Monkeypox

–New monkeypox cases continue to collapse, and there is little to suggest at this point there will be a rebound rise. This outbreak, while a little unusual in geography and scale, turned out to follow the playbook of prior outbreaks, and is largely self-extinguishing after a few generations of transmission.

So at least -one- crisis averted!

Only other news of note here is that the CDC released a report showing that most US patients hospitalized with monkeypox had co-infection with HIV they did not about (yet) and were severely immunocompromised. Outside of immunocompromised patients, hospitalization was pretty rare.

Pediatric Hepatitis of Unknown Origin

Remember those headlines from a few months ago? Yeah… So just to update that, they still don’t quite know the cause yet. A little under half appear to have an adenovirus infection, and most of the cases are actually tapering off–the biggest peak was during the summer months this year. Of the just under 400 cases under investigation (some or many of which may turn out to have a very explainable hepatitis as they are investigated, so that 400 is very preliminary and should be viewed as “at most”), approximately 6% needed a liver transplant and 4% died. Overall, while 400 cases is enough of a rise to get CDC and WHO attention, as you can guess, it’s still very, very rare for kids. So that’s good news. If they ever figure this out, I’ll update some more. But you can mostly remove this one from your wall of worry for the time being too.

Ebola

—So despite Uganda’s best efforts, the head start that Ebola had on this outbreak before it was recognized has caught up. The WHO expressed additional concern last week, as 8 of the most recent confirmed cases had no known contact with established transmission chains, and new cases have moved to the capital city, including an exposure risk at several elementary schools. That said, new case are not exploding in leaps and bounds. However, the total number is a little higher than I would like to see, and there remains a steady drip of new cases each week.

–Of the transmission chains they know about, Uganda is still a rock star in contact tracing, with confirmed follow up of 98% of just under 3,000 known exposures at the moment. Uganda also dusted off the COVID playbook to impose lockdowns in certain regions with active spread. Again, perception of effectiveness is just as good as actual effectiveness for politicians. Even politicians in Uganda. Human nature being what it is, you can expect the lockdowns to be only mostly obeyed, if at all. It’s also not clear if the new cases outside established chains were outside of these lockdowns, and in fact, the virus geographically is certainly beyond them already.

—Regardless, even in the big West Africa outbreak, and all the prior outbreaks in just the last few years, there have not been COVID-style lockdowns attempted for Ebola. There were travel restrictions and screens set up, sure. And there were quarantines imposed on those known to be exposed to a confirmed case (even those with limited success, as escapes from quarantine or lost to follow up happens about 5% of the time or better, based on the DRC experience). I have doubts that this will really do much to slow the spread of the virus, and the virus was not exactly transmitting explosively to begin with either. While more fatal on a case by case basis, Ebola definitely is NOT SARS-CoV-2 when it comes to contagiousness and ease of spread.

—On the plus side, Uganda does appear close to getting doses in and starting to distribute via ring vaccination some of the experimental vaccines more specific for the current strain of Ebola circulating. In fact, it’s not impossible that they will be starting that by the time this update goes to “press.” With their effectiveness in contact tracing, this should still be an effective strategy–so long as they finally have their arms around all the contact chains that truly exist. With those 8 cases last week that were outside the known chains, there is still some reason to doubt that they are -entirely- there yet.

—Overall, there are 109 confirmed cases with 30 fatalities so far. I expect that climb in the next two weeks, and the key factors now will be discovering all potential contacts and exposures, keeping the high rate of contact tracing going, and getting the vaccines in and distributed (assuming they are effective–this is highly probable, given that Ebola Sudan is not so different from Ebola Zaire, and vaccines are already effective against Zaire).

–No word on Chairman Xi instituting a “Zero Ebola” policy within China, although if he launched it now, we suspect it would be more effective than the on-going “Zero COVID” disaster.

Coronavirus

—Cases in Europe, which were cause for some headline alarm just a few weeks ago, appear to have crested among much of central and western Europe. Numbers are already back on the decline, and the slight pop may have more to do with people out and about, with greater numbers of COVID exposures, than a significant new variant starting to truly break through. By the end of next month, in both US and Europe, if we are NOT seeing big jumps in case numbers, our experience this fall will likely mirror that of South Africa during their recent fall/winter. We can expect a muted low burn of transmission, mostly of omicron variants.

—In the US, leading indicators like doctor visits for COVID continue to fall, as do antigen test results. There is a slight uptick in cold/flu symptom searches on Google, but ’tis the season for fall allergies and flu, which will overlap and confound that as a COVID predictor. COVID wastewater tracking shows the virus is still with us and circulating, but no indications of impending new breakouts like the big omicron wave last winter, or the delta wave before that. BA2.75.2 and BQ.1 are the new omicron variants making occasional scare headlines. BQ.1, which is a lineal descendant of BA.5, appears to be pushing out BA.4 and BA.5 in those regions of the US where it is already present. That said, there is no apparent increase in severity thus far, and the long term trend of “more contagious, less severe over time” continues unabated. Despite the low level of activity, it is still VERY possible to catch COVID, and not a week goes by that I don’t hear of someone, somewhere either currently or recently coming down with it.

Still almost invariably after they have traveled for work or leisure to someplace crowded.

If you do have high risk conditions, and especially if you never had a confirmed case during last year’s omicron wave, the new omicron boosters are still a good idea to hedge your downside risk. Otherwise, I would say, herd immunity is largely holding up.

–Speaking of vaccine controversy, got asked about the CDC’s announcement adding a COVID vaccine to the recommended schedule of childhood vaccinations.

To be frank, I consider this a tempest in a teacup. Given the political capital the CDC has expended on vaccines already, and the well-known and somehow still well traveled “sunk cost” fallacy that seems especially adept at capturing big institutions and leaders in them who take themselves very seriously, did you expect any other decision?

And before you “@” me, I don’t bring up sunk cost fallacy to criticize the decision–only to highlight that once an institution like the CDC has said “A”, it is mostly likely to continue to go on saying “A”, because someone, somewhere, in a conference room of very serious people there will remind them of everything the CDC said about vaccines before, and state that to NOT put them on the recommended schedule of childhood vaccines will destroy the credibility of the CDC and cause more vaccine hesitancy, plus give more ammunition to “crazed conspiracy theorists.” Whether that is right or not, it invariably raises the level of evidence required internally to decide NOT to recommend the COVID vaccines as a scheduled childhood vaccination.

We also stress, before you “@” from the other side, that yes, it would have been reasonable to NOT add them to the schedule of childhood vaccinations too. Again, we mentioned just last update several entire countries have stopped vaccinating kids for COVID, believing the benefit:risk ratio is just not there given how so few kids get severe COVID.

But the reason this isn’t worth getting your schismogenesis all worked up about is that <whispers> it really doesn’t matter what the CDC recommends here.

The required vaccines, and their exact schedule, for school participation is decided at the state level. Your state can decide to tell the CDC “duly noted” and go its own way on COVID vaccines. Pretty sure Florida already did… let me check…

Yep. And so did at least 11 other states so far… Hm, before I click on that, let’s play the Feud!!!!!

Show me Texas on that list too, Steve Harvey!!!!

“Alright news article…. is Texas one of the 11 states out with some form of press release stating they will not be following the CDC’s recommendation for adding COVID to childhood scheduled vaccines?”

DING!!!! Yep. Texas is definitely one of the 11…

So yeah. Don’t worry about the CDC. It’s your state government that you need to worry more about–and <also whispering> have much, MUCH greater ability to influence with your votes and interaction with your elected officials.

—So of course the other big news since our last update was a research group at Boston University releasing a non-peer reviewed pre-publication print a gain of function study that created a chimeric version of SARS-CoV-2, which turned out to be highly lethal in mice. In fact, they reported an Ebola-level 80% mortality in those mice.

As one can imagine, this created a great deal of media attention. It deserved to.

The NIH announced the day after the pre-print went live that they were starting an investigation into the research and this research group, because the creation of chimeric SARS-CoV-2 for this type of research was NOT in the intended use of funding statement and original proposal that the NIH approved. Meanwhile, Boston University went into PR crisis mode, trying to explain that this was not -really- gain of function testing.

So a couple points on this. First, “chimera,” in this instance, is science for “stuck the spike protein of omicron onto the original, more severe disease associated strain of SARS-CoV-2.” Hence, their new virus is a chimera, or fusion, of parts of one virus with parts of the other. Boston University is claiming this was not gain of function testing because the intent was not to select for a more dangerous strain in doing this, thus deliberately making SARS-CoV-2 more potent. But yes, that is exactly what they wound up doing here, making their intent, in my opinion, irrelevant. The problem with gain of function is not merely the intent of making the virus more dangerous deliberately—it’s that you have made a more dangerous virus, which now exists in the world. Yes, this is ideally done with in a highly controlled lab environment, but the risk of this entire line of research is that the downside of accidental release may be so high that, no matter how minuscule you make it, is unacceptable if the risk is anything higher than zero. Over a long enough time period, an accident will happen (if it didn’t already with SARS-CoV-2 itself). If you cannot afford to lost that bet, you should not, and I would argue, can not play in Taleb’s casino.

Imagine, for a moment, if a virus with the contagiousness of SARS-CoV-2 got loose—but now really DID have a mortality rate of 80%. That’s Ebola on steroids spreading like the common cold.

That’s a big problem.

If you think things are still pretty damn sideways after a pandemic that is a bit higher than a bad flu season, but really good at swamping hospitals quickly to jack up all cause mortality, imagine where we would be if something with the features of Boston University’s virus got loose, and could do in men what it was doing in mice.

Again, the intent doesn’t matter. That the virus exists, could get loose, and over a long enough period if not eradicated in that lab will get loose, is the problem. They have quite literally paved a road to hell with their intentions.

This WAS gain of function research in its result, even if not the intent, and should be treated as such.

What’s even worse is that to test the hypothesis they were actually after in this paper, I don’t think you needed to create this chimera. They could have gotten similar conclusions with equal rigor with other methods—knock outs, for example, rather than “add in” chimeras. Those methods might have taken longer, been more of a pain, sure, but were probably a better approach given the risks of gain of function results.

Now, that said, it is highly improbable that if the Boston University chimera were to get out it would have 80% mortality in humans. After all, omicron, its spike protein donor, is nowhere close to that. Neither is the wild type strain that is the other part of the chimera. Far from it. If we’re being purely theoretical, yes, I will concede that there could be an unexpected additive effect like what they showed in mice. However, mice ain’t humans, and many is the effect seen in mice that does not translate to humans and vice versa. And these mice are a strain that is particularly susceptible to COVID—it’s why they used them for this work. So the chances of an 80% fatal COVID strain popping out of this paper are incredibly, incredibly small. You had a better shot on your last Powerball ticket. So if Boston Chimera COVID got loose, your most likely outcomes are yet another omicron variant that most people already have antibodies to and thus can control -or-, more negative case, a strain that spreads like omicron, but goes back to having the hospitalization rate of the original wild type. While that would be a bummer development and probably get the lockdown pen twitching among the more authoritarian prone politicians out there, we do still have multiple treatments now for acute COVID, and could reduce the severity and hospitals overwhelmed risk. Since the actual pandemic threat would be covered, it would mostly be a serious inconvenience, and -ideally- not the same level of freakout as the original pandemic, when we had no vaccines, no prior immunity, and no effective acute therapies to keep people out of the hospital.

Ideally not the same level of freakout though. Your actual political overreaction to that scenario will vary.

And also in fairness to the Boston University group, the findings for the virology of SARS-CoV-2 are interesting. What the “success” of their chimera shows is that while the spike protein probably controls contagiousness, it does NOT control severity, and the other genes in SARS-CoV-2 are likely doing more of that. You can, and in fact do, become immune to some of those as well. In fact, we test for antibodies to some of those to show you were previously infected, and not merely vaccinated (as the vaccine will show a spike protein specific antibody only). This means that the reduction in severity from repeat infection that many have experienced with COVID is likely a real thing. If responses to the severity determining region of SARS-CoV-2 are longer lasting than the spike protein, many people may be already durably immune to the hospitalization risk of COVID. We might also be able to develop vaccines to those which would be longer lasting than the claims of the manufacturers who benefit from selling more vaccines and boosters suggest, avoiding the necessity for “seasonal booster” COVID shots.

Taking a brief detour on those, yes, we do note Dr. Fauci was trotted back out in the last couple weeks to encourage a seasonal booster model. I would argue if we -don’t- see a big fall wave, given that the new omicron booster uptake has not been terribly high in the US, you have an argument that herd immunity is likely sufficient for at least this season. And we may need to think about the still somehow radical idea of antibody testing before deciding if, who, and how many boosters we need for next year—if any at all.

But back to Boston University. So as far as the NIH investigation goes, I don’t know what their original proposal was to know if they have gone significantly off the reservation. I can tell you that even though it should not, that does happen. My “exit interview” with the dean at my last academic appointment memorably lamented that I never received the “correct’ mentorship about these grant applications. In his direct words, “you can submit a grant for ABC, but then do DEF, as long as you can explain why you did DEF later.”

I am no lawyer, but that still sounds like fraud to me. That dean is now up to a half dozen retractions of his prior scientific publications, as it appears grant applications may not have been the only thing he was falsifying, and abruptly “retired” from his deanship in the manner in which one fires people with certain august titles.

All I am saying is that -if- the Boston University group was off the map of their original proposed research, they are certainly not the first group to have done that. And yes the hammer should fall on it, if confirmed, and should probably be happening more often.

Anyways, you can find the pre-print paper here.

—Tangental to COVID, but worth discussing, is recent reader discussions of semaglutide and the newest entry to the class, tirzepatide. These are both GLP-1 agonists (tirzepatide also working on GIP), which is a fancy way of saying that what they primarily treat is Type 2 diabetes by improving insulin response to high blood sugar.

Before we get farther than that, I want to emphasize I have NO direct position, long or short, in the companies which manufacture these drugs, no intention to change that any time soon, and will be covering only publicly available information. As always, all medications discussed should be used according to their label and under the supervision of your healthcare professional. Talk to your doctor, folks.

They have been the talk of endocrinology boards, from what I have heard, because they are -very- effective against diabetes, and do work to promote significant weight loss. I have had endocrinologists I trust a lot tell me they have been able to take some of their patients off of insulin entirely while on these medications.

They reason they came up in conversation, though, and tangentially touch COVID, is because of the associated weight loss with their use in clinical trials. In fact, semaglutide comes under two entirely different trade names, because there is a difference in the dosages used for the version primarily treating diabetes and the one which is used and labeled specifically for weight loss. And of course, being overweight is a MAJOR risk factor for severe COVID.

So it… links…. sort of… to the main topics of this update…

Anyways, stay with me. The word is already out on semaglutide, and I have heard of pharmacies now requiring proof of diabetes before handing it out, because of concerns about the demand coming from patients who do not have diabetes, and sometimes are not even overweight (you can find entire discussion tracks on semaglutide in bodybuilding forums, for example). Tirzepatide is the newest of the two, and earlier this month, secured a fast track FDA review process for its clinical trials using tirzepatide to treat obesity and overweight/obesity related conditions. The two have been compared in a head to head study sponsored by the manufacturer of tirzepatide, which you can read here. That was mostly for their diabetes activity, but the weight loss effect is mentioned as well, although not the primary comparison of that study.

So long story short, the weight loss is real, and it’s noticeable with these drugs. However, they are quite expensive, and the chances that you will get your insurer to pick them up is zero unless you have one of the labeled conditions (primarily diabetes, but for the weight loss version of semaglutide, you can check a few weight associated conditions as well, and perhaps qualify).

Just remember that the price for these is just as likely set high so a pharmacy benefit manager (PBM) company, which dwarfs the pharma maker of the drug in market cap and profit margin, can negotiate a greater “savings” percentage off that list price–which is where the PBM makes all its money, sometimes more than pharma company itself off the drug. That might explain the question that some of the more pharma business savvy readers have about the makers of semaglutide and tirzepatide, which also make insulin–“why would two companies who make insulin want to make a drug that will leave diabetes patients needing less insulin?” The answer is that despite all of the Congressional basing of the drug companies for raising prices on insulin, over half of the money spent insulin goes to PBMs and other middle men making their money on the “discount” from that price, while the makers of insulin have been receiving 33% less despite the price increases. No joke, and you can read all about that here.

That’s how jacked up your healthcare system is–even for the big and rich participants.

So what was mind blowing when asked about these by a reader who should qualify for them was the difficulty in getting insurance to pick them up.

Not to go on a bit of a rant here, but I have no idea what the insurer adjusters are calculating on these when making coverage decisions for weight loss on these drugs, in overweight patients, with signs and symptoms of weight associated disease, but absent diabetes. I’m clearly missing something though. Considering how expensive treating a heart attack is, for example, and how closely associated the risk of that is with being overweight or obese, it doesn’t take many patients losing weight to make this a money saving preventative measure for an insurer. To say nothing of costs of treating other weight associated conditions, like replacement knees and hips, long term care, disability claims and the like. But the reader who contacted me was having a LOT of trouble getting insurance to cover, outside of diabetes.

I just don’t get it. Except it was another reminder of why I left clinical medicine. Opportunity to do research, sure, but the entire system does not appear to be designed for, or very often work to the benefit of, the patient. When it does, it’s often because of the herculean efforts of your doctors and nurses. Many of you probably don’t even realize how much full time staff is devoted just to arguing with your insurance company for treatment you should be getting.

Weight loss is hands down one of the most effective things you can do for your health and long term well being. Being at a healthy weight, and active, does so much for your general mood, your overall health, even your wallet. You’ll spend less on insurance co-pays by taking down your risk of weight related conditions which need drugs, treatments and devices to manage (not even necessarily cure and reverse). And insurance companies are not trying to make that happen? I just don’t get it.

You also don’t need the expense of pharmaceuticals either to lose weight. 90% of weight loss is in what and how, and especially how much, you eat. If you are looking to lose weight, and either don’t want or don’t qualify for semaglutide/tirzepatide, Noom is particularly useful in helping you learn how and why you eat, and changing your eating patterns in a way that works for you, and sticks with you, because it’s your new and improved habits. Trust their process. Once you are done with Noom, if you want to take it one slight step higher with your diet, check out Zoe. I have no financial relationship with either. I have used them both, and found them effective. And I would recommend them in that order.

Socioeconomic

<long, long sigh>

<stares up at the ceiling>

There’s plenty to cover here too, but frankly, less of it has to do with direct pandemic effects, and more pandemic catalyzing issues that were already happening. And you can read headlines too.

The good news is that the fall season, in Europe, has started very mild. Europe will need to root hard for global warming this winter. Yes, storage tanks are now so full in Europe that the price of natural gas has started to fall during the warmer October. However, it’s the flow that matters more, because they do not have sufficient storage capacity to meet 100% of their needs. There was no reason to build that much redundancy, when at least some level of additional natural gas would be assumed to always be arriving. So a change in the weather is still a big risk, but at least 1 month down.

The longer challenge is that energy policy, across the West, remains utterly incoherent. I have examples of this teed up from the US through Europe and beyond, but the single best is the news this week that Germany was ripping up a wind turbine farm to expand a coal mine to ensure more consistent energy availability this winter.

In short, I would continue to plan for a high likelihood of economic turmoil throughout next year, continued supply/demand imbalance resulting in crazy pricing and unexpected shortages at some point. Overall inflationary pressure seems more likely until it finally crushes demand. You will absolutely see bullwhip effects throughout the supply chain–look no further than shipping container and truck rates that have bottomed out, as orders are few and far between as retailers have a lot of unpurchased inventory still on hand from the last crack “up” of the bullwhip. And droughts in the US midwest persist, keeping rivers, the main way that the food grown here reaches the international markets especially, at historically low levels. This will severely hamper the ability of the US to alleviate food price and availability pressures, which will continue to be a problem for many places around the world.

But other than that, Mrs. Lincoln, the proverbial play is going fine.

–Your chances of catching coronavirus are equivalent to the chances that we were also cutting the socioeconomic section a little short because we’re still digging out from recent travel…

–Your chances of catching Ebola are equivalent to the chances you will win this weekend’s ridiculously high Powerball jackpot. Twice. With the same ticket.

<Paladin>