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:

–The main story of active coronavirus outbreaks is of course Shanghai, China. Shanghai is the financial center of China and the world’s busiest port, and port operations have been impacted. As it stands this week, there are 3 times as many stalled container ships outside of Shanghai than the port’s usual waiting line. Meanwhile, plenty of videos have been smuggled out of Shanghai showing the lockdowns, now heading into nearly 3 weeks. These include drone flights over totally empty city streets. Videos of children who tested positive and were forcibly removed from their parents and placed into state run treatment centers without much obvious compassion for the affected children. There are reports that food has become scarce since -no one- is really allowed out onto streets patrolled by robots with loudspeakers announcing the city wide lockdown. Rumors of civil unrest developing in Shanghai were followed by headlines of deployments of tens of thousands of troops to maintain the lockdown, along with large numbers of “hospital workers.” There is also concern about a higher general death rate, as similar to other places in the world, “bed’s taken” or delay of non-COVID related healthcare is occurring in Shanghai.

In short, Shanghai is proving a significant test of the CCP’s COVID policies.

Hat tip to a reader who sent a very nice rundown of the emerging clash between omicron and the CCP a couple weeks ago now. That article was replete with linked studies and information from high quality sources, such as the Lancet, which included this remarkable piece on the recent Hong Kong outbreak. In it you will find the truly mind blowing detail that less than a third of elderly people in Hong Kong were vaccinated, and among those in nursing homes, less than 20% were vaccinated. In short, the exact population that should have been heavily vaccinated first was not in China. There are Twitter comments that suggest the elderly were told the vaccine was not a good idea for them by their doctors, and traditional Chinese medicine could control COVID if they contracted it. That is getting a significant test at the moment.

Of course, not that it may have mattered, as recent studies from the Dominican Republic and a Shanghai school of medicine found that neither of the two main Chinese vaccines were providing clinically significant protection against omicron in particular. China is fortunate in that this outbreak is omicron heavy, and not, say, delta or the disaster would likely be greater.

Still, this is quite the failure for the CCP, and their entire population knows it. (That’s the TL;DR version for our CCP “readers,” as well)

We have discussed before how the CCP’s official death reports from COVID were medically unbelievable, and uniquely disproportionate from the increase in overall mortality all nations have experienced, including China, during the pandemic. So I presume that COVID has been more active than the CCP admits and there is, hopefully, at least some degree of natural immunity. But the fact that the rest of the world appears to have working vaccines, and is able to re-open more and more, is not lost on the Chinese citizenry. If, and how much longer until, the CCP and Chairman Xi have to answer for the clear lies about the “success” of their Zero COVID policies in the face of these inarguable facts, evident to the entire world AND their citizens, is the question now being asked inside China and throughout the world.

–We have some updates on COVID strains around the world right now. In both the US and Europe, BA.2 is pushing out its cousin omicron. Outside of a very small, but noticeable, bump in cases in New York, there has NOT yet been a significant increase in clinical COVID cases. While there is some reasonable question as to how many of them are being reported, given the access to at home testing where positives are NOT reported to state health departments, there is also no increase in hospitalization use. So if there were lots of at home tests, we should, by now, and certainly in those places where wasterwater numbers were picking up a couple weeks ago, be seeing higher COVID cases in hospitals.

That is NOT happening. At least so far. That is a lagging indicator, so give it another week or so, but at the moment, it does not look like BA.2 will generate any clinically noticeable wave in the US.

So for all my measured concern about wastewater a few updates ago, the one time, the one time, my eternal optimism that we will reach a herd immunity threshold at some point might have been warranted, appears to be now.

Because of course.

Which is my complicated way of saying that there is no evidence of a BA.2 bump in the US thus far, and if it ain’t happening in the wastewater sites we highlighted a few weeks ago by now, between vaccines and omicron, the US may avoid a meaningful BA.2 wave.

In contrast to Europe, where BA.2 activity remains high, although appears to have leveled and is falling in most countries.

–In other variant news, the UK had leveled a small bump in the last couple weeks, and announced the discovery of a fusion strain called “XE”. We hope that is a clever linguistic dig at the leader of the CCP because that Xi is in close contention with Putin for general douchebaggery, but sadly, doubt that is the case. Regardless, XE is what happened when some poor bloke (see what I did there?) in the UK caught both omicron AND its close cousin BA.2 at the same time. Omicron and BA.2 did this meme in the patient’s infected cells:

And then they swapped a few of the minor difference between omicron and BA.2 to form a recombinant virus that is not only very much like, but exactly like, if first cousins omicron and BA.2 had a Mississippi marriage and then a baby.

Which, biomedically speaking, becomes this:

They are monitoring for new cases of XE, and so far, there is no indication or expectation that it is more severe than omicron and/or BA.2. It may be more contagious than BA.2, which is already slightly more contagious than omicron, which is already so contagious that again, you may have caught it just be reading this sentence. That’s a whole lot of “may be” though, so we’ll keep an eye on it, although not even the headlines were all that worked up by any hint of severe COVID with it.

–In other coronavirus news, we have a couple relevant papers out this week. First up is a study of antibodies to various SARS-CoV-2 strains in vaccinated and unvaccinated patients, and with or without previous COVID (and what strain caused their COVID), published in the New England Journal of Medicine. The total number of patients in whom in the strain causing their COVID is known is relatively small, so the total number of samples in this study is not exactly huge, but the conclusions merit discussion.

Vaccination and prior infection with one of other, more severe strains turned out to have good protection in terms of neutralizing antibody titers in a test tube for the older, more severe strains. They were less effective against omicron, but the step off was not steep. Yes, Virginia, it was not lost on the paper’s authors that prior infection with one of the severe strains was as protective as the vaccines. Nor for those of you who got breakthrough omicron despite vaccination (and that is a surprising amount of the readership based on folks who let me know) that omicron was little more likely to get through.

One of the surprise takeaways was that this did not appear to work in reverse though. Omicron is sufficiently different from the other strains of COVID that if all you caught was omicron, you do NOT generate a whole lot of neutralizing antibodies to the previous COVID strains. If you were vaccinated, and caught omicron though, you still had the vaccine covering the previous strains. The authors used this as an argument for vaccination in their discussion, although in my humble opinion, omicron has largely outcompeted the previous, more severe strains into oblivion. Anything that comes next is much more likely to look like omicron, BA.2, or XE than not. So far, the early alterations around omicron (BA.2 and XE) have followed the expected, usual trend of “more contagious, less severe” over time for mutations in a pandemic pathogen. There is still a remote possibility that it could leap its way back into something with a high severe disease rate, but that chance is increasingly remote.

–In fact, as we look to South Africa as the “fall season bellweather”, there is still hardly any COVID activity going on.

–Perhaps because of publications like this one though, the director of the CDC was quoted this week as saying that omicron appeared to function as a pretty solid booster for those already vaccinated.

–Speaking of boosters, there continues to be headline wrangling over additional booster shots, and who should get them. To be honest, I’m not paying a huge amount of attention. If Southern Hemisphere countries in the fall season like South Africa don’t get popping, and BA.2 cannot generate enough momentum for a decent wave, the chances of another major fall wave of COVID start dropping significantly.

So hope (for the fall) springs…

–In other worthy publications this week, we had a really well done Phase 3, double blind, placebo controlled gold standard study of ivermectin conducted mostly in Brazil published in the New England Journal of Medicine as well. The patient population was appropriate (high risk underlying conditions with acute COVID symptoms in the first few days of them), the dose of ivermectin used was the level expected for any antiviral activity, and the main outcome was prevention of hospitalization or worse. It is worth mentioning that Brazil is one of the countries that has heavily used ivermectin in the treatment of acute COVID. The total number of patients on the treatment and placebo arm were adequate for analysis, and they seemed to have a fairly low trigger for hospital admission in this study, although that was balanced well between placebo and ivermectin arms. Which is another way of saying that they had more “events” (or hospitalizations) in this study than in prior ivermectin studies, making the statistical analysis more robust. Finally, the patients enrolled in the placebo and ivermectin arms look very similar to each other for all the measures that matter, ranging from age to underlying known risk factor conditions.

If this all sounds familiar, this is the final and full data set from the TOGETHER trial looking at an adaptive Phase 3 study of a bunch of repurposed generic drugs with possible anti-SARS-CoV-2 activity. We discussed some of the preliminary results here.

So what’s the final conclusion?

Ivermectin failed to outperform placebo. In their first look at the data last fall, you could argue that there is a slight trend to ivermectin, but man, that is a tough argument to make now.

The authors also correctly point out in their discussion that if you add their results to the current meta-analyses of ivermectin in the treatment of SARS-CoV-2, the conclusions of those meta-analysis would now show that ivermectin does not beat placebo, or would significantly reduce the effect size.

At this point, the clinical trial data is not clear if ivermectin is actually doing anything against SARS-CoV-2, and if it is, the preponderance of high quality evidence suggests it is not doing much. Perhaps no surprise then that some nations which had been using lots of ivermectin, like India, have recently started to remove it as an acute treatment option for COVID.

–On other hand, we mentioned in the initial data look back in September that fluvoxamine was looking really good. The TOGETHER study published that data last fall in the Lancet (was not a huge update on the previous numbers), and fluvoxamine does appear to be a generic medication with pretty good evidence of clinically beneficial effect against acute COVID. And while everyone is still up in arms over ivermectin on the internets along the political spectrum, this evidence, for reasons that are not entirely clear, appears to be flying entirely under the radar. Of course, alongside fluvoxamine, there are multiple other acute treatment options with proven efficacy against COVID out there. Yes, it continues to be a mystery why acute phase treatment is de-emphasized in lay media coverage in favor of “booster the world” vaccination coverage.

–The ivermectin and fluvoxamine arms for the ACTIV-6 Phase 3 study in COVID that would confirm these TOGETHER trial results are still open, and I have not seen early data cuts, if any, from them. Given the trickle of COVID cases at the moment, they may struggle to complete enrollment any time in the near future.

Socioeconomic

–The USDA released a closely watched “planting intention” report last Thursday. This showed that, as expected, there was a slight rotation from fertilizer intensive corn into soybeans, which bring their own nitrogen to the party. Oats and barley, which again are more commonly used as animal feeds, also saw slight bumps in expected acreage. So the good news in that is farmers are working to mitigate the cost pressures on them. The bad news is that yes, some of the acres switching from corn to soybean are likely the more marginal acres to begin with. But the good news in that bad news is that planting soybeans may not be all that bad… As we mentioned, legumes like soybeans restore nitrogen to the soil, and can improve the fertility of those acres. The classic triad of native North Americans, who successfully farmed these lands for centuries, was maize (corn), squash and beans (legume) all planted together in the same field. That worked sustainably because the legumes brought the nitrogen to the party to help the corn, and the corn provided a tall stalk that pulled the creeping bean plants that grab onto everything nearby up high above the rabbits and other rodents that would otherwise eat the beans. All three crops were also hardy enough to keep providing calories from storage through the following spring. 19th century Western European farming largely worked on the basis of crop rotation. Instead of planting all three together, you rotated those kinds of crops on your farm fields, with one corner planted with corn one year, then with beans to restore nitrogen to it the following year etc. That form of farming was also quite stable for centuries without industrial scale fertilizers from liquid natural gas, like we currently use. That said, Western European farming, and to a lesser extent native American farming, did use fertilizer–from the “man that pays the bills” as an old farming saying goes.

The family pigs.

Traditional farms of the pre-industrial era kept horses and oxen for the extra mechanical power (we use diesel in combines now), but all those livestock? Sheep, pigs, goats? They all eat different weeds and different heights of grass. And pigs do an amazing job as rototillers, as their rooting instincts will absolutely rip a field up. That’s why you read headlines about giant wild razorbacks being hunted in Texas because of the fields they are tearing up. Rotating those through the fields of your farm was natural weed control AND natural fertilizer as all of those animals poop.

“Great story about manure,” I hear you say Hypothetical Reader, “but how is any of this that relevant?”

Well, for a couple reasons. First, the great news is that the US farmer (and undoubtedly the Mexican and Canadian farmers) are rallying in the face of inflation in their major inputs of fuel and fertilizer in the more industrial and planting through the uncertainty. “So God made a farmer,” indeed. The olde ways are creeping in as well, as legume planting shows. And would it surprise you to have been reading in headlines this week about how there has been a sudden run on manure fertilizer producers this year? : )

The bad news is that while the old, pre-industrial, less fertilizer intensive methods are indeed more sustainable over the long haul, the old farmers will tell you that you only get about 80% of the yield of modern farming from them, tops.

The acreage is important. The yield per acre even more so. “Yield per acre” this fall will be the next critical question, and with fertilizer costly and in short supply worldwide, expect those yields to be down. Down how much will be the critical question.

Further, it is only industrial farming, with diesel engines and enormous external industrial fertilizer and herbicide input, that makes many acres around the globe, and in developing countries especially, arable at all.

There will be a global food crisis this year. And next year as well, as the last reserves around the globe get eaten this year. Shanghai’s lockdown is only the start of headaches for ol’ Xi, for example.

–Speaking of which, per USDA data, stocks of soybeans, corn, oats etc. all seem quite strong right now in the US. However, stored wheat is down significantly. Like 30-40% versus previous years significantly. The planned acreage for wheat this year is significantly smaller as well.

–Remember the food banks if you can spare some donations. Stocking up on a few stored things, not a bad idea either, especially if you are a reader in a place that has to import a lot of its food and fertilizer already. In North America, I think yield per acre will be enough to meet the caloric needs of the people, although prices will be high. How the food shortage manifests here will be nosebleed costs and unavailability at all of the year round, even-when-out-of-season, foods you have grown accustomed to. Spruce Eats has a fantastic “what’s in season” calendar for produce in North America. You can save money by focusing on what’s available when. The more local you can eat, the better for cost and availability–so find those farmers markets and farms that deliver locally to you as well.

–Outside of North America, it’s already getting chippy. Food and inflation riots hit Sri Lanka, Peru and Chile among others, and just this week. Greece also saw a major strike protesting the rising cost of living.

This is the tip of an iceberg by year’s end.

Deus impeditio esuritori nullus.

–For more geopolitical expertise on this, Peter Zeihan and the ride of the third horseman.

–In fact, if we project out from the now so-expected-I-don’t-need-to-cover-it supply chain knock on effects from all the shutdowns in major Chinese ports as Xi fights his losing Zero COVID battle and when the shortages of food and sustained food inflation are likely to level up the max pain, this September on in is shaping up to potentially be as dark, if not darker, than the very worst of the last two years. To say nothing of a few months for Russia to regroup and get stupid again, +/- whatever the fallout and decisions made in China might be on the geopolitical scene.

Brace, prepare yourselves now, and hold fast.

–The podcast I listened to for some COVID related stuff (that was an aside to main the points of the discussion) turned out to have nothing worth covering in detail as neither guest nor host are experts. And it was a minor part of the overall episode anyways. To clarify one surprising statistic the host and guest discovered while making some criticisms of pharmaceutical “direct to consumer” marketing (which I am personally not a fan of either), specifically their claim that “75% of TV advertising is from pharma companies”, that’s not what the article they read actually says. As much as I dislike the business aspect of the industry, in fairness, as a percentage of total TV advertising, pharma advertising is not quite that much. In 2020, the data they are citing, pharma companies spent $4.58 billion (with a “b”) on TV advertising and yes, do indeed heavily favor TV mainstream news for those ads.

Take some guesses why TV mainstream news, Hypothetical Reader, and I will answer in a moment.

Meanwhile, total TV advertising in the US was $60 billion. So pharma spending is nowhere close to 75% of all TV advertising–it’s closer to 15%. Still a healthy chunk for sure, but not the majority. The stat they were quoting on the podcast is that 75% of pharma advertising across the industry is directed to TV ads. And again, mostly TV news to place those ads.

Got your guess why?

Because your answer is here, and is “advertising to the target market 101”:

Regardless, there is good to come out that podcast though! A very useful link, especially for those of the female persuasion, or those with friends/spouses/kids/relatives of the female persuasion, and ways to be proactive about personal defense in an increasingly dangerous world: www.giftoffear.com. All of these videos are worth watching. Also worth mentioning that these lessons do not just apply to the ladies, although the emphasis is there for the statistical reasons Gavin quotes. Because speaking statistically, despite the dire numbers Gavin rattles off for women, men are 78% of all homicide victims and more likely to be victims of all violent crimes except sexual assault. But also to Gavin’s gender based point, overwhelmingly the perpetrator is male when the victim is male too.

–Sedona, Arizona is a small town nestled in a unique erosion of the Colorado Plateau by the surrounding rivers and streams. The past hundreds of thousands of years of that erosion have been kind to us and Sedona in the modern era, carving through the upper layers of rock in the plateau to reveal the spectacular iron rich hematite layers below in the hills, cliffs and mountains that surround Sedona. The famous red rock of the great American West. The town has wisely captured these with a bewildering number of very well maintained hiking trails that course over every amazing overlook and view. Of course, with the word out now, traffic can be surprisingly dense through the roundabouts that lead to the trailheads, and parking at the most popular trails a problem unless you are out early.

One trail less traveled was suggested to us a few years ago by our driver for a Grand Canyon day trip, who grew up in Sedona. The “Broken Arrow” trail starts a little ways into a neighborhood on the southeast of town, reached by a quick turn off one of the main roundabouts. Most who visit the trail do so on one of the professional jeep tours, or privately by locals or the adventurous who think they have enough ground clearance–I have seen one 4×4 get stuck on the rocks on the motor trail portion of Broken Arrow. But you can walk it as well, and walking takes a very different path from the off road motor trail. Off roaders and hikers will meet only in a couple flat, open rocky outcroppings with views of the surrounding hills, and at Chicken Point, at trail’s end. The hiking trail enjoys shade for significant stretches, which can be huge depending on the time of year you are visiting Arizona, and can be done at reasonable pace over about an hour and a half to two hours.

Like every trail though, you start with a guidebook or word of mouth that the trail is worth it, the view or goal at the end worth all the work and struggle to get there. You have a map, which may or may not be all that great; a guide who has been on the route before if you’re lucky; hopefully some obvious markers along the way to help you know you are still on the path.

I’ve done Broken Arrow a few times now, this last with the kids who had never been on it before. We went in the morning to take advantage of the East Coast/West Coast time difference to us, and to ensure parking at the trail head. The high was 60 this time (90s the previous times I’ve been on it), so it was a cool and fast walk, with a known payoff.

To me, at least.

Watching my daughter especially on this trail, I remembered back to the first time I had been on Broken Arrow. We hit it midafternoon after tackling a longer trail in the morning, and the 90 degree weather felt every bit of that. Each stretch of shade of along the trail was a welcome respite. Although the distance hadn’t changed, the first time through the trail felt so much longer, both on the way there and back. You could kind of estimate how far along you were with the map, but it was just an estimate. The heat, the elevation, the fatigue, and it was natural to wonder how much longer it really was. And just as importantly, was the goal really worth all of this. Should we just stop or turn back?

All the same questions my daughter was asking.

Fortunately, the kids are still in the age where parents still have their credibility. Plus, their father knew the way, what was at the end, and how far from it they were from complete knowledge of this trail.

This time, at least.

So while it seemed long at the time, interminable through the rocky and rough parts, and the steep and the slippery portions where the danger of falling was greatest, and the parts where the correct path was not so obvious and it would have been easy to get lost in the wilderness, the kids soldiered on. In hope that we were right, and the views along the way and at Chicken Point especially would be worth it. In faith in their parents. In trust.

With surprisingly little bickering too. Best way to ensure a long and miserable experience, and the greatest chance of never making it to the payoff on the other side, is to fight amongst or mistreat each other. Kids avoided that mistake this time, with very little course correction needed from us.

And at the end, they played in the sun at Chicken Point, which has the best views of all the surrounding red rock. All the misgivings, any doubts, all the hardship and hard feelings melted away. My daughter took out her Polaroid to practice her photography on all the views, and have something to inspire her classmates from her spring vacation. My son all but ran most of the way back–his sister too.

I know, I know. Cool story bro.

But I haven’t been able to shake the sense that there is something else to it.

“Of course, my brothers, I really do not think that I have already reached the goal; the one thing I do, however, is to forget what is behind me and do my best to reach what is ahead…”

“At present we see indistinctly, as in a mirror, but then face to face. At present I know partially; then I shall know fully, as I am fully known. So faith, hope, love remain, these three; but the greatest of these is love.”

Saul of Tarsus, dated somewhere between 53-59 (possibly up to 62) AD.

–Your chances of catching COVID, in most places in the world, are declining. Still quite possible, don’t get me wrong, but declining.

<Paladin>