever it was, a [i]lot[/i] of people in my area had it. It was just whatever was "going around" at the time. Nowhere near as serious as the flu.

I've had the flu more than once. The worst by far was the Hong Kong flu (late 1968). Fever of 102, terrible headache, body aches, barely able to totter across the hall to pee, in the twilight zone when I was supposedly conscious.

I've had run-of-the-mill seasonal flu a couple of times since then. Both times I developed laryngitis and could barely speak. One time it was followed by green-phegm bronchitis that had me on antibiotics. Both times it was way worse than whatever I had this past winter, but much less bad than the Hong Kong flu.

I've gotten my flu shot every year for a number of years. Haven't had the flu since. The first couple of times I had a very minor reaction, felt like I was coming down with a slight cold, cleared up within a day. Compared to getting the flu, insignificant.

[QUOTE=Dr Sardonicus;542953]What Is a Pandemic?
David M. Morens, Gregory K. Folkers, [b]Anthony S. Fauci[/b]
The Journal of Infectious Diseases, Volume 200, Issue 7, 1 October 2009, Pages 1018–1021, [url]https://doi.org/10.1086/644537[/url]
Published: 01 October 2009

The article gives eight features of pandemics:

Wide geographic extension, Disease movement, High attack rates and explosiveness, Minimal population immunity, Novelty, Infectiousness, Contagiousness, and Severity
[/QUOTE]
High attack rates and explosiveness.
That is where AIDS fails.
In the USA it took 4 years to go from basically 0 cases to 10,000 cases. COVID-19 did that in less than 2 months. Jan 22-March 18. It peaked ~11 years later at about 65,000 ([URL="https://www.researchgate.net/figure/Number-of-acquired-immunodeficiency-syndrome-AIDS-cases-by-major-transmission-category_fig1_281611405"]source[/URL]), COVID did that in 2 months and 3 days (CDC [URL="https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html"]source[/URL]) .

The USA government's own site about HIV calls it an epidemic:
[url]https://www.hiv.gov/federal-response/ending-the-hiv-epidemic/overview[/url]

Population sampling in Santa Clara County California indicates prevalence far higher than confirmed cases would indicate; 50-85 TIMES. [URL]https://www.medrxiv.org/content/10.1101/2020.04.14.20062463v1[/URL]

Major League Baseball of the USofA will be getting most employees tested. From janitorial staff to the executive suite. 10,000 people. That should be a useful data set.
[url]https://www.npr.org/sections/coronavirus-live-updates/2020/04/15/834946026/major-league-baseball-joins-the-fight-against-coronavirus-in-a-big-way[/url]

[QUOTE=Uncwilly;543000]High attack rates and explosiveness.
That is where AIDS fails.[/QUOTE]
And those are traditionally -- and also presently -- criteria for what constitutes an epidemic. They fit perfectly with the dictionary definition I quoted. So, you're saying AIDS is [i]not[/i] an [i]epidemic[/i] disease. Fair enough...

[QUOTE=Dr Sardonicus;543013]And those are traditionally -- and also presently -- criteria for what constitutes an epidemic. They fit perfectly with the dictionary definition I quoted. So, you're saying AIDS is [i]not[/i] an [i]epidemic[/i] disease. Fair enough...[/QUOTE]
No agency wants to set a data driven definition of epidemic or pandemic. Because if they do, then if something doesn't hit the marks, a segment of the population will complain. But, if something hit the marks and the agency does hit the marks that means they are obligated to act certain was. Just like politicians try to avoid using the "G" word when discussing ethnic cleansing. Once they say that something is it, then they are obligated to respond. Find me a data delineated definition of pandemic and epidemic. We can then discuss if 0.5% of a population or 0.75% or 3% or 0.01% is a good threshold.

[COLOR="DarkRed"][B]Do you not accept that the US Government on their own website about HIV calls it an epidemic not a pandemic?[/B][/COLOR]
Isn't that a location that should call it a pandemic if it is one?
As noted in the link that you provided, the terms pandemic and epidemic get used for things that are not biologically contagious. In the scientific realm the terms get misapplied, but less so than in the general media (in the broadest sense.)

It is because of 'political' (in the broad sense) reasons that HIV gets labeled by some as a pandemic. It is also because of 'political' reasons that it did not get a more comprehensive effort early on.

In [B][U]December of 2018[/U][/B] the WHO called it an epidemic.
[url]https://www.who.int/hiv-aids/latest-news-and-events/why-the-hiv-epidemic-is-not-over[/url]

[quote=Uncwilly;543020][color=darkred][b]Do you not accept that the US Government on their own website about HIV calls it an epidemic not a pandemic?[/b][/color][/quote]
I would say, you make an excellent case that AIDS is not an epidemic disease. No rapid spread, not a high "attack rate" -- hey, makes perfect sense.

And, not being epidemic, it can't be pandemic.

And I certainly can't accept "official" designations of AIDS being, on the one hand, "epidemic," but on the other, [i]not[/i] "pandemic." If one posit that it be epidemic, then it's epidemic in a whole [i]lot[/i] of widely separated countries, and so, practically by definition, consequently pandemic.

The WHO designation of AIDS as not just an epidemic, but a [i]global[/i] epidemic -- but [i]not[/i] a pandemic -- is IMO raving lunacy. "Global epidemic" is practically a [i]definition[/i] of pandemic.

There is an unusual aspect to AIDS, that people don't "get over" it. Once infected, always infected. So the number of cases keeps going up. Without effective management with antiviral drugs, the outlook would be bleak for most who get infected. Some people seem to have a natural capacity for keeping the virus at bay -- it seems the trait that protected people from the Bubonic Plague has served their descendants in good stead with HIV.

[quote]As noted in the link that you provided, the terms pandemic and epidemic get used for things that are not biologically contagious.[/quote]
High attack rate and explosive spread -- the hallmarks of an epidemic disease -- do not require contagiousness. I have no problem with non-contagious diseases that meet those criteria being designated "epidemic," or, if epidemic in enough places, "pandemic."

Cholera, AKA the Bengal Plague, has met these criteria a number of times (and there were cholera "pandemics" in the Nineteenth Century), even though it is usually contracted from contaminated water. The "Black Death" in the Fourteenth Century certainly met the criteria, but was largely transmitted by flea bites. Flea-transmitted plague also appears as an epidemic disease in prairie dogs. Whole colonies are often annihilated in short order.

(Bubonic Plague [i]can[/i] become contagious, if it gets to the lungs, in which case it is called "Pneumonic Plague." Then it can be transmitted person-to-person like the common cold. Nowadays, there are sometimes isolated cases of people contracting Pneumonic Plague from their pets, which got plague from an infected animal, or hungry fleas that abandoned an animal that died of plague.)

Another vector-borne epidemic disease is "epidemic typhus," for which the vector is body lice. My dad told me about an epidemic of typhus in Europe around the end of WWII that was stopped "right now" with the use of a new insecticide, DDT. I've never heard of a "pandemic" of typhus, though.

There is another designation that seems to fit HIV/AIDS better than "epidemic," namely [i]endemic[/i]. It is certainly persistently present in the areas where it originated, and now in other areas also (though my old dictionary distinguishes "endemic" from "introduced" or "naturalized").

An endemic disease can have high incidence without being epidemic. Perhaps the best-known instance is malaria. The most recent figures I've seen are for 2018, stating there were 228 million cases and 405,000 deaths from malaria that year.

[quote]It is because of 'political' (in the broad sense) reasons that HIV gets labeled by some as a pandemic. It is also because of 'political' reasons that it did not get a more comprehensive effort early on.[/quote]I'll buy that!

AIDS also had the stigma of being considered a "lifestyle choice", rather than just a normal-daily-activities infection route. So intravenous drug users, and other ways of getting blood transfer (wild animal bites, etc), weren't considered "normal", so the response was mostly "tough, sucks for you to have made those choices".

It isn't a pleasant way to treat people with the infection, but that is human nature. Naturally, in these enlightened times we no longer think that. Nowadays we have drug companies realising the lucrative market for treatment income, and people can get treated in the open, if they have the funds.

Federalism has become another casualty of Trump and the coronavirus

Hmm. Federalism replaced by Feudalism. Or maybe Neoliberalism replaced by Neofeudalism.
[URL]https://www.theguardian.com/commentisfree/2020/apr/18/federalism-another-casualty-donald-trump-coronavirus[/URL]
[QUOTE]Many American institutions and traditions have been challenged in the era of Donald Trump. The latest is federalism, the idea that power should be shared between the federal government and the states. The president’s response to the coronavirus epidemic has had a curious impact, overturning the historical preferences of both parties. Put simply, coronavirus has meant federalism for Democrats who have been abandoned in the face of the pandemic, and slavish devotion to federal authority for Republicans.[/QUOTE][QUOTE]The particular way that Trump exercises power has also contributed to the reaction of governors from both parties. Trump has made clear that he will dole out federal largesse according to political loyalty, even preventing Colorado’s Democratic-led government from purchasing ventilators on the open market and later sending a hundred units “[URL="https://www.vox.com/2020/4/10/21215578/trump-ventilators-coronavirus-cory-gardner-colorado-jared-polis-patronage"]at the request[/URL]” of the state’s Republican senator, who is facing a tough re-election battle. The message is clear: Democratic governors need to help themselves, because Trump sure won’t. And Republican governors need to stick close to a president who sees himself as his party’s feudal patron rather than the leader of the entire nation.[/QUOTE]

In Massachusetts multiple anonymous testing methods indicate Covid19 spread there was far greater than indicated from case count and testing of symptomatic people.

Blood test launched early April on random sample [URL]https://www.bostonherald.com/2020/04/05/massachusetts-lab-launches-coronavirus-antibody-test/[/URL]
32% of randomly sampled people on the street tested positive for Covid19 antibodies
[URL]https://www.foxnews.com/science/third-blood-samples-massachusetts-study-coronavirus[/URL]

Estimates of those that are or have been infected based on sewage system sampling for Covid19 RNA content are far higher than known cases count [URL]https://www.newsweek.com/coronavirus-traces-massachusetts-wastewater-levels-higher-expected-1497141[/URL]

[QUOTE=Dr Sardonicus;543022]High attack rate and explosive spread -- the hallmarks of an epidemic disease -- do not require contagiousness.[/QUOTE]

Yes, they do, and every example you went on to give demonstrated this - perhaps you meant 'contagiousness' in the narrow sense of intraperson transmission, but that is not required to meet the definition of 'epidemic', which simply connotes 'widespread in a population', both in its modern sense and in its Greek-language roots. Vectors come in many forms - contaminated water for cholera, infected fleas for bubonic plague, mosquitoes for malaria, etc. Covid-19 is especially nasty in this regard in that the vector need not even be a living thing - surfaces that have been touched by an infectee, often days previously. Unlike contaminated water, that is *really* hard to guard against - see my link to [i]The Age[/i] story in my followup post below.

Re. smallpox, as Paul notes, with the gene sequence in hand, any world-class biolab can reconstitute the viral genes. Going back further, there are still reservoirs of the 1918 flu virus with recoverable gene sequences - from the editorial intro to an article in the 7 Oct 2005 issue of [i]Science[/i], "Resurrected Influenza Virus Yields Secrets of Deadly 1918 Pandemic":
[quote]As worries about a new flu pandemic mount, researchers have figured out the traits that made the 1918 influenza virus, which killed between 20 million and 50 million people, so virulent. Although a study on page 77 sheds new light on these questions, it raises a host of others because the researchers reconstructed the complete virus, which no longer existed anywhere on earth.

The team resurrected the 1918 pandemic virus by using gene sequences fished from a 1918 victim. The virus is as lethal as expected, killing mice more quickly than other human flu virus known ... the research grows out of [US Armed Forces Institute of Pathology] pathologist Jeffrey Taubenberger's efforts, begun in 1995, to sequence the genome of the 1918 flu virus. Working mainly with tissue from a victim found in permafrost in Alaska, he and others have been piecing together the virus's eight genes and characterizing their protein products.

Last year, this wor revealed the structure of the 1918 hemagglutinin (HA), the crucial surface protein that flu viruses use to latch onto host cells ([i]Science[/i], 9 March 2004, p.1866); in a separate study, Yoshihiro Kawaoka's group at the University of Wisconsin, Madison, showed that a virus containing this HA was unusually potent. This week in [i]Nature[/i], Taubenberger's group publishes the sequences of the last three genes, which together encode the virus's polymerase, the machinery for virus replication.

With those final sequences in hand, Peter Palese's team at Mount Sinai [Schoold of Medicine in New York City] then stitched the eight 1918 genes into a regular flu virus genome contained within bacterial DNA. They shipped those inert plasmids to [lead author Terrence] Tumpey at CDC, who inserted them into cells to make live virus.[/quote]

o Example of local-outbreak-cluster beginning with a single seeding event, this via a friend Down Under: [url=https://www.theage.com.au/national/victoria/a-lecture-a-textbook-an-illness-like-no-other-inside-a-melbourne-covid-cluster-20200416-p54kgo.html]A lecture, a textbook, an illness like no other: Inside a Melbourne COVID cluster[/url] | The Age

o And a long-but-worthwhile discussion of vaccine prospects and expected timelines -- I quote the full text because the layout was completely unreadable in my older version of FF, so I had to go to the html source to find the article text in semi-readable form:

[url=https://blogs.sciencemag.org/pipeline/archives/2020/04/15/coronavirus-vaccine-prospects]Coronavirus Vaccine Prospects[/url] | In the Pipeline | Science Magazine
[quote]Time for another look at the coronavirus vaccine front, since we have several recent news items. [url=https://www.statnews.com/2020/04/14/glaxosmithkline-sanofi-coronavirus-vaccine-collaboration/]Word has come[/url] from GSK and Sanofi that they are going to collaborate on vaccine development, which brings together two of the more experienced large organizations in the field. It looks like Sanofi is bringing the spike protein and GSK is bringing the adjuvant (more on what that means below). Their press release says that they plan to go into human patients late this year and to have everything ready for regulatory filing in the second half of 2021. For its part, Pfizer [url=https://www.statnews.com/2020/04/09/pfizer-coronavirus-testing-fall/]has announced[/url] that they're pushing up their schedule with BioNTech and possibly starting human trials in August, which probably puts them on a similar timeline for eventual filing.

"But that's next year!" will be the reaction of many who are hoping for a vaccine ASAP, and I can understand why. The thing is, that would be absolutely unprecedented speed, way past the current record set by the Ebola vaccine, which took about five years. More typical development times are ten years or more. But hold that thought while you peruse another news item today from J&J. They have an even more aggressive timeline proposed for their own vaccine work: they have already announced that they have a candidate, and they say that they plan first-in-human trials in September. Data will be available from those in December, and in January 2021 they say that they will have the first batches of vaccine ready for an FDA Emergency Use Authorization. Now [i]that[/i] is shooting for the world record on both the scientific and regulatory fronts.

So let's talk vaccine development, because everything is going to have to work [i]perfectly[/i] for any such timetable to be realized. [url=https://www.nature.com/articles/d41573-020-00073-5]Here's a good overview[/url] of the coronavirus vaccine world in [i]Nature Reviews Drug Discovery. [/i]The official WHO list is [url=https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus-landscape-ncov.pdf]here[/url], and at BioCentury they have constantly updated open-access summaries of the vaccines and other therapies that are in the clinic and the ones that are still preclinical. They have also just published [url=https://www.biocentury.com/article/304919]this excellent overview[/url] of the vaccine issues; I recommend reading that one after you've picked up some background from this post.

[i]NRDD[/i] counts 115 (!) vaccine programs, of which 37 are unconfirmed (no further information available on them) and 78 are definitely real. Of those 78, five of them are in the clinic, although that number will be climbing rapidly. You have Moderna's mRNA1273, which as the name tells you is an mRNA candidate, and Inovio's INO4800, which is a DNA plasmid, There are two cellular candidates from Shenzhen Geno-Immune Medical Institute: LV-SMENP-DC, a dendritic cell vaccine that's been modified with lentivirus vectors to express viral proteins, and an artificial antigen-presenting cell (aAPC) vaccine along the same lines. And finally there's a more traditional protein-fragment vaccine, Ad5-nCoV from CanSino.

Let's go into what all those mean. You will note the diversity of approaches in that list, and that's not even the whole spread. When you go back into the preclinical candidates, you have in addition "virus-like particles", viral vectors, both replicating and non-replicating, live attenuated viruses, inactivated viruses, and more. From this you may deduce correctly that there are a lot of ways to set off the immune response. What are the differences between them?

[b]Types of Vaccines[/b]

For starters, "Live attenuated virus" is just what it sounds like, although as always there's room to argue about whether the word "live" should ever be used when talking about viruses at all. At any rate, this would be a real infectious virus that just doesn't give you much of a disease but does give you immunity to the wild-type virus. The smallpox, chickenpox, rotavirus, and MMR vaccines are all of this type, and they can be very effective -- in fact the most effective vaccines are mostly of this type. The protection comes on more quickly and completely, with less need for booster shots and with longer-lasting effects. The tricky part is developing one of those attenuated viruses in the range where it produces effective immunity on infection but is definitely [i]not[/i] effective at putting people in the hospital. There is a process of getting milder with time that happens with many viruses in general as they co-exist with their hosts, and the idea here is to [url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC136581/]speed that up[/url] in the lab by passaging the virus through human cells again and again and letting it mutate. Ideally, you want a strain that has ended up with a very long path to mutating back to virulence, of course!

The next class are the inactivated virus types. In that case, even if you think virii are alive (I don't), these are dead, having run down the curtain and joined the bleedin' choir invisible. This was originally done by exposing pathogen preparations to high temperatures, but now is often done by through nasty denaturing disinfectants like formalin or beta-propiolactone, things that alter the proteins enough to keep the virus from working, but perhaps not so much that they don't set off the right immune response. That's a bit of an art form, of course, and this generally has to be tried a number of times in order to get a reproducible immune response and a reproducible way to manufacture the inactive virus. As you would imagine administering a pile of disabled protein pieces in this manner is often not as effective as the live-virus approach above, which makes the human cells crank out viral proteins on their own. You're into big ol' injection plus booster shot territory for the most part. The hepatitis A vaccine and the seasonal flu vaccine are of this type.

Yet another common sort of vaccine uses just a particular protein, protein fragment or subunit piece of a pathogen. (For some bacterial diseases, you can also try to raise antibodies to some protein toxin that the bacteria produce, rather than to the bacteria themselves). The key is to pick one that provokes a strong immune response, and since there are a lot of possibilities, working through them can be a process all its own. The good part is that you can then produce the protein recombinantly and in quantity, once you've narrowed down. There are other possibilities, of course -- this could be a glycoprotein, or even just a piece of polysaccharide from an organism's outer coating, since those can be quite distinctive. The tricky part here is getting enough response -- the immune system can be very sensitive to pathogen attack, but these pathogen pieces can be less effective in triggering antibody production, and generally need adjuvants to work well (see below!) Vaccines of this class include the ones for shingles, hepatitis B, HPV, meningococcus, and more.

A more recent approach is a [url=https://en.wikipedia.org/wiki/DNA_vaccination]DNA vaccine[/url]. This uses a circular DNA plasmid, coding for some antigen protein, which has been engineered with strong promoter signals and stop signals at both ends of the sequence. The plan is that this will be taken up by cells, where the DNA may well then be transcribed into RNA and that then translated into protein, which sets off the immune response. A nice feature, as with the attenuated-virus technique, is that you're taking advantage of all the cellular machinery to make your antigen proteins for you, so they come out folded correctly and with the necessary post-translational modifications already done for you. If you want to really stack the deck for protein production, you can take a known virus (which doesn't have to be related to the pathogen you're vaccinating against) and re-engineer its nucleic acid payload to deliver just the piece you want. In that case, you're back into the "live attenuated virus" technique, but by sort of cobbling one together from different parts. This may sound pretty similar to gene therapy, which also generally uses viral vectors, and if so your intuition is right on target -- the two fields have had a lot to teach each other. There is no human vaccine yet that uses any DNA technique, although there is a Zika DNA vaccine for horses. Some candidates have been tried, but haven't elicited enough of a response. Another tricky part is stability of the DNA plasmid, both on storage and on injection, but these problems have had a lot of money poured into them from the gene therapy end, and the situation has improved over the years. Overall, though, I would say that a DNA vaccine for SARS-CoV2 would be a real come-from-behind story.

Similary, the [url=https://www.nature.com/articles/nrd.2017.243]mRNA vaccine idea[/url] has had a great deal of work put into it in recent years. That's conceptually similar to the DNA vaccine idea, only you're jumping in at the messenger RNA stage. I wrote a bit about it in [url=//blogs.sciencemag.org/pipeline/archives/2020/03/16/curious-case-of-curevac]the CureVac post[/url] -- basically, the immunogenicity was noticed as an unexpected side effect in experiments giving mRNA to animals, and people have gradually taken it from there. As with the DNA vaccines, you can actually get two kinds of immune response -- the innate immune system can recognize foreign nucleic acid sequences floating around as a sign of infection, and the adaptive immune system can generate antibodies to the resulting proteins. One of the challenges has been getting a bit less of the innate response and a bit more of the adaptive one (which is what counts for the long-term immunity that you want from a vaccine). The mention the other day of younger recovering Covid-19 patient who don't seem to have developed antibodies is an example of that very problem: a really robust innate response could clear the virus in an infected person, but leave them without much long-term immunity.

mRNA has some potential advantages over DNA, and (perhaps) over all the virus and protein techniques laid out above. It's pretty much the most stripped-down vector that you can imagine, so you don't run into so much immune-response-to-the-vector trouble, which can be a problem on repeat dosing with other vaccine technologies, and it can't possibly be inserted into the genome. A big problem over the years has been getting the mRNA species to last long enough on dosing, to be taken up into the cells efficiently, and to be well translated into protein once that happened. The first link in the preceding paragraph has a great deal of information on this, with links to yet more reviews, and I won't even try to summarize it all. But there have been extensive modifications made to the RNA sequences themselves and to the formulations that they're dosed in (a lot of this by pretty brutal trial-and-error work), and the technique might be ready for prime time. We don't quite know that yet, though. The DNA vaccines have been around longer and (as mentioned) haven't produced a human therapy yet. Are the mRNA ones better, or is it that we just don't know about the disappointments to come? We're going to find out more quickly than we had planned.

[b]Adjuvants[/b]

There's another key vaccination technique that I haven't mentioned, and it applies to all of the techniques above: [url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494348/]adjuvants[/url]. Obviously, the big thing you want from a vaccination is a robust, long-lasting immune response, and it turns out that various additives can provoke just that. These are all about that balance between the innate and adaptive immune response mentioned above; the idea is to get the best carryover from the immediate innate mechanisms to drive the antibody-centric adaptive ones. [url=//blogs.sciencemag.org/pipeline/archives/2020/04/02/antibody-tests-for-the-coronavirus]See this post[/url] for a quick immune-system primer, and there are of course many other places to learn about this -- the key here is the handoff to the [url=https://en.wikipedia.org/wiki/Antigen-presenting_cell]antigen-presenting cells[/url] and the helper T cells.

The adjuvant field started out, frankly, as about the closest thing to voodoo that you'll find in infectious disease treatment. Antibodies were generated by injecting horses and extracting their plasma, and a veterinarian (Gaston Ramon) noticed in the 1920s that the yields were higher from animals that had developed a strong reaction at the original injection site. He started experimenting with additives to induce such reactions, including things like tapioca starch. In the same era, Alexander Glenny was formulating various diphtheria vaccines and noticed that the ones that included aluminum salts were much more effective. No one really knew the details of how these things did what they did, but aluminum salts are still very common in vaccines nearly a century later. We've learned more about what's going on -- in the 1990s, the first new adjuvants in decades began to show up, and more have been added. For example, the GSK shingles vaccine (Shingrix) has lipoproteins from Salmonella bacteria added to it along with [url=https://en.wikipedia.org/wiki/QS-21]terpene glycosides[/url] from the [url=https://en.wikipedia.org/wiki/Soap_bark_tree]Chilean soap-bark tree[/url], which seems to be an especially powerful combination. I can tell you that the reaction at the site of injection for that one is very impressive, especially on the second shot! GSK's expertise in this field is in fact what they're bringing to the collaboration with Sanofi mentioned in the first paragraph, and they're collaborated with many others as well.

[b]Developing a Covid-19 Vaccine: Efficacy[/b]

OK, back to the broad picture of developing a coronavirus vaccine: the question is, which of all these possible techniques is the most effective and safe? That we are only going to find out, in the end, by dosing people. Lots of people. With therapies targeting the immune system, there is in the end no other way to know, because of the complexities of the human immune response and its wide variation in the human population. Rushing the process is going to take a vast amount of effort, and some of the steps are going to have to be done on a scale never before attempted. There's another point that can't be ignored, either: if we want this done as quickly as we would like, there are going to have to be some shortcuts.

To that point, one reason that the Moderna vaccine got off the mark so quickly is that the mRNA route can be intrinsically faster, but a bigger reason is the step of seeing how well it works in animals was [url=https://www.statnews.com/2020/03/11/researchers-rush-to-start-moderna-coronavirus-vaccine-trial-without-usual-animal-testing/]entirely skipped[/url], a very unusual step indeed. That's partly because it's still unclear which animal model will be the most informative. We have a bit of a head start thanks to the work that's been done on the earlier human coronavirus pathogens [url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550498/]for SARS and MERS[/url], but you may recall [url=//blogs.sciencemag.org/pipeline/archives/2020/04/13/omeprazole-as-an-additive-for-coronavirus-therapy]Monday's post[/url] talking about how SARS and the nCoV-19 virus do show real differences in various tests (there are many lines of evidence for that). We can expect those differences to carry over to the animal models as well. One approach that I know that people are taking is to breed animals that have been engineered with the human form of the ACE2 protein which seems crucial for viral entry -- one way or another, we should be able to find a small animal (mouse, hamster, etc.) that can be useful, but will it be found in time to actually [i]be[/i] useful? My guess is that several other clinical vaccine candidates will end up going the same route as Moderna's, and skip past animal efficacy entirely. Believe me, that's a shortcut, and there will be others.

Fortunately, testing for vaccine efficacy can be (fairly) straightforward, and it involves many of the same issues that are being frantically beaten on for antibody testing: does a vaccinated patient develop antibodies? How many? Are they the right kinds to neutralize the virus? And how long do they last? Those first three are the subject of a huge amount of work right now, and although it's nerve-wracking at the moment I have no doubt that these are questions that can be and will be resolved. We're going to have a lot to think about with what endpoints we'll be measuring for efficacy, to be sure -- surrogate ones will be faster, but will regulatory agencies want to see more patient-focused clinical endpoints as well?

[url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/] Here is a review[/url] from the dear, long-gone days of 2016 of the standard development process for a new preventative vaccine. Take a look at the lengthy, detailed, overlapping, interlocking system of trials that such vaccines have undergone in the past, and reflect that we're not going to be able to do all of that if we want a vaccine on the timelines stated at the beginning of this post. Ideally, you want to study these efficacy questions in Phase II trials in different populations (age, gender, pre-existing health conditions and range of medications being taken), all with different dosing schedules, and carefully tune things up for bigger Phase III runs. We'll be able to deal with some of that by running a lot of simultaneous trials instead of doing things more sequentially, but that's not going to cover every issue. Not by a long shot. Remember, there are at least 78 of these things under development right now -- there will be fierce attrition, and only a few (low single digits) will make it deep into the process, but it's still a fearsome process to get all this organized.

And some things cannot be accelerated by any means known to humanity. The last point above, how long immunity lasts, is a big question for both people naturally infected by SARS-Cov2 and for those given a vaccine, and unfortunately there is no way to answer that one other than time, which is in short supply these days. The field provides many examples of vaccines whose protection has not held up as well as expected as the years went on. My guess is that we may end up with a first-round vaccine that doesn't last as long as it might, but will provide enough immunity to do the job and provide cover for us to collect more data on an optimized candidate.

[b]Developing a Covid-19 Vaccine: Safety[/b]

But that takes us to the second question for any new therapy: safety, and its balance with efficacy. This is an especially fraught question with any therapy that's targeting the immune response, because the downsides are gigantic: a runaway immune reaction can disable someone for life or even kill them within minutes where they stand. [url=https://en.wikipedia.org/wiki/Guillain–Barré_syndrome]Guillain-Barré syndrome[/url] is an example: your body reacts to an antigen (a viral infection or a vaccination) by deciding that the myelin sheaths around your nerves are also the enemy, and starts destroying them. Very bad news, and although most people recover, a few die. Roughly estimated, even a seasonal flu vaccine might kill about one out of every ten million recipients though such a reaction -- we give it to everyone possible, though, because far more people will die if we don't. The [url=https://www.discovermagazine.com/health/the-public-health-legacy-of-the-1976-swine-flu-outbreak]1976 swine flu debacle[/url] shows what can happen, both in perception and in reality, when you get this balance wrong. But you can't avoid the problem: the huge person-to-person variation in everyone's immune system means that these severe events can [i]never be ruled out[/i] at some low level if you're dosing enough people.

Now you see the exact bind that vaccine development has always been in, because the whole point is to treat millions, even billions of people [i]who are not currently sick[/i], to protect them against disease while not doing more harm along the way by setting off the body's fiercest and most alarming biological responses. I have no doubt that the companies and regulatory agencies involved will be doing everything they can to address safety issues, but if you're looking at a vaccine getting an EUA early next year, well. . .

[b]Developing a Covid-19 Vaccine: Logistics[/b]

Another big problem is going to be manufacturing and distribution. Many readers will have heard about the difficulties that sometimes occur during the flu-vaccine production process, leading to shortages. Depending on what vaccine technology comes out on top, manufacturing enough doses in a reproducible fashion could be quite challenging -- space and finger fatigue don't permit going into all the details, but they are many and complex. Keep in mind as well that many vaccines need "cold chain" distribution and storage, which is always a layer of complexity. What if an eventual vaccine needs more than one round of administration, as many of the adjuvant-formulated ones do? Keeping track of that and following up on it is yet another issue.

My guess is that scale-up and manufacturing could well be the biggest chance for the timelines mentioned earlier to blow up, so there is going to be a massive effort to front-load the work on these problems -- this is why, for example, Bill Gates has already indicated willingness to fund factories for up to seven vaccines up front. The live-virus, attenuated virus, recombinant protein, and nucleic acid vaccines will all involve completely different production methods and formulations, and since we don't know which way we'll be going, this would seem the only way to address the issue. Pfizer and others have already said that they're going to be working on production even before the efficacy data come in, which needless to say is not the usual business practice. I think we'll get vaccine efficacy, one way or another, although it sure won't be characterized as thoroughly as it normally would. And I think we're already agreeing to cut corners on safety, whether anyone says so in as many words or not. But producing the vaccine on scale could be a bigger issue yet, and as the process goes on, that's where I would keep an eye out for trouble.

It is a tightrope, folks, and we're going to be trying to run across it. Watch closely; with any luck we will never see anything quite like this again.[/quote]

Some numbers from the trenches

County by county figures for Wisconsin. Population density is bad, rural life is mostly good. Statistics on death rate are meager, in the sense of very low counts in most counties, and that is very good.

[QUOTE=kriesel;543103]Population density is bad, rural life is mostly good.[/QUOTE]Do you mean [b]high[/b] population density is bad, and rural life is mostly good (for avoiding diseases) because of a low population density?

[QUOTE=kladner;542959]Regarding your January experience, did you have head or body aches? Crazy-making headaches are frequently reported.
EDIT: From the front page of the Guardian:[/QUOTE]

Not really. Only a slight headache occasionally. I imagine what I had was influenza.

[QUOTE=storm5510;543108]Not really. Only a slight headache occasionally. I imagine what I had was influenza.[/QUOTE]
Flu is bad enough. Hope you are well over it.

COVID-19 in the USA: a question of time The Lancet

Editorial from the Lancet. A PDF is attached
[URL]https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30863-1/fulltext[/URL]
[QUOTE]With more than 600 000 confirmed cases and close to 27 000 deaths, the USA has become the current centre of the global coronavirus disease 2019 (COVID-19) pandemic. Fewer than 3 months have elapsed since the first severe acute respiratory syndrome coronavirus 2 infection in Washington State was confirmed by the US Centers for Disease Control and Prevention (CDC). Initially appearing slow moving and constrained in contrast to the scale of outbreaks in China and Italy, COVID-19 has given way to a nationwide public health catastrophe. For the first time in US history, a disaster declaration has been put in place for all 50 states and most US territories, and 95% of Americans are at least temporarily under some form of stay at home order. The increasing gravity of the situation in the USA has drawn public health and infectious disease experts, policy makers, and partisans across state and federal government into a fitful clash for control and direction of the COVID-19 response. Putting the USA at odds with the international community and global pandemic strategy efforts, President Trump announced his intention to withdraw funding from WHO (about 22% of its budget). Caught amid the chaos are the American people grappling with the fear of a deadly and poorly understood virus, conflicting messaging around their protection and safety, fear of financial fallout, absence of a cohesive national strategy, and volatile, incompetent leadership.[/QUOTE]

[QUOTE=kladner;543121]Flu is bad enough. Hope you are well over it.[/QUOTE]

Yes, well past it. Thank you. :smile:

I have been reading were a lot of state governors want to start easing restrictions in May. They are talking about this as the number of cases, and the death toll, continues to rise. My son works at a local manufacturing facility. He told me his current return-to-work date is May 4. I feel all of this is way too soon. Allowing people to start mixing this soon could cause the infection rate to skyrocket. Then what?

A 50 minute crash course in Covid19. Check out the comments praising the teaching style. [URL]https://www.youtube.com/watch?v=PWzbArPgo-o[/URL]
36 minutes on treatment, from same presenter. [url]https://www.youtube.com/watch?v=rdoN_XsHWBI[/url]

[QUOTE=storm5510;543154]Yes, well past it. Thank you. :smile:

I have been reading were a lot of state governors want to start easing restrictions in May. They are talking about this as the number of cases, and the death toll, continues to rise. My son works at a local manufacturing facility. He told me his current return-to-work date is May 4. I feel all of this is way too soon. Allowing people to start mixing this soon could cause the infection rate to skyrocket. Then what?[/QUOTE]California and Massachusetts sampling of the general populations in small survey areas have indicated about a third of the general public have antibodies already. That figure is far higher than the case count indicated. Some areas have declining case counts and if the current restrictive measures are responsible, that decline will continue for the next 3 weeks. Government will likely be much quicker to slam on the brakes than the first time, if case counts start climbing again. Vaccines that work and are regarded as safe enough to use widely are a year or two away. It's likely we'll have fitful returns to work and stoppages again, and still get herd immunity before vaccines are ready for general use.

To avoid Fed confiscation Illinois Governor secretly bought PPEs from China. White House unhappy!

Over $1.7 million paid to Fedex to get around the federal blockade. :poop: :censored:

[URL]https://www.dailykos.com/stories/2020/4/18/1938492/-To-avoid-Fed-confiscation-Illinois-Governor-secretly-bought-PPEs-from-China-White-House-unhappy[/URL]

[URL]https://chicago.cbslocal.com/video/4517049-secret-flight-from-china-brings-ppe-to-chicago/[/URL]
[QUOTE][INDENT]The White House issued a sharp rebuke Saturday to Illinois Governor J.B. Pritzker, who [URL="https://chicago.suntimes.com/coronavirus/2020/4/14/21221459/pritzker-secret-flights-china-illinois-ppe-trump-coronavirus"]reportedly[/URL] spent over $1.7 million on flights bringing medical supplies from China in secret—out of fear the Trump administration would seize the cargo for the federal stockpile.
[/INDENT]To put this into perspective, and step back for a second here: Pritzker, who was specifically told by Trump that he was on his own to buy medical supplies in the open market, does so, and the White House is not happy with this because he did this without notifying them, he did it in secret? Why did Pritzker do this in secret? Because many shipments to states were diverted, seized, and confiscated for the federal stockpile, stolen, even though these states paid Millions of Dollars for these essential supplies, just to have them taken away right under their noses in an act of highway robbery.
[/QUOTE][QUOTE][Pritzker] said that because “the federal government [B]seems to be interrupting supplies that are being sent elsewhere in the nation[/B]” he “wanted to make sure that we received what we ordered,” and also told CNN that he had “[URL="https://www.cnn.com/2020/04/14/politics/pritzker-trump-coronavirus-help-cnntv/index.html"]given up[/URL]” on receiving help from the Trump administration.[INDENT]White House deputy press secretary Judd Deere responded, [URL="https://www.realclearpolitics.com/articles/2020/04/18/wh_counters_pritzkers_claim_of_stinginess_with_covid_aid_142979.html"]telling[/URL] RealClearPolitics that Pritzker, “through ignorance or incompetence or a propensity to politicize everything,” was wrong, and that the administration had been providing Illinois with resources.
[/INDENT][/QUOTE]

[url=https://www.medrxiv.org/content/10.1101/2020.04.16.20060566v1.full.pdf]Delayed clearance of SARS-CoV2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs[/url] | medRxiv (preprint, not yet peer reviewed)

Being a habitual wearer of testes, my first thought on reading the headline was ‘nuts!’ Next thing you know, they’re gonna mandate that all men practice social distancing with respect to their ‘nads’ … “but Dr. Fauci, I’m really rather attached to them!”

Is there such a thing as an N95 jockstrap? If not, someone needs to design one, ASAP.

[QUOTE=ewmayer;543204][url=https://www.medrxiv.org/content/10.1101/2020.04.16.20060566v1.full.pdf]Delayed clearance of SARS-CoV2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs[/url] | medRxiv (preprint, not yet peer reviewed)

Being a habitual wearer of testes, my first thought on reading the headline was ‘nuts!’ Next thing you know, they’re gonna mandate that all men practice social distancing with respect to their ‘nads’ … “but Dr. Fauci, I’m really rather attached to them!”

Is there such a thing as an N95 jockstrap? If not, someone needs to design one, ASAP.[/QUOTE]... expression [b]in[/b] testes ...

Suggests to me that the outer covering (the scrotum) isn't what is being talked about there.

Somebody make that cuckoo clock quit chiming!

[url=https://www.bbc.com/news/uk-england-52164358]Mast fire probe amid 5G coronavirus claims[/url][quote]There have been fires at masts in Birmingham, Liverpool and Melling in Merseyside.

A video, allegedly of the blaze in Aigburth, was shared on YouTube and Facebook, claiming a link between the mobile technology and Covid-19.
<snip>
Fact-checking charity Full Fact [url=https://fullfact.org/health/5G-not-accelerating-coronavirus/]has linked the claims to two flawed theories[/url].

One suggests 5G suppresses the immune system, the other claims the virus is somehow using the network's radio waves to communicate and pick victims, accelerating its spread.[/quote]

[QUOTE=ewmayer;543204][URL="https://www.medrxiv.org/content/10.1101/2020.04.16.20060566v1.full.pdf"]Delayed clearance of SARS-CoV2 in male compared to female patients: High ACE2 expression in testes suggests possible existence of gender-specific viral reservoirs[/URL] | medRxiv (preprint, not yet peer reviewed)

Being a habitual wearer of testes, my first thought on reading the headline was ‘nuts!’ Next thing you know, they’re gonna mandate that all men practice social distancing with respect to their ‘nads’ … “but Dr. Fauci, I’m really rather attached to them!”

Is there such a thing as an N95 jockstrap? If not, someone needs to design one, ASAP.[/QUOTE]

:missingteeth:

Sorry! This is the best I've seen in a very long time. Every time I get an unexpected sniffle, I wonder if those little buggers are laying dormant somewhere. Now, I know where they are. Perhaps a jockstrap with Uranium stitching might be better. :grin:

[QUOTE=kriesel;543162]California and Massachusetts sampling of the general populations in small survey areas have indicated about a third of the general public have antibodies already. That figure is far higher than the case count indicated. [/QUOTE]

These dark figures are indeed very high. Do you have references?

[QUOTE=Till;543257]These dark figures are indeed very high. Do you have references?[/QUOTE]I don't have references but question your choice of the adjective "dark".

If true, those people are both unlikely to infect others and are likely to be able to live relatively normal lives. In particular, they should be able to partake in activities which are to the benefit of others.

[QUOTE=xilman;543265]I don't have references but question your choice of the adjective "dark".

If true, those people are both unlikely to infect others and are likely to be able to live relatively normal lives. In particular, they should be able to partake in activities which are to the benefit of others.[/QUOTE]

How do you conclude that if the "dark figures" are that high, people are unlikely to infect others? That is utter nonsense. If the dark figures are that high, then there has been an immense amount of people infecting others for several weeks.

[QUOTE=Till;543267]How do you conclude that if the "dark figures" are that high, people are unlikely to infect others? That is utter nonsense. If the dark figures are that high, then there has been an immense amount of people infecting others for several weeks.[/QUOTE]I am making the (plausible?) assumption that infection leads to at least temporary immunity.

To me, that is an encouraging sign, not a dark one.

[QUOTE=xilman;543269]I am making the (plausible?) assumption that infection leads to at least temporary immunity.[/QUOTE]

I hope so. But some of those infected by people with little/no symptoms are dying. So a huge "dark figure" means that many are dying, many more necessary than if there had been an appropriate amount of testing.

[QUOTE=Till;543267]How do you conclude that if the "dark figures" are that high, people are unlikely to infect others? That is utter nonsense. If the dark figures are that high, then there has been an immense amount of people infecting others for several weeks.[/QUOTE]

The post you cited is "antibodies", not "testing positive". A large number of people with antibodies is good for the future, not bad, right? All else equal, we'd rather discover that everyone has already been exposed versus learning that only 5% of the population has been exposed.

[QUOTE=VBCurtis;543274]The post you cited is "antibodies", not "testing positive". A large number of people with antibodies is good for the future, not bad, right? All else equal, we'd rather discover that everyone has already been exposed versus learning that only 5% of the population has been exposed.[/QUOTE]

VBCurtis, I understood that pretty well.
"testing positive" are the official numbers, and
"antibodies" are supposed to reflect the "true" situation (on a small sample base)

And Kriesel posted that 1/3 of the population of selected regions already had antibodies.
That was such a high number that I was asking for references.