EXTRA: Welcome, Omicron!

 

Even before the variant announcement that got the whole world in a tizzy, this week was packed with important news about treatments and vaccines. So I thought I’d post a Stethoscope EXTRA to help people make sense of it all. (With a special treat at the end.)

Treatment updates

Molnupiravir: Assiduous blog readers may recall that I was always unimpressed by the efficacy of Merck’s anti-COVID-19 pill, and concerned about its potential for breeding new variants, fetal malformations, perhaps even cancer. Well, the chickens are coming home to roost: molnupiravir works even less well in the final analyses of Merck’s Phase 3 trial than it did in the interim ones reducing hospitalizations not by 50% but by merely 30%, similar to the repurposed and harmless fluvoxamine, colchicine, and inhaled steroids. Molnupiravir may also be ineffective in vaccinated individuals with breakthrough infections, it brings severe fetal malformations in rats, and test-tube studies continue to hint that it could cause cancer. The Guardian comments, damningly, “Regulators also noted that Merck collected far less safety data than was gathered for other Covid-19 therapies.” An FDA advisory panel seems likely to advise approval next week nonetheless, with just a pregnancy caution. The EMA has already done so. I say: forget it. Molnupiravir carries too damned many risks for too little benefit. The FDA should defy Merck and act now as it did with thalidomide in the early ‘60s. After 5 years of that drug being sold over the counter in Europe, causing thousands of babies to be born with terrible malformations, the FDA held the line and refused approval, saving Americans from the scourge. 

Magic bullets: The European Union is letting each country order its own supplies, with Italy apparently contracting for 50,000 courses of treatment each with molnupiravir and Paxlovid. Though I’m hoping they’ll cancel molnupiravir, this is a drop in the bucket even if new cases don’t shoot above the current 12,000 per day. Nearly 3,000 of those daily patients are over 60, and many more are otherwise at high risk. The pills are supposed to start arriving in January, but there’s no guarantee – the UK approved molnupiravir several weeks ago and hasn’t (fortunately!) seen a single pill yet.

Regen-Cov: Regeneron is claiming that a single dose of its monoclonal antibody cocktail can reduce the risk of COVID-19 by 82% for 8 months. It might make sense to use Regen-Cov instead of or in addition to vaccination for people who are so immunosuppressed that they can’t make antibodies in response to vaccines.

AZD7442 (Evusheld): AstraZeneca’s new monoclonal antibody. It supposedly not only cuts hospitalizations by 88% but, like Regen-Cov, can prevent 83% of COVID-19 cases for 6 months. This could be a helpful addition to our therapeutic armamentarium, as per my previous paragraph.

Inhaled budesonide: Beneficial effects seen in open-label studies, where both the patients and their doctors know whether they received the real drug, often shrink when proper placebo-controlled trials are performed. According to a meta-analysis this was true for inhaled steroids – they decreased the risk of hospitalization of high-risk patients by only 10% in two placebo-controlled trials instead of the 20% found in open-label studies. Both of those trials used not budesonide but a more obscure product called ciclesonide, and results were mixed. One of them found a statistically significant benefit from ciclesonide in preventing clinical deterioration, but the other, which was smaller and enrolled younger patients less likely to deteriorate (mean age 35 vs. 45) did not.

Colchicine: A BMJ metaanalysis of 6 studies garnered newspaper headlines by claiming to show that colchicine is useless in COVID-19. But the authors’ conclusion is incorrect. The drug is indeed useless for hospitalized patients, the subjects of 5 of the 6 studies, but the sole trial among outpatients – the group in whom most of us are using colchicine – was grossly misrepresented. Patients with swab-confirmed cases of COVID-19 who received colchicine were a hefty (and statistically significant) 30% less likely to develop pneumonia and 25% less likely to wind up hospitalized or dead, than those who received placebo.

 

 Variant watch

Omicron (B.1.1.529): You all know about the latest worrisome variant. This multiply-mutated virus was first seen in Southern Africa two weeks ago, reported to the World Health Organization on November 24^th, and declared a variant of concern 2 days later. Some think its high number of mutations suggests an origin among the region’s countless citizens living with poorly-controlled HIV. But whether or not that’s true the multiple mutations do mean that Omicron, like its earlier compatriot Beta, is likely to be relatively resistant to existing vaccines and perhaps to monoclonal antibody therapies (though Pfizer’s pill should still work fine). There have also been hints that it may be more likely to bring repeat infections in COVID-19 survivors. But we still have almost no concrete evidence. Within weeks we should know from laboratory studies whether serum from vaccinated individuals contains antibodies capable of neutralizing Omicron. It will be hard to get more solid evidence, since only 28% of South Africans are even partially vaccinated.

Omicron is widely claimed to be more transmissible on the basis of its many mutation, making it a kind of Delta on steroids, but there’s no direct evidence of that either, and the low number of recent cases in South Africa tends to speak against it. The variant is spreading fast among unvaccinated young people in that country, but that’s not a new phenomenon. Take Italy’s worst surge, in fall of 2020. The responsible viral strains then were early and not highly transmissible, but they first hit young people, who then proceeded to infect their elders. 

South African Omicron cases seem thus far to be mild, with no deaths reported, but coming from officials with skin in the game those reassurances have to be taken with a grain of salt.

The world responded to the South African announcement by instantly slapping travel bans on the entire region, knocking the ground out from under the tourist industry in high season and stranding foreigners including (it happens) Parma’s entire rugby team. Stock markets crashed. But cases have already been detected in Belgium, Holland, Hong Kong, Israel, Italy, Germany, Canada, Australia, the UK… so travel bans may be useless, closing the barn door after the horse has escaped; targetted quarantines and contact tracing would be more helpful. Zeynap Tufekci has rightly called out absurd “pandemic theatrics” such as excluding American citizens from the US travel ban.

Moderna and Pfizer are actively researching how well their vaccines work against Omicron, and working on variant-specific fixes that they claim could be available as soon as 3 months from now. For now, though, panic is not warranted – we really don’t know much about this variant. Governments have been blasted so hard for previous slow responses that they may be going overboard now; the whole kerfuffle could still turn out to be, as the head of the South African Medical Association brightly suggests, “a storm in a teacup.” The most crucial thing to do is exactly what it was a week ago: vaccinate the unvaxed and boost the vaxed. Current vaccines will almost certainly continue to protect well against hospitalizations and deaths.

Omicron’s arrival makes it urgent to check vaccine effectiveness, attempt to secure our borders, and increase our rates of viral sequencing. It will hopefully also push rich countries to get HIV drugs and COVID-19 vaccines cheap to poor ones. Otherwise nothing changes. Ordinary mortals should keep up masking, distancing, handwashing, and ventilation. Countries should make vaccines mandatory for healthcare workers, teachers, and first responders, consider “vaccine passports,” and lock down as appropriate. 

How’s that working out in practice? Well, scores of passengers on two KLM flights from South Africa to Amsterdam tested positive for COVID-19. The airline’s website warns: “Onboard you are required to wear a face mask. Even if you have been vaccinated against or have recently tested negative for COVID-19. Without one, we cannot allow you to board.” But health journalist Stephanie Nolen, who was on one of those flights, tweeted:

-       The kind @superernie who's updating me says 110 results from my flight + the other from SA are in. 15 are positive for Covid (variant unknown) - a positivity rate of 13.6 percent. Works out to 85 total fr. 2 flights. (How many more now that we've been crammed together 24 hrs?)

and then, hours later:

-       And if you would like further evidence of why there is no hope for humans, now we know that stat and still probably 30% of ppl are wearing no mask or only over mouth. Dutch authorities not enforcing. We’re just all in this unventilated room at hour 12, breathing on each other.

Alas!!!

 

 

Vaccine news

AstraZeneca is at it again: The British press has always rooted inordinately for their home-grown vaccine. Now, under headlines like the one above, they’re publicizing company executives’ claims that “AstraZeneca may offer longer-lasting immunity than other vaccines,” promises of “Longer-lasting protection against severe disease in the elderly,” and speculation that “The jab has helped Britain avoid the latest Covid wave in Europe.” All 3 statements are demonstrably false:

-       Far from being longer-lasting, AstraZeneca’s mediocre efficacy wanes more quickly than either Pfizer’s or Moderna’s: in British analyses AstraZeneca’s effectiveness fell off more quickly than Pfizer’s, and in a Swedish study AstraZeneca had become entirely ineffective after just 4 months. 

-       Older people? Studies in Scotland and England have shown that a single shot of AZ, its usual dosing in the UK, lowered the risk of COVID-19 hospitalization in the elderly by only 70%-80%, far below the 95%-plus for properly-administered Pfizer or Moderna.

-       Then there’s that latest Covid wave in Europe. Fantasy: in a BBC interview, AstraZeneca CEO Pascal Soriot said widespread use of his company’s vaccine was why the UK was “seeing not ‘so many hospitalisations relative to Europe’ despite a high number of cases.” Fact: in the last two months the UK has had not only 7.5 times as many cases per capita as Italy, but 2.9 times as many deaths. Italy, Spain, France, Portugal, and Germany are all having many fewer hospitalizations per capita than the Brits. 

-       The only support to the AstraZeneca fantasy is case-fatality rates, the proportion of diagnosed cases who die: 0.31% in the UK, 0.84% in Italy. But the UK does twice as many tests per capita, so more asymptomatic people are being diagnosed. And probably UK cases are younger as well – the mean age of new cases in Italy is now 42, but though it’s impossible to locate that basic statistic for the UK, there’s reason to guess it’s lower.

-       Bottom line: I can understand why AstraZeneca makes this stuff up – their goal is to sell vaccines – but I don’t see how the Oxford scientists who are lending the company prestige and credibility can live with themselves. 

Pascal Soriot of Astrazeneca, Sarah Gilbert of Oxford

Abdala and Soberana: Cuba seems to be gearing up to send not only vaccines but vaccine-making technology to developing countries, especially ones snubbed for political reasons by other donors such as the US (Vietnam, Venezuela, Iran, Syria, Nigeria). This is in line with Cuba’s usual active role in promoting health worldwide – in March 2020 it even sent doctors and nurses to northern Italy! Cuba has essentially completed its vaccination campaign, with nearly 90% of the entire population having had at least one of the 3 necessary doses and 80% fully vaccinated. And for the first time now we can see a manuscript reporting a large-scale Phase 3 trial, though it’s not yet peer-reviewed: Soberana showed 71% efficacy after two doses, rising to 92% after dose 3 – and 100% against severe disease or death.

Sputnik V: The Russians are claiming their vaccine’s benefits wane much less than Pfizer’s or even Moderna’s, remaining at 80% 6-8 months after the second dose. As usual I’d like to see a real manuscript, and, as usual, the quality control issues with this vaccine remain a concern.

Waxing and waning: If any of you feel like wonking over the evidence about how much protection falls over time with the Pfizer, Moderna, AstraZeneca, and Johnson & Johnson vaccines, you now have a place to go.

 

Treats from the Department of Deep Pseudo-Science:

-       COVID-19 vaccines contain programmable electromagnetic field nano particles.

-       Graphene oxide, which turns people into magnets plus causes blood clotting and pneumonia, is the main ingredient (99%) in the Pfizer vaccine (masks and test swabs also contain it).

-       Vaccinated people pass their magnetism and “lethal frequencies” to the unvaccinated via 5G Grid tranmission, using “bioresonance” and “harmonic resonance.”

-       Vaccines are designed to eliminate the “God gene” that predisposes humans to spiritual or mystical experiences.

-       Bathing in borax, a highly toxic household cleaner, will clean out the nanotechnologies that vaccines put in your body.

-       Vaccines connect your body to a supercomputer which sends codes that can make you hear voices or feel pain or can “take over all 5 of your senses at the same time.”

-       “Are humans being transformed, through the COVID vaccine into prototypes of Earth-based Greys? Is this what an alien invasion looks like? Are we a generation away from becoming genderless Borgs with no personal will, mere nodes on a network? It appears so, if the Globalists (aliens) have their way.”