Category: pandemic

The lab leak theory for the origin of the Covid virus is once again deep-sixed

July 1, 2024 • 9:30 am

Yes, I fell for a recent NYT article (June 3) by Alina Chan, a piece dismantled in the article below by infectious disease specialist Paul Offit.  Chan’s piece was called “Why the pandemic probably started in a lab, in 5 key points,” and it was a long and animated op-ed.  Being ignorant of the data, I took her bait and said that Chan’s article buttressed my own view that a lab-leak theory was becoming increasingly credible. (She’s a postdoctoral fellow at the Broad Institute.)

But since I consider Offit the most credible source of information about Covid, I’ve now let go of the bait, and agree with his arguments, in the Substack article below, that a wet-market origin of the Covid virus is the best hypothesis by far.

I guess a lot of other people fell for Chan’s article, too, but I’m especially culpable because I already knew Offfit’s arguments, for last March I’d posted his defense of the “wet market theory” for the origin of Covid.  I simply forgot!

From the new piece, here’s Offit dismissing the lab-leak theory once again:

On June 3, 2024, the New York Times published an op-ed titled, “Why the Pandemic Probably Started in a Lab, in 5 Key Points.” The article was written by Alina Chan, a molecular biologist at the Broad Institute in Boston. Chan had also written a book titled Viral: The Search for the Origin of Covid-19, which also supported the notion that SARS-CoV-2 virus was created in a Wuhan laboratory. Chan’s book has been roundly criticized by scientists who investigated the events in Wuhan. Nonetheless, two thirds of the American public, independent of political affiliation, believe that SARS-CoV-2 virus leaked from a Wuhan laboratory.

Chan’s book, by the way, was coauthored by Matt Ridley.

Click below if you want to see Offit defending the wet-market theory, and, along the way, making Chan and the NYT—which should have had an expert vet her assertions—look sloppy and ignorant.

First, Offit isn’t alone in his opinion; in fact, a wet-market origin seems to be the consensus of Those Who Know:

In her op-ed, Chan wrote, “Although how the pandemic started has been hotly debated, a growing volume of evidence — gleaned from public records released under the Freedom of Information Act, digital sleuthing through online databases, scientific papers analyzing the virus and its spread, and leaks from within the U.S. government — suggests that the pandemic most likely occurred because a virus escaped from a research lab in Wuhan, China. If so, it would be the most costly accident in the history of science.” Chan was wrong to claim the existence of a “growing body of evidence.” On the contrary, her op-ed contained only conspiracies, innuendos, and blatantly false claims. Although several scientists have stepped forward to counter Chan’s claims, the best single take-down was by Dr. Vincent Racaniello, a virologist who hosts a popular podcast called This Week in Virology (TWiV).

In a one-hour video, the TWiV team addressed each of the “Five Key Points” proffered by Chan. The group consisted of Vincent Racaniello (virologist), Alan Dove (microbiologist), Rich Condit (viral geneticist), Brianne Barker (immunologist), and Jolene Ramsey (microbiologist). The video was released on June 10, 2024, one week after Chan’s publication in the New York Times. This wasn’t the first time that the TWiV team had discussed the origin of SARS-CoV-2; it was the ninth. Previous guests have included evolutionary biologists who had directly investigated the events in Wuhan; specifically, Michael Worobey, Kristian Anderson, Eddie Holmes, Marion Koopmans, and Robert Garry, who had collectively published a paper in the journal Science in 2022 titled, “The Huanan Seafood Wholesale Market in Wuhan Was the Early Epicenter of the COVID-19 Pandemic.” This paper showed that all the early cases of SARS-CoV-2 clustered around the southwestern section of a wet market in Wuhan where animals susceptible to coronavirus were illegally sold and inadequately housed. Worobey and his team had shown that 1) the early cases had direct or indirect contact with the market and 2) none of the early cases occurred around the Wuhan Institute of Virology. This single paper was devastating to Chan’s hypothesis.

Chan’s arguments about a lab leak are already cast into doubt by Worobey et al.’s paper described in the second paragraph above (I haven’t heard the TWiV podcast, but readers say it’s very good.)  The epidemiology alone is almost dispositive.

But Offit goes on to dismantle each of Chan’s five arguments.  I’ll put them in bold and give a very brief summary of his refutation.

1.) “Bat corona spillover events in humans are rare.” Not true: many people who live near bats show antibodies indicating exposure to coronaviruses from bats. Further, the potential for spillover events is high given the frequency of contact between humans and carriers like civets.

2.) The Wuhan lab was researching how to make bat coronaviruses more infectious. Although the Wuhan lab studied coronaviruses, there’s not the slightest evidence that those viruses could be precursors to those causing covid.

3.) The Wuhan lab worked under insufficiently strict biohazard conditions. Offit says that the conditions were “Biosafety Laboratory-2”, which, even if the Chinese viriologists were working with SARS-CoV-2, are considered “adequate”.  But they weren’t working with that virus!

4.) Chan says that there was “no way to distinguish between the market [origin] and a [human] superspreader.” Further, she said, “not a single infected animal has ever been shown to be infected with SARS-CoV-2.”  Here Offit destroys her, and I’ll have to quote him.

Re distinguishing origins:

It is at this point that Chan’s op-ed defies common sense. Two different lineages of SARS-CoV-2 virus were detected early in the outbreak. Chan would have us believe that two different SARS-CoV-2 viruses were created in the laboratory and then taken directly by human superspreaders to the southwestern section of the Huanan Wholesale Seafood Market exactly where you would have expected an animal-to-human spillover event to occur. Why didn’t one or both superspreaders go to any of the 10,000 other places in Wuhan to begin a pandemic.

And re the lack of infected animals:

Chan wrote, “Not a single infected animal has ever been shown to be infected with SARS-CoV-2.” When the outbreak began, Chinese authorities shut down the Huanan Wholesale Seafood Market, disinfected the area, and killed the animals likely to have served as intermediates between bats and humans. In other words, no animals were available to test. This was in direct contrast to SARS-1, another animal-to-human spillover event that originated in a Foshan, China, wet market. In that case, the market continued to operate. For that reason, animals that were the likely source of SARS-1 were available for testing. This is perhaps Chan’s most disingenuous comment. You can’t go back in time and test animals that no longer exist.

This relates to Chan’s fifth point:

5.) “Chinese authorities have not done an intense search for animals infected with SARS-CoV-2.”  Again I’ll quote Offit:

True. Mostly because all the animals in the southwestern section of the Huanan Wholesale Seafood Market were immediately slaughtered. Researchers did, however, find genetic evidence of SARS-CoV-2 virus in carts, drains, a feather-and-hair remover, a metal cage, and machines that process animals after they’ve been slaughtered in wet market stalls that were at the epicenter of the outbreak. In the same specimens, they found mammalian DNA consistent with raccoon dogs, bamboo rats, and palm civets, all likely intermediate hosts as bat coronaviruses spilled into the human population.

Given Offit’s credentials and accomplishments, and his strong defense of the wet-market theory above, I agree with his conclusion that the evidence for a wet-market origin is “overwhelming.”  And yes, given that he knows his onions, I’ll apologize for having been so credible with respect to Chan’s NYT article.  The first thing to correct is Chan’s piece, but I don’t expect that the NYT, who could have had her piece looked at by people like Offit, went with it.  And that despite the fact that in 2021 the paper had already reported controversies about Chan’s theories, which included the lab-leak hypothesis.

But let’s put aside the paper’s lack of due diligence, for it’s really important to pinpoint the origin of this virus.  If we want to prevent future pandemics, we need to know whether wet markets can give rise to them, for in that case we can do something tangible to prevent them. On the other hand, if foreign scientists were manipulating coronaviruses and an infectious one escaped the lab, there’s not much we can do.

Fortunately, the first hypothesis seems to be the case, and Offit suggests several fixes: hold the Chinese government accountable for not supervising wet markets, including those that sell illegal animals prone to carrying bat-derived viruses (Offit says that 31 of 38 species in the market were animals protected under Chinese law). Further, he argues that once there’s evidence of a pandemic starting, the Chinese government must allow international teams of scientists into the country, which they didn’t at first dp in Wuhan.  Offit ends by saying, “It’s time we put aside the fruitless, dead-end hypothesis of a lab leak and do the work that is necessary to prevent the next pandemic.”

I’ll keep an eye out for further developments, and again I’m sorry for being credulous about Chan’s paper.  She may be craving the limelight, or may really passionately believe she’s right (or both), but given that the evidence against her theory was already known when she published her op-ed, she’s not acting like a good scientist. And in this case,sloppy science can put people in severe danger.

 

h/t: Frau Katze

Should you get that bivalent booster shot?

October 4, 2022 • 12:00 pm

My primary-care physician, Dr. Alex Lickerman, discusses the question everyone’s asking: should you get that bivalent booster? (For most people it would be their third booster and the fifth Covid shot). You can access Alex’s post by clicking on the screenshot below. (Be sure to look at the graphs and read it all.)

Alex always looks at the science before he decides what’s to recommend, and by that I mean the primary literature. When I first asked him about whether to get a booster, he said he didn’t know because the data hadn’t been published, and all the existing studies were on antibody levels in mice. Now he looks at more data. I’ll give his conclusion below but do have a look at his post.

My own decision was to get the booster simply because I’m traveling tomorrow, but, as always, consult your own doctor or decide from the data themselves. People tend to get covid on airplanes these days (a friend who just returned from Boston said only 5% of the passengers on her Southwest flight wore masks), and Alex said that it couldn’t hurt me to get one before traveling—but it might not help me much, either.

CONCLUSION: Should you get the bivalent booster? In the absence of human trial data, we might think about this question as follows: We can be reasonably certain that the bivalent booster will produce a level of neutralizing antibodies that diminishes the risk of infection from COVID. We don’t know how long that protection will last, but a fair guess would be from 3 to 6 months. If there is some reason you feel the need to reduce your risk over the next 3 to 6 months, say, for travel, getting the bivalent booster would seem reasonable. On the other hand, if in addition to being vaccinated, you’ve had COVID recently (meaning you’ve been infected with an Omicron variant), likely the same level of protection accrues, obviating the need for the bivalent booster. If your main concern is dying from COVID and you’ve already received the primary series and one or two boosters, your risk is so low that getting another shot would seem superfluous. If you are at high risk for dying from COVID, while there is no data to suggest the bivalent booster might further reduce your risk beyond levels afforded by the primary series and one or two boosters, there is also likely little risk of getting it. In the absence of data to guide us, this would then be a personal decision.

Often Alex answers questions in the comments, so if you have any, put them below. I’ll tell him that he might look at the comments.

How to get your free covid-19 home tests from the U.S. government

July 25, 2022 • 9:00 am

Just a note that all Americans are now entitled to their third free set of rapid antigen test kits for covid-19.  Most of you are familiar with these: you swab your nostrils, swirl the swab in a special liquid, and then squeeze the liquid into a depression on a small plastic device (first picture below) In 15 minutes you get a simple readout that says whether or not the kit has detected antigens: the spike proteins presented by the SARS-CoV-2 virus that is responsible for COVID-19. (The vaccine is designed to prompt your body to produce antibodies to these antigens.)

The devices look like this; you also get a swab, a vial of liquid, and detailed instructions with diagrams.

And the results look like this after 15 minutes. If you have the one on the left with a “C”, no antigen was seen; you’re negative. (That does not mean for certain that you’re free from infection; these tests do give false negatives.) If you have two lines, at both site “C” and site “T”, you have antigen and are infected (again, there can be false positives).  A faint line a “T” still indicates infection.

These are not as good as PCR tests, which remain the gold standard for testing for covid, but they’re useful to have around, and when I was feeling stuffy the other day, I gave myself two tests a day apart (I was fine.)

I think they’re expensive if you buy them, but the U.S. government is sending Americans two free kits in a third round of distribution. Each kit has FOUR tests, so you can test yourself eight times. (It’s easy to do!).

To get yours, and you should get them now, go here to the government website, which explains the kits and allows you to order by phone, or go here to order them by email, as I did, by clicking on the blue button the first website. All you do is fill in your name and address, and the Postal Service will ship you two packages of four kits. There is no charge for anything, but be sure to push the green checkout button.

Two points. I’m not a doctor, so ask your physician for help in interpreting the results or finding out when to test and what to do if you are positive. Also, this is for American citizens only, provided as a service by the gubmint.

Covidiocy: Cathy Young’s take

March 16, 2022 • 11:15 am

Cathy Young often seems to me a voice of reason in the same way John McWhorter is: someone who’s not afraid to call things as they are. In her latest piece at Bulwark (click on screenshot below to read), Young, while reminding us that Covid is still with us, and Ukraine has not ended the virus narrative, calls out the various “covidiots” who were either stupidly wrong and overly precipitous in their take on the pandemic, or, worse, exacerbated it with their pronouncements. While Young gives both Left and Right their lumps, the Right turns out lumpier.

Here’s an example of party-typical behavior that Young sees as business as usual, but not explicitly dangerous:

Almost from the very beginning, responses to COVID-19 in the United States were (like everything else these days) polarized along political lines. Being Team Blue meant that you saw COVID as a very serious threat and supported drastic measures to contain and mitigate its spread. Being Team Red meant that you thought COVID wasn’t that big a deal and that its danger was being overhyped by safety freaks, people who wanted to give the government extraordinary powers, and Democrats who wanted to weaponize the pandemic to bring down Donald Trump. Obviously, not everyone fell neatly into those categories; but the tendency was undeniable.

This kind of stuff, however, she considers politically-based prognostications that can sort of be excused. Then the lump-production begins:

Chronicling Team Red covidiocy could easily fill a book: The estimate from Hoover Institution senior fellow Richard Epstein, a law professor, that just 500 Americans would die of COVID—followed by his comically desperate attempts to say he had really meant 5,000. The claims by talk-radio king Rush Limbaugh that COVID was just “the common cold” and was being overhyped by the media as part of “an effort to bring down Trump.” Trump’s rant at a rally about the Democrats’ “new hoax” and about the flu being far worse. (Yes, if you pick apart his word salad, he technically didn’t call the disease a hoax, only claims that he was mishandling it; but it’s ridiculous to deny that such talk boosted the “COVID hoax” narratives.) The #PlanDemic and #DemPanic hashtags (which still exist, but don’t look if you want to avoid brain damage). The war cries to “liberate” locked-down states. The obsessions with alleged miracle drugs, especially hydroxychloroquine and ivermectin. The Anthony Fauci Derangement Syndrome. The anti-vaccine propaganda and scare tactics peddled by the likes of Tucker Carlson.

And she also indicts the Left for being so eager to blame Trump for everything, noting this:

Did Trump’s feckless rhetoric and lack of leadership encourage irresponsible behavior with regard to social distancing and vaccination and thus cost lives? Most likely; but counterfactuals are always iffy, and it’s difficult to say with any confidence how different the outcomes would have been under a different president.

As for lockdowns, school closings, and mask mandates, Young takes a judicious position, saying that perhaps the “elite”, who could work from home, were too eager to embrace lockdowns, yet there is some evidence that mask wearing was indeed effective. Her point is that even now we have no strong and unilateral answers to the efficacy of these actions:

How well lockdowns, mask mandates, and other pre-vaccination COVID-19 mitigation strategies worked in reducing the spread of the virus and the resulting deaths is a massively complicated question.

She cites evidence on both sides, but reserves her strongest opprobrium for those whose actions were positively dangerous, contributing to the spread of the virus.  These include the ivermectin-pushers and the anti-vaxxers—again, mostly people on the Right. Curiously, though, she includes among this group Bret and Heather Weinstein and Bari Weiss, who by their own lights are liberals. We’ve discussed some of their stands before.

Young says this:

But no part of Team Red COVID discourse has been more insidious than anti-vaccine propaganda, often abetted by the “anti-anti-vax” crowd. Some of this discourse comes from people who are not, strictly speaking, Team Red but are part of the “anti-woke” side in the culture wars (a side with which I broadly sympathize). Brett Weinstein and Heather Heying, husband-and-wife biologists who attracted a lot of support a few years ago when they were run out of Evergreen College for opposing an “anti-racist” exercise in which white people were asked to stay away from campus for day, have emerged as two leading voices of COVID vaccine skepticism—rejecting scientific evidence for quackery.

Former New York Times editor and anti-“cancel culture” dissenter Bari Weiss initially urged her newsletter readers last May to get vaccinated and start living a normal life (and advised the vaccine-hesitant to “consider the data” and get with the program); but later, she shifted toward platforming vaccine skeptics as a legitimate side in the debate and giving sympathetic coverage to vaccine resisters including the protesting Canadian truckers, with no balancing pro-vaccination message or criticism of anti-vax agitprop and conspiracy theories.

It’s hard to say whether this is contrarianism or audience capture. Either way—and I say this as someone who generally admires Bari Weiss—it’s, well, deplorable.

Note, though, that the link to Bari Weiss supposedly giving “sympathetic coverage to vaccine resisters” actually goes to an article by Suzy Weiss, Bari’s sister (it’s a family act now), and the link to sympathy with the Canadian truckers goes to a piece by Rupa Subramanya.  While one can assume that Bari Weiss sympathizes with their views, especially after her announcement on Bill Maher’s show that she was “done with covid”, it should have been more explicit that Weiss hosts posts by people she agrees with, and that these two posts were written by others. (Young does say she “platforms” vaccine skeptics.)

As for Weinstein and Heying’s vaccine skepticism and enthusiasm about ivermectin, this was and is unforgivable, especially in view of the very weak or nonexistent evidence for ivermectin as a “palliative” (except when worms are a comorbidity) and the fact that the best single-blind study we have shows no effect of the drug.

At this stage, a true scientist would admit that this advice was misguided, especially in view of this unchallengeable statement: during the pandemic, unvaccinated people who took ivermectin were much more likely to get sick, die, and pass on the virus than those who were vaccinated and didn’t take the de-worming drug.  This itself warrants an apology from people who consider themselves wedded to data. It is, in my view, reprehensible to question properly tested vaccines at the same time you promote ivermectin.

At any rate, let us remember that although the headlines are dominated by the Russian invasion of Ukraine, covid is a problem that will remain with us for years to come.

This trip cancelled because of Covid

March 11, 2022 • 2:33 pm

All the passengers had an antigen test today, and I was okay, but I guess some people tested positive. The upshot is that our captain has informed us that this cruise, which is supposed to last another six days, is cancelled, and we’re heading back to Punta Arenas in Chile.

I don’t know what this means for me personally, as I was scheduled to be on another two-week journey after this one was over. For sure it means that at the very least I’ll be cooling my heels in Chile for a week, and it may be that Hurtigruten decides to cancel the next trip, too, in which case there will be quarantine, PCR testing, and an early trip home. None of us knows anything beyond that we’re headed back to our destination in Chile, and will get more information soon.

All I ask of readers is that they not tell me what I’m in for if we have to stay in our cabins for days or so. I’m already bummed out enough. I’ll convey what we learn when we learn it.

Predicting ivermectin and hydroxychloquine use by political affiliation

February 20, 2022 • 1:15 pm

This is a strange paper, though it makes sense . But the rationale for publishing it seems to be to say: “See? The Republicans took the quack drugs.” That happens to be true, but how does documentation help public health? Well, the authors of this JAMA Internal Medicine paper give a reason at the end, but it’s hardly convincing.

The paper—rather, a “letter”—was meant to determine how prescriptions for various drugs, including the bogus Covid remedies hydroxyquinone and ivermectin—were correlated with both time and with the political sentiments of the region where the drug was prescribed. The patterns are interesting, but I suspect the authors (all from Harvard or affiliates) were Democrats and really wanted to show that quackery is higher among Republicans.

They did—at least after mid-2020.

 

 

The authors looked at prescriptions written under insurance for four drugs from January 2019 to Dec 2020. The drugs were, as I said, ivermectin and hydroxychloroquine, as well as as the two drugs specified below, which are in effect “control drugs” not used to treat (or rumored to treat) Covid-19. The sample size was huge: 18,555,844 adults, pretty evenly divided between men and women, with the mean overall age of 49.1

The hypothesis:

We hypothesized that the county-level volume of prescriptions for hydroxychloroquine and ivermectin—but not other, similar medications—would be associated with county-level political voting patterns in the 2020 US presidential election.

What they’re trying to say is, “We hypothesized that Republicans fell for quack remedies more often than Democrats.” (I bet the authors are all Democrats.) And their hypothesis was confirmed, except for one brief span of time (see below).

The methods:

In this cross-sectional study, we used deidentified medical claims for all outpatient visits by adults aged 18 years or older in counties with 50 or more enrollees from January 2019 through December 2020 included in the OptumLabs Data Warehouse, which includes medical claims for commercial and Medicare Advantage enrollees, as well as US Census data and 2020 US presidential election results. The institutional review board at Harvard University deemed the study exempt from review and waived the requirement for informed consent because deidentified data were used. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

We divided the county-level Republican vote share in the 2020 presidential election into quartiles. We assessed county-level rates of new prescriptions for hydroxychloroquine and ivermectin (ie, patients with no fills for the medication in the previous 6 months) per 100 000 enrollees and 2 control medications, methotrexate sodium and albendazole (which have similar clinical applications as hydroxychloroquine or ivermectin, respectively, but are not proposed as COVID-19 treatments).

The four plots below show drug prescriptions throughout the survey region over two years. The first two show both methotrexate and hydroxychloroquine.

Plot A) shows total prescriptions, plot C) new prescriptions. In both graphs methotrexate (in orange) doesn’t change over time, while hydroxychloroquine (in green) spikes around April, 2020, and then goes down almost immediately, except for new prescriptions, which also shoot up around July of 2020, nearing election time (more on that later). The April spike for hydroxychloroquine presumably reflects the FDA’s allowing emergency use of hydroxycholoroquine for Covid-19 on April 3 and then revoking that usage on June 15. (I’d forgotten about that!)

Remember that there was a time when people thought hydroxychloroquine might be useful. The graph below is for ivermectin (green) versus Albendazole (orange). Total prescriptions on top, new prescriptions on the bottom. Prescrptions for Albendazole don’t change over the two years, but Ivermectin shoots up beginning in August, 2020, both in terms of general usage and new prescriptions. As we’ll see below, this reflects a general increase in Americans trying to get prescriptions for ivermectin, but most of the rise is due to Republicans seeking prescriptions.

The next four graphs show only new prescriptions for drugs, and this time there are four plots reflecting four levels of Republican voting by country in which prescriptions were written. Orange shows the highest quartile of counties (most Republican) and then in descending order light blue, gray, and green (most Democratic). During the two months of hydroxychloroquine being allowed (period between numbers 1 and 2 on the first graph), people of all political stripes got more prescriptions, but in fact the more Democratic counties got more prescriptions. This presumably reflects Democrats following health guidelines a bit more assiduously than Republicans, though the difference is tiny.

Towards election time, though, new prescriptions for hydroxychloroquine again rose steeply, though much more steeply for more Republican than for more Democratic counties (remember, these are quartiles for Republicanism, so blue, green, and grey lines don’t necessarily mean “Democratic-voting counties”).

Ivermectin doesn’t show the April-May spike that hydroxychloroquine does, as the government didn’t allow and then disallow ivermectin, but there’s a huge spike in new presciptions towards election time, again much more pronounced in the more Republican counties. Note that in the second graph, the numbers 1-4 correspond to different events that might cause more usage of ivermectin. I’ve put the ivermectin key in bold in the paragraph below:

Here’s what the numbers on the X-axis mean:

Arrows show key dates for hydroxychloroquine: (1) announcement of the US Food and Drug Administration’s emergency use authorization on March 28, 2020; and (2) revocation of the emergency use authorization on June 15, 2020. Key dates for ivermectin include: (1) the initial in vitro study claiming a potential antiviral effect of ivermectin5 on April 3, 2020; (2) the National Institutes of Health recommendation against ivermectin use2 on August 1, 2020; (3) release of a now-retracted manuscript preprint that described a clinical trial claiming 90% efficacy of ivermectin against COVID-196 on November 13, 2020; and (4) a widely publicized hearing of the US Senate Committee on Homeland Security and Governmental Affairs that included testimony by Pierre Kory, MD, of St Luke’s Aurora Medical Center, who promoted using ivermectin to treat COVID-19 on December 8, 2020. . . . . .

Not much going on with the two control drugs:

 

The conclusions. If you’re a Democrat, you’ll want to say that the Democrats were following the science (including the April-May spike in hydroxychloroquine use, since the government said it was okay), but the Republicans followed the rumors against the science, accounting for the higher number of new prescriptions at election time. But, as the authors emphasize, what we have here are correlations, not causations.

Why a spike around election time? The authors don’t really say, but i suppose one could theorize that Trump was whipping up Covid-19 sentiments with his pronouncements, making his people more liable to go for quack remedies. Note that the rise in all four quartiles doesn’t really imply that Democrats were taking more ivermectin around election time; the spike could be caused by prescriptions for Republicans in counties that were more likely to vote Democratic overall. I could dig deeper into that, but I don’t think the paper’s worth it.  Here’s the authors’ brief discussion:

In late 2020, the number of new prescriptions for hydroxychloroquine and ivermectin was higher in counties with higher Republican vote share, whereas in early 2020, before revocation of the Food and Drug Administration’s emergency use authorization, prescribing volume for hydroxychloroquine was higher in counties with a lower Republican (ie, higher Democrat) vote share. These findings were absent before the COVID-19 pandemic and for 2 control drugs.

This study has limitations. In an observational study, we could not address the causality of the association between county-level political voting patterns and prescribing of 2 ineffective COVID-19 treatments. Also, we were unable to assess the specific contribution of patient, physician, or other factors to the prescribing patterns.

These limitations notwithstanding, our findings are consistent with the hypothesis that US prescribing of hydroxychloroquine and ivermectin during the COVID-19 pandemic may have been influenced by political affiliation. Because political affiliation should not be a factor in clinical treatment decisions, our findings raise concerns for public trust in a nonpartisan health care system.

Here’s what I think the authors are saying, translated into normal language:

We found what we thought: Democrats follow the science and Republicans follow rumors and conspiracy theories. This raises concern for the American system because it shows that the damn Republicans endanger everybody by mistrusting the government.

Now of course I’m a Democrat and have exaggerated the “translation”. But if you read the paper, don’t you think this is what the authors really want to say?

Once again: Ivermectin doesn’t work

February 20, 2022 • 10:00 am

The paper at issue today reports the most thorough and well controlled study of the effect of ivermectin on Covid-19 around, and it was just published in JAMA Internal Medicine. What it supports, contra the claims of Joe Rogan, Bret and Heather Weinstein, and a whole slew of Republican loons, is that the drug ivermectin—as already asserted by the FDA—neither prevents nor cures covid-19. Or rather, this study shows that once adults over 50 who get the virus and are hospitalized with comorbidities, Ivermectin doesn’t help them get better. (An earlier study published in BMC Infectious Diseases, both randomized and double-blinded, and including a placebo, showed that taking ivermectin had no significant effect on keeping people out of the hospital.)

The upshot is that every well controlled study shows that ivermectin is useless in helping you once you get the virus. Another meta-analysis of reasonably well done studies that included prevention concluded that there was no good evidence that the drug even prevented infection.  The only studies that may show value of ivermectin are those in which many participants have high loads of worms as comorbidities. In such studies (which don’t apply in the US or UK), the drug may, by helping you get rid of worms (see below), make recovery from covid more likely. But even in that case there’s no excuse not to get vaccinated.  And of course you wouldn’t take ivermectin unless there was evidence you had worms.

Ivermectin is used in humans to cure parasitic worms and head lice, but can be dangerous if taken in doses high enough to kill viruses in vitro. Nevertheless, in this age of conspiracy theories and general lunacy, even credentialed scientists like the Weinsteins have recommended ivermectin and criticized vaccines, even though it’s beyond doubt that the vaccines prevent severe illness and hospitalization. You’d have to be crazy or paranoid to pass up vaccination in favor of ivermectin But thousands do it, so there you are.

With luck, you should be able to get the new study by clicking on the screenshot below, especially if you have the legal Unpaywall app. There’s also a link to the pdf, and if all else fails, make a judicious inquiry.

First, the background: the authors summarize what’s know about Ivermectin in studies to date. As I and others have mentioned before

Although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses. In 2021, 2 randomized clinical trials from Colombia and Argentina found no significant effect of ivermectin on symptom resolution and hospitalization rates for patients with COVID-19. A Cochrane meta-analysis also found insufficient evidence to support the use of ivermectin for the treatment or prevention of COVID-19. [JAC: The meta-analysis is linked above.]

The new study was done in Malaysia (other studies are ongoing, I believe), and iswasrandomized with respect to patient condition and age, but there was no placebo control. That is, half the infected patients were given “standard of care” (none were vaccinated) and the other half were given “standard of care” plus Ivermectin. The outcomes were followed over time.  The result: not only did Ivermectin not work, but there was a slightly higher, though nonsignificant, risk of the ivermectin treated patients progressing to the phase that required supplemental oxygen. That is exactly the opposite of what you would expect if some patients were taking placebos, for you might expect that if there’s a placebo effect, then placebo-ingesting patients would do better than those not taking placebos (i.e., the patients in this study). But despite the absence of placebos, there was still no effect of ivermectin in this study using any measure of “disease progression”.

I’m not going to summarize the results in detail, because the authors do a good job of that themselves.

There are three summaries of the results. First, the “TL/DR” version:

Note below that the 490 patients observed were all over 50 and had documented comorbidities—factors that make them more susceptible to complications and death.  Here is the protocol (indented, bolding is mine except in headers).

The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients’ symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease.

Interventions  Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care (n = 241) or standard of care alone (n = 249). The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging.

Note again: no placebo pills were given. And here’s how they measured outcome:

Main Outcomes and Measures  The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events.

The results are below. Note that slightly more patients in the ivermectin-dosed group (4% more) progressed to severe disease (i.e., requiring supplemental oxygen than those in the group treated the same but without ivermectin. Incorporating still other measures of “progression to severe disease,” there was again no significant difference, although there was slightly more deaths (nonsignificantly more) in the ivermectin versus control group. Finally, the most common side effect, diarrhea, was found more often in the ivermectin versus control group,but I can’t find the statistics for that difference.

Results  Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group).

And the upshot:

Conclusions and Relevance  In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19.

Here’s the entirety of the discussion (bolding mine); note that the authors, as is proper, point out the limitations of the work.

Discussion

In this randomized clinical trial of early ivermectin treatment for adults with mild to moderate COVID-19 and comorbidities, we found no evidence that ivermectin was efficacious in reducing the risk of severe disease. Our findings are consistent with the results of the IVERCOR-COVID19 trial,17 which found that ivermectin was ineffective in reducing the risk of hospitalization.

Prior randomized clinical trials of ivermectin treatment for patients with COVID-19 and with 400 or more patients enrolled focused on outpatients.16,17 In contrast, the patients in our trial were hospitalized, which permitted the observed administration of ivermectin with a high adherence rate. Furthermore, we used clearly defined criteria for ascertaining progression to severe disease.

The pharmacokinetics of ivermectin for treating COVID-19 has been a contentious issue. The plasma inhibitory concentrations of ivermectin for SARS-CoV-2 are high; thus, establishing an effective ivermectin dose regimen without causing toxic effects in patients is difficult.27,28 The dose regimens that produced favorable results against COVID-19 ranged from a 0.2-mg/kg single dose to 0.6 mg/kg/d for 5 days29–32; a concentration-dependent antiviral effect was demonstrated by Krolewiecki et al.29 Pharmacokinetic studies have suggested that a single dose of up to 120 mg of ivermectin can be safe and well tolerated.33 Considering the peak of SARS-CoV-2 viral load during the first week of illness and its prolongation in severe disease,34 our trial used an ivermectin dose of 0.4 mg/kg of body weight daily for 5 days. The notably higher incidence of AEs  [“adverse effects”] in the ivermectin group raises concerns about the use of this drug outside of trial settings and without medical supervision.

Limitations

Our study has limitations. First, the open-label trial design might contribute to the underreporting of adverse events in the control group while overestimating the drug effects of ivermectin. Second, our study was not designed to assess the effects of ivermectin on mortality from COVID-19. Finally, the generalizability of our findings may be limited by the older study population, although younger and healthier individuals with low risk of severe disease are less likely to benefit from specific COVID-19 treatments.

Note as well the “limitatation” that placebos were not given. Another limitation is that this study didn’t assess the chance of getting infected in the first place when you take ivermectin, or of being hospitalized if you get infected, though other work (see above) has suggested no effect of ivermectin on either of these measures.

I was prepared to admit that my criticism of ivermectin was wrong had these properly-designed studies shown an effect, but of course because ivermectin is usually suggested as a substitute for getting vaccinated, the real thing you want to know is whether, compared to getting the jabs, you’re better off swallowing ivermectin.  Given the efficacy of the vaccines, which has now been conclusively demonstrated (and yes, the effects wane over time, so we may need a yearly booster), I was already pretty sure that those who touted ivermectin as a better substitute for vaccination were wrong.  But this study does nothing to convince me that I was wrong.

More studies will come out, and eventually we’ll have a pretty solid conclusion. And I’ll bet any reader $100 that it will show that ivermectin is no substitute for vaccination or the other new drugs that are being used to relieve symptoms and combat the virus.

The question now is whether people like Joe Rogan or, especially, Bret and Heather Weinstein will admit that ivermectin—at least in this study—has no effect. Ideally, scientists will admit when they’re wrong, and, as Richard Dawkins has emphasized, that is an admirable trait. Such admissions move science along faster than waiting for a generation wedded to an idea to die off and be replaced by those who have different ideas. Now I haven’t been wrong about ivermectin yet, but when I see a study showing it’s more efficacious than vaccines in keeping you out of the hospital, or alive, I’d like to think I’d say whose three words. Will the Weinsteins say them?

I predict no. We will see a lot of hemming and hawing frothe Quacksters, and perhaps qualifications like “well, the study showed X but didn’t show the real prediction, which is Y.” In fact, I don’t remember hearing anybody pushing quack remedies admit that they were wrong.

The reason I’m so dogged about this is because people who tout quack remedies when there are good ones can do harm. And it’s far worse if they push the quackery while wearing the mantle of science.

But listen up: STAY AWAY FROM THE DAMN IVERMECTIN!

 

h/t: Alex, Leslie