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, the WHO acknowledged this week that cases around the globe continue to fall. However, you do still have considerable activity in a number of countries. Japan, for example, continues to have high cases. That includes a huge chunk of professional sumo wrestlers, which may put the March sumo tournament in jeopardy. Hong Kong continues to struggle with an omicron outbreak, especially given the “zero COVID” approach in China. That same approach saw Baise, a city of 4 million in China on the border with Vietnam, get locked down this week for an outbreak. South Africa continues to see minimal, but still present, activity. Nearly every state in the US is showing declining cases. Indiana, again for example, is showing abrupt declines in new positive cases, census of positive patients in the hospital, and slowing admissions with COVID–even accounting for the weather disruption last week. The UK shows much lower activity than the omicron outbreak, but still persistent, and may have much to do with a number of other European countries at or just about over the peak in their omicron heavy waves.

–During an interview this week, we got quite the about Fauci (see what I did there?) from Fauci. Anthony told the Financial Times that the US is past the “full blown” pandemic phase, and “we are looking at a time when we have enough people vaccinated and enough people with protection from previous infection that the COVID restrictions will soon be a thing of the past.”

That is quite the sudden admission of natural immunity efficacy, Batman.

But wait, there’s more! When asked specifically about boosters, Dr. Fauci had this to say:

“It will depend on who you are, but if you are a normal, healthy 30-year-old person with no underlying conditions, you might need a booster only every four or five years.”

Yes, it was just last week we covering the CDC’s data dump in the MMWR extolling the virtues of boosters in the delta/omicron period. We did mention that benefit in terms of death and hospitalization looked strong in those over 50 (definitely over 65), but marginal at best for younger age groups. And yes, just this month, Dr. Fauci has been fretting and confessed in other interviews to being mystified as to why there was not greater booster uptake, since the data was clear that an additional booster after 6 months was required. Now, in fairness, Dr. Fauci may be referring to the possibility of a fourth shot here (the Financial Times interview is paywalled) and believe in his heart of hearts that the third shot is necessary now. That’s possible. But why if the data is so “compelling” (quotes deliberate–see our previous discussions of the level of evidence in the Coronavirus Archive at the web site) for waning immunity to necessitate “Booster the World!!!” after 6 months are we suddenly talking about stretching boosters 4 or 5 years for healthy 30 year olds?

Other than sudden consistency with the CDC’s original booster recommendation for the 65 and up and other high risk populations. Which the CDC changed two months later for reasons that are still not entirely clear, but hopefully not based solely on that underwhelming Pfizer study of antibody levels in 20 some odd patients.

–It has been said a lot this week that “the science has changed” and that is why some of these pivots are now happening.

I want to stress that this is just my opinion, but there was no sudden flood of new landmark papers driving this new tone. The science has not changed, and in fact, this week at least, looks an awful lot like interpretations of the existing data we have drawn together in these updates covering the major papers that have come out these last many months.

The science has not changed. Interpretation has changed. And yes, Hypothetical Reader, I find that interesting as well.

–This week, at least, they are landing closer to themes we have emphasized from the data. And the point where the political understanding of risk to the healthcare system from omicron or less meets the medical understanding does appear to be getting closer.

Baby steps, folks. Baby steps.

–Although I’m suddenly very afraid for Dr. Fauci’s podcast deal with Spotify–“misinformation” warnings have been tagged to episodes for less than some of his quotes above… : )

—TO BE CLEAR, WE MAY NOT BE COMPLETELY DONE WITH COVID YET. In terms of social fatigue and “let’s just get on with it” sure. But biologically, we’ve been on a 2-3 month cycle with SARS-CoV-2 so far; let’s give it that 2-3 months. We’ll be looking to the Southern hemisphere for early signs as they start to head into their fall. Whatever follows omicron is likely to be, again, more contagious but less severe. Omicron was already not even a bad flu. If the next variant is just a nuisance cold, we should be golden.

But yes, there is a non-zero chance that the last of these coronavirus updates could be coming this spring/summer, with maybe a few to follow in the fall depending on if and how serious the fall season of COVID appears to be (and we may settle into a fall COVID season for at least a few years).

–The White House has also announced a task force to try to clean up the variation in hospital reporting around COVID, to get a better idea of who and how many have been admitted for COVID and who and how many have been admitted with COVID. This will take awhile, and I suspect will result in some quiet revisions to hospitalization rates attributed to SARS-CoV-2. I don’t think they will be too huge though–COVID, particularly delta variant, did a pretty solid job of putting people into the hospital on its own. Especially high risk patients.

–Another big story this week, at least in my opinion, is the interview with Dr. Angelique Coetzee. Dr. Coetzee is one of the South African scientist physicians who first identified omicron. In the interview with Australia’s “Daily Telegraph” (which I was able to read before they paywalled it–sorry if that is happening to you too on the link), Dr. Coetzee admitted her surprise at the pressure she was getting about the description of South Africa’s clinical experience with omicron. As you may recall, the South Africans not only identified omicron rapidly, but doctors like Dr. Coetzee were very quick to provide the relevant clinical context, warning early that omicron appeared clinically much more mild, even if it was definitely more contagious than prior variants. The pressure on Dr. Coetzee was about the claims of mild disease, and she mentioned unnamed European scientists and even governments pressuring her to revise them, since they were incredulous that a disease that had been severe in many hospitalized cases had become more mild. Most of the disbelief apparently stemmed from these European folks conviction that more mutations must equal more severity.

How the general pandemic trend of mutation in a “more contagious, less severe” trend over time escaped them, I am not sure, but it appears to have done so.

There may also have been concern that the “average person” would not take the threat seriously if it were reported that omicron was clinically more mild–which is a political problem.

I would be more surprised if this was the first time this had happened to scientists and doctors in this pandemic. Yes, Hypothetical Reader, one’s mind does drift back to the recent and sudden resignations of very senior people in the FDA’s vaccine division who cited pressures on the decision making process. I think this interview with Dr. Coetzee is merely the most directly it has been stated that this occurs. Science must still be performed by humans; humans are a political animal. Usually, it is merely the long road to acceptance of startling new data that upends an established theory. Avery, McCloud and McCarty had to wait decades before their experiment showing DNA was the molecule that transmitted genes was accepted (protein was the leading candidate at the time). Barbara McClintock Nobel Prize for “jumping genes” (transposable elements in DNA) was a long time common for similar reasons. The scientific method at least offers a way to demonstrate by experimental proof where the truth is more apt to lie.

When the science affects public policy, especially public policy affecting so many people directly with heated opinions on either side, political pressures are likely inevitable.

In fact, there is an excellent play about a medical scientist whose data driven conclusion was inconvenient to the goals of others, and the pressure campaign to get him to ignore or alter interpretation of his own data. This was one of the works studied in what was sneakily one of the best courses I took as an undergrad called “Public Life and Private Lives”, examining what happens when an individual’s conscience and beliefs run counter to that of their community. One of the oldest continually taught courses at the school, and for good reason.

Anyways, to their credit, Dr. Coetzee and the South Africans stuck to their guns.

She also highlights that the experience of the frontline physician in dealing with COVID has been underweighted in policy discussions and media coverage. I agree on both counts, as the frontline physician has been absent short of the sensational stories meant to evoke a specific emotion when cases are running high, or to put a human cost to vaccination decisions.

–Back to the CDC and boosters, the CDC announced this week that 4 doses are recommended for the immunocompromised ONLY at this point. They also extended the interval between the 1st and 2nd shots of the primary vaccination series for COVID to reduce the myocarditis risk.

–Regarding the myocarditis risk, since there was a push last fall to up the vaccination rate in European soccer clubs around reports that players were keeling over with sudden cardiac and chest issues, the headlines about more high profile collapsing soccer players have been palpable by their absence these past few months. I would still like more detail on the collapsed players vaccination status and any COVID test results around the time, but you may recall that we postulated it could be the virus itself and not the vaccine given the surprisingly low vaccination rate in European soccer leagues versus US professional sports, where the player collapse problem did NOT happen to any great extent. This was also during a period where more severe strains were circulating heavily. Omicron may not have the same capacity for myocarditis.

–There is some tangential evidence to the idea that the cardiac events in European soccer players, if not just a statistical aberration, may be due to complications of SARS-CoV-2 itself this week. Although it’s not perfect evidence–there are significant differences between top tier professional soccer players and the study population. But the Department of Veteran’s Affairs published a big study of cardiovascular risks and COVID-19 in Nature Medicine this week. This is a really well done study overall, and the main takeaway is that the risk for a number of cardiovascular and clotting events go up after recovery from COVID-19, but the mainstream article I saw recapping this study does not mention some of the important limitations that keep this from being a fully generalizable statement.

First, as with any VA study, is the patient population. VA studies, because obviously, skew to a heavily male study population (about 90% in this study). In addition, the average age of the patients studied was 63, with a standard deviation of 16 years. That means that ~84% of the patients in the study were older than 47–so definitely an apples to oranges comparison to a large chunk of the population, let alone dudes playing professional soccer. It also means in the main results tables in the paper that their correlation of age to cardiovascular risk is basically meaningless–they use 65 and up and under 65 as the sole age variable examined. Most of their “under 65” was closer to 65 than not. Beyond that, only 20% of the study population had a normal BMI (<25). The average blood pressure was 132/77 with standard deviations on the systolic (top number) of 12 and diastolic (bottom number) of 7. This means in their study population ~84% were at least pre-hypertensive (systolic 120 mmHg or more). So by age and blood pressure alone, this population was higher risk for COVID in general. On top of that, 23% of the study groups were diabetic (versus 10.5% in the US population as a whole).

All of that is a long way of saying that this population was probably higher risk for COVID complications (and heart disease) than many of you readers are based on your age and underlying health–keep that in mind.

But since they were looking for cardiac events, a population heavily enriched for them was a good to place to look, since you should find a lot to study. If you are NOT these demographics though, how closely it applies to you is a very open question.

So what does pop to me in that study is that risk of any cardiac or clotting event was elevated after COVID-19, after controlling for all other risk factors, across age etc. (although more like “age” for the reason discussed above). The biggest, and most believable jumps, were for myocarditis, arrhythmia, cardiac arrests, cardiogenic shock and clotting. These were 2.5 to more than 5x as likely with COVID infection and recovery, and if any of these outcomes will be higher risk in other demographics, they are the ones I am putting my money on. That is only my hypothesis though, to be clear. And I suspect that in, oh, say young high performing professional soccer players, the risks will be smaller than 2.5 to >5x more likely–but higher than not catching COVID to begin with.

The authors also show pretty strongly that risks are only a little higher if COVID did not require hospitalization. Unsurprisingly, they go up with severity of COVID. Hospitalization due to COVID had higher risk of subsequent cardiac or clotting event (more than 30 days after recovery from COVID), and ICU with COVID had the highest risk. My hypotheses are that the lingering risk is due to the Ah-nold reaction, which is mild at best if you don’t need the hospital for COVID, but is the main pathology of what keeps you in the hospital with COVID as we have discussed before. You can also speculate that vaccination, by reducing the chances of landing in the hospital with COVID, reduces the risks of subsequent cardiac or clotting events. The authors do present evidence in support of that idea, as myocarditis was 5x more likely among the unvaccinated than the vaccinated when they controlled similar groups of patients and looked at myocarditis for this specifically.

No, unfortunately, they did not compare myocarditis with the vaccine versus their historical control population. I don’t think the VA wanted to go anywhere near that landmine (no pun intended).

But the study certainly shows elevated cardiac and clotting risk in older dudes often with underlying risks for these things, even after recovering from COVID. Risks were lower if COVID did not require hospitalization, and the vaccine may reduce some of those risks. I think it is fair to hypothesize that there may be elevated cardiac risk in patient populations NOT already at high risk for them–proving that will require truly massive studies though, since the events you are looking for are already not very common. But again, if not vaccine related and not a statistical aberration, prior COVID exposure, especially if the player was NOT vaccinated when they caught COVID or caught a pretty bad case of it, might explain some of the headline grabbing on field collapses of European pro soccer players.

–In rumors hitting major news wires, J&J has reportedly stopped production its COVID vaccine to transition the manufacturing line to make an experimental vaccine for an unrelated virus for an upcoming clinical trial. J&J confirmed the rumors, but clarified that the halt in manufacturing COVID vaccines is temporary and will resume when the clinical trial material is finished. They also told Reuters they have millions of doses of the COVID-19 vaccine still in inventory.

I have no additional comment on that and thank you for your understanding.

–In its 4th quarter earnings report, Pfizer adjusted its forward looking risks statement in the COVID section to include “potential pre-clinical and clinical data integrity issues.” That raised some eyebrows, and no, there is still no update on the whistleblower claims around data integrity problems in the critical Phase 3 study of their vaccine that impacted a contract research organization (CRO) that was running some sites for Pfizer. As we mentioned at the time, unless those issues are more widespread across other sites not being run by that CRO with data integrity concerns, the number of impacted patients was unlikely to significantly impact the overall clinical trial results. But yes, that is an interesting change.

I have no additional comments on that either, and thank you for your understanding.

–In other news, thank you to a reader who sent along the following article about a group of South African scientists who made their own batch of Moderna’s mRNA vaccine, replicating the “recipe” from publically available data. They won’t be running off a generic version of the Moderna vaccine though, as they intend to honor Moderna’s IP. But it does show that mRNA vaccines require just a little bit basic molecular biology knowledge and equipment. If there is a secret sauce to them at all, it is getting them into and stablizing the lipoparticles that will carry them, and then scaling up manufacture with appropriate quality control. As the article mentions, one of the excuses arguments to not sharing the manufacturing details for the mRNA vaccines is that the technology was too advanced for anyone but fully developed, first world nations to pull off, although this may have restricted access to these vaccines in the developing world. South Africa’s proof of concept with their Moderna knock off is that this technology is not “rocket medicine” as one of my old attendings would put it, and necessity being the mother of invention, may spur some low cost competition for future mRNA vaccines from burgeoning mRNA vaccine development companies in less developed nations. Now that they -know- they can do it too.

Another upside would be the greater incentive of mRNA vaccine start ups in the developing world to target parasites and other viruses that are an afterthought to major pharmaceutical companies in the developed world, as they are not diseases seen in the US, UK, Japan, China etc. (the major pharma markets) to justify the return on investment. Is there a mRNA vaccine for malaria? For Lassa fever? Someone in South Africa may try to find out now, eh?

Socioeconomic Effects

–For supply chain issues, it was the best of times, and the worst of times yet again. For the good news, the CEO of Maersk, the world’s biggest shipping line, told Bloomberg this week that rates were leveling off and they expect a “normalization” in shipping in the second half of this year. Consistent with that, you had the first signs that the port congestion was leveling off, and possibly even starting to be processed down as the average number of ships waiting for a port of Los Angeles/port of Long Beach berth fell from about 100 per day the week of January 20th to a little under 80 per day last week, according to published data.

For the bad news, finding the supply of basically all the commodities is an issue according to Goldman Sachs. Ford had already planned to idle 8 factories due to persistent chip sourcing issues. As of this morning, multiple major auto manufacturers ranging from Ford to Toyota and Chrysler were idling US/Canadian plants as the Canadian trucker protests clogged the Ambassador Bridge all week long. This bridge connects Detroit and Canada, and is the busiest land border crossing between the two countries. It also happens to be where an enormous amount of parts of new cars being built in Detroit or across the bridge in Canada transit daily. Because those parts cannot cross the bridge, plants are now going idle.

–Speaking of that trucker strike in Canada, Trudeau is still refusing demands to meet with the truckers, although more provinces (including Alberta this week) continue to roll back vaccine mandates and restrictions as demanded by the protestors. As similar movements spread (as we mentioned last week), the US is monitoring calls for similar protests here, but they do not appear to be picking up too much steam as yet, and likely won’t as many of the “more restrictive” states have been announcing social distancing and mandate rollbacks this week as the “science changes.”

–The CPI measure of inflation in the US was closely watched this morning, and hit a 40 year high print. I am sure that comes as a surprise to none of our US readers who have had to buy just about anything in the last month. Although, as President Biden mentioned today, there have been nominal wage gains on average in the US, it is worth mentioning that those average gains have NOT been enough to keep pace with inflation:

You are now at 10 consecutive months of real wage declines versus the rate of inflation, and it seems likely that the Federal reserve will begin hiking rates. This will increase the interest paid on new mortgages and car loans, same for credit cards, and any adjustable rate debt will see an increase as well.

–In this week’s first think piece (a 14 minute video), Russell Brand got called “right wing” on the internet and his response describes what we have been referring to as schismogenesis, its drivers, and how he thinks we can combat it.

The bonfire rages high, and I wonder if we are not getting closer to a modern version of this, the high water mark of McCarthyism.

–In examples of restriction decisions going on around the world, Israel is opting to end COVID-19 vaccine passport in most places, after being one of the first to adopt passports. On the hand, you have examples like Austria, which will be having police officers do random stops of citizens for proof of vaccination, and fining those who are out and about without vaccine papers.

–After the waves of plague had abated, we mentioned that sweeping social change took place.  In some places, the conventions of serfdom and authoritarianism grew stronger.  In others, in particular the Italian city states, there was a liberation from some of serfdom’s conventions and the eventual rise of a vibrant middle class and the Renaissance.  That’s why you should read this thread as another think piece, not for agreement or disagreement, and look at the trucker and farmer protests gathering around the world (and the response to them). Look at calls from seats of power, such as those from the White House podium, for media outlets to engage in what the embattled institutions call “greater responsibility for accuracy of their content” and “combating misinformation”, but what many others call “censorship”.  Because all of these crumbs lead you along a path back through history, to that moment after the Black Death, where the balance was tottering between authoritarianism and greater liberation, and their institutions were shifting to a new equilibrium.

Here’s the Cliff’s Notes of the other major socioeconomic aftermaths of the Black Death. 

See what other rhymes you can find!   Second paragraph, especially ; )

And the Cliff’s Notes doesn’t mention the other immediate social aftermath—there was a substantial spike in violent crime in the years immediately after the Black Death, likely for the social discohesion reasons in that short article.  Understand what a “substantial spike” to even merit mention by those contemporary commentators is though! The violent crime rate in the Middle Ages per capita has been calculated as up to ten times the modern rate, all across Europe. What happened after the Black Death made that look peaceful to those living in that era. Does that echo as well in the modern era? In places, perhaps.

“I, Agnolo di Tura… buried my five children with my own hands.”

Agnolo di Tura, Siena, Italy 1348

Is it because we were spared that degree of catastrophe (thank God for a less fatal although more contagious pandemic, and modern medicine!) that we did not listen to Agnolo and his contemporaries from the beginning? When they calmly, from a state of shock and seriousness in their pandemic aftermath, told us what happened?

All of what happened?  Before, during and especially after?

Or have we been too smart to listen?

There is nothing new under the sun, and history is said to rhyme.  We forgot that, but now with clearer eyes, we can re-read Agnolo and his colleagues, and feel the chill in our spines when we reach those parts that seemingly could still be written today.  Pandemic appears to be a common catalyst of these types of challenges.

But remember this, if you think that bleak reading and dark thoughts… 

You are reading it -at all- because humanity got through.  The Renaissance and the rise of modern medicine argue that things can even be better on the other side–once you make it through.  All of you reading this, no matter where your ancestors hail from, are here because your ancestors -got- -through-. 

So can you. 

So will you. 

So will we.

–Your chances of catching coronavirus are going down around the world, but there is definitely still activity. They’re equivalent to the chances that no one is watching–so go ahead and hit those air drums hard when the beat drops: https://www.youtube.com/watch?v=YkADj0TPrJA

<Paladin>