As reminders…

Alpha–Variant first identified in the UK

Beta–Variant first identified in South Africa

Gamma–Variant first identified in Brazil

Delta–Variant first identified in India

Omicron–Variant first identified in South Africa

Updating the chart above:

Ancestral: B.1.1.529 Omicron

Transmissibility: All the +

Immune Evasiveness: All the +

Vaccine Effectiveness: Check (for hospitalization)

Also as a reminder:

Coronavirus

–Around the horn, most places in the world continue to emerge from their omicron wave or are at least about to crest it. I saw an article this morning calling Denmark a cautionary tale of releasing restrictions to soon as its omicron wave case numbers are high, although all the Danish health officials in it pointed out that hospitalizations and deaths were way down versus previous waves. And the cases appear to be cresting this week, and likely to drop like a rock shortly. In the US, the omicron wave continues to come down rapidly. Case numbers, census and admissions are all dropping with greater velocity from omicron than previous waves. At present, the powers that be estimate at least 73% of Americans are now immune to omicron. As bellweathers, the UK and South Africa continue to have very muted activity and no new waves. In China, you still have occasional cities shut down for “no COVID policy” reasons, and they are getting a little pissed at Hong Kong which is struggling to contain an omicron outbreak.

–First, in news I cannot comment on, there is this press release. Thank you for your understanding.

–And in news I cannot comment much on, the British Medical Journal published a report last week detailing Pfizer’s partner BioNTech’s efforts to dissuade the South African government from backing the effort to duplicate the Moderna mRNA vaccine that was ultimately successful. You can (and should) read the BMJ’s coverage here. Thank you for your understanding.

–Also in the vaccine news, Pfizer has withdrawn its application for emergency use authorization of its mRNA COVID vaccine in India. You can read about that here. It is not uncommon for countries to request a country-specific study for safety and sometimes efficacy if the data on the drug has mostly come from studies conducted on patients elsewhere. Japan is pretty famous for insisting on a Japan specific trial before approving much of anything. India’s regulator reported on its website that they wanted a India-specific safety and immunogenecity study due to reports of side effects elsewhere in the world that were still being investigated. Pfizer has opted not to do that study, and has instead withdrawn the vaccine from consideration, meaning that the Pfizer mRNA vaccine will not be available in India. We have mentioned before some other ways India is attempting to meet its vaccination needs with other products though (and the article covers a few as well). Thank you for your understanding.

–In related news, the FDA has delayed consideration of Pfizer’s COVID vaccine for kids under 5. There is a cohort receiving three doses that is still generating safety and efficacy data, and the FDA has decided to wait until that data is more mature before reviewing the data package and making a recommendation. You can read about that here.

–Another big news story making the rounds is a Project Veritas recorded interview with Christopher Cole, the FDA’s Executive Officer of Countermeasures Initiative that has been played up a lot for its “gotcha’!” value regarding the FDA’s position on the COVID vaccines. Having listened to the available clips, and read the transcripts, I will give you my take. For what it’s worth, the FDA has stated that Mr. Cole is -not- involved in decisions on the vaccines and does not work on them. The Medical Countermeasures Initiative works with local, state, national and international governments, NGOs, universities and industry to further develop medical countermeasures for public health emergency preparedness, according to the FDA’s website on the initiative. In short, they work on FDA regulated devices and drugs to be used in the event of a terrorist attack with nuclear, biological or chemical weapons, or a naturally occurring emerging disease. Their job is to let governments know what is available for what possible agents (ranging from diagnostics to gloves to vaccines and drugs) and work with industry or academia to doing research to plug gaps or on emerging threats. While SARS-CoV-2 is either a naturally occurring emerging disease or an accidentally occurring emerging disease (depending on your take on the strength of available lab leak evidence), the Countermeasures Initiative is indeed NOT the part of the FDA that is making determinations on approval of the vaccines.

It’s possible Mr. Cole is aware of discussions about vaccine schedule that he discusses on camera. I could see a “heads up” coming into his professional purview. But he’s not on those actual committees.

I also keep in the back of my mind that his off camera interviewer sounds young and female, and Mr. Cole would not be the first guy in history to try and make himself sound more important.

Regardless, as to the actual “gotcha’!” content. So one of the statements Mr. Cole makes that is getting a lot of attention is he is definitive in saying “yeah, it’ll be you’ll have to get an annual. I think what’s gonna happen is it’s gonna be a gradual things, schools are gonna mandate it.” Other spliced in cuts of the interview include Mr. Cole stating that “it hasn’t been talked about on [media]” because “they don’t want to rile everyone up.” In another splice, Mr. Cole is following up on a question about why, and he states “It means your ability to fight wanes, so the three will bolster your system. And then there’ll be an annual eventually, just like the flu shot . . . for everyone.”

Now, I could see this being a heads up on policy given to him. On the other hand, I think that’s also a reasonably educated guess to anyone who has been reading the tea leaves. I think I have even said, some months ago, that schools are likely to mandate a COVID vaccine at some point, at least in some places. I think I also said an annual vaccine similar to the flu vaccine is not out of the question. I think we quoted Fauci doing an about Fauci last week stating that a healthy 30 something might need a booster every 4-5 years. So the implication is that they have this guy with a big sounding title at the FDA stating what I think is a pretty probable case. Now, has the FDA already made that decision, which is what the “gotcha'” of the video actually is? I dunno. They should be looking at data for a seasonal booster decision, and my guess (and I can ONLY guess, although it might be available in the byzantine approval documents FDA releases) is that they are asking the vaccine manufacturers to collect additional data on antibody levels, variants, and breakthrough rates as part of post-marketing surveillance, now that the vaccines are fully FDA approved for adults.

Is there a good medical reason for it? I’m not entirely sure. I don’t think we have the data yet.

The reason you get a flu vaccine every year is that the flu mutates like crazy–that is why flu is still the single greatest pandemic threat to humanity. The Spanish flu could easily have been worse. And yes, I am aware of the flu spreading among turkeys and chickens in the US right now–no known human jumps that I have heard about yet. While SARS-CoV-2 has been a more effective mutator than I gave it credit for at the beginning of the pandemic (I think that has surprised everyone), the question is whether it mutates enough, and often enough, to necessitate an annual shot. I am not sure it does, a relatively high omicron breakthrough rate notwithstanding. After all, most of those did NOT require hospitalization–and it went through the booster in a number of cases anyways. I think the initial protection, priming the immune system to recognize the SARS-CoV-2 spike protein in any configuration, lets the immune system catch up quickly enough to NOT go Ah-nold and keep breakthroughs to pretty typical cold/flu that does NOT take up a hospital bed. As we have covered, most cases of breakthrough on vaccine, even from dangerous strains like delta, are a few days of symptomatic misery, but little real chance of hospitalization. That’s not exactly dissimilar from catching the flu even when you get the flu vaccine, because the flu vaccine either “guessed wrong” and was not enough of a match to stop the flu cold or the flu you caught already mutated around the vaccine enough that you get a few days of symptoms. But, in general, even when that happens with flu, it’s a shorter duration and less severe symptoms than if you had not gotten the vaccine at all.

As you know from your plethora of other vaccines, most other viruses don’t mutate often enough or differentially enough, to require annual boosters. It’s really only flu. There’s a few that you might need a booster for once a decade, and that is likely because your immune system never saw the virus much and is devoting the memory immune resources to other things it is encountering more often.

So when Dr. Fauci was mentioning just last week that a “healthy 30 something might need a booster only every 4-5 years” (if that) and this week that they are looking at data for a fourth shot or annual dose, that’s what is going on. Besides Dr. Fauci just talking to be talking (he does a LOT of interviews). My sense is they are trying to gauge the mutation rate and risk to set an appropriate vaccination schedule that balances risk and benefit. I wish they would be incorporating antibody titers more into that discussion as an easier way to select patients who might benefit from a booster, but I don’t run that show.

To flog the dead horse some more, hospitalization rate is the pandemic threat. The individual threat is if you have the known high risk factors (or are planning to get pregnant, if a lady) for severe COVID. If you are one of those people, yeah, I would be more inclined to get a booster–even an annual one for a few years until we get a better handle on how much risk to you there still is from SARS-CoV-2. If omicron was its last hurrah, and the next variant is just an infectious mild cold, then the need for annual boosters even for the at risk starts to dwindle. If you’re not high risk, absent mandates for a booster (and it’s a challenge to see truly compelling reason for those outside of some health professions), a COVID booster will likely be similar to a seasonal flu shot–kind of your call about the level of risk you want to take. I still hold hope that routine antibody titer testing can be used to inform your choice some day.

Even then, although hospitalization was rare and mostly in those 75 and up, recent studies did show that the risk of hospitalization from vaccine side effects -was- higher in the day or two after a second dose of the vaccine in a patient who had already had coronavirus. As we have discussed before, anecdotal and similar evidence to this paper have suggested that going in with a COVID vaccine shot into an immune system that -just- got over actual COVID (in ~ the last month) is a little more prone to side effects. You’re making an immune system still loaded for bear suddenly see bears everywhere. That has predictable consequences.

Cole also told the Project Veritas reporter that he doesn’t “completely agree with their process” regarding extending the vaccine to kids age 6 months to 5 years old, and when pressed on that by the reporter, said “they don’t have all the tests aren’t there [sic] . . . you can’t give the parents as much assurity as you’d normally want to.” Now, in the video clips I saw, the discussion of “three shots” and waning ability to fight quoted above came at this point, probably alluding to the FDA canceling its review of the under 5 vaccine data until cohorts getting three doses on the ongoing clinical trials have more patients and more data to review. So the delay in review is already happening to get more data–as we just linked above in that section. I am underwhelmed by this as a “gotcha’!” as a result. Mr. Cole is also, to me at least, clearly expressing his own opinion about the process on these pediatric trials.

In fairness, this is also a point Dr. Malone raised in the now infamous Joe Rogan Experience interview we took a deep dive on, as Dr. Malone also believes that some of the preclinical testing was abbreviated. Again, Dr. Malone has had two vaccines himself AND a booster. Every time you see him labeled as a “skeptic”, it’s not the vaccine efficacy he doubts–it was the approval process, as in his mind, as was clear in that podcast interview, there were potential safety signals that were glossed over in the rush to get vaccines to fight the pandemic. As we also discussed, with billions of doses out now, many of Dr. Malone’s concerns, if a real and significant risk of the vaccines, should be more obvious by now.

At best, I would say the excerpts I have seen suggest that Mr. Cole may agree with Dr. Malone that some of the usual pre and early clinical data may not be as robust, and certainly, there will be no long term data on possible side effects that show up months to years later, as the trials have not been running for years. As we have discussed, the mRNA in the mRNA vaccine likely lasts no more than 4 days, and probably less than 48 hours in your cells (and is why two doses of the vaccine were probably necessary to get enough immune response to being with). The spike protein carried by the other vaccines is similarly short lived. Risks of unexpected longer term side effects are not zero (biology has a “fun” way of screwing with us like that sometimes), but are not very likely at all given the mechanism of action. We’ll cross that bridge when the, you know, actual data for the under 5 cohorts is available. It’s not right now.

And the other big “gotcha'” is really just a blinding statement of the obvious that is made by editing to sound more nefarious. So Mr. Cole states that “the drug companies, the food companies, the vaccine companies, they pay us hundreds of millions of dollars a year to hire and keep the reviewers to approve their products. If they can get every person required an annual vaccine that is a recurring return of money going into their company.”

So Pfizer and AZ and Moderna and all the other vaccine manufacturers have a financial incentive to be flogging as many doses of the vaccine as possible? Do tell. The Pfizer CEO has been the least subtle about this.

As for the “pay [the FDA] hundreds of millions of dollars a year,” that is absolutely true, also no secret, and is, in fact, the law. No joke. They are called “user fees” and are levied on food and drug companies whenever they submit a new regulated product for approval to the FDA. For drugs, that approval is necessary, or it is illegal to market the product. Even then, you can market it only for the claims that the FDA deems have sufficient evidence to back up. User fees are also levied on companies based on how many products (and what type) they currently have on the market. A very balanced discussion of all of this, why it exists, and why it’s the law can be found here (and I encourage you to read it).

Those user fees are millions upon millions of dollars, and yes, are part of the reason it costs so much money to get a drug to market. A small part of that total cost, but not an insignificant part.

“Aha! But this is corruption! Surely the FDA just waves approval over everything that comes across its desk with a multi-million dollar user fee check attached!” I hear you say, Hypothetical Muckraking Reader.

Believe me, some of the business guys in Pharma really and truly wish it were that simple. The truth is that if the FDA doesn’t think your evidence is good enough, they are not at all shy about rejecting your new drug. Happens all the time, in fact. Just last month, despite the check for millions in user fees for the review, the FDA told Merck in a “complete response letter” to science harder before they would approve its chronic cough medicine. Similar happened just last week to Eli Lilly, where an FDA Oncologic Drugs Advisory Committee meeting was, well, not exactly positive for a chemo available in China that Lilly was trying to bring to the US–you can read Lilly’s press release on that here.

In short, if the user fees required by law guaranteed marketing approval from FDA, every pharmaceutical company on the planet is doing it wrong, because they have all felt Lilly and Merck’s pain above at some point for some drug.

That’s not to say the temptation for corruption is absent though. Let’s be honest–for some drugs and some indications, there are billions of dollars in a pile on the table, riding on a completely binary regulatory decision. You are either approved, and now collecting those billions of dollars–or you are not, and you have spent a billion dollars and anywhere from 5-10 years of your life, but cannot market the drug and thus get absolutely nothing. Those are high stakes and high incentives, and the devils of our lesser natures can sadly get more persuasive in those situations. The balanced take on user fees and their history mentioned above linked this story, which is paywalled, but gets to the point in the paragraphs that are available about the cost to the FDA if they wave through something widely used that turns out to be less safe than they advertised (and especially if they might have known about it already).

There are also bona fide heroes that work at FDA, through the temptation for corruption, who take their jobs very seriously. You can read about a very famous one here.

–And yes, her story is why calling Dr. Malone’s concerns about possible side effects from the vaccines in the Joe Rogan interview just blanket “misinformation” and censoring them is misguided. You -want- to hear those out, treat them as a hypothesis, and then, per the scientific method, gather data that might disprove the hypothesis. If the hypothesized side effect holds up, the data shows it could be real, then they have done a great service. Primum non nocere. (again, as mentioned in our review, a lot of what Dr. Malone is specifically concerned about should already be obvious with billions of doses out–and again, his concern is mostly that he would have preferred additional testing have been done to discharge the issues he was worried about BEFORE billions of doses were out, which is a procedural argument).

–Anyways, I’m underwhelmed by the Project Veritas footage. If this is the smoking gun for a deep and evil conspiracy around vaccines, as it is being headlined in some quarters, it’s pretty small caliber.

–The second Plandemic! moment hitting social media this week was a pretty innocuous announcement by the CDC’s Twitter that “if you had a COVID test, there is a 10% chance your sample was selected for genomic testing–find out more here!”

I can’t tell you how many people smart enough to click through that link and pause long enough to learn what genomic testing the CDC was actually doing clearly chose instead to NOT click the link and then just re-tweeted with varying degrees of inflammatory inference that the CDC -must- be up to clandestine genomic testing on the population, without their knowledge or permission!

And then just… confessed to that completely on Twitter? This is like the world’s worst evil genius plan if that is what CDC was really doing.

But it’s not!

The genomic testing the CDC is doing on a 10% random sample of positive COVID tests?

It’s the SARS-CoV-2 genome that is being tested–not yours! They aren’t doing anything with your DNA in that sample. Sequencing the virus is how they identify the variants, and the 10% random sample of them is how they tell which variant is where, and if there is more or less of it than the last several weeks. This is exactly what we covered in our review of the Dr. Malone interview with Joe Rogan, where Dr. Malone fumbled the question from Joe about “how do you know which variant you caught?” You can find the relevant section here.

The CDC has not been at its best during the pandemic. But secretly doing mass DNA sequencing of the population, using the pandemic as a cover, and on a random sample for… reasons… which are probably evil… and then confessing to the world that they are doing it on Twitter completely with a link to a 4 minute YouTube video on how they are doing this Bond villain plan… is not one of the dumb things the CDC is doing.

–Besides, and I don’t want to hurt anyone’s feelings on this, no one cares that much about your DNA anyways–unless you are a bona fide outlier for a rare genetic disease, or have some freakish beneficial trait, like the speed Usain Bolt. Or they are looking at thousands of patients to see how small differences might interact with something else that is very common, like your diet, or a disease–but they are usually not looking at nearly enough patients or controlling enough variables for those to be meaningful. John Ioannidis used this exact kind of genome wide association study as his example (Box 1 at the link) of a kind of published science paper that finds statistical significance in something by accident, and later focused studies prove is probably not real.

Everyone’s genes are 99.99% similar, and there is not that much they are really going to learn from yours.

Sorry.

–And if you doubt that, just think back to high school, because odds are good that you offered a sample of your genetic material to someone you hoped was interested in it–and turns out they were not interested. At all.

Fortunately, you are a reader of this update, and thus much more intelligent, attractive and desirable than most, so those moments have undoubtedly been rare for you. Still, they happen, and anytime you think someone evil government/group/company is mass collecting DNA for some kind of unspecified but probably dark and devious genetic manipulation, remember those times–when you wanted someone to care about your DNA, and they did not. It will help keep you grounded on the likelihood that these conspiracy stories are real.

–For ways the CDC has been less than spectacular, in a “COVID science section” thought piece (for once), a heme-onc gets more truculent than me regarding the CDC’s publication track record during the pandemic. This includes similar or slightly different criticisms of studies we have sciencepalooza’d on these pages. And of course, since it agrees with me, it’s clearly genius.

Clearly.

But the piece then segues into how this contributes to a crisis of confidence–a bonfire of the credibilities, if you will.

Which makes it a great transition to…

Socioeconomic Issues:

–The Economist Intelligence Unit (I have no idea who they are either) apparently conducts an annual survey of liberty around the world as part of its Democracy Index. As the Washington Post reports, and coming as no surprise to anyone reading this if they have paid any attention to news over the past two years, individual liberty and democratic institution strength are at record, “dismal,” lows. You can read the entire thing here. Of note, the report states that the change is not due to the pandemic itself, but accelerating of already authoritarian trends prior to the pandemic.

Yes, the headlines in Canada where the Trudeau administration invoked emergency powers and announced it will freeze the business accounts of anyone participating in the “trucker” protests do come to mind. Along with the nearly immediate, strident condemnation of invoking what is in essence martial law by the Canadian equivalent of the ACLU. The premiers of several of the largest provinces also immediately protested the implementation of these powers in peace time. As the protesters have mentioned that their bank accounts are frozen and they are having difficulty getting any bank to take their business, the “strident condemnations” of these groups to the invocation of emergency powers by Trudeau do not appear to be all that effective. But let the record show they object, sir, they strenuously object! The debate in Canada’s parliament is going as you might expect (but the British parliamentary system with the back and forth one liners and constant “rabble, rabble” from the back benchers is at least entertaining).

Meanwhile, overnight 5 of the largest banks in Canada suddenly went offline and social media posts showed Canadians banking there unable to access their money at ATMs. No real plausible explanation was given.

Across the border, mainstream news media were hitting social media for all the wrong reasons, using a list of donors to one of the funds supporting the trucker protests in Canada that was doxxed via illegal hacking to contact those donors and demand their on the record “justification” of their donation. This included people on the list who gave as little as $40. Those who made the mistake of replying to the “journalists” doing this were blasted on social media. Fortunately, condemnation of that behaviour by the “journalists” appears to be a rare bipartisan moment:

All of this in response to a political, if inconvenient, protest over COVID policies by groups the Trudeau administration hailed as “heroes” when they were “essential workers” out on the roads delivering the food and goods that allowed everyone else to lock down not so long ago. Personally I can’t help but think back to the hard, “two weeks to flatten the curve” lockdowns in 2019, where the only other vehicles on the interstates as I was driving in to do COVID testing for the state were the occasional semis.

I seriously regret not setting up my phone as a dash cam just to record how eerily lonely that drive was…

At any rate, trucker/farmer protests and government and media reactions to them grow in scale, particularly in nations that either protest everything anyways (France) or still have rather draconian policies in place (Canada, Australia etc.).

So just a reminder, where one major aspect of the political consequences of pandemic is concerned…

–On a more practical level, official or unofficial strikes are the next logical step for the protestors, if they do intend to carry through to their political goals. As grocery stores have about 3 days worth of groceries before the next truck needs to roll up, a Teamsters strike can be devastatingly effective. And has potential to impact you. Similar to the height of the coronavirus, having some extra supplies of essentials around while government and the populace are at loggerheads over the pace and totality of coronavirus restriction roll backs may be wise, to hedge a trucker strike potentially landing where you live.

–It is precisely the chaos that supply chain disruption can cause that is undoubtedly the reason Trudeau has acted with such a heavy hand–against their political enemies. Deus impeditio esuritori nullus.

–Speaking of which: https://www.fao.org/worldfoodsituation/foodpricesindex/en/

–Great thread here by a former journalist about why the incentives and pressures journalism now faces are creating bad journalism, which in turn is fostering schismogenesis.

–Yes, I too saw Twitter explode over all the celebrity and LA politician crowd shots at the Super Bowl, none of them wearing the N95 masks that were handed out at the gates or any other mask–despite masking and vaccination being a pre-announced requirement to attend the game. No, none of them appeared to be getting ushered out of the stadium either. In fairness, the Great College Football Experiment in the early part of last season demonstrated that these were not exactly super spreader events. But the cause for much social media consternation was the persistence of mask requirements and social distancing in some places–including LA, where the game was held. Much was made in particular of the fact that LA school kids would be in masks for 6-8 hours the next day, and socially distanced–but none of the celebrities or politicians paying tens of thousands for their Super Bowl tickets were. Considering food inflation hit a record last month around the globe, and producer price index for January came in much higher than expected (while Congress debates suspending the 18 cents a gallon Federal gas tax as gasoline is now anticipated to average $4 a gallon this summer), the optics of unmasked revelers at a game where the average price per ticket was $6,697 was… not great.

–Lastly, although my understanding from one of our UK readers is that the title of “oldest pub in England” is in some dispute, “Ye Olde Fighting Cocks” pub, open since 793 AD, has closed its doors.

The heartbroken owners said that the long period of COVID restrictions had made continuing operations untenable, and the relaxation of some of the COVID rules in the UK has been too little too late to keep the pub open.

Thus, a pub survived Vikings, the War of the Roses, the Spanish flu, the Blitz, and the Black Death–only to succumb to SARS-CoV-2.

–Your chances of catching coronavirus, although dropping many places in the world, are still equivalent to this being the most true meme to come from the Super Bowl:

<Paladin>