Friday, May 8, 2020

Rainbows Ahead? Or Storms?

A newly opened Barcelona shopping street last Saturday

Treatment update
Convalescent serum (= convalescent plasma): Now both the United States and the United Kingdom are actively recruiting potential donors, both among previously diagnosed patients and among people who think they had COVID-19 but were never tested. Sign up!!!
In Italy they’re unfortunately still “Don’t call us, we’ll call you,” and precious little calling is going on. Some 4000 patients have already been treated in the States, but as far as I can tell no more than 200 in Italy despite a vast pool of potential donors. What are they waiting for?
Remdesivir: The usually circumspect Anthony Fauci went wild, for him, over the preliminary results. For Fauci to say they show “A clear-cut, significant positive effect” and are “Proof of concept” is as over the top as Trump saying hydroxychloroquine was “one of the biggest game changers in the history of medicine.” Fauci himself has more or less admitted he was jumping the gun, and I am worried that his saying patients currently on placebo “Should be switched to remdesivir” might mean this crucial trial is being stopped before it can give definitive results. Until we see an actual manuscript, I and many others will keep our enthusiasm less starry-eyed. Did Trump got tired of waiting for good news and put a (hopefully figurative) gun to Fauci’s head? The fact that the White House has blocked the good doctor from testifying to Congress under oath certainly looks suspicious. 
Alongside the randomized, placebo-controlled international remdesivir trial funded by the National Institutes of Health, there’s a randomized (but apparently not placebo-controlled) trial, “Solidarity,” ongoing in more than 100 different countries under the auspices of the World Health Organization. Unfortunately the other drugs the World Health Organization chose to include are lopinavir/ritonavir (Kaletra), lopinavir/ritonavir with Interferon beta-1a; and chloroquine or hydroxychloroquine, all of which except interferon have already been proven useless or near so.
Hydroxychloroquine: Just when I thought Plaquenil had been quietly retired from Fox News, there it was again Tuesday night on Laura Ingraham, with a triple defense from “experts” against the accusation of making the heart go berserk: 1) lots of drugs do the same thing, 2) the only people who care are commies, 3) how about all those people who take it for years for autoimmune diseases without dropping dead? Sigh. The point isn’t that Plaquenil is such an awful drug, the point is that it doesn’t help COVID-19 patients, that if anything it seems to make them worse, and that the main guys pushing it are shysters (Didier RaoultVladimir Zelenko). If hydroxychloroquine really were a “game changer” that could outweigh its side effects, but it’s not. The reason it doesn’t poison the hearts of lupus patients is because the people who are taking it are walking and talking, basically healthy, not deathly ill with their poor hearts already strained and fragile.
New entries in the treatment sweepstakes: 
Leronlimab: I once mentioned this antibody, which is chiefly intended to counter “cytokine storm” in very ill patients but also has some antiviral activity. Its manufacturer spins some promising results in a couple of dozen patients as “we believe we were able to save the lives of four patients.” They’re plunging optimistically ahead, with properly controlled Phase 2-3 clinical trials.
Oddball long shots: the chemical element selenium, the antidiabetes drug dapagliflozin (Farxiga, which is usually considered contraindicated in COVID-19 patients), the antipsychotic chlorpromazine (Thorazine), the female hormone progesterone, the antihistamine clemastine (Tavist).
Brand names: I tend to avoid using brand names but maybe I should reiterate a few that people keep asking about. The arthritis drug sarilumab, which performed badly in a recent trial, is sold as Kevzara. Its cousin tocilizumab is Actrema. The Japanese antiviral favipiravir is sold in Asia as Avigan. Hydroxychloroquine is Plaquenil.
For a good review of treatments and vaccines, see last Saturday’s Daily Kos.

The vaccine derby
The German company BioNTech has now, in collaboration with the American giant Pfizer, begun Phase 1-2 studies in human volunteers, joining the 3 or 4 other groups jockeying for pole position. I expect the Trump administration is delighted that they’ll be doing much of their testing (and their production, if it ever happens) on US soil.
A correction: my last post mixed up two Chinese vaccine companies. CanSino is doing Phase 2 trials in people, as I said, but it’s SinoVac Biotech that, with the Oxford team, is the second group to have shown its candidate vaccine works in monkeys.
The European Union – rapidly joined by Japan, Israel, Turkey, and the Gates Foundation but conspicuously not by the United States government ­– is raising 8 billion dollars in a collective effort toward COVID-19 treatments and vaccines. Hopefully a global perspective will help prevent an eventual vaccine from being used only to protect people in the world’s north.
While scientists begin thinking deeply about how to hurry along a vaccine, the media are unfortunately giving more visibility to the truly awful idea of deliberately infecting human beings in order to move the process forward more quickly. There are already plenty of places where people are experiencing disease challenges every day – meat-packing plants, jails and prisons, long-term residential facilities, ICE detention centers – and that’s where the vaccine should be tested (in addition to enforcing social distancing in factories, closing those ICE centers, and releasing as many prisoners as possible).

Shoot first, think later
Mask culture meets gun culture: A security guard at a Family Dollar store was shot in the head and killed after he told a customer to wear a face covering, which is required in Michigan. This was no fit of anger – the customer’s family went home first to fetch their gun. 
Mask culture meets police brutality: On Sunday a small squad of New York’s Finest noticed a couple chatting nose-to-nose in front of a brownstone. When they declined to move on, the cops instead of pulling out their social distancing summons book deliberately picked a fight. One brandished his Taser and punched out a casual bystander, before all three civilians were violently arrested, apparently for the crime of socializing while non-white. 

Hot spots
America’s West Coast and New York are now, thankfully, weeks into a slow recovery phase from the COVID-19 pandemic. The new hot spots popping up are far from the coasts. A state prison in Ohio: 78% of inmates positive for COVID-19. Another in Louisiana: 98% positive. Federal prisons: 70% positive. Inmates at ICE detention centers: 50% positive. It seems wherever the disease is looked for there it is lurking, ready to spread from inmates to staff and out into the community. Remove New York State from your daily United States death statistics and this discouraging upward curve is what you get: 
Then there are long-term residential facilities, where well over 10,000 Americans have died, accounting in many states for more than half the COVID-19 deaths. Similar institutions may account for half the deaths from the epidemic in Europe.
Don’t forget the infamous meat processing plants whose employees are picking up COVID-19 from their co-workers – factories in North CarolinaSouth DakotaIndiana have close to 1000 cases each – and bringing the disease home to their families and communities. One of the most shocking moves of the White House, and that’s saying a lot, is attempting to order these plants to reopen whatever their hygienic conditions may be. 
In Italy something similar may possibly be happening in the factories of the industrialized North, especially Lombardy, many of which were allowed to restart operations several weeks ago. After several weeks of good numbers, the number of COVID-19 deaths in Italy went up for 3 days in a row, and most of those deaths were in Lombardy. Were they among factory workers infected 3 weeks ago when they went back to work? The timing jibes, but nobody’s talking and I’ll try not to be alarmist.

Department of stable geniuses
The World Health Organization is no longer a shiny enough object to draw public attention away from Donald Trump’s inadequacies in handling the COVID-19 crisis. Now he’s moved on to dumping blame on China for COVID-19, including the lab accident origin myth. His new fixation seems to be working better, in part because China really has behaved pretty miserably – keeping the outbreak under wraps and understating its death toll. Trump has managed to recruit other Western partners to the anti-China brigade, and to goad the Chinese government into producing an animated video that went so viral that within four days I received the link from three different friends.
Trump blaming China for not warning people about the coronavirus is, of course, the proverbial pot calling the kettle black. 
Exactly 9 days ago the University of Washington group, Trump's favorite experts, predicted that the number of COVID-19 deaths in the United States by early August would be 72,433. Whoops – we whizzed past that milestone yesterday. Turns out that all their models, which have repeatedly trailed reality, depended on the twin assumptions that social distancing orders would stay in place and that people would follow them. On May 4thhaving noticed that neither assumption was holding up, the Washington crew nearly doubled their estimate, to 134,000. This plunged them so deep into the President’s no-fly zone that mention of their model disappeared from the CDC website, where it had been featured, within hours.
But then, the CDC as we once knew it seems to have been taken over by a dybbuk. On May 1st Rachel Maddow documented a disappearing act that occurred precisely between April 20 and April 22, 2020 (see a transcript or a video). On the 20th the “old” CDC issued a report to a factory beset by COVID-19 cases, ordering them to take specific steps to avoid further contagion. On the 22nd the “new” CDC issued a report to another such factory, similar except that the measures were not ordered, but were to be done “when feasible” or “if possible,” or even just “considered.”

Plowing ahead…
If we want to return responsibly toward normality we need to be ready to:
-       Test everybody with possible symptoms of COVID-19
-       Trace all the contacts of positives, and either test or quarantine them
-       Continue social distancing
Test test test?
Two months ago today Donald Trump declared that anybody who needed a COVID-19 test could get one. It wasn’t true then, and it isn’t true now. In some areas of the United States, though, drive-by swab testing is being offered free to symptomatic patients by pharmacies or health authorities. On demand to anyone who wants it? Not clear. The California government website says that “Local health departments and healthcare providers determine who needs testing,” but from their screening questionnaire it seems you can get an appointment without a request from a doctor.
Italy’s opened up similar testing centers, which were originally billed as accessible on your GP’s prescription. In reality, though, you can only get tested on the say-so of the official COVID-19 call center (hotline number: 1500). If they say yes they will either give you an appointment at a drive-by center or send someone to your home to take the swab. A few enterprising patients manage to be tested by going straight to the triage tent outside a local infectious disease hospital, but there’s no guarantee.
Contact tracing
The United States, Germany, Italy, France, the UK, and others are dreaming that a cellphone app will be able to trace COVID-19 patient contacts on the cheap, by automatically detecting people who have been within six feet of one for more than 15 minutes. But privacy rights that Europeans are unwilling to sacrifice mean that the app must be voluntary, making it much less useful. Not to mention that you can always leave your cellphone on the shelf at home when you go out for a stroll. I personally don’t think any technological solution can substitute for old-fashioned one-on-one contact tracing, by personnel carefully trained in scientific and human skills. Of 41 US states that responded to a National Public Radio query, only four thought they’d be able to hire contact tracers at the up-to-par rate of 30 per 100,000 population.
Phase 2 or bust?
Germany has hoped to be the first on its block to restart professional soccer, though with teams playing in empty stadiums. They even began allowing professional players to start training. But their plan received a blow last week when ten players from two major teams tested positive for COVID-19.
Germany and Austria are also the countries taking baby steps toward reopening the entertainment industry, not generally considered a priority. The theater, music, and dance worlds are currently in despair – nobody, especially a symphony orchestra or an opera company, can afford to perform to a three-quarters-empty socially-distanced house. As the wife of a musician and the sister of an impresario I may be overly optimistic, but I do think that venues and artists may be willing to take enough financial cuts – better some income than none at all – that opening those red curtains could make economic sense. Maybe there could be free entry to performers and spectators holding COVID-free certificates, good for a week after a negative swab? Or COVID-immune certificates, good for a month after a positive blood test? (I confess the World Health Organization is still skeptical.)
The UK has now surpassed Italy as home to the most COVID-19 deaths in Europe. It’s still not the worst per million population – Spain, Belgium, and tiny Andorra and San Marino beat it out. But it may soon attain that dubious honor if its daily death toll stays high – Boris Johnson dragged his heels on social distancing even longer than Trump did – at the same time as it falls in other countries. Nonetheless, and despite having nearly died from the disease himself, Mr. J. is gearing up to reopen the UK despite grossly inadequate testing and contact tracing capacity.
Encouraged by the steady drop in the number of severely ill COVID-19 patients, this past Monday Italians were allowed for the first time in 7 weeks to take their kids outside, enjoy springtime in the parks, call on close relatives, even get in their cars and drive off (if they still remember how) to a hiking trail. All well and good, except that the vital need to keep other people at more than arm’s length doesn’t seem to have been hammered home. The Phase 2 rules decreed social distancing when visiting relatives, even indoors, but shots of nonni happily embracing their grandchildren were apparently aired on Italian television Monday night without a word of criticism. 
A friend in Spain gives a similar report of reopening day 1: shopping streets packed with people, as in the photo at the top.
Maybe Americans will do better, but I doubt it. A friend wrote on May 1, “I just live in [a state] where most people still believe this is all a hoax amd Dem plot to make Trump look bad, so they're the ones protesting and going to rallies, etc. Of course, I am bombarded every day with their newest pick for "expert" doctor who tells them this is all a big lie and meant for billionaires to vax us all and... I don't know.. control us?” 

Still a hoax, after 70,000 deaths? At first I refused to believe people could be that dumb. But then I reminded myself that 40% of American adults are convinced the earth was created less than 10,000 years ago, complete with human beings – and dinosaur bones.

15 comments:

  1. These posts are phenomenal, Susan. That includes your technical skills enabling you to include all the graphs, not to mention the broad overview you provide for us. They're well organized and well written. Thank you so much.

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  2. Regarding remdesivir, the Atlantic has an article about an almost identical drug, GS-441524, used to treat feline infectious peritonitis in cats:
    https://www.theatlantic.com/science/archive/2020/05/remdesivir-cats/611341/

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    1. True, true, unrelated is what I think. Thank you for turning me on to the article, which I'll cite in my next blog post, but I tend to doubt this drug has any future in treating covid-19.

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  3. Well said, Dotoressa! I wish I could figure out how to share?

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    1. Directly under the final sentence, the one with dinosaur bones, there are little share buttons for Facebook, Pinterest, Twitter, and one or two others. If you click on a button the sharing is easy - I just tried it myself with Facebook to check. If you want to share to a medium that's not listed I guess you'll have to just post the url. ...but also please tell me what social media you need and I'll see whether I can add it to that little bar. ...and you're reminding me that I keep forgetting to announce my posts on Twitter!

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  4. On the marketing of remdesivir:
    https://www.statnews.com/pharmalot/2020/05/08/gilead-remdesivir-covid19-coronavirus-patents/

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    1. Yes, this is a common story in the pharmaceutical industry. The government uses taxpayer money to pay for all the basic research behind the development of a new drug, then a commercial entity steps in to make all the profit.

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    2. Thank you for pointing out the role of this mechanism in the case of remdesivir.

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  5. It would be nice if politics could be left out and be focused only on the medical treatments. All the medications are giving some results so they are all useful in this moment to save lives.

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    1. Thanks for posting, George, and I appreciate where you're coming from. However: First of all, would that it were true that "all the medications are giving some results" or that they were "all useful...to save lives." Almost no medications have any evidence for benefit, and several have evidence for harm. Second, the two ways we DO know to counter this terrible pandemic, social distancing and the appropriate use of testing, are both being seriously undermined by major political forces in the USA and some other countries (most notably the UK). Vigorously pointing this out, as I try to do, is a matter of medical science and saving lives, not of politics.

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    2. Since the role of the state is defend its citizens in times like this, and the state is driven by political and economic groups representing their interests, it's almost impossible to be apolitical when discussing the solutions put forward to deal with this disaster.
      Keep doing what you are doing Susan - great work!

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    3. Well said, better than I could, and thanks a lot.

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  6. Jerome R Hoffman, MA MDMay 12, 2020 at 1:59 AM

    Thank you for this wonderful post, Susan. I'd like to add two comments. 1) Please consider abandoning the phrase “social distancing” in favor of “physical distancing.” Not because the latter is more accurate (although it is), but because if anything good is to come from this catastrophe, it will be that more of us understand the critical importance of social connection (and community) — concepts woefully undervalued in the US during business as usual. 2) Please do not avoid telling unpleasant truths, even when they reveal the incompetence and stupidity of political “leaders” (which actually gives them the benefit of the doubt, because it assumes that their awful behavior is not willfully evil). It is always worth remembering the great Rudolf Virchow’s dictum about the inextricable link between medicine and politics.

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    1. Thanks so much, and I appreciate your support of my position about politics. About the other point, I agree with you 100% about the accuracy and desirability of the phrase "physical distancing." But by now the word social in that context has become so entrenched that I fear avoiding it might lead to misunderstandings. This said, I'll try to notice when I'm about to use that phrase in the future, and consider changing the terminology.

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