Tuesday, June 29, 2021

Strange Bedfellows and Executive Privilege


Masking the goddess

Not much treatment news but lots on vaccines, from the FDA to privileged European executives to bullshit that’s hit the fan. Sideshows: magic animations, retracted research, and chefs with crystal balls.


Treatment updates

Natural immunity: I’ve mentioned a bone marrow study that suggested immunity after COVID-19 could last years. Now that study has been published – and the journal, Nature, offers an article explaining the science clearly. But having had the original virus doesn’t necessarily protect you against variants.

REGEN-COV: Good news. I’ve been asking for months why Regeneron wasn’t testing its monoclonal antibody preparation for COVID-19 patients in the same low-dose, single shot in the arm, version that wards off disease in family members. Well now they’ve quietly halved the recommended dosage, and say it’s permissible (though for some reason not advised) to give it by subcutaneous injection instead of intravenous infusion. The lower dose was apparently just as effective in clinical trials, but we don’t know whether they examined the relative efficacy of the two routes.

…more good news: it looks like REGEN-COV can help hospitalized patients too, if they haven’t yet developed antibodies of their own, cutting mortality by 20% in one large trial. So maybe it did help save Trump after all. (Plus it knocks out the Beta and Gamma variants.)

Lilly: Bad news. After 8 states de-authorized the Lilly antibody combo because of poor efficacy against the Beta and Gamma variants, now the FDA has withdrawn it entirely

Antibodies down the drain: After Regeneron showed its one-shot antibody concoction could prevent COVID-19 in household contacts, AstraZeneca tried its hand at the same trick. Unfortunately the effort has tanked.

Anticoagulants: I never thought they made sense in mildly ill outpatients. Now that’s been confirmed by an important trial, for both apixiban (a heparin type anticoagulant) and aspirin – mainly because outpatients simply don’t get clotting complications.

Aspirin: In the RECOVERY trial's latest report, patients given daily aspirin left the hospital slightly sooner and were slightly more likely to leave it alive, but the trial was considered a failure because overall mortality did not differ significantly. Call it a maybe.

Ivermectin: This deworming drug has been called “the new hydroxychloroquine,” for the undeserved hype it attracts; the person who coined that phrase has written an article debunking it in excruciating detail. Despite inconclusive results from a number of small trials, and guidelines recommending against its use, ivermectin gets prescribed to COVID-19 outpatients in many countries. Now it will finally be given a proper test, in the context of the UK’s PRINCIPLE trial.

Interferon: This drug looked promising against severe COVID-19 but has largely fallen by the wayside, with US and European Union guidelines advising against using it outside clinical trials. Two small recent methodologically awful studies, one from Spain and one from Saudi Arabia, plus one marginally better but even smaller study from Iran, have hinted it might decrease mortality. A proper Phase 3 trial of an inhaled version is now happening, at last.

EXO-CD24: In early February I mentioned that this novel inhaled drug aimed at “cytokine storm” was said to have kept 29 out of 30 moderately-severely ill Israeli patients from deteriorating. Five months later the developers are finally starting a proper placebo-controlled Phase 2/3 trial – in Greece, this time, which unlike Israel still has many COVID-19 patients in the hospital. The fact that we haven’t heard a peep about this drug from Brazil, where it’s been used en masse for more than 3 months, suggests it may not be as miraculous as promised.

Tofacitinib: This oral Janus kinase inhibitor seemed to work wonders in 189 Brazilian patients hospitalized with COVID-19 pneumonia, cutting deaths nearly in half, considerably better than baricitimib (the other drug in this category). One study can’t be considered definitive, though.

Tocilizumab (Actemra): Since March 2020 I’ve been describing this drug’s roller-coaster ride: one trial says yes, one says no, one says maybe. Now the FDA has decided to authorize it for emergency use in severely ill COVID-19 patients, based on 4 clinical trials. In one the drug decreased the death rate by 12%, in one treated patients were 38% less likely to wind up dead or on a ventilator, and the other two found no effect whatsoever. I remain unimpressed.

Remdesivir: I somehow missed the fact that last November the World Health Organization actually recommended against its use in COVID-19. My bad. But though it’s never been great shakes it’s practically all we’ve got, so it’s still routine in both the United States and Europe for patients hospitalized with pneumonia.

Dollars for pills: The United States has decided to invest $3.2 billion of the COVID relief funds into developing effective oral antivirals. Unfortunately there’s not much in that particular pipeline besides Pfizer’s PF-07321332, which as of mid-May hadn’t been tested in animals much less humans.

Prayer: Workers at a Japanese temple to the Buddhist goddess Kannon have, on their own initiative, mounted a face mask on her statue hoping she’ll end the pandemic.


Vaccine updates

Novavax: Good news. The long-awaited top-line results of a Phase 3 trial of this novel vaccine in 30,000 US and Mexican volunteers have now been announced. Overall efficacy was 90.4%, with no severe cases in vaccinated subjects. Efficacy was similar in people over 65, with co-morbidities, and against “variants of concern” (though the press release only specified the relatively docile Alpha). Flu-like side effects seemed to be relatively mild, and no other safety concerns arose – yet. 

CureVac: Terrible news. Their vaccine is only 47% effective at preventing COVID-19, far worse than AstraZeneca, worse even than Sinovac. The company blames these poor interim results on variants, but they had once specifically promised excellent efficacy against at least variants Alpha and Beta. This news – if confirmed by final results – is a severe blow to the European Union, whose campaigns had bet heavily on CureVac.

Tripling down: French investigators tried giving an extra dose of Pfizer vaccine to organ transplant patients, 2 months after the second. It hiked the percentage of patients with anti-SARS-CoV-2 antibodies from 40% before dose 3 to 68%4 weeks later. Excellent, though still lower than in healthy individuals. I suspect an extra booster for immunosuppressed patients will quickly become standard practice.

Heartbreak: American cases of myocarditis or pericarditis following Pfizer or Moderna vaccines have now surpassed 1200, some needing intensive care unit treatment. A CDC conference on June 23rd concluded that there was likely a causal relation, but that the cardiac risks from COVID-19 far outweighed the risk from the vaccines. This complication occurs after one in 80,000 doses overall, one in 30,000 among males under 30. (Btw, Eriksen’s cardiac arrest couldn’t have been related to mRNA vaccines ­– he was unvaccinated. Do your homework, novaxxers.) 

Breaking through (West): A study from the UK clarifies the subgroups less protected by COVID-19 vaccines: people who are old, frail, poor, obese, or malnourished. Breakthrough cases are usually mild, though, and – curiously – more likely to cause sneezing. They are also 40-50% less transmissible, even if patients had only a single vaccine dose.

Breaking through (East): Scores of countries, especially in the developing world, have based their vaccination campaigns on Sinovac and SinoPharm. I’ve always suspected those Chinese vaccines might be less effective than claimed, and that this has contributed to COVID-19 surges in Turkey, Chile, and Indonesia. The latest example is the Seychelles, now having its first real spike despite the highest vaccination rate in the world. And dozens of Indonesian doctors and nurses have been hospitalized with severe COVID-19 despite being fully vaccinated with Sinovac… similar experiences also in Mongolia, Bahrein, and the United Arab Emirates.

Lasting long: Dire predictions that we’ll need frequent boosters seem less and less probable, based on new evidence that post-vaccine immune memory cells are ready and waiting to produce fresh supplies of antibodies.

Sputnik: Here I am being suspicious yet again of the Russian vaccine… This time because of reports from Mongoliasaying it’s even less effective than Sinopharm. No details, unfortunately.

AstraZeneca: More trouble. A dozen atypical cases of Guillain-Barré syndrome (sudden paralysis) have been described in the UK and India 10-22 days after doses of AstraZeneca. Plus a few in the United States following Johnson & Johnson. Guillain-Barré has been reported sporadically after various vaccines, though the 1976 Swine flu shot was most notorious.

Bye-bye Phase 3?

Not really. The Oxford guys merely showed that antibody levels correlate with vaccine efficacy, and I doubt that means scrapping Phase 3 trials. Take the CureVac story: in Phase 1 it elicited “strong immune responses,” both anti-spike and neutralizing antibodies. When push came to shove, though, the damn thing didn’t work.

Defanging Delta: The highly contagious and possibly more virulent Delta variant has swept the UK, accounting now for 99% of new cases. It hasn’t made inroads in Continental Europe or the US yet, and Italy, at least, has imposed new quarantines on travelers from the UK in hopes of keeping things that way. What’s the latest on vaccines? I’ve mentioned that in England full Pfizer vaccination protected 88% against Delta COVID-19, AstraZeneca only 60%, in Scotland 83% vs. 61%. A single dose of either vaccine, though, gave only 33% protection. Many Brits are only half vaccinated, because of their 12-week gap policy, which accounts neatly, in my opinion, for the UK’s current surge. Word to the wise: Italy, please stop stretching out the time between doses (currently 12 weeks for AstraZeneca, 5 for Pfizer and Moderna) and get those boosters into arms.

Much is being made of Israel’s recent “surge” with the Delta variant, and of the fact that half the recently infected adults were fully vaccinated with Pfizer. I think it's much ado about little: the spike is tiny, and the country has had a total of 5 severe COVID-19 cases and 2 deaths since June 10th.

We now have two studies of how well vaccines protect against Delta-variant hospitalization. In a Scottish one, published in the prestigious Lancet, full vaccination with two doses of Pfizer was 79% effective, with AstraZeneca 60%. But an English preprint without peer review claims effectiveness of 96% and 92% respectively. Which should we believe? (China affirms that SinoVac is effective too. No evidence provided.) With Johnson & Johnson, like AstraZeneca, only protecting 60% against severe Delta COVID-19, some suggest J&J vaccinees receive a booster with Pfizer.

The persuasion gameCarrots: cash, from $50 in California and $100 in West Virginia all the way up to $500 for Colorado’s prison staff; a free Krispy Kreme donut a day (1.5 million distributed so far); free passes to state parks; plates of spaghetti and meatballs. Maybe those bribes could workSticks: You can’t get hired by US airlines, or Saks, or get listed by Pimlico Plumbers (motto: “no jab, no job”), without proof of vaccination. Following Houston Methodist, hospitals from Alaska to Chicago are threatening to fire unvaccinated staff. One US college is planning on charging unvaccinated students $1500 per semester to cover biweekly testing. In Pakistan – where many believe anybody who gets vaccinated will die within 2 years – two provinces are threatening to cut off cell phone service to anybody who refuses vaccination. Some might find that an even worse punishment than the jail time Rodrigo Duterte is threatening for unvaccinated Filipinos. Personal pitches: 18% of Italians over 60 still haven’t had a dose, so the National Health Service is cross-linking vaccination records with patient lists. That way General Practitioners can contact their patients personally and urge them to get vaccinated. Polls suggest something like this might help in the US too, primary care providers being apparently more likely to succeed than, say, Anthony Fauci, who in an hour and a half of going door to door was only able to talk 6-10 people into getting their shots.


Vaccine politics makes strange bedfellows

All the COVID-19 vaccines are currently approved only for “emergency use,” but Pfizer and Moderna have applied to move on to full authorization. Now 27 scientists, physicians, and patient advocates have petitioned the FDA not to grant it for at least another year, for fear awful new adverse effects will emerge. I think on the contrary that full approval is not only appropriate but urgent, both to help convince the hesitant and to put vaccine mandates on a more solid legal footing. Vaccine complications seem always to happen within a few weeks, and vaccines approved by the FDA in the last decade averaged only 6 months’ followup in their Phase 3 trials and only 5000 subjects each. The COVID-19 vaccines now seeking approval in the United States enrolled 30,000-40,000 volunteers, and have already followed them for at least that long. So I decided to take a close look at the signatories – who turned out to include many questionable characters.

-       Peter Doshi and Hamid Merchant are reputable researchers. Both expressed healthy skepticism, initially, about the high efficacy of the mRNA vaccines. Those doubts seem irrelevant by now, though, in view of those vaccines’ superb real-world effectiveness in multiple countries.

-       Kim Witczak became a patient advocate after her husband’s suicide following an inappropriate Zoloft prescription. Her specific objections last December to the Pfizer and Moderna vaccines have been largely overridden by later research.

-       Peter C Gøtzsche, a well-known vaccine skeptic. His degree of judgement about COVID-19 was already clear in March, 2020, when he wrote: “What if the Chinese had not tested their patients for coronavirus or there had not been any test? Would we have carried on with our lives, without restrictions, not worrying about some deaths here and there among old people, which we see every winter? I think so.”

-       David Healy, whom I’d term a vaccine half-skeptic.

-       Byram Bridle, an opponent of lockdowns and COVID-19 vaccines whose bizarre spike protein theories I discussed in my last post.

-       Peter Aaby, a standard-bearer for the discredited theory that DTP vaccine increases childhood mortality.

-       Anthony J. Brookes, a signatory of the notorious Great Barrington Declaration promoting a herd immunity strategy.

-       Angela Spelsberg, a German epidemiologist who in October 2020 thought it was time to stop COVID-19 suppression measures (in the picture she’s saying, “Corona is no great danger to us”). Literally days later, her country’s vicious second wave took off.

-       Patrick Whelan, who has demanded that the EMA withdraw approval from Moderna and Pfizer vaccines – because of AstraZeneca’s clotting issues! Even his “facts” are at least “partly false.”

-       Joseph A. Ladapo, from the right-wing COVID-19-denier group, “Frontline Doctors.” Early on he advocated against shutdowns, and a year and 600,000 American deaths later was still complaining about “overreaction to the virus.”

-       Peter A. McCullough, a cardiologist who as recently as March 2021 kept on pushing hydroxychloroquine.


When the bullshit hits the fan

This is the tweet that got Naomi Wolf kicked off Twitter, crowning what the New York Times has called a “long, ludicrous career.”

Yup, that school is not requiring teachers to be vaccinated, but threatening to fire them if they do. That’s because people who are vaccinated with RNA vaccines not only put their own fertility at risk (old “news”) but “may be transmitting something from their bodies” that can mess with the menstrual cycles of any female within range. (Centner has a history. It forbade students from going near windows, fearing radiation from 5G cell towers, until they installed electromagnetic frequency “shielding blockers.”)

Great news for Centner Academy! Except there is, of course, no such thing as spike proteins shed. The supposed active ingredients of the tea, suramin and shikimic acid, also happen to be toxic… 

The head of Pfizer research of course said no such thing, and Dr. Yeadon is a well-known conspiracy theorist. Since time zero, no-vaxxers have been claiming the vaccines can make women sterile. This claim sometimes comes dressed up in pseudoscientific clothing, has spread like wildfire in what Mayo Clinic has called a “sophisticated disinformation campaign,” and is one of the main reasons given by American nurses and Orthodox Jewish women for refusing the jab. The infertility claim is nonsense but, yes, there is anecdotal evidence that a dose of vaccine can sometimes make your next period come earlier or heavier. This can also happen after other vaccines, particularly those against HPV and influenza, without affecting fertility. Incidentally, there’s already fairly good evidence that vaccination during pregnancy doesn’t cause trouble.

According to the videomaker, this image proves that Bill Gates has laced COVID-19 vaccines with microchips, turning the human body into a giant magnet. A similarly convinced nurse, Joanna Overholt, pressed a key onto her skin at an Ohio House hearing to show how the vaccine had magnetized her, but it wouldn't stick.


Bullshit matters

Vaxx shedding and vaccine magnetism may be nutcase ideas, but they have dire practical consequences. No-vax sentiment in the US used to be falling, but the proportion of hardcore refuseniks hasn’t budged for months now.


So many Americans are saying no that the number of doses administered daily is barely a fifth what it was in April, even though a third of adults still haven’t received even one shot. India, where the logistics are infinitely more complicated, is beating the US per capita by 2 to one, and Italy by 4 to one. And I’m proud to report that despite a late start and supply shortages Italy has surpassed the US in the percentage of the population with at least one shot (55.5% vs. 53.7%)!!!


Can I take it back, please?

Jade amulet, Ghanti temple bell, Thali plate

The busy bees at Retraction Watch are now up to 128 scientific papers about COVID-19 that were subsequently retracted. Many were withdrawn over relatively minor issues such as data duplication and ethical concerns – one used data recycled from a 2018 paper! – but others ventured deep into quack territory. Some of the star claims: coronavirus aerosols can travel 5 meters near-instantly (see my last post), SARS-CoV-2 long predated the pandemic in Italyartificial intelligence is a great diagnostic tool, people should refrain from sex during the pandemic, COVID-19 causes psychosissmoking protects against COVID-19 (written by a tobacco industry consultant, natch), COVID-19 originated in India (written in China, natch), and quarantines cause wife-beating. Not to speak of articles claiming miraculous benefits from vitamin Djade amulets, clanging dinner plates and temple bellshomeopathyivermectin,hydroxychloroquine plus antivirals, ivermectin again, and vitamin D again and again and again.

The trophy for the most COVID-19 retractions (26) goes to Victor Grech, a pediatric cardiologist from Malta who also published 19 prepandemic articles detailing the light shed by Star Trek on everything from the evolving role of nurses to the horrors of Nazi doctors.


Watch it go!

Set your computer to view it full screen, then click on play. I’ve enjoyed this one-minute animation a dozen times. The numbers should be taken with a grain of salt, though – underreporting is likely enormous in India and substantial in China and Russia. Even in the US, which we think keeps better track of stuff, the true pandemic death toll has been estimated at double the official figure.


Executive privilege

Mario Draghi, Angela Merkel

Italy recently joined France and Germany in a mix-n-match vaccine policy, whereby people at risk for clotting complications by virtue of being under 60 are (sensibly) offered the option of having Pfizer or Moderna as their booster after AstraZeneca. 

But on June 19th we learned that Italian Prime Minister Mario Draghi, age 73, was going to get Pfizer as his second dose. Not surprisingly, the story sowed chaos. The Governor of Lombardy declared anybody who wanted could emulate Draghi, but he was quickly overruled by his health department with, “This option is available only to the Prime Minister.” Piedmont and Campania now seem to be offering freedom of choice at all ages, as recommended bythe national undersecretary of health, Pierpaolo Sileri, but their generosity may be hampered by an rumored shortfall in Pfizer doses.

A few days after Draghi, German Chancellor Angela Merkel similarly pulled rank, to my great surprise, receiving Moderna as her second dose at the age of 66. When I first read the linked Times article it specified that Prof. Merkel would be the one and only person allowed to mix-n-match her second dose, but that overly explicit phrase was dropped from the current version.


Prescience in the kitchen…

Did supercelebrity chef Anthony Bourdain really say this? USA Today checked: “This tweet does not exist on Bourdain's official Twitter page. There is no evidence he ever traveled to Wuhan and ate bat soup. Claims that COVID-19 is linked to bat soup have been debunked.” 

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