|A bone marrow plasma cell
Natural immunity: In a large Qatari population, COVID-19 protected survivors from reinfection for at least 7 months– at a 95% level, as good as the best vaccines. These patients were mostly young, with strong immune systems. But in another study, 100% of US military personnel hospitalized with COVID-19, and 82% of outpatients, still had antibodies a year later, including those over 65. And bone marrow samples from patients 11 months after mildCOVID-19 all included specialized plasma cells, ready to produce antibodies if the body were reexposed. These results suggest that infection (and, likely, vaccination) will give long-lasting immunity, unless variants throw spanners in the works.
Leronlimab: I once commented: “’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.’” An updated CytoDyn press release goes even further: “Majority of Patients Have Demonstrated Remarkable Recoveries.” The FDA has now slapped the company with a public reprimand for misleading reporting.
Dexamethasone: Someone sent me a recent metaanalysis claiming that corticosteroids not only don’t help severely ill COVID-19 patients, but actually increase mortality. I was suspicious when I saw it was in an obscure Indian medical journal with a low impact factor – an extremely odd place to publish a bombshell paper debunking our only decent treatment for critically ill COVID-19 patients. Careful reading revealed that the bomb had fizzled. Of the 3 key articles supporting the authors’ thesis, one had been grossly misinterpreted, the second enrolled mildly ill patients (well known to do worse on steroids), and the third was not a trial but a retrospective case series in which patients given corticosteroids – generally because they were extremely sick – were, unsurprisingly, more likely to die. Total b.s.
Colchicine: An excellent trial among 4159 high-risk swab-positive COVID-19 outpatients has now been publishedand the results, though not spectacular, are good: over a month, subjects in the colchicine group were 25% less likely to require hospitalization and 44% less likely to die. Not bad for a low-cost, low-risk oral drug that’s been around for 3000 years.
Regeneron: In preliminary results on 275 high-risk outpatients treated early, their antibody cocktail cut negative outcomes in half. Now the top-line results of the full trial, involving 4567 patients followed for a month, have been presented at a medical conference and are even better: those given the drug got well faster and were 71% less likely to die or need hospitalization. Some patients had received doses low enough to be given by a single shot in the arm, an approach I’m praying someone will test soon.
Regeneron is also a variant blaster. It works fine against B.1.1.7, and at least in testtubes it looks good against P.1., B.1.526 (New York), and the difficult B.1.351. Lilly’s monoclonal antibody product bombs against all except B.1.1.7.
Sotrovimab: This monoclonal antibody, already authorized in Europe, has now been approved for emergency use by the US Food and Drug Administration in high-risk outpatients. Unfortunately it too requires intravenous infusion.
Ivermectin: Last week the Indian state of Goa started handing it out to all adults, to ward off COVID-19. The same day, the manufacturer told Indian media that its product is useless in treating COVID-19 – as confirmed by a systematic review of all the randomized controlled trials. Articles by ivermectinist-in-chief Pierre Kory and by an anonymous “we” claiming the opposite are laughable – I won’t waste time discussing them. Ivermectin hasn’t yet been proven useless for preventing COVID-19, but I’m not holding my breath.
Vaccine updates (see also Alternative Facts, below)
|Robert Kramer testifying before Congress
Johnson & Johnson: On May 19th Democrats in Congress spent 3 hours grilling the CEO of Emergent Biosolutions, Robert Kramer – the guy who sold off millions of dollars in stock just before his company was revealed to have ruined 15 million doses of vaccine. He admitted that his factory had moldy walls and peeling paint and that a total of 100 million doses are being held up right now pending testing. It turns out, too, that while the pandemic was racing across the country last year, the federal government handed Emergent hundreds of millions of dollars for, of all things, anthrax vaccine.
Mix ‘n’ match: Researchers combining a first dose of one vaccine with a second one of another claim to be close to real results. In the meantime they’re finding that various combos boost immune response, though at the cost of increased side effects. I won’t comment until I see a proper manuscript.
AstraZeneca: Remember when the Brits swore they hadn’t seen a single case of those nasty clotting complications? As of May 20th they were admitting to 332 domestic cases and 59 deaths, including that of a BBC radio presenter, and had lifted the minimum age for AstraZeneca from 30 to 40. (In the European Union there were only 316 cases as of May 28 despite a 7-times higher population, due to age limits and bans in member states.) It is also now officially no good at all against the South African variant (21.9% efficacy).
Tweedledum and Tweedledee: Yet another CDC study confirming the real-world effectiveness of Pfizer and Moderna vaccines against symptomatic COVID-19: 94% in a case-control study involving 500,000 healthcare professionals. Both companies have now requested full approval, rather than just emergency authorization, from the US Food and Drug Administration. This would allow intensified appeals to the unvaccinated, including direct-to-consumer advertising, and make it easier for employers to require vaccination.
Moderna: After Pfizer, Moderna is the second vaccine to shine in a Phase 3 trial among adolescents ages 12 to 17: 100% efficacy at 2 weeks after the second dose. I do think, though, along with the WHO, that headway should be made on vaccinating adults in the global South before we start vaccinating kids in wealthy countries.
Pfizer: Good news: it turns out unopened vials can be stored in the fridge for a month rather than going bad after 5 days. This makes life easier for vaccination centers and office-based physicians, though the vaccine still needs to br shipped under deep freeze. More good news: it knocks out the Brazilian P.1 and the Indian B.1.617.2 variants, as well as the English B.1.1.7, the California B.1.429, and the South African B.1.351. And its 100% efficacy in 12 to 15-year-olds has now been published.
Bad news: 62 cases of myocarditis (inflammation of the heart muscle) among 5 million Israelis who had received the Pfizer vaccine, usually men after their second dose. Most cases were mild, but two died. A vaccine link has not been proven – people also get myocarditis from viral infections including COVID-19. “Rare” cases are under investigation in the United States, mainly in male adolescents and young adults following dose two. I’m unhappy that the Israeli authorities, unlike the Americans, apparently tried to keep this under wraps. If myocarditis is ascertained to be a side effect, the Israeli rate of 1 in 20,000 vaccinees under 30 could be high enough to cause concern. Also: Norwegian scientists are attributing 10 deaths to the Pfizer vaccine, out of 30,000 vaccinated nursing home residents, presumably related to fever and other flu-like side effects. They suggest, reasonably, that among extremely frail individuals with a very limited life expectancy, the benefits of vaccination might not be worth the risks.
Sanofi: After this French company’s original candidate vaccine flunked Phase 2, they hooked up with GlaxoSmithKline to produce a new version. That one is apparently promising enough to move forward with Phase 3 trials earlier than expected.
Sinopharm: In a newly published Phase 3 trial in the Middle East, vaccine efficacy was 72.8% for one of their vaccines (WIV04) and 78.1% for the other (HB02). Unfortunately virtually all the participants were under age 60, and 85% were men, limiting generalizeability. Four weeks ago World Health Organization declared the HB02 vaccine acceptable for emergency use.
Sinovac: …and now the WHO has also given its blessing to the other major Chinese vaccine, Sinovac’s CoronaVac, despite the absence of properly published data and despite wildly inconsistent efficacy in Phase 3 trials – 84% in Turkey, but only 51% in the larger Brazilian trial the WHO rightly prefers to cite. It’s easy to ship and store, and potentially cheap, so a good match for the COVAX initiative.
Novavax: Its moderate efficacy the South African B.1.351 variant (60.1% efficacy in HIV-negative volunteers, 49.4% overall) has now been published.
Rochelle, Rochelle, what hast thou wrought?
|CDC Director Rochelle Walensky after throwing the first pitch at Fenway Park
We were already bad enough off at the beginning of May. Among the numerous American adults who didn’t intend to get vaccinated, 63% (vs. 19% of those who’d already had a shot) thought it was fine to socialize indoors with other unvaccinated people without wearing a mask. One can only imagine what that number is now, given the CDC’s liberalized guidelines.
Here’s one thing we do know happened in the days after those guidelines were announced (red arrow):
Another is that many indoor workers are starting to panic.
|Wuhan Institute of Virology, pangolins at an Asian wildlife market
I’ve avoided wading into the origins-of-COVID morass, but I’ve generally considered myself, along with most virologists and the World Health Organization, on the “came from a bat via a pangolin” side rather than the “escaped from a lab” side. Aside from anything else, the lab leak notion often came bundled with implausible conspiracy theories about the Chinese engineering the coronavirus as a biological weapon or deliberately unleashing it on the world. But I’m starting to harbor some doubts after reading an article by science writer Nicholas Wade, from whom I have also learned that some of the opposition to the lab leak theory was self-interested. Many others have been changing their tune, including Anthony Fauci… especially after the stunning “leaked intelligence report” in the Wall Street Journal on May 24th that 3 researchers at the Wuhan Institute of Virology were hospitalized for COVID-19-like symptoms at the beginning of November 2019, weeks before the first official case.
That WSJ article remains entirely unsubstantiated, though, and China has issued vociferous denials. Everybody dismissed the Chinese statements but now, in what seems to me an equally stunning twist, it’s been pointed out who Michael R. Gordon, the lead author on the WSJ piece, is. He turns out to be the guy who in 2002, together with Judith Miller who lost her job over it, notoriously “leaked” in the New York Times major lies about Saddam Hussein’s supposed nuclear ambitions that had supposedly been fabricated by Dick Cheney and arguably led to the war in Iraq. He’s a repeat offender: in 2014 he wrote another phony intelligence article for the Times, this time risking war with Russia, that had to be followed within days by a retraction and an apology. Sick Wuhan researchers would have been a smoking gun – without them the lab leak theory may revert to improbability.
In possibly related news, Italian researchers claim to have found antibodies to SARS-CoV-2 in frozen blood samples taken in September 2019 for an unrelated study. Knowing the virus was in Europe months before it appeared in China could, they rightly say, “reshape the history of the pandemic.” I’d take the reshaping with a grain of salt, though. The lack of symptoms in any of these research subjects suggests the antibodies may have been to a slightly different virus; the inaccessibility of the full article is suspicious; and the manuscript was published in an obscure journal with the extremely low Impact Factor of 0.89 (though it succeeded in hitting the news anyway).
SARS-CoV-2 antibodies have also turned up in blood samples from California, Oregon, and Washington in mid-December 2019, suggesting the virus reached the American mainland a month before anyone knew. This report is more plausible than the Italian one, both because December is later than September and because of the close ties and high rates of travel between the West Coast and China.
The vaccine mysteries of red America (and not only…)
|Ivanka, unlike Daddy, immortalized her first shot
Do Republicans positively crave COVID-19? We already knew they lopsidedly avoid masks, patronize packed bars and restaurants, and view public health measures as impingements on their liberty. They always trended vaccine hesitant, but in one poll 43% of them (vs. 5% of Democrats) still have no intention of getting a shot, despite their friends and neighbors getting vaccinated without incident. Many confess they’d snap up a fake vaccination card if they could.
But after all, they’re just following the model of their political leaders – only 44% of Republican members of Congress have been vaccinated (vs. 100% of House Democrats).
Experts trying to persuade Republicans seem to have thrown in the sponge, with focus groups suggesting that novaxxers have only hardened in their convictions. Hectoring, arguing, experts’ explanations, endorsements from GOP politicians all flop. Appeals to Trumpian boosterism haven’t helped either, but many think an enthusiastic public service announcement from the man himself might. Some think the best messenger will be primary care physicians, if they can be enlisted in the cause and especially if they can administer vaccines in their own offices.
Then there’s what one New York medical colleague wrote about trying to convince his condo staff to get vaccinated: “People who would eagerly ask me for curbside medical advice about family members and themselves suddenly, and with no logical reason, didn't want to accept my recommendations. That is UNTIL they discovered that they couldn't get into a Yankee (yay!) or Mets (meh) game without a vaccine certificate. No rock concerts, no ball games, no bars (except "red" Staten Island), no planes, without a vaccine or an expensive and cumbersome negative Covid test proof. Suddenly they were getting vaccines.”
|Antivaccine flyer in a Hasidic neighborhood of Brooklyn
The American no-vax chickens have been coming home to roost. The number of daily vaccinations has fallen to a third what they were as in mid-April, states are turning away deliveries of fresh doses, and growing numbers of scientists doubt the United States will ever achieve widespread herd immunity. Besides Republicans, who else is saying no?
|Kaiser Family Foundation poll, late April
- Young people. A third to half of them are ducking the jab, becoming the main driver of the epidemic now that older Americans are vaccinated.
- Health care workers. I was discouraged to see in an online poll that 15% of physicians, 26% of medical students, and 32% of nurses said they had no intention of being vaccinated. Barely half of US health workers had received a dose as of early March (hopefully many more now).
- Police. In various large departments, including Los Angeles, fewer than 40% have gotten even one shot. Think of all the people those guys come in contact with up close and personal.
- Ultra-Orthodox Jews. In January – the latest stats I can find – only 12% wanted the vaccine.
- Inmates. In the California state prison system, only 66.5% of those offered a vaccine chose to take it, in New York apparently only 45%. Disturbing, because physical distancing is impossible in prisons and jails and at least 3000 American inmates have died of COVID-19.
No such problem in my adoptive homeland, Italy. In March 20% of Americans but only 7% of Italians were dead set against vaccination. In late April 79% of unvaccinated Italians said they’d jump at the chance for a shot – compared with only 46% of unvaccinated Americans. So the vaccine train keeps going full steam ahead whenever there’s enough coal to shovel into the furnace.
Italy has shown it can deliver as many as 600,000 doses a day, which per capita beats the US peak of 3.3 million. Despite a sharply limited supply of vaccine, the country has gotten one or more doses into 47% of people over 16, and 79% of those over 60 (in the US, compare 86% of people over 65), with 25% fully vaccinated. The authorities hope to return to near-normal life in mid-July, and this seems to be a realistic goal. If they can average even 500,000 shots a day, 72% of Italian adults (61% of the entire population) will be at least partially vaccinated by then, which if you add in the COVID-19 survivors should add up to herd immunity.
Alternative facts, vaccine department
|Trump advisor Kellyanne Conroy, who invented the concept of alternative facts
One vaccine may work better than another to prevent mild COVID-19, but they all work equally well against worse outcomes. Have you heard that? Here’s what it says at my favorite Italian vaccine site about “efficacy against severe cases.”
That’s what I call the Big Vaccine Lie.
In reality Pfizer and Moderna protect about 97% against severe disease, Johnson & Johnson and AstraZeneca both between 70% and 80%.
That Big Lie seems chiefly promulgated in and by the UK, and I am starting to suspect something fishy is going on.
To start with, take the research. First came the truly awful initial Phase 3 trials. Then peculiar studies claiming a single dose worked great and the longer you put off the booster the better. Manuscripts followed that spun the initial mediocre real-world results in England and Scotland as brilliant. Now the Brits are mostly taking aim at Pfizer, with studies purporting to show either the equivalence of AstraZeneca and Pfizer or the validity of a 12-week gap between Pfizer doses, though when squinted at from close up they turn out to show nothing of the kind. And dare I mention the American Phase 3 trial, where the researchers inflated their efficacy figures?
One recent example is a preprint about Pfizer boosters, titled “Extended interval BNT162b2 vaccination enhances peak antibody generation in older people.” However:
1) The Results section of the Abstract reads, in full, “In donors without evidence of previous infection the peak antibody response was 3.5-fold higher in donors who had undergone delayed interval vaccination. Cellular immune responses were 3.6-fold lower.” So why isn’t the title “Extended interval BNT162b2 vaccination degrades peak cellular immunity in older people”? The article seems basically aimed at defending the UK’s controversial 12-week gap.
2) Since the proof of the pudding is in the eating, effectiveness – not immune measures – is what really counts. And real-world UK studies reveal that after a mere 5 weeks a single dose of Pfizer already loses effectiveness, reducing hospitalizations by only 68% instead of the 90% to 99% it achieves after a 21-day booster.
Another preprint claims to show AstraZeneca is just as good as Pfizer, on the basis of PCR swabs and antibody titers in nearly 400,000 individuals. The crucial text goes: “There was no evidence that reductions in odds of new infections differed between the Pfizer-BioNTech and Oxford-AstraZeneca vaccine (Figure 4A; Supplementary Table 7).” But here’s the relevant chunk of Supplemental Table 7:
In other words, symptomatic COVID-19 was reduced 63% by a single dose of AstraZeneca, 75% by a single dose of Pfizer, and 91% by two doses of Pfizer. All these results are comparable to those found elsewhere except for 91% being lower than the usual 95-97% – probably because the second dose was given after 6-12 weeks rather than 3. So, again, the point seems mostly to defend the home team.
Yet another analysis of the UK’s vaccination campaign, done from a different angle, similarly equates the two vaccines. The researchers focussed on hospitalizations among people over 70 who received a single dose of vaccine: they fell by around 80% with either AstraZeneca or Pfizer. That would sound pretty good if not for the fact that Pfizer used properly, with a second dose after 3 weeks, reduces the risk of hospitalization in the elderly by 97.5%.
Onward to Italy, where a study in Pescara supposedly found that a single dose of AstraZeneca reduced SARS-CoV-2 infections and deaths by 95% and clinical COVID-19 by 99%, beating out Pfizer. I can’t find any details, but even without them these results are likely nonsense. First of all, because nobody has ever found results that good for anyvaccine. Even Pfizer’s effectiveness in Israel, the highest ever reported, was only 92% against infection (97% against clinical COVID-19, 97%-99% against death). And secondly, because AstraZeneca has never done anywhere near this well. An enthusiastic Reuters article could boast only that “AstraZeneca’s (AZN.L) COVID-19 vaccine has been shown in clinical trials to be 76% effective against severe disease.” If the researchers really got 95-99%, their methodology was probably off.
Enough about the research, now check out the messaging. One Reuters article carried the title “Post-vaccine COVID infections and deaths rare, UK study finds,” but 10 days later they had to recalculate and admit that a single AstraZeneca shot lowers death rates by only 80%.
Another example, this time involving a highly-regarded scientific source, was posted by a Facebook friend in mid-May: “Vaccination is not a total cure. In the UK there were 87 known positive tests after the first jab and 31 after the second (report by Tim Spector on 28/4/21).” I replied, “Unfortunately this is utter nonsense. In Scotland alone there were more than 220 hospitalizations, with obviously many times more positive tests, 2 weeks or more after the first jab, in a paper published as long ago as mid-February. And in England there were at least 1400 confirmed symptomatic cases among people over 70 who were two weeks or more after being vaccinated between January 4thand mid-February.”
|Russian anti-AstraZeneca ad, January 2021
Some social media influencers in France and Germany report that mysterious soi-disant British actors are offering them vast sums of money to disparage Pfizer. But the scheme may have actually originated in Russia. This is a bit curious, since as you may recall the Russian disinformation cannons were originally aimed not at Pfizer but at AstraZeneca.
I thought I’d seen them all, but this one takes the cake!