Flu

–We’ll start here since it’s short, and mostly in case you saw headlines about bird flu jumping over. So the reason eggs are so expensive everywhere is because a H5N1 flu that is brutally infective (and deadly) to birds has over the past year or two cut an enormous swath through flocks of chickens. This includes culls of exposed birds to prevent additional spread.

The headlines include an isolated case jumping to humans in Asia in someone working frequently with chickens. One offs like this happen to those who work a lot with birds and other farm animals, and as far as I know, the patient is fine. The real worry is if it goes person to person from there. Other headlines include a recent jump over to infect minks. The threat there is that it’s a sign the virus is sustainably transmitting in mammals.

The headlines are not entirely alarmist. As I have said many times before in these updates, it’s flu that fills me with pandemic dread more than any other pathogen typically mentioned. Bird flu certainly looks to be gearing up for a sustained jump to humans. Several of the last pandemic flus were avian flus that made the leap, and there are genetic reasons to suspect that the big one, the 1918 flu, was also avian derived. Recent avian flu epidemics have shown above average mortality (although rates are inflated, as later antibody testing suggested many more mild or nonsymptomatic cases occurred), and were better in general at getting to young and healthy and kiddos. I do think signs are slowly pointing to “when” we have a nasty avian flu based season versus “if.” Chances that it’s a pandemic kind of flu are never great, and it’s more likely than not you’ll just have an above average nasty flu season.

“Didn’t the 1918 flu get nasty because it spread among wounded soldiers and thus got selected for ability to spread rapidly among the young and healthy?” I hear you ask Hypothetical Reader Who Read That Mention In A Prior Update And Remembers.

Yes. So yes, I do see your eyes drift to a map of Ukraine-Russia, particularly as that has slogged down into trench warfare over the mud season. Not the ideal setting, and I realize history rhymes, but wars were an all the time thing somewhere in the world over the 20th century, and it took the end of a BIG war with MASSIVE casualties because full frontal infantry assaults of massed bayonet charges into entrenched machine guns and pre-sighted artillery took WW1 to figure out those are terrible, terrible ideas.

Odds will remain more likely than not that a breakout avian flu will just be a rough flu season, and not full blown pandemic, but geopolitical events and the continued socioeconomic fallout ripples over this decade do shift a few percentages here and there.

Plus, unlike in 1918, we can vaccinate flu and yes, we have acute treatments for flu.

This part risks sounding gloom and doomy, or scare headline-y, so I want to stress that NONE of the challenges I am about to mention are insurmountable. But they are not being mentioned in the lay reporting, and I think it fair you know about some of them ahead of time.

Again, do NOT worry about flu until it is time to worry about flu. Now is NOT the time, and again, the most likely “bad” outcome is just a bad flu season from an avian based strain in the next few seasons. And nothing worse.

There are some challenges unique to avian flu though. First, the “H” and “N” in a flu’s name refer to the parts of the flu your immune system makes antibodies to. They’re like the spike proteins of COVID, just not blamed for every medical malady known to man (especially in vaccine form, apparently, per the internets), including Jumping Frenchmen of Maine Syndrome like COVID spike protein has been.

Yes, that’s a historic thing, and it’s still debated if there is a biologic or merely psychosocial cause of the reports of Jumping Frenchmen of Maine Syndrome.

To return to the point, the “H” and “N” on recent avian flus have not been as good at triggering an antibody response. For example, they have taken a sort of “pre-emptive” vaccine of avian “H” and “N” into clinical studies, to see if they could at least increase a baseline resistance. However, the antibody response was not particularly impressive. The typical flu vaccine is based on a best guess of the season’s likely most common “H”s and “N”s based on what starts circulating in Asia this spring and summer. Before you ask if it can be made on the fly, the answer is no, as large scale manufacture of flu vaccines still requires the flu virus be grown in eggs (don’t ask–that’s a longer explanation. Just accept that’s why they ask you about egg allergies on your flu vaccine).

If eggs are already expensive and in short supply because the avian flu has already stomped chicken populations, you can see the emerging challenge. On top of that, avian flus tend to bad things to eggs, because the virus is more likely to infect the egg itself.

Yes, before you ask, they are trying some of the newer vaccine technologies from the COVID vaccines including adenoviral vectors and yes, mRNA vaccines. These are going the traditional vaccine testing development route currently. Results in animal models have been promising for the mRNA vaccines in particular.

Will that matter if a pandemic happens in the next few years and the fastest way to roll out effective vaccination is a mRNA vaccine? My guess is “no.” Thanks, COVID, for a historically catastrophic public vaccination campaign!

But we can still treat acute cases of flu, right?

We can! Probably! The mainstay of treatment are the neuraminidase inhibitors, of which Tamiflu is the one you have likely heard of. In a prior outbreak of H5N1 flu specifically, getting Tamiflu on board within 6-8 days of symptoms had a 49% reduction in mortality. However, other pandemic potential avian flu combinations of “H” and “N” were not so lucky, as treating an H7N9 version with Tamiflu had no benefit on mortality. You may be old enough to remember the “swine flu” epidemic of 2009. Using Tamiflu and similar treatments to slow spread was NOT particularly successful in the US and UK, while early detection with rapid diagnostic tests, prophylactic use of antivirals for close contacts of positive patients, and rapid, often empiric treatment of hospitalized patients in Japan was more successful.

I am equally cynical that even if the lessons learned from the swine flu experience are employed, they will “stick”, considering rapid diagnostic COVID tests used to be the cool thing for the internet to complain about, and getting the COVID antivirals on board even in high risk patients continues to be a surprising challenge based on readers who have contacted me after coming down with acute COVID.

There are also resistance mutations to these drugs that are known–fortunately, they have been not particularly common in most seasonal flus, and hopefully would not show up in a pandemic flu. However, similar to selection pressure for variants that can get around a vaccine, in a bona fide pandemic, we should expect eventual resistance to the existing flu anti-viral medications.

I do want to re-iterate that avian flus, including H5N1, have been threatening a “break out” for over a decade, and even if one occurs, the most likely outcome is still just a bad flu season. But I also want to mention that some of the “concern” headlines are not entirely out of place, and you should keep a bit of an eye on an rumblings about an especially nasty flu seeming to pop up somewhere in the world. Just in case.

Coronavirus

–Yes, I too, saw that the US government plans on formally ending the national and public health emergency due to COVID.

–But a few points of interest for this update. First, we heard from some readers about a case of new onset pulmonary embolism (clots spreading to the lungs), which can be life-threatening and very nearly was, in a healthy, active young patient. Even on the young side for some the genetic things that can associate with this, but those are all now, obviously, being tested for to try and rule them out. If they do, the question arose whether this could be COVID related. The patient had COVID (not severe, not even close–the patient has no risk factors whatsoever) a few months ago though. However, we do know that acute COVID infection is a hypercoaguable state. COVID does directly infect endothelial cells lining your blood vessels, and that damage can make your blood a little more likely to clot. Also, the sharp immune reaction COVID triggers can predispose clotting. Yes, the internets are probably right blaming spike protein for that sharp immune reaction, and there are some clotting abnormalities that definitely affected the adenoviral vector vaccines, and there are some reports with the mRNA vaccines, but no hard data that it’s a significantly elevated risk.

Clotting events like this have not been as common with the omicron cousins, and certainly it’s been awhile since I have heard about “COVID toes”, the probable microcirculation clots in fingers and toes that some patients saw who caught original COVID or the more serious variants.

But could a mild COVID infection several months ago really contribute to, if not outright cause, a pulmonary embolism months later?

Turns out, maybe it can. Really interesting cohort study here that looked at basically all of Sweden’s COVID cases and the risk of serious blood clots after COVID infection, and by time from COVID infection, including deep venous thrombosis and pulmonary embolism. The long story short is that the risk of pulmonary embolism in patients after acute COVID is eye poppingly higher than matched controls who did not catch COVID among nearly 5 million patients reviewed in this study. We’re talking a more than 20-fold chance within 30 days, and it stays 2.5 times more common out to 90 days, not drawing equal until around 100-110 days.

Keep in mind that is a relative risk of a still rare event. There was less than 0.01% of the population overall, COVID or not, who had a PE.

Unsurprisingly, the risk of PE was higher with the earlier, more aggressive variants AND more likely the more severe the acute COVID was. However, even mild cases of COVID had a 6.5 fold greater chance of throwing a PE after COVID than age and underlying condition matched controls that had NOT caught COVID by then.

So other causes of clotting risks need to be ruled out in our young champion, for sure, but if no other reason can be found, COVID associated is at least still plausible.

–I’m just as surprised at the duration of that risk as you.

–That said, maybe we shouldn’t be. There was a VA study published about a year ago looking at 1 year incidence of cardiac outcomes, ranging from heart attack to myocarditis to yes, some clotting events, staring the count more than 30 days after COVID infection. This also looked at basically ALL the VA data, with a post-COVID cohort of 153,760 patients matched to 5.6 million COVID years controls and 5.8 million historic controls. So a GIANT cohort control study. Long story short, all cardiac outcomes are found at an elevated risk more than month after COVID, and stay a little higher over at least a year in those who have recovered from recent COVID infection. Again, more severe is greater chance, but mild cases saw mildly increased risks of all the things like heart attack, clots, myocarditis etc. The overall increase in pulmonary embolism risk in even mild cases was similar to the Sweden data–more smoke to suggest a fire there. Myocarditis risk, in particular, was sharp, with a nearly 10 fold increase overall in COVID patients. Again, FROM THE VIRUS, not the vaccine–I know there are parts of the internet that still need to hear that. In fact, in this study, they controlled for possible vaccine effects first by dropping patients from cardiovascular outcome analysis at the date of first vaccination (so vaccination couldn’t confound as a possible cause) and then a second analysis using vaccination date as a variable. In BOTH analyses, the risk from the virus itself, for myocarditis and all other heart health outcomes, exceeded that of the vaccine.

They did not control for virus strain like Sweden did though, but I think it’s safe to make some educated guesses.

Also, I want to stress this is all still elevated risk of what were still quite rare events.

The way to think about it is like buying 10 tickets for the Powerball drawing instead of just 1. The chances that any of those 10 hit is still really, really small, and will almost certainly not happen to you–but you do have 10 times better chances of hitting the Powerball.

–I do want to stress from these though that the duration of these elevated risks of really bad cardiovascular things, even from mild COVID is -shocking-. Certainly something to keep in mind, and maybe keep a lower threshold to check in with a doctor with any signs of these things for longer than you might think after a recent rumble with COVID.

–The VA study shows that vaccination may reduce the risks of these by reducing chance of severe COVID, but I don’t think anyone knows what it does for risks or duration from mild cases overall. I also don’t think anyone knows how these risks or duration are modified by the acute COVID treatments, other than some likely reduction by making your COVID less severe.

–Keep those points in mind about duration of some of these serious health risks and even after mild cases of COVID. There continues to be some chatter trying, in various degrees of desperation, to attach causation to correlation between overall mortality statistics and vaccination start dates. Just for illustration of the error that is common in all of these articles (typically with some snark about “following the science”), we’ll take the following from an update on a whistleblower letter from four US Department of Defense personnel, including a flight surgeon, regarding a big increase in all cause morbidity and mortality found among military pilots in defense medical databases. The data in question are summarized here:

There is indeed a big jump in all cause morbidity and mortality reported. To be clear, that includes increases in everything ranging from anxiety to HIV to accidents. It’s literally all cause. The whistleblower argument has basically been that you see a ten-fold plus increase in all cause reports during the pandemic years, and tried to correlate this to introduction of the COVID vaccines, which were mandated for this patient population.

But I am sure you, astute readers, have noticed what immediately jumped out to me–when that jump first took place. The ten-fold leap started in 2020, and thus before the vaccines were widely available. The whistleblowers were quoted as anticipating this obvious objection by Epoch Times, stating “Some would ask why the numbers start increasing in 2020, you have to remember the Pfizer/DOD study with 43,448 participants started on July 27, 2020.”

Well, okay, I’ll keep that in mind, but I cannot find a study of the Pfizer vaccine that was expressly limited to DOD personnel. Plus, the DMED data is for pilots, as far as I can tell. From what I can find on Google, there are only 21,000 of those in the Air Force. Maybe half again for fighter pilots in the Navy and Marines, and then helicopter pilots in all the branches? Even if they study the whistleblowers mentioned enrolled only military members, it would need to have enrolled all the pilots, plus more military members.

Pretty sure that “only pilots” clinical study didn’t happen?

The study I can find from that time period that wound up enrolling exactly 43,448 participants was the original, main safety and efficacy study. This was split almost 50:50 vaccine to placebo (you can find the original report here), and enrolled from 168 sites world wide–not just DOD as the whistleblower explanation seems to intimate. So even if we assume that all 20,000ish patients in that study who actually got vaccine (and not placebo) were all military pilots, the 2000+ events in just 5 months of 2020 would be a STRONG safety signal that should have been noticed at the time. Wasn’t seen. In fact, those patients in the actual study were all followed for two year safety signals, and you can find analysis of those plus re-analysis of original safety signals here.

(If you want the TL;DR of that revised safety analysis, they calculate that risks of some form of severe adverse event with the vaccines may be higher than the risk of COVID hospitalization they prevent, although severe COVID effects may be more disastrous than come of the adverse events. In short, they call for a risk:benefit re-analysis of the vaccines in their discussion, ideally with patient level data from these studies, because it’s tough to discern which patient populations are at particular risk for some of these events. Unstated is that as the hospitalization rate falls with less severe variants, the adverse event rate that is seen from the original studies looms larger, and should part of a broader discussion of risk:benefit to vaccinating a less severe disease–which, per the above, may still have some long term risks of rare coag and cardiovascular events. Whole situation remains a little messy, frankly. There may also be a coagulation signal in the Pfizer vaccine, but I kind of doubt it, because they did not correct for multiple analyses [I think the finding becomes not statistically significant if you do] and there is no good reason that should NOT be a class effect and seen in Moderna considering the interchangeability of the two mRNA vaccines.)

It is unlikely that the ten fold increase in adverse events between 2019 and 2020, in a year where COVID itself was spreading among this same population, is entirely attributable to the vaccine. The timing just doesn’t work, and there was way more exposure to SARS-CoV-2 itself than the vaccine for the pilots in question–unless they made up pretty much the entire study arm of the one study enrolling patients then. And looking at the age and gender breakdown between the study and placebo arms, I haz my doubts that the study arm was entirely made up of Air Force pilots. This also assumes you even believe that COVID had a major impact on the accidents and HIV infections that this data also captures. Even in the subsequent years where more of this population was vaccinated, the jumps generally correspond equally well to the larger waves of COVID itself. This data does not control for date of vaccination OR date of COVID infection, since we know from the sections just above this that some long COVID risks, while rare, are real. To attribute these increases to the vaccine, solely, is a HUGE stretch. Especially is you are simply pointing at a rise in numbers and saying, “well, vaccines were starting in these years too” without getting more granular on at least date of vaccination AND COVID infection history, severity, and time from symptoms

This confounding variable, that COVID itself was also spreading, and quite significantly, during these years plagues all of these “gotcha'” kind of epidemiology claims based on broad, all cause mortality and morbidity data. Correlation is not causation, and in addition to risks of COVID, there were definitely knock on effects from the social reaction to the pandemic, such as lockdowns and swamped healthcare systems, plus the general malaise of these years that is likely contributing to the all cause numbers.

–What the persistence of these articles speak to, as well as continued Project Veritas’ rumblings over their questionable Pfizer “scoop”, is an emotional state. Some of the outlets are really mind bending, because the vaccine doesn’t actually work to stop COVID, which wasn’t that severe anyways, but somehow the vaccine which doesn’t work is really far more dangerous and capable of causing a huge array of symptoms long, long after vaccination and boosting are complete.

In fairness, I think a lot of this is reactionary to the lecturing tone that the disastrous vaccine rollout used, coupled with all of the very provable mis-statements and obfuscations made by the major institutional spokespeople of the pandemic. We suggested a better approach to vaccine rollout at the time, not based on the tribalism that utterly failed and has now left us with something like 35% of parents surveyed opposing any mandatory vaccinations for schools, last I saw. That was not the road taken though. Time and again. Instead, we get a long, long list published by the WSJ in the last week of all the institutional bonfire of credibilities committed during the pandemic sent to us by a reader with a simple comment of “yep” (we’ll add another here, just since our last update).

I don’t, as a rule, watch “State of the Union” addresses. I am weary of the game of “stand up and clap or boo” for your tribal cheer lines, and my understanding is that was last night’s speech, with the D team president taking jabs at the R team, and the R team being rude and interrupting. Much politic. Such entertainment.

The breathless spectacle of it all is meant to engage emotions, reinforced by all the clapping and booing and hawt takes. More recently even including an “opposition response” speech too, which I’m pretty sure never happened when ol’ George Washington was doing these, or when TJ was just sending a letter to Congress. But when we televise, and live chat, and meme -two- speeches, well, the cynic in me suggests one “benefit” is that both tribes get a highly visible chance to present and cheer their applause lines, and boo the disapproval lines, and the crowd gets to watch the crowd the whole time, so the appropriate common knowledge is transmitted.

Hevel. All of it. Hevel.

Regardless, I heard, and trust to be true, that the government patted itself on the back and declared the success of all its efforts in the COVID pandemic. That is…well… sad and predictable and predictably sad. But appearance of effectiveness is just as good, right? Would only that they had even appeared to be effective. After all, if this is “victory,” it is pyrrhic. Just look at how persistent and vocal vaccine skepticism is, while at the same time vaccine maximalism is persistent and vocal, despite a clearly shifting risk:benefit ratio. With strong, emotional, and tribal affiliation undertones to both of those positions.

Again, if H5N1 or another avian flu makes a bona fide pandemic leap, God help us all, thanks to the “victory” of public health measures against COVID. I don’t see how the global society survives if that happens within the next few years.

Indeed, seeing raw, petty, unproductive tribalism on display in the US government, especially at a State of the Union Address, you understand why aliens are turning to strippers in Vegas–just for someone serious to talk with.

–Before you feel completely Ecclesiastes though, we did get some good anecdotes back after the last update, and have seen for ourselves, green shoots of greater connection and understanding between each other among the generation behind us.

Seneca the Younger once said we do not choose our parents, but we can choose whose children we will be. Put another way, we all follow the example of our parents–either as example of right action, or example of mistakes not to be repeated. (this is a theme a Ramble may well return to, come to think of it…)

If the kids are looking at the zeitgeist, at the measures of growing distrust and feeling of unbridgeable divide, and actively doing the opposite, they are making the right choice, and we should encourage that. The great advantage of youth is time, and there is, in this moment, opportunity for them. Before the machine turns its ravenous eyes to them and their preferred channels of communication, set to unleash its pursuing demons of narrative and schismogenesis among them. Act now, and perhaps the best minds of their generation will avoid madness, starvation and hysteria. The kids may just be alright.

Fungus

–So with “The Last of Us” kicking off on HBO, it was easy articles for reporters on deadlines to ask “what if” about the premise of the show. For those unfamiliar, it’s based on a very successful video game franchise, set in a “zombie apocalypse” world where the “zombies” are all the result of a pandemic fungal infection. I was all set to do a small section covering the science behind the science fiction on it, but then Esquire went and did a great interview with a mycologist from West Virginia that covers all my main points. So I will take the lazy way out and just link you here for a quick read if you are interested on the likelihood of a fungal pandemic, let alone a fungal based zombie apocalypse.

My only add is where he talks about ergot poisoning in flour, especially rye flour, it’s not just the Salem Witch Trials that have a historic link. There is good reason to believe other outbreaks of odd behavior, like St. Vitus’ Dance, in the Middle Ages were due to ergot poisoning of flour stocks to say nothing of the thousands of deaths attributed to St. Anthony’s Fire, another presentation of ergotism.

–Somewhere in Washington DC, the Chinese ambassador is settled into a chair in the office of the National Security Advisor to the President of the United States to discuss the recent, quite public, diplomatic kerfluffle over lost equipment.

National Security Advisor: “We have ascertained the balloon’s final position, but given the depth of the water, and the fact that the wreckage is spread out over such a wide area, be some time before anything is recovered. However, your people are interviewing the meteorologists now, and making arrangements for the return of their…weather…equipment.”

This has been a terrible tragedy, Mr. Ambassador, and I can only stress that if you had come to us earlier, it might have been avoided.”

Chinese Ambassador: “I appreciate your candor in the matter.”

National Security Advisor: “And I, yours, Qin Gang.”

The National Security Advisor takes advantage of the awkward pause to grab a candy from a dish on his desk.

Chinese Ambassador: “Perhaps in the future the technology will be available for a more thorough investigation of the wreckage.”

National Security Advisor: “Perhaps.”

Chinese Ambassador: “There is another matter, one that I am reluctant to…”

National Security Advisor: “Please,” while gesturing that the ambassador should continue, sensitive to the expressed reluctance.

Chinese Ambassador: “One of our weather balloons was last reported in the area of South and Central America. We have not received data from it for… some time.”

Long, awkward pause….

Your chances of catching coronavirus are equivalent to the chances that China really needs to improve on retention of its meteorological devices. Lest others grow suspicious.

(Final note on the “why wait to shoot it down” question that was hot all this past week–I’m not in intelligence, nor have I worked for intelligence before. However, -if- I had a way to jam transmission from the balloon, I -might- be curious to follow its entire intended path, just to see what areas Chinese meteorologists thought would be most informative about US….weather. I think I could probably learn useful things from that. Then I might try take it down in shallow water (so its electronics had a fighting chance versus 60,000+ feet into solid ground) to see what measurements of US weather they might have been taking based on the pieces found, or who made them and might know what they were used for. To be helpful in reassembling the parts while returning the damaged balloon back to China, of course. Coupled with where they were looking, I might be able to learn something about what they know, or think they know, or want to know, about US weather. I would probably also make some calls to NASA, because I am willing to bet the guys and gals that can put shit on Mars and jury rigged that Apollo 13 air filter on the fly can probably come up with a creative way to drag the next errant weather balloon gently back to Earth. So we can return it to China -intact- next time. After all, they seem to be having such difficulty keeping their balloons on the intended weather research path, and recovering these stray balloons for themselves…)

<Paladin>