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

Also as a reminder:

Nipah virus:

–No reports of new cases in India, and we are safely out of the incubation period. So yet another Nipah outbreak goes into the books, with one unfortunate 12 year old the only significant case.

Coronavirus:

–For once, it’s actually a pretty slow week on the coronavirus front. Most of the action is in the “socioeconomic” category, which we will get to in a bit. Around the horn, new cases of confirmed SARS-CoV-2 are falling across much of the globe. The delta outbreak in southeast Asia is in retreat. Russia having a minor wave, but they are really the outlier at the moment. In Western Europe, the UK is still hovering with a slight elevation in new cases (food and fuel are the bigger issues there right now).

One of the UK readers also sent along an article from the Telegraph (but others also available) of the “worst cold ever” circulating in the UK right now. As restrictions have lifted and folks are interacting more, all of the cold viruses that were not circulating as well during lockdowns and restrictions are making the rounds again. The “worst cold ever” is the re-introduction to the multitude of non-SARS-CoV-2 viruses that can cause cold like symptoms. You may recall us mentioning this recently (lead “update”, so no jump link–just scroll to right below the Star Trek). In that update, we said re-introduction to other cold causing viruses and co-infection was a better explanation for the data in a disastrously half-baked paper the CDC managed to schlep out, where the CDC ludicrously concluded that vaccine immunity was waning.

Back to epidemiology around the world though… More Scandinavian nations are releasing COVID restrictions. In the US, the delta wave continues to abate. The epiforecasts Rt is 0.9 or less all week. Pressure on the hospitals is starting to ease, but again this is very local, and has much more to do with staffing issues than anything. For example, four hospitals around Indiana have deployed National Guard medics deployed to alleviate staff pressures.

None of them are due to staff firings over vaccination status, for the record (their deadlines are in a couple months).

In all four hospitals, it is because of “staff fatigue.” Which you should translate as “burnout”, and anecdotally, I think will be a growing concern as the pandemic finally wanes.

–No, mass firings of staff will not help this. On the plus side, most healthcare systems are reporting jumps in vaccination rates well into the high 90s. New York let go 86,000 healthcare workers as the deadline hit and they chose not to get vaccinated–while a big number, there are over 1.1 million people in New York classified as healthcare workers. So they let go what I would approximate as 5-7% of the total work force. There will be local variation in that, of course.

On the one hand, I understand the requirements for vaccination for healthcare workers. We all already have a number of vaccines required for the job. This isn’t anything new, and is for patient protection. On other hand, if some of those fired had recovered from COVID and could prove it, well, I’m sure at least a few will lawyer up.

I also wonder, given the level of “fatigue” and burnout, and going from heroes at the beginning of the pandemic to… well… I am sure that every physician on this list, including me, can tell you stories of getting an earful from someone who is upset about political responses and policies to the pandemic, but blaming the doctors and nurses for those policies as if we were the politicians making them.

The medical institutions of the time did not survive the Black Death reputationally intact among the general public, either : )

So I also wonder, given “fatigue” is getting National Guard deployments to hospitals, if among some of the vaccine holdouts in healthcare there are not a few who are just burned out and used up, and choosing to go out defiantly. Rather than admit they have nothing left to give, and are just done with the whole edifice of modern healthcare systems. Easier on the ego to get gloriously, “unjustly” fired than to quit.

I bet it’s at least a few.

What’s the M*A*S*H theme song called again? “(Career) Suicide is Painless“–or something similar?

–For all of the new variants, both variants identified in South America and South Africa, so far so good. There have been no new waves attributable to these variants; they are not displacing delta. Thus, so far, the epidemiology in the real world suggests their ability to evade the vaccines is minimal if any. In fact, the mu variant, first identified in Colombia with much angsty headlines in the last month or two, was reported extinguished in the US this week. There have been no new cases of this variant identified in the US in the last two weeks.

–In other news, Pfizer has submitted the data package to the FDA this week for its clinical trial of its mRNA vaccine in kids 5-12 years old. So we’ll wait to see what the FDA says and what safety data is published from that package.

–Pfizer has also entered Phase 3 trials for a protease inhibitor as a treatment for SARS-CoV-2. You may have seen this jokingly referred to as “Pfizermectin” online, because yes, one of the ways that Ivermectin is theorized to be effective against SARS-CoV-2 is interaction with this same protease. Ivermectin is also theorized to interfere with spike protein binding too, so they are not -quite- the same molecule (and Pfizer’s was selected to be a very potent inhibitor of this protease). Pfizer’s main challenge may be enrollment of the study, given the slowing disease activity world wide.

That said, Goldman Sachs has actually had a pretty decent epidemiology track record of late, and here is their latest projections of where the world stands versus potential future SARS-CoV-2 waves:

–As for ivermectin itself, the Together Trial (run by McMaster University in Canada, looking at repurposing ivermectin among several other generics to treat COVID) has data on the Ivermectin arm:

Again, this was a Phase 3 study, randomized, with placebo control. Ivermectin was NOT statistically significant from placebo in reducing “extended ER observation” or hospitalization.

Which is to say ivermectin struck out in this study.

That being said, the “squint so hard you see it” trend is in favor of ivermectin, and a larger trial might reveal a slight benefit.

And there is a larger trial going on! The next study to watch is the Phase 3 ACTIV-6 study sponsored by the NIH, which is using an almost identical dosing regimen to the Together study. The study has been actively enrolling during the delta wave, although it is a giant study looking to enroll 15,000 total patients. Because of that ambitious recruitment goal, they do not expect completion until December 2022, but I suspect will look to announce or publish “in progress” data sometime this year.

–On the other hand, one of the other generics in the Together study, fluvoxamine, showed interesting signs of life and was statistically superior to placebo with very strong trends for subcategories like viral clearance. Fluvoxamine is also being tested in ACTIV-6. Fluvoxamine is a SSRI also known as Luvox (for the record, my employer does NOT manufacture or market this drug). This is one of the SSRIs known to have anti-inflammatory properties, and it may be disrupting the Ah-nold immune reaction in severe COVID. It may also interfere with ACE2 receptor binding and viral entry into the cell. All of the interest comes from observational studies which noted that among patients with COVID, there were fewer intubations necessary in the early days of the pandemic among patients already taking this SSRI. So far, the Together study, at least, is consistent with these observations.

–On to socioeconomic issues… especially as SARS-CoV-2 wanes a little bit, these are the most likely candidates for significant upheaval in your life for the rest of this calendar year and likely next year too. This is continued supply chain disruption (which is now affecting energy supplies in terms of nat gas and coal), whatever the hell is going on in China, and inflation.

Supply chain disruption we have already covered a lot. It’s continuing, and in some places, getting worse. CostCo, for example, is restricting sales of toilet paper again. I know that it has been a bit of a roulette at the supermarket in terms of what will be oddly unavailable this week. At least here, where the food grows, that’s largely been restricted to randomly empty shelves of bottled teas or bottled waters. Maybe some frozen items. If you can access local, direct sales from farmers in your area, might be worth considering. Meat especially if you are in the US, given continued supply chain pressure there and recent presidential saber rattling towards the four largest meat processors.

Inflation in food prices continues unabated. As we mentioned above, coal and natural gas prices have gone parabolic as well. While that is not likely to persist (those prices will increase supply at some point), more and more businesses are looking to pass along those costs to consumers. “Why not just eat the cost in their margin?” I hear you ask, Hypothetical Reader. Just Google “issues profit warning” or “adjusted guidance down” and set the filter for articles in the last 90 days or so. Many of them already have soaked up their rising costs for energy and materials, at least as comfortably as they can. So now you are starting to get headlines like this–yes, that is Dollar General announcing it is going to have to start pricing above $1.

You may want to consider quietly stocking up on a few extra items you like with long shelf-lives with every grocery trip for awhile. Supply chain collapse is unlikely, but energy inflation, and continued supply chain disruption is absolutely capable of screwing up the “just in time” delivery model to grocery stores–which relies on warehousing and cold storage of bulk goods sourced from around the world, and then shipping en masse. You may want to start hedging in making sure there is enough around come spring (the starving time), just in case. Again, the worst you are out is food you just eat later or donate. It’s a low cost hedge against an improbable, but highly significant if it occurs, event. A classic black swan…

–I have no idea what is happening in China, but because it is all happening in China, it matters–if only because of China’s continued importance in global supply chains as a major producer of lots of stuff. I know that Evergrande is slowing defaulting on its debt, and is multiples the size of Lehman brothers. China has increased liquidity into its banking system by the most since the pandemic began in the last week or so to try to stabilize falling real estate values. Again, this is because 70% of the average Chinese person’s wealth is in real estate–and real estate in China, as a whole, is the world’s most expensive asset class as a result. So I know they are trying to control the detonation there. The reports of blackouts involving hundreds of millions of people in China, all across the country, is…odd. This is even impacting factories making key components for companies like Tesla and Apple, to show the supply chain ripple ramifications of all of this. Goldman has reduced their expectations for growth in China’s economy this year to 0%, instead of the usual 5-8%, all based on pandemic lockdowns and this new power problem China seems to have.

I have seen explanations ranging all over the place. Some of the most common chalk it all up to (temporary) increased demand exceeding available supply. This idea is that the re-opening economy led to spikes in demand from energy intensive industries like steel and iron manufacturing, plus a hot Chinese summer and air conditioning use was more energy demand than Chinese companies were used to–they burned through their existing and allowed coal and natural gas and are now getting sticker shock trying to get more in. But those industries are only just getting back up to speed, and only in fits and starts with occasional lockdowns still happening. Plus, they booted energy intensive cryptocurrency mining out of the country already. So it’s not immediately obvious to me that this is increased demand over what the system should be used to from years prior. Now, it’s possible the pandemic reduced coal and natural gas supplies and production, but, as we mentioned before, China gets the majority of its energy from abroad and those shipments have been pretty steady globally throughout. I’ve seen other arguments like consequences of Chairman Xi trying to reduce natural gas and coal use to clear the skies before the Winter Olympics in China start in February, and to finally live up to China’s climate change commitments. But China has -never- cared about those commitments before. Further, this is a society that places great importance on “face” and has a government intent to project that China is a, if not the, new pre-eminent global superpower. Particularly as, after Afghanistan, the Pax Americana wanes. For a country trying to convince the world of its rising economic might, trying to build the New Silk Road and Road and Belt infrastructure initiatives across the globe, massive rolling blackouts are awfully embarrassing. Why enforce arbitrary reductions in coal and natural gas use now if you are China–to the point that you are getting these huge, embarrassing blackouts? How do you sell African nations on new power plant and factory deals to join the New Silk Road when you cannot keep the lights on reliably at home? That’s either very poor planning to change power sources to meet climate commitments (best case) or you have a very serious problem in your economic core or infrastructure (worst case). Neither is a rousing vote of confidence for the CCP to meet its commitment to economic prosperity and rising standard of living for the Chinese people, forever and ever amen. That doesn’t look like the Mandate of Heaven resides with the CCP–and that is a MAJOR problem for the CCP.

No surprise then, that they came out just this morning with edicts to “use all measures possible” to secure adequate coal and natural gas to keep the lights on.

First, that the problem exists and that is the reaction to it makes me think that all the “explanations” offered in the media so far are incomplete. I’m not sure what is going on behind the scenes–is this the first cracks, similar to the ones in the Berlin Wall that brought the USSR down? But I know there are important pieces missing here.

Second, if China is going to be throwing bands on the table like woah to make sure they get theirs coal and natural gas, prices are going up for everyone. And every shipment China buys for the rest of the year is -not- going to someone else…

Inflation will not be “transient” for at least a little while longer.

–Lastly, Life in the Times of Coronavirus:

This past week saw a case report published of a 77 year old male who recovered from acute COVID-19 only to apparently suffer a new debilitating consequence: restless anal syndrome.

That is pretty much exactly what you think it is. Restless leg syndrome, which keeps you awake at night through the compulsion to move your legs. Except…not… your legs. So very not your legs.

Now, I notice that this article was submitted to this journal on April 20th of this year, which leads me suspect it may have been hastily written that specific day, or, perhaps composed about three weeks earlier. Otherwise that is… quite the association there.

Oh, to be a fly on the wall when they are going through a job interview, and someone is flipping through the “publications” section of their CV and asks about this one…

–Now, this daring is case report is not my all time favorite strange-but-really-did-it research paper. That’s still the time the NIH locked 6 healthy male volunteers in an unventilated room and lit a ball of crack on fire–and then in Phase 2 of their study, paid volunteers to hang out and watch movies with crack heads while they smoked crack, all to see if second hand crack exposure could pop a drug test positive for cocaine in either laboratory conditions or field conditions. Spoiler alert–second hand crack exposure cannot pop a drug test positive, and a positive test is strong evidence you were, in fact, using cocaine.

It’s tough to beat that study. But this case report comes close…

–Your chances of catching coronavirus this week… In 1985 Sports Illustrated profiled one of the most unique Major League Baseball prospects to ever play the game. He was late to baseball, having dropped out of Harvard in 1976, and got an invite to the Mets camp by running into one of their executives and demonstrating his fastball. The adopted son of an archeologist, he had been raised in Tibetan buddhist traditions since his adopted father had died in an accident in Tibet. Part of his meditative practice, it turned out, was pitching. And as the prospect himself proclaimed when introducing himself to the Mets exec, he had mastered the art of the pitch even as he had mastered his mind and spirit since leaving college some 9 years earlier. His fastball was inerrant and clocked at 168 mph. For comparison, the modern era record is 105.8 mph by Arlodis Chapman. But here’s the crazy part. He didn’t even have a contract at the Mets training camp, and insisted on complete secrecy, since he was trying out the Mets as much as the Mets were trying him out. He had never played organized baseball–again, to him, the simple pitch and catch was a spiritual exercise, a way to tune out the distractions of the universe. Similar to this. Pure zen. The only other time this pitcher came close to the state he could achieve with pitching was playing the French horn. Despite having the greatest fastball in the history of the game, he wasn’t sure he wanted to play baseball. The purity of the pitch was all he needed, and he worried the French horn may ultimately offer him more in terms of spiritual practice. Enlightenment through music might just be his destiny.

On April 8th, the week after the Sports Illustrated story ran, the New York Mets announced the retirement of Sidd Finch, before he ever signed a contract, or pitched a single game. He had the courage to pursue his life’s ambition, to follow his own path, and left the allure of a life in professional sports to pursue music, Zen and the French horn.

Your chances of catching coronavirus in most places in the world are equivalent to the chances that the authors of the “restless anal syndrome” after SARS-CoV-2 may know where to find Sidd Finch these days.

<Paladin>