Death By Delta

 

Treatment updates

Ivermectin: In a placebo-controlled, randomized, double-blind trial in Argentina, outpatients who were given ivermectin not only got hospitalized at the same rate as controls, but they were more likely to wind up on a ventilator. Scientifically the study should be a death blow to the use of ivermectin to treat COVID-19, but this cat has more than nine lives. More or less simultaneously a bunch of UK researchers released a metaanalysis claiming to show ivermectin not only works, but works far better than any other therapy, reducing deaths in moderate-severe cases by 56%. The article is junk. Few of the 24 trials it includes were either peer reviewed or published, 8 were privately shared data that hasn’t even been prepublished, and none were placebo-controlled. As the IT folks say, garbage in, garbage out. A British Medical Journal commentary billed it as “Misleading clinical evidence and systematic reviews on ivermectin for COVID-19,” and there are calls for the paper to be withdrawn. Perhaps it has been! The version I saw last week had watermarked on every page “accepted for publication,” supposedly in the obscure journal Open Forum Infectious Diseases. The current posting has been downgraded to “a manuscript that has not completed peer review at a journal.” 

Prone positioning: Invented last spring as a simple way to keep COVID-19 patients off ventilators, keeping patients with respiratory failure in a belly-down position has struck out in one randomized trial. But the trial was small, and I suspect it probably won’t change clinical practice.

Tocilizimab: in a recent metaanalysis Actemra lowered mortality from 25% to 21% in highly selected patients. Patients on ventilators didn’t benefit at all, and editorialists were unimpressed. But the drug was approved 2 weeks ago in the USA for emergency use, on even more mixed evidence, and is now recommended by the World Health Organization for patients with severe or critical COVID-19. A big win for Roche, at least.

Proxalutamide: Brazilian researchers claim this experimental prostate cancer drug reduced mortality in hospitalized COVID-19 patients by 78%. Far too good to be true.

 

Vaccine updates

Cuban vaccination center, with Che and nuns

Novavax: Its Phase 3 trial in 14,000 British volunteers has now been published. Much is positive. Efficacy a week after the second dose was 89.7% overall and 100% against severe disease, half the volunteers were in high-risk categories, and side effects were relatively mild. But there’s a downside. When Hilda Bastian wrote in the Atlantic that the vaccine had “an efficacy rate of more than 90 percent even against coronavirus variants,” she simply hadn’t read the article right. Novavax was 96.4% effective against the original Wuhan strain and 86.3% against the easy-to-zap Alpha variant. But we already knew from a trial in South Africa that its efficacy against the Beta variant was a paltry 51%. And since this British trial was completed before Delta hit, we have no idea how effective it is against the most troublesome variant of all. Plus its volunteers were overwhelmingly white. A larger trial in the United States and Mexico should soon tell us more. In any case I hope the vaccine wins emergency approval soon.

The recent COVID-19 surge in Cuba

Abdala and Soberana 2: Cuba only started administering their home-grown vaccines in mid-May. A month later, with only 4% vaccinated, they claimed they were already seeing positive effects, but within days a terrifying surge had taken off. Now they’ve scrambled to get a dose into 27% of the population. The Abdala vaccine, 3 doses given at 2-week intervals, is said to have proven 92.8% effective in a 48,000-volunteer Phase 3 trial, putting it in the top tier alongside Pfizer and Moderna. Russia’s Sputnik V would be there too – but I and others continue to be suspicious of its published results and quality control. Frankly, I trust the Cubans more than the Russians – they’ve always staked their reputation on medical prowess and generosity. Not everybody is so skeptical of Sputnik, though, and effectiveness studies are ongoing in Argentina and Venezuela.

Coronavac: Sinovac initially claimed 91% efficacy against COVID-19 – downgraded to 83.5% in the published article– in a small Phase 3 trial in Turkey, but only 50% in a much larger trial in Brazil. Now analyses from the vaccination campaign in Chile split the difference: the vaccine was 66% effective in preventing symptomatic COVID-19, 88% against hospitalization, 86% against death.

Johnson & Johnson: The FDA has announced a new warning about the cases of Guillain-Barré syndrome that I mentioned in my last post. This type of temporary immune-mediated paralysis has been reported sporadically after various vaccines. But one case in 128,000 Johnson & Johnson doses (and, probably, AstraZeneca) is nearly the rate after the 1976 Swine flu shot and has to be taken seriously.

Pulled from a 10-gallon hat: While Pfizer and Moderna were inventing mRNA vaccines from scratch, a group in Houston had a head start – they’d already developed a vaccine against the SARS coronavirus that, like Novavax, used protein subunit technology. They plunged into work and came up with a COVID-19 vaccine that’s now undergoing Phase 3 trials in India. The researchers hope approval for widespread use could come as early as September. They say it could be produced fast and copiously, at a cost of just $1.50 a dose. I confess this one caught me unawares!

 

Vaccine controversies

Lined up for Johnson & Johnson at Rome's Santo Spirito Hospital

Mixing and matching: On June 17^th Canada became the first country to allow anybody who received AstraZeneca, regardless of age, to have Pfizer or Moderna for their second dose, which heightens antibody responses. Germany then raised the ante: they’re not just allowing everybody to get that mRNA second dose but emphatically recommending it. In Italy it depends on the region. Piedmont and Campania are following the German example while Tuscany, Marche,Lombardy, and Lazio among others are thus far giving the mix-n-match option only to people under 60. Note that the heightened immune response is a one way street – giving an AstraZeneca second dose to people who’ve had Pfizer has flopped.

Emerging from emergency: Eric Topol, editor-in-chief of Medscape and one of the most influential physicians on the planet, has written a New York Times op-ed endorsing full US Food and Drug Administration approval for the Pfizer and Moderna vaccines, as I argued in my last post. He points out that the hundreds of millions of doses already administered far outnumber the testing of any other drug in history, and contrasts the FDA’s foot-dragging with its recent controversial approval, possibly on corrupt grounds, of an Alzheimer’s drug that aside from being scandalously expensive has virtually no evidence it works. 

An experimental microneedle flu vaccine

Delivering the goods: For several years scientists have proposed using skin patches with myriad microneedles as replacements for injections. Now some suggest microneedle COVID-19 vaccines could help vaccinate the developing world. I don’t really see this, to be honest, since shots are simple, low-tech, and vastly cheaper. In any case patch vaccines won’t help in the US – when novax Americans are asked their reasons, fear of needles doesn’t make the list.

Vaccinating kids: A New York Times op-ed in favor of vaccinating even tiny children argues that the risks to them from COVID-19 are far greater than from vaccines. But this reasoning rests on the dubious assumption that sooner or later all kids in the United States (and, by implication, in the world) will get infected with SARS-CoV-2.

Vaccinating the marginalized: Italy kicked off its vaccination campaign with a grand promise to include everybody living on its territory regardless of legal status. Until recently, though, unless you were working for a United Nations agency you could only get vaccinated if you had legal residency and were enrolled in the Italian National Health Service. Finally now they’re starting to deliver on their promise, with a drive to reach some of Italy’s 700,000 undocumented immigrants and homeless – the Times even gave it a feature story. In the US the undocumented are theoretically entitled to vaccination, but in practice they often encounter barriers. 

Vaccine equality: COVAX has called on countries to accept travelers who’ve had any WHO-endorsed vaccine. This sounds fine until you realize that the WHO has given its imprimatur not only to Western vaccines, which already vary considerably in efficacy, but also to Sinopharm and Sinovac, suspected of contributing to worldwide surges because of limited effectiveness. Sinovac in particular weighed in at only 42% real-world effectiveness in Brazil, well below the WHO’s 50% threshhold for approval. The subject remains controversial, and probably most people who died in countries that used the Chinese vaccines were not in fact fully vaccinated.

Timing: In a pro-vaccine article, the BBC unfortunately cites as fact someone’s opinion that having a second dose earlier than 8 weeks will shorten your protection. There is absolutely no evidence in favor of this position, and solid evidence against it from the UK itself – a single dose of vaccine gives only 33% protection against the Delta variant. 

Boosters: Pfizer has already leapt on recent Israeli reports of lower effectiveness (see Death by Delta, below), and evidence of waning antibody levels, to say we’ll all need a booster soonest. Neither the CDC nor the FDA are buying it yet, and I think they’re right. For one thing, the Israeli experience doesn’t show waning immunity, it shows reduced efficacy against the Delta variant. For another, no one has shown that 3 doses will work better than 2. And, finally, we have good evidence that immune memory for COVID-19 lasts a long time, regardless of antibody levels. Pfizer is using the value of a third dose in immunosuppressed patients as an argument for a universal booster shot, which mixes apples and oranges. What would really be useful is a new vaccine, tweaked to target Delta, that could be used as both a primary vaccine and a booster. Pfizer is in fact working on that, but it could take a while. 

Spin: Maybe you’ve noticed that vaccine news always sounds great. Is it really? A distinguished scientist, Robert Kaplan, accuses pandemic pundits of overoptimistic opinions based on confirmation bias, interpreting the evidence according to their prejudices and expectations. Especially, he says, by minimizing vaccine side effects, for example reassuring pregnant women their babies will be fine on the basis of studies of only 114 pregnancies. (I’ve talked abouthow UK researchers and writers exaggerate the efficacy of AstraZeneca.)

Hesitancy: The Kaiser Family Foundation has come out with its latest monthly vaccine hesitancy poll, and it’s not encouraging. The number of Americans who were vaccinated or planned to be as soon as possible rose only from 66% to 68% between May and June, while the group dead set against it rose from 13% to 14%. Another poll found that 45% of Fox News viewers, and a scary 68% of fans of hard-right Newsmax and One America News, were hesitant or unwilling to get a Covid-19 shot.

One KFF finding is cheering, though: 31% of the unvaccinated said they would be more likely to get the shot if the FDA gave a vaccine full rather than emergency approval, as is expected soon. 

The CDC reports that only 0.5% of Americans who died of COVID-19 in the last 6 months were fully vaccinated. Anthony Fauci has rightly called out the other 99.5% of deaths as “avoidable and preventable.” 

It seems COVID-19 fairly often leads to long-lasting impotence. If that fact gets widely publicized maybe some of those Republican he-men will get their shots!

Italy has few novaxxers to contend with. Fully 79% of unvaccinated adults plan to get the jab (compare 46% of Americans). But there are a few skeptics among them. La Repubblica published 3 interesting interviews the other day. One man said if a home-grown vaccine had come through he’d have taken it, but he didn’t trust the foreign ones. Another mostly objected to the government’s hard sell, though he admitted with the Delta variant his mind might change. Only the third used American reasoning: vaccines kill people, and he doesn’t want to be a guinea pig. Check out the latest IPSOS poll for fascinating worldwide hesitancy data. 

 

Gifts from our forefathers

Artist's rendition of a Neanderthal

About 20-30% of people in Europe and Asia have one particular scrap of Neanderthal DNA on their 12^thchromosome. If those people are infected with SARS-CoV-2, they have a 22% lower risk of developing severe COVID-19. And that turns out to be only one of the ways intermingling between our ancestors and Neanderthals boosted our immune system.

 

Death by Delta 

Percentages of recent COVID-19 cases that are due to the Delta variant

The high contagiousness of the Delta variant has been seeding new surges worldwide, and causing panic everywhere from South Africa to Thailand. There are hints it may be more virulent as well. It’s already causing more than half the new cases in the United States, and one out of 4 in Italy despite borders closed to India and the UK. Delta is generally said to be twice as contagious as the original coronavirus, but an even more alarming factoid has been splashed across media in Australia, the UK, Italy, and the US: you can catch Delta on the basis of 5 to 10 seconds of casual contact. When I went to track that claim down, I found it seems to be based on surveillance camera footage of 2 individuals in Sydney, Australia, one of whom supposedly passed the virus to the other as they walked past each other in a mall. I don’t find this or similar anecdotes about other variants extremely convincing, but in Australia they’ve led to new lockdowns. (For some reason this reminded me of a line in the Neapolitan song Tammurriata Nera, about getting pregnant: A 'e vvote basta sulo na guardata, Sometimes all it takes is a glance.)

We know Delta is a bit less susceptible to vaccines. According to UK data full vaccination with Pfizer was only 88% effective against Delta (vs. 95% against Alpha), with AstraZeneca only 60% (vs. 66%-72%). This goes far to explain why half of the recent COVID-19 deaths in the UK are among the fully vaccinated. Canada and Singapore have reported similarly decent effectiveness for Pfizer. But on July 5^th a troubling new announcement arrived from the Israeli health ministry. In May the Pfizer vaccine had been 94% effective against COVID-19 overall but in June, when most infections were due to the Delta variant, it was only 64% effective. Very worrisome. But as a Reuters journalist pointed out, June was also when Israel dropped masking and social distancing, another explanation for a surge. Also, contrary to what you might think, only 57% of Israelis are fully vaccinated (vs. 51% in the UK and 47% in the US), and vaccination of adults has now slowed to a crawl.

Fortunately even in Israel the vaccine remained good (93%) at preventing serious illness and hospitalizations. But the discrepancy between 87%-89% and 64% effectiveness is huge, and will remain inexplicable at least until the Israeli data are presented in some other form than that terse announcement.

As I pointed out above, a single dose of either Pfizer or AstraZeneca does little (33%) to prevent Delta disease. That’s been confirmed now by a laboratory study of neutralizing antibodies: there are virtually none after one dose. Even after full Pfizer vaccination Delta antibodies are scarse, despite the company’s assurances. Please, all you countries who allow 8-, 12-, even 16-week (Canada, I’m looking at you) gaps between the doses, start giving those boosters pronto!

There’s no real-world Delta data for other vaccines, only studies of neutralizing antibodies. Moderna induced lotsagainst Delta, fewer against Gamma, almost none against Beta. In 8 people, Johnson & Johnson yielded decent levels against Delta, fewer against Gamma and Beta. Some claim Johnson & Johnson is 60% effective against Delta, but I can’t track down any supportive data so that claim may just be an assumption based on J&J’s similarity to AstraZeneca. (J&J works better than AstraZeneca against the Beta variant, though, so it might perform better against Delta too.)

The real problem is not that the vaccines have limitations but that most people in the world are unvaccinated, creating a vast petri dish for the spread of COVID-19 and the evolution of ever-more vicious variants. The 98% of Africans and 34% of American adults who still haven’t had a single dose, the former from lack of access and the latter largely by choice, are entirely unprotected. Anthony Fauci warns that there may soon be “two Americas,” one where people are vaccinated and returning to near-normal life (New England, the Mid-Atlantic, the West Coast), the other where people are unvaccinated and potentially returning to the horrors of earlier waves of the pandemic (mainly the South and the upper Midwest). We’re already seeing those horrors in Missouri (39% of residents fully vaccinated, vs. 47.5% in the US overall) and they are looming in Mississippi (30%), Arkansas (35%), and Alabama (33%).

At least one vaccine dose as of July 1st (Note: the previous paragraph counted the fully vaccinated)

Meanwhile, across the ocean in the Delta-striken UK, insanity reigns. Boris Johnson insists he’ll lift all pandemic restrictions later this month – pubs open at full capacity with no mask requirements – even while saying, “We must reconcile ourselves, sadly, to more deaths from Covid.” Isn’t it nice he’s sad at having blood on his hands? As Lady Macbeth put it, “All the perfumes of Arabia will not sweeten this little hand.” Johnson’s own health secretary warns that daily cases may soon reach 100,000, nearly twice what they were at their previous peak. 

 

The mysteries of India

 

For a long time the mystery was how well India was doing – as recently as February it had reported only 250,000 COVID-19 deaths among its 1.3 billion inhabitants, 1/7 the deaths per capita in Italy or the USA. Everybody explained this by India’s youth (only 6% of Indians are over 65, vs. 23% of Italians) and unreliable statistics. It was even speculated that some areas of India might have achieved natural herd immunity, with 56% of Delhi inhabitantspossessing SARS-CoV-2 antibodies. 

More recently, of course, the mystery was how terribly India is doing and why the disease spread like wildfire: 350,000 new cases and 3000 deaths every day, hospitals running out of oxygen, nocturnal cremations lighting up the sky. Fortunately that scenario is fading now.

Many Indians are blaming the Delta variant, which was first detected locally, and there’s definitely something to that. But Western experts also point out that: 

-       India uses the relatively ineffective AstraZeneca vaccine.

-       Their vaccination campaign was sluggish despite India being vaccine maker to the world; it’s picked up now, getting a dose into 22% of arms.

-       Complacency and lax behavior were modelled by Prime Minister Narendra Modi in full Trump mode. 

-       Magical thinking is widespread. A Modi crony said that because the Kumbh Mela festival was held on the banks of the Ganges River, “There should be no corona.” Vast numbers of the massed millions of celebrants developed COVID-19 despite the holy setting, including one in 5 of the festival’s doctors and paramedics, mostly catching the bug not at the outdoor event itself but on the packed trains there and home.

Another mystery is the low case fatality rate: 1.3% of diagnosed cases are reported to have died, vs. 2.8% in Brazil and 2.6% in the UK. Prime Minister Modi has even bragged this demonstrates India’s superior medical care. In reality the official Indian death toll, and therefore the case fatality rate, are hugely undercounted:

-       Cadavers are being hidden or cremated on the sly. When journalists are on hand to count the bodies, they count 7 times or even 10 times the official number.

-       The New York Times estimated less directly that at least 5 times more people had died than the official figures claimed, garnering fierce denials from Modi’s government.

-       National and state governments are suspected of deliberately doctoring the figures.

-       Excess deaths in just two of the 29 Indian states were estimated at 360,000 for 2020-2021, proving the official figure of 400,000 Indian deaths total is way off… 

-       Excess deaths are the best measure of true pandemic mortality – the United States saw 522,368 more deaths during 2020 than the average in recent years, which is already 47% over the official COVID-19 death toll…

-       …But excess deaths can’t be calculated accurately in countries lacking the infrastructure to keep accurate records. In India specifically, the United Nations estimated that only 2 out of 3 deaths in 2011 were ever recorded. Doubtless reporting is even worse during the pandemic.

-       Bottom line: the truth may never come out, in India and not only.

 

Novax idiocy

As a Pfizer vaccinee explains in the Spanish voiceover, this video shows a cellphone detecting his vaccination site as a new Bluetooth device, HBPC-J43. Only… HBPC-J43 is actually a Bluetooth speaker sold in Chile. Poor schlemiel.