Friday, May 14, 2021

Of Masks And Men

 

Treatment updates

Budesonide: The study I discussed as a preprint in February, giving high-dose non-absorbed steroid inhalers to outpatients with early disease, has now been published. The trial is placebo-controlled, and its results (fewer severe outcomes, faster healing) make sense, so even though the study wasn’t done “blind” I still believe its results. I’ve prescribed this inhaler several times already.

Marine barracks

Natural immunity: Judging from a study in Marine recruits, young adults may be less protected than older ones by previous exposure to SARS-CoV-2, perhaps because they get less sick. But this article played down its most disturbing finding: nearly half of the recruits who started out susceptible got infected in the course of the 6-week study. This is insane. Aside from anything else, shouldn’t the recruits’ obligatory 2-week quarantine have weeded out anybody who was infectious?

Tocilizumab: I’m getting tired of reporting mixed results. This time it’s one study in the UK where desperately ill patients getting the drug were less likely to die (though the difference was only 31% vs. 35%), and a meta-analysis where they were not.

Bamlanivimab plus etesevimab: Eli Lilly’s monoclonal antibody combo is running into trouble – not with its science but with its assembly lines. Whistleblowers accuse the company of sloppy quality control and substandard sanitation (!) in its factories, and of lying to the US Food and Drug Administration to sweep its problems under the rug. 


Resveratrolo: Google “resveratrol COVID-19” and you get 7 million hits about how pills of the famed red wine component can prevent or cure COVID-19. Dream on. But why not get it the natural way?


PF-07321332: In March, Pfizer CEO Alfred Bourla created momentary chaos by forseeing boosters of his company’s vaccine once or twice a year, forever, for all human beings on the planet – a prediction Tom Frieden, previous head of the Centers for Disease Control, blasted as being made “for their corporate benefit.” Bourla’s latest exploit is announcing that Pfizer could get an effective anti-COVID-19 pill into pharmacies by the end of 2021. Like some successful AIDS and Hepatitis C treatments, PF-07321332 is a protease inhibitor. Given that other antivirals have done very little for COVID-19 and that this new one doesn’t seem to have even been tried in sick animals, much less humans, the announcement seems more a dream than a prediction.

 

Vaccine updates


Escherichia coli bacteria

New kid on the block? After mRNA vaccines (Moderna, Pfizer), adenovirus vector vaccines (AstraZeneca, Johnson & Johnson, Sputnik), spike protein vaccines (Novavax), and weakened coronavirus vaccines (Sinovac, Sinopharm) now a brand new kind may be in the works: a piece of viral DNA is synthesized and allowed to multiply inside specially pared-down Escherichia coli, the bacteria are killed, and the liberated DNA, in a pill, stimulates a response from the immune system. A single vaccine could supposedly protect against a wide range of coronaviruses, including variants present and future. This platform has already produced a vaccine against one pig virus. Though the process sounds complicated, it is said to be so easy that existing factories could gear up in weeks to churning out tens of millions of doses, so cheap that they’d cost a buck each, and so easy to transport and store that it could sweep the global South. Sounds like a dream – but no such vaccine has yet been given to a single human being. 

Johnson & JohnsonBack on board in the United States after investigation of clotting complications, it carries a new warning label but no restrictions by age or gender. At least 15 cases and 3 deaths have now surfaced, mostly in women under 50, double the original number. Europe has received very few doses, and Italy and France (at least) are giving them preferentially to older people. For women in their 30’s, the risk of developing life-threatening clotting complications seems to be about 1 in 80,000. That’s less than the risk from birth control pills or the AstraZeneca vaccine, but given the excellent alternatives, and given young women’s low risk of serious COVID-19, I agree with Paul Sax and Leana Wen that women under 50 should be warned off Johnson & Johnson (and AstraZeneca too). 

The J&J Phase 3 trial has now been properly published, confirming an overall efficacy of 66.1-66.9% against clinical COVID-19 and 85.4% against severe or critical disease, as good in the old as in the young.

…did you hear that the guy whose factory ruined 15 million J&J doses sold off $10 million in stocks during the weeks before that disaster came to light? 

Sinovac: A real-world study analyzing Chile’s vaccination campaign says this Chinese vaccine was 67% effective in preventing symptomatic infection, 85% effective in preventing hospitalizations, and 80% effective in preventing deaths, beating the 50% top-line efficacy previously reported. And in the Indonesian campaign it supposedly prevented 94% of COVID-19 cases, 96% of hospitalizations, and 98% of deaths among 120,000 healthcare workers… Who are we to believe?

 


AstraZeneca

 


This headline deserves at least a couple of Pinocchios. First of all, according to the preprinted manuscript, single-dose AstraZeneca elicited more of a T-cell response but less of an antibody response than single-dose Pfizer. Second, immune responses are reported 5 weeks after a single dose of vaccine, when most countries will have already given Pfizer’s second dose. Finally, while admiring AstraZeneca for achieving a T-cell response in 31% of people over 80, the FT article admits that two-dose Pfizer does twice as well.  

Act I: UK authorities claimed they had given millions of doses of AstraZeneca without seeing a single case of anomalous blood clots. Act II: they admitted they had actually seen 30 cases, 7 of them fatal. Act III: the number of cases is now 242, with 49 deaths. Enough to make the Brits raise the lower age limit for AstraZeneca vaccination from 30 to 40

Pfizer: That giant study of 600,000 Israeli vaccinees and 600,000 matched controls has now been published. People were already 57% protected just 2 weeks after their first dose, and 74% less likely to need hospitalization. Those numbers rose to 92% and 87% a week after the second dose, and were if anything better in the elderly. Asymptomatic infections were cut by a hefty 90%.

Anybody wondering how much Pfizer is making off their splendid vaccine? In the first quarter of 2021 it brought in $3.5 billion, with pretax profits pushing a billion bucks. Its CEO, Albert Bourla, made a cool $21 million last year.

Germany and France have now extended the time between doses to 6 weeks. Their reasoning makes some sense: elderly people are mostly vaccinated, and youthful immune systems are vigorous enough to tolerate a longer gap. And the medically vulnerable will get their second dose on schedule. This is very different from the UK’s decreeing a 12-week gap for everybody, from the get-go, including the very old. Oddly, now that the Italians are playing copy-cat, they’re getting pushback from Pfizer. I’ve always wondered why the company let the UK get away with it… 

But how about that 12-week gap? Has the UK won its gamble? Is it OK to give the second dose of the Pfizer vaccine 12 weeks after the first. From the statistics since the vaccination campaign began on December 8th you'd likely say yes. 




But doubts remain. First there’s the Scottish vaccination campaign suggesting protection starts fading after a mere 5 weeks. Then there’s the fact that nobody’s yet reported a single dose to give protection approaching what you get from two doses – a very recent BMJ article estimates protection against hospitalization among British elderly at 80% from one dose, to be compared to 97% from two doses in Israel. And many, including Anthony Fauci, fear that protection may wear off early if the second dose of vaccine is substantially postponed. Recent reports of outbreaks among one-dose vaccinated elderly people  are particularly worrisome. I certainly hope other skeptics and myself are all wrong. 

Sputnik: Soon after its boost from San Marino came a slap in the face from Brazil, where regulators voted unanimously not to approve the Russian vaccine despite a raging epidemic. They cited concerns over efficacy, side effects, and quality control, and said the Russians had blocked factory inspections. The Brazilians apparently found potentially infectious adenovirus in every lot they tested, risking vaccine efficacy and putting vaccinees at risk for adenovirus disease. Gamaleya could find no better response than “fake news.” Slovakia, incidentally, approved the vaccine but then returned its first batch to sender for not matching the product that was promised – the Russians called this “an act of sabotage.” A few days later, the British Medical Journal published a detailed critique of the rôle its brother journal The Lancet had played in the ascending trajectory of Sputnik. Let the games begin…

Italians do it better: I felt utterly undeserved pride in seeing, soon after the Washington Post and the New York Timestrashed the Italian vaccination campaign, Politico singling out the Lazio region (which includes my home in Rome) as an example of excellence. 

 


Face masks: suits of armor or theatrical costumes?

Celebrating Joe Biden's win in front of the White House – jammed together but masked

It is somewhat amazing that a year into the COVID-19 pandemic we still don’t know how well face masks work.

Researchers have tried to examine the question using three approaches:

1)    Case-control studies asking people with and without COVID-19 whether they wore masks:

study in Maryland found that physical distancing was highly and indoor masking moderately protective, and that risk was increased moderately by using public transportation and greatly by attending places of worship.

Then there’s the CDC survey finding that 85% of people with COVID-19 said they had habitually worn masksbefore getting sick – a finding that got deliciously Trumpified into “85% of the people wearing masks get it.” 

2)    Studies of mask mandates, mostly comparing areas with one to areas without. 

In Tennessee, counties that instituted mask mandates had fewer COVID-19 hospitalizations than those that didn’t. But those same counties generally introduced other mitigation mandates simultaneously, related to gatherings, restaurants, bars, etc., so it’s impossible to sort out the impact of masks.

German study comparing regions that introduced mask mandates sooner vs. later reported that masks decreased COVID-19 cases by 45%. Alas, as in Tennessee, the most virtuous regions were also particularly quick to close bars and restaurants, require returning travelers to quarantine, etc., causing hopeless confounding.

3)    Randomized, controlled trials. 

There’s only been one, a Danish study that assigned 6000 people to wear or not wear surgical masks outside their homes (about 4.5 hours a day). Mask wearers had 42 infections and controls 53, a non-significant difference. But the trial’s ability to detect an effect was limited: there was little disease around, people were careful about physical distancing, and mask compliance was mediocre. The lead author himself recommended afterward that people mask up. 

I’ve dumped on outdoor masking repeatedly in this blog, based on everything from Chinese contact tracing studies to examinations of infection patterns following Black Lives Matter protests. Recently many prominent authorities are leaning in my direction, from epidemiologists Dr. Paul Sax  and Monica Gandhi to aerosol expert Linsey Marr and sociologist Zeynep Tufekci. Israel no longer requires any masks outdoors, and the first major loosening of CDC guidelines said it was OK for vaccinated people, at least, to be barefaced outdoors. 

Rand Paul, Anthony Fauci


In one famous argument between Anthony Fauci and Rand Paul I was shocked to find myself on Paul’s side. The question was whether it’s “theater” for vaccinated people to keep wearing masks outdoors – Paul and I both think it is. In fact I’d double down: it’s theater for anyone to wear masks outdoors, except in exceptional circumstances.

Indoors, too, masks on vaccinated people are often de trop. Between 95% fewer infections and lower viral loads if they do get infected, people who’ve had both doses of RNA vaccines are extraordinarily unlikely to make other people sick or to get sick themselves. Now the CDC is on the same page, or has even turned it, saying vaccinated people (presumably only those who are not immunosuppressed) can leave their masks off indoors too, except in crowded unventilated spaces, in congregate settings, or near high-risk unvaccinated people. The unvaccinated, though, absolutely must keep wearing proper masks whenever they’re in indoor spaces with unrelated people, even with 6 feet in between and good ventilation. How will any of this work? Vaccinees don’t wear a brand on their foreheads… 

Many scientists will be turning pale at the leniency of these latest guidelines. Just this month 95% of epidemiologists told the New York Times they thought people should generally keep wearing face masks indoors at least through the summer. Even I think the CDC has gone too far with this one – and it will be impossible to walk back.

Surveys find that fewer and fewer Americans are wearing masks – especially the unvaccinated! Mask avoidance and vaccine avoidance seem to reflect the same devil-may-care attitude.

We may find out more soon from semi-natural experiments. Researchers in the UK threw a giant club party on April 30th – no masks, no distancing – to study what would happen. And Florida Gov. De Santis has forbidden all mask requirements in his state, at a moment when there are thousands of new cases daily and scores of deaths.

Rapper NLE Choppa and fans in a Tuscaloosa nightclub, April 2021

Unfortunately all vaccines were not created equal. Johnson & Johnson is not as good as Pfizer or Moderna at protecting the vaccinee. AstraZeneca is even less effective, and doesn’t prevent asymptomatic infection. So people who received those vaccines really ought to keep masking up in most circumstances, to protect themselves, as long as there is considerable SARS-CoV-2 virus around in the community, and those vaccinated with AstraZeneca really ought to keep masking up to protect others.

Some time back a friend forwarded me a rather astonishing article in “The Fort Fairfield Journal.” It was titled “Maine’s Rise in COVID-19 Cases Linked to Face Masks” and claimed, with a slew of reputable-sounding citations, that “The Data Shows Prolonged Face Mask Use Increases Risk of Catching Respiratory Illness.” This pseudo-scientific screed, nicely cited articles concluding masks have limited value, but cited none (because none exist) showing masks to increase risk of infection. The Fort Fairfield Journal article was written by its sole contributor, David Deschesne, “the paper’s Editor, Publisher, Graphics Designer, Advertising Sales, Journalist, Researcher, Photographer, IT Support, Legal Advisor, Marketing Representative, Mail Subscriptions, Proofreader, Accounts Receivable/Payable and Website Administrator.”

Then there’s an Israeli character named Baruch Vainshelboim, who claimed to be affiliated with Stanford University but wasn’t, and published an antimask article last November that only lasted a millisecond before Medical Hypotheses, a wild-and-wooly journal to start with, yanked it

So many people think face masks are hazardous to your health that one group of researchers felt moved to see whether they caused elderly people’s oxygen levels to drop. Nope – oxygen saturation was 96% before putting on a face mask, 96% while wearing one, and 96% after they took it off. The researchers have been criticized for even trying, since conspiracy theorists are unlikely to be moved by scientific evidence.

 


Variant variations

 


Remember the boy who cried wolf? The one in Aesop’s fables who lied so often about a wolf on the prowl that when a real wolf came around nobody believed him? That’s what the British B.1.1.7 variant story was like. The warnings it was extra-contagious were so overblown that until quite recently I didn’t believe real evidence that it is… 

What’s not clear is whether B.1.1.7 is also more virulent. In early March there were reports that Danish patientsinfected with it were more likely to need hospitalization, and studies in the UK claimed it was deadlier than the Wuhan original by a dizzying 55% to 64%. Then came two other reports that were reassuring: users of a tracing appand hospitalized patients had similar symptoms and disease severity whether they had B.1.1.7 or the wild strain. In the latest twist two new UK studies, one following matched pairs of cases and the other analyzing a large dataset, are again reporting higher mortality. At least we do now have solid evidence that the Pfizer vaccine works well to prevent it, and AstraZeneca and Moderna probably do too.

Brazil’s P.1 variant is more contagious, and from what we see in testtubes it may resist current monoclonal antibody therapies. But it seems the AstraZeneca, Moderna, and Pfizer vaccines will all prevent it.

Unfortunately the same is not true of the South African B.1.351 variant. We already knew the Novavax and Johnson & Johnson vaccines didn’t do much against it, that it escaped AstraZeneca altogether, and that current monoclonal antibody therapies are likely ineffective. Moderna is working on a specially-designed booster, though. It’s promising but quite toxic – generally speaking, it apparently should be pretty easy to engineer mRNA vaccines to protect against new variants. Pfizer already shines. We had hints it was less effective against B.1.351 in a study in Israel. But now we have real-world data from Qatar, where half the COVID-19 cases are due to B.1.351 and people are getting Pfizer: 75% protection against infection, 100% against severe disease. Though 75% is less than perfect it’s better than what either AstraZeneca or Johnson & Johnson do against any strain. 

Then there’s B.1.526, familiarly known as the “New York variant,” now causing about half the cases in the city. It may be a bit more contagious, but the Pfizer and Moderna vaccines seem good at warding it off.

Some are very worried about the Indian B.1.617 variant and locals often blame it for their current terrifying surge, but most scientists are skeptical and what little evidence we have tends to be reassuring. The World Health Organization has now shifted from calling it a “variant of interest” to a “variant of concern,” but it thinks existing vaccines should work. UK authorities warn that their 1700-plus cases might block reopening plans.

There was also worry when a California variant showed up, CAL.20C/B.1.427/B.1.429, but it now seems it may actually be protecting that state against surges elsewhere in the country, by knocking out the more contagious B.1.1.7 version.

 


What could possibly go wrong?

 


Military scientists engineering a groovy microchip that will be implanted under your skin and test you continuouslyfor SARS-CoV-2, detecting COVID-19 before it gives you any symptoms. As per the Facebook post above, offering the Russian government’s take on a 60 minutes interview. And the Russians aren’t the only ones to bite:

 


Well, not exactly… It turns out that 1) it’s not a microchip but a bit of glowing green goo; 2) it can’t connect to the internet or track you or transmit anything; 3) it is intended to detect nothing as specific as COVID-19 but molecules like oxygen, glucose, lactate that might possibly conceivably maybe reflect a nonspecific state of sickness, like a cold; 4) tissue levels of lactate do increase in desperately ill patients, including if they have COVID-19, but an increase is unlikely to be detectable while you’re feeling well.



6 comments:

  1. Susan: Has there been any research to determine how long one is protected by the Pfizer/Moderna vaccines? Will this have to be a yearly vaccination, like the flu? Could it be only effective for 6 months or less? Or for years? I have seen no information, yet the assumption is that it lasts forever.

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    1. There's reasonable evidence that Pfizer lasts at least 6 months, but remember that the very first people to be given it, in the trials, only got their shots about 8 months ago, so it's impossible to say for sure. I'm actually optimistic, though. Having a cold from a coronavirus leaves you immune to that particular virus for something like 2 or 3 years, and vaccines tend to be more potent than natural infection. The problem is with variants - Pfizer may protect for 3 years against the Wuhan and UK strains, starting at 95%, but against the S. African variant it only protects 75% to start with. And new variants will surely pop up. But, on the positive side, mRNA vaccines can be engineered to handle variants.

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    2. Thanks a lot for your useful blog! I saw a youtube video made by John Lee, a British pathologist, critiquing the way the western countries handled covid. Much of it seemed true or at least plausible to me. (I have no medical training by the way. Just a lay person.)
      What do you think?

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    3. Could be interesting. If you can give me a url for the video, and if the video is longer than 5 minutes point me to the 5 minutes that are most important, I will be glad to look at it and see what I think.

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  2. Thanks again Susan for an excellent post. The anti vaxx mob have been unable to answer the question of how the vaccinator would ensure there is one microchip per does when using a multi-dose vial. I read that T cell immunity to SARS1 persists after 17 years which could be the case with SARS2. (My nomenclature). Also, T cells have been show to do the business in people with MS or cancer who have been treated with B cell depleting monoclonals.

    https://multiple-sclerosis-research.org/2021/05/injection-site-reactions-covid-19/

    I find this very encouraging, especially as a lateral flow antibody test I took 12 weeks after my first AZO vaccine for the REACT study was negative. Keep up the good work Susan!

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    1. I can't remember the details of that study - did they give you a second dose after 4 weeks, I hope? Anyway, AZO seems particularly strong on T cell response. (About the multi-dose issue, I'm sure the vaccinator just needs to give the vial a real good shake and the microchips will distribute "like magic.")

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