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 (and cousins)

Transmissibility: All the +

Immune Evasiveness: All the +

Vaccine Effectiveness: Check (for hospitalization)

Also as a reminder:

Pediatric Hepatitis:

Updating the CDC and WHO calls for monitoring of new or recent cases of severe acute liver disease or liver failure in young kids (mostly less than 5 years old), the current count of suspected cases is up to 220 in 20 countries. Again, these are kids with diarrhea and evidence of liver damage, some require transplant and including a few fatalities, but no evidence of the usual suspects of hepatitis viruses (Hep A, B, C, D or E). Around 50% of them have been positive for adenovirus, and as we discussed before, adenovirus CAN invade the liver, usually in severely immunosuppressed patients. There has been no further detail on co-morbidities in these kids to know if and how many are immunosuppressed. Given the number of kids who have contracted some form of adenovirus in the same span, this is likely still rare. They are also casting a wide net for suspected cases–a number of these will likely be due to known, but otherwise non-virus associated reasons, like toxicity either from drugs or something else the kid got into and their liver didn’t like. The list of possible exposures that can accidentally blow up a liver in an unfortunate lottery ticket “winner” is huge. Of the rest, I suspect they will narrow down to a few adenovirus types or a new adenovirus type that is a little more likely than usual to get into the liver of young kids, who have relatively immature immune systems. We’ll continue to monitor, but this will be a slowly developing story.

Coronavirus:

–Around the horn, cases in the US continue a gradual rise, which is approximately alpha-wave in its velocity. This may be underestimated, however, as there are state departments of health which are not recording at home testing results. The key metric, hospital admissions, remains WAY down, so even if there is high activity from omicron’s cousins, they do not appear to be causing severe disease at the rate of previous variants.

Elsewhere around the world, North Korea recorded its first official case (of the entire pandemic) and has gone into lockdown. This begs the obvious question–if North Korea goes into lockdown, will anyone notice?

China’s cases are flat to falling per official statistics. More on China later.

And southern hemisphere bellweathers are suggesting that there will be a winter wave of positive tests. No signs of severe variants with high hospitalization rates, but South Africa is definitely riding a sharp wave up right now, and Australia and New Zealand are both showing brisk activity too.

–The announcement was just going to press when we did last week, but the FDA did indeed put new restrictions on the J&J vaccine. As a reminder, J&J is NOT a mRNA vaccine, but instead delivers the SARS-CoV-2 spike protein DNA into cells by packing it into an empty adenovirus shell. Since there are not complete instructions for a full virus, it does not cause SARS-CoV-2, but does cause the cell to make the spike protein, which goes through ribosome QC and triggers an immune response by T-cells playing varsity level “Among Us.”

The main serious side effect risk of the J&J vaccine that popped up was a rare risk of severe blood clotting, mostly in women under 50, where it appeared pretty soon after the vaccine. We noted at the time that German scientists had associated a similar to risk in the AstraZeneca COVID vaccine (which works by the same mechanism as the J&J) to unexpected production of anti-platelet factor 4 antibodies, causing a similar clotting syndrome to heparin induced thrombocytopenia (HIT), where the same antibody is mysteriously made by rare patients receiving heparin. This association was borne out for the AZ vaccine in the UK, among others.

Unsurprisingly, given the same rare complication and the same mechanism, anti-platelet factor 4 antibodies were found in patients with a HIT like clotting syndrome after the J&J vaccine, and the entire side effect is now getting its own name: vaccine-induced immune thrombocytopenia and thrombosis (VITT). Which is a fancy way of saying that for mysterious reasons, a anti-platelet factor 4 antibody is made by the immune system after the AZ or J&J vaccines, and -activates- your platelets even as they are circulating in your bloodstream. This causes clots, with an apparent drop in the total number of platelets as they are activated and used up all over.

This caused a short pause in administration of the J&J vaccine last April as data was collected on the incidence of these cases. Now, the FDA has decided that it happens rarely, but juuuuust often enough that they are limiting the J&J vaccine to those who cannot take another vaccine or request it by name. For the record, this is 60 total cases out of 18.7 million shots out in the US–but 9 of those cases were fatal, and the other 51 were not a very good time either.

If you got the J&J vaccine, you’re really only at risk of this for the first 30-60 days or so, so no worries if you got the J&J forever ago.

–In other updates of COVID treatments, the FDA is evaluating reports of “rebound” viral load in patients treated with Pfizer’s anti-COVID pill combo, Paxlovid. As currently labeled under its EUA, Paxlovid is intended to be taken as an oral dose twice a day for five days. What has been happening in rare instances is that patients symptoms and viral loads measured by PCR will improve over those 5 days, only to spike the viral load, and sometimes see symptoms return with a few days of completing the treatment. Right now, the FDA is examining cases to understand how infectious the rebound period might be. Pfizer is pointing to data in its clinical trial where this rebound in viral load was seen in 1-2% of patients, but in both the Paxlovid arm AND the placebo arm, and at approximately the same rate. The company’s implication is that this is biology, and Paxlovid proved its ability to reduce hospitalization rate a bunch in that trial regardless. The former point may be true; the latter definitely is true. If confirmed and common enough, I would not be surprised to see the FDA ask Pfizer to run a quick trial increasing the treatment duration from 5 days to something a bit longer than 5 days.

–In more actual COVID science, this study made headlines for the surprising claim of evidence that omicron was really at least as severe previous waves’ dominant strains (with the thrust of the articles tut-tutting that you should get vaccines and any boosters you are told to). I know this goes against a LOT of previous reporting that suggests omicron was not as severe, but this paper is here to tell you that your eyes noticing the dramatic difference between hospitalization rate and total known positive cases were lying to you, and omicron was bad.

So your eyes can deceive you too, we can examine the CDC’s data on case rates and hospitalization rates on their website. We find that the winter wave of 2020 peaked at around 475 cases / 100,000 people per week, with ~20 hospitalizations / 100,000 people during the same. So ~4.2% hospitalization rate. The delta wave starting late summer 2021 peaked at 290 cases / 100,000 people per week, with ~12.5 hospitalizations / 100,000 people, or 4.3% hospitalization rate (despite vaccines, remember). Meanwhile, the omicron wave this past winter peaked at ~1600 cases/ 100,000 with a hospitalization rate of 32 / 100,000 people in the same window — an ~2% hospitalization rate. And for the early part of that, delta was still circulating quite heavily, and thus inflating that hospitalization rate a bit.

But alas, I am not from Harvard and authors of this pre-peer review paper are. And I have some concerns about their method.

There are a couple problems with this paper, one the authors themselves admit and one they don’t. In the “limitations” portion of the discussion, the authors, to their credit, freely point out the elephant in the room:

“Additionally, we counted cases as positive PCR SARS-CoV-2 tests. This likely undercounts the number of real SARS-CoV-2 infections since it does not include patients who had an at-home rapid test, visited a facility outside of MGB, or chose not to get tested.”

To say their definition of positive tests (PCR performed ONLY at their facilities) “likely undercounts” the total number of infections since they did not account for at home testing, no testing, or testing in other facilities in Massachusetts is quite the understatement.

Considering that MOST omicron infections I am aware of in this period were picked up with at home or non-hospital testing (CVS and the like), they are grossly underestimating total infections, and thus the severity rate they calculate.

Second, the major limitation they -don’t- really discuss is the statistical method they use does NOT match patients 1:1 by comorbidities, age, other risk factors etc. Which is unfortunate, because that 1:1 matching is the best way to determine relative risk in a study like this as it controls for all of those other potentially confounding variables.  Instead, in the method they used, a probability is calculated for unmatched patients based on weighting set by model the investigators determine.  

“Is it possible to goal seek the model weights to the outcome you want?” I hear you ask Cynical Hypothetical Reader. 

Yes!  Yes, you can Hypothetical Reader! 

That is partly why this method is typically used when you don’t have many cases, and thus have trouble matching them, so you can at least get some guessestimates about possible correlations and effects.  They have 130,000 cases here.  That’s not a small number of cases where the method they used would be a good choice. Frankly, better statistical methods and matching should really have been done here. Even Kentucky’s Department of Health, in papers we covered previously, managed to cohort match patients looking at vaccine efficacy.

Bridge too far for Harvard, apparently.

Perhaps applying the wrong method and a poor definition of positive that invariably excluded a HUGE number of less severe, but still quite positive, COVID cases, is why this conclusion flies in the face of the South African clinical experience with omicron, the UK’s clinical experience with omicron, numerous front line treating physicians in the US on relative omicron severity during the omicron wave, AND back of the envelope with the CDC’s far more robust data set. All of which generally agree that omicron is less severe, more contagious on average, making this paper’s conclusion the outlier.

So you’re left with two possibilities here.  One, I have met some really sharp people from Harvard.  I have also met some from Harvard and/or with Ivy League degrees who were, to be polite, underwhelming. Their proportion is not especially different than from other schools, and I will leave you to conclude which broad category (really sharp or useless) I believe this paper’s authors belong.  Because if they were the other category, well, that would imply that a method which easily goal seeked a conclusion contrary to enormous amounts of better data about omicron severity was deliberately chosen, rather than a carefully designed observation of the data. And I doubt that is the case.

Left unexplained is why lay legacy media reporters covering COVID cannot seem to ask basic questions, or even compare and contrast prior reports making a COVID claim versus newer ones, but merely roll with the most spectacular claim. It’s the same direction, every time.

–Fortunately, we also have better studies to talk about this week. A recent Lancet publication looks at the VA population and adds to mounting evidence, discussed previously, associating a higher risk of new onset diabetes as a late complication of COVID infection.  

–There is not much data on it yet, as this attempted meta-analysis attests, but I have been hearing rumblings from the front line about alopecia (hair loss) 1-2 months after recovering from COVID as an uncommon, yet definitely happening, late complication. Most patients appear to recover without issue, and there is at least one provider webpage out there (also covering some vaccine associated reports of hair loss): https://healthcare.utah.edu/healthfeed/postings/2022/03/hair-loss-covid19.php

Socioeconomic effects:

–The baby formula shortage persists, and is a combination of COVID supply chain woes coupled by a recall of Abbott Nutritional products made in their plant in Sturgis, Michigan, due to contamination with a bacteria that can cause nasty infections in newborns. While that recall was back in February, manufacturing has remained halted at the Sturgis plant since. Which is unfortunate, since that is a giant plant. The out of stock rate for baby formula has jumped to ~40% nationwide, although the FDA is working with other manufacturers to maximize production and to get the Sturgis manufacturing issue straightened out. It will not be an overnight fix, and in fact a few more months delay is being officially predicted. Abbott is being allowed to release certain specialty formulas that have been on hold in Sturgis, but apparently are not manufactured on the same line. If you or someone you know needs one of these specialty products (and you will know what they are if you do), you can contact Abbott directly at 1-800-881-0876 to arrange supply.

–Other supply chain issues with medical impact include contrast dyes for imaging studies like CT scans. This has caused some hospitals to triage contrast to more emergent cases, and defer contrast studies whenever possible. This is mostly due to prolonged “Zero COVID” shutdowns in China, which has the currently available supply of the chemicals used in contrast.

–Speaking of unexpected shortages in the US, as oil is diverted to Europe to reduce dependence on Russian energy supplies as part of economic measures to end the Ukraine-Russia war, several major truck stop chains and trucking companies have raised the alarm this week that the Northeast and Mid-Atlantic may face serious diesel shortages near term. In some places, diesel may not be available at all. Energy companies in the Northeast and West, which have reduced energy production capacity using on demand high density energy sources like coal and LNG as a result of political choices over decades are warning there may be insufficient energy production from their renewable sources to meet energy demand. What on demand capacity they have may not have enough supply at all, let alone affordable supply as coal and LNG are in high demand everywhere, to meet any supply-demand mismatches in hot summer months or cold winters. They are warning of significant risk of brownouts and blackouts this year. Other parts of the US grid have also warned that unusual spikes in demand may create brownouts as stocks of coal and LNG are relatively low for the season.

To say that all of that is a problem is an understatement–but the diesel is actually the most immediate threat. The trucks that bring the food to the cities run on diesel. They also move the widgets the keep just in time supply chains going. Diesel also runs the tractors and combines for farms. The still rising cost of diesel in the US will continue to be an inflationary pressure.

We wrote this a little over a year ago, but it’s worth a re-read now (it’s the “money” part of a longer discourse). Our world as we know it runs on a predictable supply of energy, and at predictable prices. You can see the dependence of our modern industrial, globalized world here just in the amount of energy consumed over the past 200 years (also broken down by source–“traditional biomass” is burning wood and brush):

That has a direct correlation to the amount of people we can support because that energy makes modern industrial farming, and its “orders of magnitude” better yield per acre, possible:

And it goes almost without saying that the rise in worldwide GDP is equally closely correlated. We have turned back famine and poverty, and have the level of human development we do, because of the uses we have put all of that energy to.

Right now, we have a serious supply mismatch in energy, and that is causing prices to escalate rapidly, and fluctuate wildly. Those charts above are why insufficient total energy into the system will feel like collapse, or more metaphorically, as if the economic stars in heaven were falling, and the earth beneath our feet rent by earthquakes. As it affects food, as it must at this point this year, the political and institutional stars will also be shaken from their courses, and the dark seas of chaos will start to rise.

I think we are still at “cascading disruption”, but we are getting uncomfortably close to “cascading failure”. I am not picking out a Mad Max outfit yet, nor stockpiling a bunker. I think calorically sufficient nations will still be alright food wise, but everything will cost more, and the global poor (and poor even in food secure nations) will suffer greatly. Be a good neighbor. And the non-zero chance of cascading failure is ticking up. Still unlikely–there is a LOT of inertia to overcome–but if energy supply in particular does not find a solution, the risks of failure grow.

–Cases in point include Nigeria, whose airlines were grounded early this week because they could not afford fuel to fly. Spain’s prime minister announced that they will create a price cap on natural gas of 40 euro per MWh, until the end of the year. Meanwhile, natural gas in European markets is trading at about 106 euro per MWh. There are few possible outcomes from this, and one of them is guaranteed to happen in Spain. Spain will either A) abandon the price cap before the end of the year or B) equally embarrassing to the government, walk the price cap up to something higher than the cost of producing natural gas, or C) probably most likely, Spain will start rationing natural gas because it simply will not be available (or only available on the black market and at a much higher price more reflective of the true clearing price of natural gas). Price controls always end this way.

Yes, I did see Nancy Pelosi propose a bill that would allow President Biden to impose price caps on gasoline by executive order. If that passes, read the three options for Spain again, because they will apply to the US for gasoline as well. Nancy blamed excessive profit taking on “Big Oil” right now, which is great politics, but read just a few paragraphs up. The northeast is short of diesel, despite record high prices for diesel. If Big Oil were maximizing profits, they should be selling as much diesel as they can at these high prices. They’re not. Prices are high because there is not enough diesel. The problem is not an artifical shortage for profiteering–the world is really and truly capped on energy right now.

I don’t know who needs to hear this (besides maybe Spain and Nancy Pelosi), but if you cap the price at which a good can be sold below the cost to produce or secure that good for sale, the good will never make it to market. Price caps do NOT increase supply. Black markets, sure, but the price on the black market will be higher than the official price (and the price to produce the good), because you cannot actually get the good anywhere else.

I can promise you that Nancy Pelosi, and Spain’s government officials, are way too important to be affected by rationing if price caps ultimately lead to that. As they tend to historically. So if the US returns to 1970s era gas lines (due to a similar shortage in supply) and rationing based on “even” or “odd” license plates, Nancy is gonna’ be alright. She’s already shown that rules for you do not apply to her. Hopefully, though, calmer heads in Congress prevail. As for Spain, best of luck guys.

Other examples of supply crunches starting to impact geopolitics are Sri Lanka, which may be imploding. But cautions about reporters getting things wrong in areas I know and thus likely in areas I don’t know as well apply to reports like that linked. I am old enough to remember when South Africa was facing similar challenges in riots and at least local economic disruption and was being reported on as inches from a “Mad Max” dystopian failed state. Regardless, times are not good in Sri Lanka right now.

It’s also getting froggy in Iran, if videos leaked to Twitter are any indication (sound on). Those are being blamed on the sharp rise in the price of wheat, and thus bread.

Deus impeditio esuritori nullus.

–Speaking of inhumane regimes whose people deserve some change, there were more first hand reports of out of Shanghai on the state of lockdowns there sneaking onto Twitter. You can read an illustrative one here: https://mobile.twitter.com/JaredTNelson/status/1522597026982252544

Note these lockdowns are tightening despite a decline in new cases. The rumor is that this is because the CCP has set targets for a specific “elimination” of new cases in different zones of Shanghai, and there is great pressure to hit the number decided by some faceless bureaucrat somewhere, no matter the cost. Otherwise, the courageous, visionary and totally effective policy insisted on by the wise, benevolent Chairman Xi might be interpreted as the unmitigated disaster that it has been.

Chairman Xi is most unamused by my (and MANY others’) suggestion that his “Zero COVID” policy is idiocy and doomed to failure, which may also explain the beatings for Shanghai continuing (literally) until their morale improves.

Just a nice little reminder in real time that, historically, any form of communism tried ends up doing ish like this.

Oh, and this (which you should absolutely click and read). Welcome to the party European Parliament! This has been an open secret in China for awhile, but better late than never.

Anyways, how’s the whole “Zero COVID” thing working out economically, considering the large number of companies around the world that increasingly inexplicably, for a multitude of moral reasons, continue to do business there? Well, bad for China, for sure. But you should also check this out. One example among many.

As another quick one, Ford has halted new orders on the F-150, its best selling vehicle and presumably a HUGE driver for its bottom line, because they do not believe they can build enough this year to close out the existing list as it stands, mostly due to microchip constraints. They have already done the same for many other models this year. That this is now affecting the F-150 is a sign of significant stress at Ford.

And it’s mid-May folks.

Some of the necessary widgets and raw materials for the F-150 involve China, I have no doubt.

May Xi and the CCP continue to live in interesting times.

–This is a must read think piece this week (https://doctorow.medium.com/about-those-kill-switched-ukrainian-tractors-bc93f471b9c8) because it is emblematic of the ethics, thinking, and decision making of the “leaders” we have selected for in all of these institutions these past many years. We have no one but ourselves to blame. We created this by letting these ideas be rewarded, or at least delayed from punishment, for far, far too long. The political tribes are all complicit. All. Hubris and a complacency that allowed Virtue (capital “V”) to be unrewarded, if not outright selected against, has set this table. The Bonfire of the Credibilities has been long overdue, as has the adjustment that will take place this decade. That this adjustment will be so jarring is our penance for these errors.

May the echoes of the virtues remain and rise in us to meet and overcome the challenges we face this decade.

–Your chances of catching coronavirus this week are equivalent to the truth here: