Wednesday, April 7, 2021

From Robots to Zombies

 

Pepper, a robot already working in banks, fast food joints, and elsewhere


Treatment update 



Molnupiravir: Merck has announced some very preliminary results for their new oral antiviral: COVID-19 outpatients who took it cleared virus from their noses faster than patients given placebo. This drug isn’t likely to hit your local CVS any time soon.  

Natural immunity: Reinfection may be somewhat more common than we had thought. A study from Austria found a bout of illness to give more than 90% protection from reinfection, similar to what’s afforded by the best vaccines, for at least 7 months. But one from Denmark was less encouraging, reporting only about 80% immunity at 3-10 months in people under 65, and less than 50% in the elderly. The discrepancy is likely due to the routine testing done in Denmark; many of the cases picked up by their screening program were asymptomatic, so perhaps shouldn’t count.


Colchicum autumnale

Colchicine: The first oral medication thought to help COVID-19 outpatients has now done well in another trial, from Canada. In patients sick enough to be hospitalized, though, its value is uncertain. One small study in Brazil found highish doses to cut the duration of hospitalization by 25% and the number of days on oxygen by 40%. But in the much larger UK RECOVERY trial colchicine struck out, at least for its main endpoint of 28-day mortality. 

Tocilizumab: Yet more mixed results, with 2 papers about critically ill COVID-19 patients in a single issue of the New England Journal of Medicine, one positive, one negative. They did have one crucial difference: in the positive trial, most patients were also being given steroids. Based on these results, the National Institutes of Health COVID-19 Treatment Guidelines Panel is now suggesting the drug be given together with steroids in very sick patients with high inflammatory markers in their blood, saying it “offers a modest mortality benefit.”

Baricitimib: A study of this “Janus kinase inhibitor” in hospitalized patients has now been published, and it looks pretty good: when the drug was added to remdesivir mortality fell from 7.8% to 5.1%. 


 


This headline, “In Ancona robots help Covid patients with monoclonal therapy,” got visions of humanoids dancing in my head, rolling from bed to bed to stick needles into veins. Alas! The “robots” turn out to be just machines that help measure out doses. 

Azithromycin: After failing to help hospitalized patients, this antibiotic has now proved equally useless in getting outpatients well faster or keeping them from getting worse.

Bamlanivimab: The good news is that Lilly’s monoclonal antibody is now available in Italy. The country has bought and paid for 150,000 doses, about equal to its number of new cases every week. The bad news is that the sacs are arriving in dribs and drabs, such that as of March 30th only 230 patients had been treated. More bad news: bamlanivimab has been withdrawn in the USA as a stand-alone therapy, because of poor efficacy against variants, though it can still be used in combination with another antibody, etesevimab. But there’s good news in the bad news: Bamlanivimab may be ineffective against the South African variant, but it seems to still be valid treatment for the B.1.1.7 English variant and the original Wuhan strain, the ones currently dominant in Italy. Whew. 

VIR-7831: This new monoclonal antibody from GlaxoSmithKline performed brilliantly in a Phase 3 trial, reducing hospitalizations and deaths in high-risk outpatients by 85%. Judging from laboratory studies, it ought to work not only against the wild-type Wuhan strain and the B.1.1.7 variant, but against the South African and Brazilian variants as well. This could be a huge step forward, and the company has already applied for emergency use authorization in both the United States and the European Union.

Monoclonals Italian style: Toscana Life Sciences has begun Phase 1 human studies of a home-grown product. It has one huge advantage, being given as a single shot in the doctor’s office instead of an intravenous infusion in a hospital. But there’s many a slip ‘twixt Phase 1 and pharmacy shelves.

Protocols, redux: A month ago a court in Italy ruled in favor of some physicians who wanted to treat COVID-19 outpatients with a package of azithromycin, heparin, and corticosteroids (a gentler Indian version is illustrated at the top). One enthusiast told me on Facebook: “Hospitalizations will drop dramatically in the next few months and, hopefully, they will have no more reasons to continue with lock-downs and other restrictions.” Actually the court was merely pointing out that any doc can prescribe the ordinary medications in the protocol (none of which is indicated for COVID-19 outpatients) however he or she sees fit. But it’s a free-for-all – the Piedmont region has now, believe it or not, ordered that COVID-19 outpatients be given that old standby, hydroxychloroquine

 


Vaccine news

The AstraZeneca stock rollercoaster

AstraZeneca: AstraZeneca is in ever deeper doodoo, starting when the soap opera around its American Phase 3 trial dominated the vaccine news for days. Scientists who had seen detailed results accused the company of palming off as 80% a vaccine efficacy that was more like 70%, while an infectious disease epidemiologist reminded the world that the vaccine’s previous history was tinged with squalor. Now the company has readjusted that topline efficacy level to 76%, but the damage is done and United States authorities will be dissecting every word and number in the data before recommending authorization. 

Whatever that figure may be, the trial provides one novel result that will be vitally important, assuming the AstraZeneca vaccine survives its dire current straits: it works much better, at least in the elderly, with a 4-week gap between doses. Older people were protected 100% from hospitalization and death, rather than the 70-80% reported in the UK where the booster is given after 12 weeks. I hope that the European Medicines Agency will change its recommendations, and European countries will change their practice, on the basis of these data. I have even managed to find a back channel and contacted the EMA personally to make this argument.

But the EU is already retreating from AstraZeneca for other reasons. Several countries, including France, Spain, Holland, and Germany but not (so far) Italy, have restricted its use to older people, because blood clots on the brain have largely occurred in people under 60. Germany has gone farther, proposing that people under 60 who have already received a dose of AstraZeneca be given one of the RNA vaccines for their booster. And just today the European Medicines Agency concluded that the vaccine is in fact at fault, though it hasn’t yet drawn practical conclusions. The company itself is nervous enough about the clot issue that it’s suspended its ongoing trial among children. It didn’t help AstraZeneca’s case when the British regulatory authorities last week “discovered” dozens of cases of those rare clots, 7 of them fatal, that they had previously neglected to mention.

Given that the vaccine carries some risks in the young and is relatively ineffective in the old, I ask why not just say nuts to AstraZeneca and stick with vaccines that are less problematic? True, a 63-70% efficacy in younger people is much better than nothing, and the 1 in 600,000 clotting events (perhaps as high as 1 in 100,000 in people under 60) are likely outweighed by the dangers of COVID-19 in most parts of the world. But this latest among a controversial vaccine’s many controversies may end up dealing a death blow to its use in wealthy countries.

Pfizer: The Pfizer vaccine, on the contrary, goes from triumph to triumph.

Super news #1: Pfizer has completed a Phase 3 trial in adolescents in record time with great results: zero cases of COVID-19 among vaccinees, 18 in the placebo group. It’s still just a press release, not an article, but I believe these numbers. Soon we should be able to start vaccinating everybody from age 12 up.

Super news #2: After researchers in Texas reported that the Pfizer vaccine is likely to be relatively effective against the South African variant, a similar Israeli study came along. And now – even better – there is some direct evidence. A small trial in South Africa found 9 cases of COVID-19 among volunteers who’d gotten placebo (6 of them with B.1.351), and none among vaccinees. B.1.351 is particularly dreaded because it escapes both vaccines and monoclonal antibodies, so this is splendid news.

Super news #3: We already knew the vaccine works at 95-98% level in the short run, but new data from the Phase 3 trial show that protection remains over 90% for at least six months. Every month we’ll have more data.

But fairly soon an unexpected axe may fall. Pfizer, along with Moderna and Johnson & Johnson, plan to hike up their prices the moment they can declare the pandemic over, with one Pfizer guy noting that vaccine prices are “normally $150 to $175 per dose.” I guess he means in the United States... Vaccine list prices in Italian pharmacies: influenza $10, tetanus $11, polio $18, meningitis $24, oral typhoid $28, measles/mumps/rubella $33, Boostrix (tetanus/diphtheria/pertussis for adults) $34, hepatitis B $39, Pneumovax $47, hepatitis A $65. And all the crucial ones are free if you’re on the National Health Service.

Schedules: A new study among nursing home patients in England confirms how quickly protection from a first dose of vaccine falls off. The efficacy of AstraZeneca peaked at 67% after one month before slipping to 36% at 7 weeks. Despite these data and the similar Pfizer results from Scotland, some people are foolishly suggesting we muck around with the dosing of vaccines that we know work really really well when given properly. 

One of the muckers around, an influential American physician, offers what I would call a classic bait-and-switch in an article called “Forget second COVID vaccine doses for now.” If you read his argument carefully you’ll see it’s based on real data from Johnson & Johnson – which is absurd, that being a single-dose vaccine! – and on a set of hypothetical models about the Moderna vaccine making what I see as utterly unwarranted assumptions. But, good heavens, is he right that only 62% of the vaccines distributed in the United States have been administered at any given time? This is truly shocking. The need to hold back doses for boosters is irrelevant, since the US has a guaranteed steady supply, so the reason must be an appalling level of inefficiency. In notoriously chaotic Italy, where the vaccine supply is limited so it’s imperative to hold some in storage, doses get used as soon as they arrive, with the proportion of distributed doses that have made it into arms at any given moment varying between 86% and 97%.

Sputnik V

March, 2021


Russia has extremely low vaccination rates – only 2% of the population have had a dose – and the highest level of COVID-19 vaccine hesitancy among major countries. Some people have used those facts to cast aspersions on the Sputnik vaccine. But no, Russian vaccine hesitancy is an old story. When I travelled to the Soviet Union in 1990, I was horrified to learn that nobody we met had vaccinated their kids, even against polio and measles. So the low uptake of COVID-19 vaccine is about Russians’ longstanding mistrust of their governments, not about Sputnik. 

It seems that Sputnik will carry a price tag of around $10, half the cost of the RNA vaccines but much higher than AstraZeneca, thus less accessible to the poor countries where the Russians hope to peddle them. Doubts about the veracity of its trial results persist, and may become louder now that the President of Argentina has come down with COVID-19 6 weeks after his second shot. 


The Johnson & Johnson / AstraZeneca plant near Baltimore

Johnson & Johnson: Fifteen million doses went ruined at a Baltimore production plant when someone dumped ingredients intended for AstraZeneca into a batch of Johnson & Johnson. To err is human, of course, but that particular factory happens to have already flunked FDA inspections in the past.

A pill of prevention: An Israeli company is working on an oral vaccine, though it’s still in very preliminary phases. Somewhat surprisingly, the company aims to start studies in human beings within months, perhaps even before demonstrating that it works in animals. This drug seems unlikely to come through before most people in industrialized countries are vaccinated, but it could be a godsend for the developing world, also in case we need yearly boosters.

 

Big question, little question, no question


We already know plenty. Studies in Israel previously showed that complete vaccination with Pfizer cut asymptomatic infection by 94%. Now a study among California health care workers screened weekly with PCR swabs puts the protection even higher, at 98%, with Moderna doing just as well. So both RNA vaccines have laudable potential to block silent spread of the pandemic. 

According to the documentation presented to the US Food and Drug Administration by Johnson & Johnson, its vaccine protects 74% against asymptomatic infection. Pretty good, though not in the same league with Pfizer and Moderna.

AstraZeneca, though, is unfortunately lousy at preventing asymptomatic infection. This has huge potential impact, since so much of the vaccination campaign in the UK, Europe, and developing countries is based on this vaccine.

Please, journalists, stop saying it’s a Big Question – it used to be, but now we know the answer.

Key facts about asymptomatic infection: 1) Two-thirds of COVID-19 cases are caught from people who have no symptoms at the time. 2) 80% of people who get infected do eventually develop symptoms. 3) The 20% who never become ill have lower peak viral loads and are only half as infectious. But since they don’t know they’re infected they’re out and around and more likely to contact other people, probably outbalancing their lower contagiousness.

 

Batty or battier?



Robert Redfield, who directed the Centers for Disease Control for Donald Trump, has joined the “COVID-19 came from a Chinese lab” gang.

Here’s a quote from the article: “Redfield added he didn’t believe it made “biological sense” that the virus could spread so easily between humans if it originally came from an animal, saying "I do not believe this somehow came from a bat to a human.””

Any scientist who could say something this dumb doesn’t deserve to have his opinion taken seriously on any subject. Diseases easily passed from person to person that originally came from animals include EbolaHIVbubonic plague, and the 1918 pandemic influenza. I’ll refrain from commenting on the guy’s tenure as CDC director.

 

Long and longer



Post COVID-19 issues are rapidly turning into a plague within the plague. A new study in the UK showed even worse post-discharge outcomes from previously hospitalized patients than the previous one. Nearly one in 3 wound up back in the hospital, and 12.3% died. Survivors faced new diagnoses not just of respiratory disease but also of diabetes, liver disease, kidney disease, and heart disease. Not to speak of the neurological and psychiatric disorders developed by one-third of all COVID-19 patients during the 6 months after diagnosis. Substantial numbers of patients, including many never sick enough to hospitalize, still have symptoms a year later. I fear that long COVID may cause as much ill-health during 2021-22 as acute COVID-19 did in 2020.

Of course the pandemic affects everybody on the planet, infected or not. I was touched by every word of Sarah Lydell’s Op-Ed in the Times last week, “We Have All Hit a Wall,” but here’s the passage that hit closest to home:

Just recently I myself spent half an hour struggling to retrieve a word from the faulty memory system that has replaced my prepandemic brain. (“Institution.” That was the word.) Sometimes, when I try to write a simple email, I feel I’m just pushing disjointed words around, like peas on a plate, hoping they will eventually coalesce into sentences.

Yes, I’ll confess, even writing this blog is more of a struggle than it used to be. 

Psychological scarring has been particularly profound in places such as Bergamo where the disease hit hardest, but it occurs everywhere. Last fall 85% of American college students told pollsters that poor mental health was negatively impacting their academic performance. Pandemic despair has been so severe and so widespread that in the United States 25% of young adults “seriously contemplated suicide” during the first 6 months of the pandemic.

 


Shadow on the shot

 


The defeated President may be out of power, but he still casts a shadow. When Trump had COVID-19 last October it was obvious to any medical observer that he was sicker than anybody was admitting. We now know that he was worse off than even I thought, narrowly escaping being put on a ventilator. Now we’ve learned that the guy had himself and his wife vaccinated secretly, in early January when he was still President. At that moment 55% of Republicans (versus 15% of Democrats) were telling pollsters they wouldn’t take a COVID-19 vaccine, even FDA-approved and gratis. If that shot had gone into Trump’s arm on live television instead of behind closed White House doors, how many of his worshippers might have changed their tune? How many lives would have been saved? After Anthony Fauci and some of Trump’s own people called on the ex-President to campaign for the vaccine among his followers, he did say something of the sort when asked directly during a Fox News telephone interview: "I would recommend it and I would recommend it to a lot of people that don't want to get it and a lot of those people voted for me, frankly.” He then undermined the message with “But again, we have our freedoms and we have to live by them.” No enthusiasm, no fervid speeches, certainly nothing resembling the collective public service announcement made by all the other former Presidents and First Ladies.

We may have an explanation for why he’s kept quiet. After the Wall Street Journal broke the news that Russia is running an elaborate campaign to discredit the Moderna and Pfizer vaccines, some have speculated that Trump’s silence about his own vaccination – and his failure to urge the MAGA crowd to get vaccinated –  has a precise purpose: to help out his old pals at the Kremlin publicize Sputnik V at the expense of Western products, whether American-German or Anglo-Swedish.

 

Republican lawmakers refusing masks

As many had feared, one spinoff from Trump’s January 6th insurrection was a COVID-19 superspreader event. Lawmakers were forced to share a crowded hiding place with maskless Republican colleagues, at least one of whom was infected. Eight of the people taking shelter tested positive in the two weeks that followed. Of course the rioters themselves were at high risk after prowling those halls without masks, but if they’re coming down with COVID-19 in droves they’re not advertising the fact.

 

School daze


A Swedish classroom


I’ve generally stayed away from the school reopening debate, beyond backing in-person elementary schools – perhaps the only issue that’s ever found me and Donald Trump on the same side. 

One December study concluded that closing schools was one of European countries’ best tools against COVID-19, along with closing businesses and strictly limiting gatherings, with strict lockdowns adding relatively little. But I suspect the benefit was mostly from keeping adolescents, not kids, at home.

Some interesting data from Sweden. As part of their generally “soft” approach, the Swedes closed high schools but left kept elementary and middle schools open. Now researchers report that this approach was a little less benign than many thought, even recently in one highly-criticized research letter. Parents of last-year middle school students were 17% more likely to get COVID-19 last spring than parents of first-year high school students, their teachers were twice as likely to be infected, and teachers’ life partners were at 30% increased risk. Closing middle schools, the authors calculate, would have prevented 620 cases of COVID-19, 33 hospitalizations, and one death. Perhaps face masks and stricter distancing (see photo) would have helped too. 

  


As Abe Lincoln said, don’t believe everything you read on the internet 


This fake UK government announcement, from a no-vax website, was featured in a Facebook comment on my last blog post. Those terrifying numbers refer not to documented vaccine reactions but to Yellow Card reports, explained at the real gov.uk website as

. . . a mechanism by which anybody can voluntarily report any suspected adverse reactions or side effects to the vaccine. It is very important to note that a Yellow Card report does not necessarily mean the vaccine caused that reaction or event . . . It is often coincidental that they both occurred around the same time.


Next up was this helpful video:

 


And then, just when I thought I had heard it all:



Ummmmm…. somebody sure makes this stuff up, folks. Not one of the countless complaints about possible vaccine complications has mentioned Parkinson’s, Alzheimer’s, Prion Disease, Lou Gehrig’s disease, or any other serious neurological disorder. The “scientific” article, published in a "predatory" journal, is not retrievable, but the Zombie Preparedness page is for real. Enjoy!

2 comments:

  1. Alas, there's still no therapy for Trump Derangement Syndrome. Sorry, Doctor, you've lost me (and your veneer of no-nonsense skepticism) with the link to another ridiculous Trump/Russia conspiracy. Anti-vaxxers aren't the only ones making things up.

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    1. I'm sorry to lose a reader. About your content I'll only point out that I said "some have speculated," not "I think," but will add that it is possible to get something positive from articles by people one doesn't agree with politically. I do so often enough myself, though at certain moments I may have to let my eyes glaze over.

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