Ebola– Thanks to those who sent along this week’s lead news in Ebola. Specifically, sequencing of the virus causing the outbreak in Guinea has traced it to a re-activation of virus in a male survivor of the West Africa outbreak of 2014-2015. The re-activated virus was sexually transmitted by this survivor, and off the new outbreak went.

For what it’s worth, we knew Ebola could do this. I am going to post sections of an email the OGs got from me back in July of 2015 (thanks “sent” folder!). The context is that there was a small re-ignition of the West Africa outbreak shortly after the main outbreak was finally curtailed, and the WHO had buried this little show stopper in the middle of their report:

“Preliminary evidence from genomic sequencing strongly suggests that the most likely origin of transmission is a re-emergence of the virus from a survivor within Liberia.”

So let me clarify my “holy f***” reaction to that:  at best, it means the “all clear” period after Ebola infection is MUCH longer than we currently expect.  At worst, the specific use of “re-activation” raises the possibility that some Ebola survivors have effectively chronic Ebola–which they can transmit -again- when it re-activates.  If they are asymptomatic when this happens, well, you’re basically talking a Typhoid Mary.

Except it’s Ebola Jane.

The only question to ask, and it will be -vitally- important, is how often you get an Ebola Jane in Ebola infections.  “Typhoid Marys”, asymptomatic carriers of the bacteria that cause typhoid fever, are pretty damn rare.  HOPEFULLY, it’s the same for Ebola (and rarity of Ebola Janes is likely–I want to be clear on that).  But you now have so many potential exposures and survivors of Ebola in the current outbreak that at least ONE Ebola Jane already may be running around Liberia.  There could be more.  As much of a social stigma as Ebola survivors in West Africa currently have, it could get a -whole- lot worse… 

...Bona fide endemic disease with significant long term risk of spread to other countries is possible.  Maybe even probable depending on how “chronic” Ebola is, how many people get “chronic” Ebola, and if they have to be symptomatic with reactivation to be infectious to others.

Now, I will say that Ebola Janes do (fortunately) turn out to be vanishingly rare. I did not anticipate a 5-7 year latency period for Ebola to just hang out quietly in a survivor and then re-activate, transmit, and start another outbreak. That’s a long time for a virus to evade detection and eradication. Further, Ebola is a ssRNA virus, and so does NOT (so far as anyone is aware) incorporate into the host DNA. Some viruses can, indeed, do that. HIV, for instance, is a virus that hops back and forth between RNA and DNA and uses an integrase protein to attach its DNA to the DNA of host cells it infects. Once that happens, the cell is a permanent carrier of HIV unless the T-cells figure it out, call the cell “sus” and take it out as we discussed before in the section on how mRNA vaccines will work. There is an entire class of HIV drugs that block the integrase protein for this exact reason. It’s also why HIV persists for life once you have been successfully infected.

Again, though, Ebola does NOT have a DNA phase and does NOT have an integrase that anyone knows about. How it is persisting like this is thus a bit of a mystery, but I think the hint is in how it was transmitted here and some of the long term problems that Ebola survivors in the West Africa outbreak in particular reported.

To make that story short, the most common long term complaint of survivors was trouble with vision, sometimes for months after Ebola. Ebola virus RNA was found in samples from the eyes in these patients. It was also found long term in semen from survivors. That suggests to me that Ebola is pulling this trick off by getting into immunologically privileged sites. That’s a fancy way of saying that certain tissues in your body get scanned a little differently by T-cells. Testes and ovaries are a great example, because a mature egg or sperm is no longer “you”–it has half of your gene content (and usually some mix and matching of your genes) so that the baby is eventually half from Mom and half from Dad. So the T-cells are not quite so quick to call “sus” in these tissues, or they will wind up wiping out all the eggs or sperm and sterilize you! This generally works because testes and ovaries are really hard tissues for things like viruses to even reach to begin with, and only very few are capable of infecting the cells there which are running a different replication program than the virus necessarily wants in order to make and sustain sperm and eggs. Same for your eyes. The inside of your eyes is just a tough place for anything to reach, from viruses to your own T-cells. Hard to get into, and hard to spread from, is not a place a virus really wants to be… except it does mean that the immune system that is kicking your ass everywhere else is not as likely to kick your ass there.

So that’s the trick I think Ebola is playing. The virus is so deadly because in the acute phase it makes SO MUCH VIRUS that by sheer force of numbers in your body it can get places other viruses don’t. It’s also capable of infecting cells in immune privileged sites, at least at a very low level, and clearly can sustain itself there for a long, long time. If enough re-activation occurs, or there is contact with the latent, infected, immunologically privileged site (like sexual transmission), that may be enough to spread Ebola virus again from a survivor.

What does this mean practically?

For coronavirus, don’t read anything into it. No evidence that SARS-CoV-2 hides out like this and re-emerges.

For Ebola, in my humble opinion, this should change the approach in vaccination from ring/carpet bomb and control new outbreak Whac-A-Mole style to smallpox-like eradication with a global vaccination campaign.

I say that with no dog in the Ebola vaccine fight (my employer does not make them; I don’t have a stake in them).

The reason is this. There are still a lot of survivors of the West Africa, and other, outbreaks out there. We don’t know how many of them are Ebola Janes, and under what circumstances the virus will re-emerge and re-infect to start new outbreaks. We do know it has done that twice now. We know that this is a contagious, highly fatal disease until vaccine and treatment can ring and choke off outbreaks. We are getting outbreaks of this virus at increasing velocity as the years go by. You used to go several years, even decades with no outbreaks. We’re starting to get multiple outbreaks per year.

It’s only a matter of time until Ebola hops on an airplane, either in a chronically infected survivor who does not know they are a carrier, or in a patient possibly infected by an Ebola Jane who does not know they have Ebola yet. If you recall from the West Africa outbreak, Ebola that gets to someplace without a lot of experience in what Ebola looks like can lead to misdiagnosis and disaster. West Africa happened because a raging Ebola outbreak was not caught until it was well out of hand (and admittedly before there was a vaccine). But so did Texas. Yeah, remember that? The case that traveled to the US was in a patient with a travel history who presented with only the early flu like symptoms of Ebola. I mean, had the patient had the hemorrhaging to go with the fever and the travel history, it might have been caught. As it was, Ebola is so far down the list of what the average ER doc in Texas faces on a “guy walks in with flu-like symptoms” that they sent the case of Ebola back home.

And that’s the risk. A chronic Ebola patient gets on a plane. There is no current outbreak in the world. They meet someone in a foreign country. Their Ebola has reactivated, and infects someone in the host country–with no known history of travel. They catch Ebola. Their Ebola is not diagnosed quickly enough because there is no history of Ebola in this hypothetical country for it to cross anyone but a zebra chasing hero’s mind. In fact, it’s not until you get a cluster of cases in our hypothetical country, with 40-80% mortality off the drop, that they even know they have a problem. And by then, tracing all the contacts becomes a MUCH greater challenge.

We don’t need to, and probably should not, play Whac-A-Mole with a disease whose mortality is double that of the Black Death. We have a vaccine. We have solid evidence that there exist some number of carriers of this exotic, highly fatal disease. That’s enough to push for universal, vaccinate-the-world efforts like SARS-CoV-2, just to keep last year’s experience from repeating.

With a disease that again, is 40-80% fatal in those who come down with symptoms.

Anyways, counts on active cases in Guinea and the DRC this week are hard to come by. The weekly surveillance report from the WHO in Africa is not loading for me, and it’s my main source of numbers. None of the news reports have anything substantial. Assume both outbreaks are still rolling at simmer–that’s a safe bet for now.

Coronavirus:

–First, in articles I cannot comment on (but you should read the whole way through):

https://www.fiercepharma.com/pharma/lilly-s-solo-antibody-rollout-halted-3-states-over-variant-concerns?mkt_tok=Mjk0LU1RRi0wNTYAAAF75Wz8wwbbsYDfz9TRQpep0A_rYaa4qfrPJ4rENFoMTR11pSzeC2RIp9xVkRZ3t3xLWruz4U6zF5exVuE2UdbGg7_03ytj6S7iJZT25CetCQbR0kQ&mrkid=698583

Thank you for your understanding.

–In other news I am only going to lightly comment on:

The AstraZeneca virus has drawn some fire in certain European countries this past week, with claims of side effects including rare forms of blood clotting. There appears to be a dichotomy right now in the incidence of the reports of these kind of side effects, as countries which have distributed much more of the AZ vaccine have not been seeing these kind of side effects. Countries which have distributed less vaccine have been the ones raising sudden side effect concerns.

I will leave you to make of that what you will.

–Speaking of the AZ vaccine, a group of researchers in South Africa published this week in the NEJM. The AZ vaccine, in a human study this time (not just test tube), did NOT protect against mild to moderate SARS-CoV-2 infection from the variant first identified in South Africa (B.1.351). There were no cases of severe disease (only 42 patients caught SARS-CoV-2 during the entire study period), so no idea what efficacy is in stopping severe disease from this variant.

They also, to their enormous credit, included data on T-cell response. They only had T-cell from 17 patients, all sent from the UK after receiving the full AZ vaccine. Of 87 regions of the SARS-CoV-2 targeted by the T-cells as “sus”, 75 remained “sus” despite the mutations in the variant first identified in South Africa.

This suggests, but does not prove, that there may still be significant T-cell response to SARS-CoV-2, even among the variant of I would say greatest current clinical concern (the South African variant). Further, there is increasing evidence that the T-cell response may be what prevents severe disease, so that’s all good signs.

Overall, expect this to ratchet up some pressure on the mRNA vaccines to get some data on their responses and efficacy in patients who are exposed to the variants of concern, especially the variant first identified in South Africa.

–In possibly unrelated news, many of those same countries in Europe which have lagged in their vaccine distribution efforts (and in fairness, there have been some manufacturing hiccups over there as well), are seeing a significant increase in new cases, and quite possibly the beginning of yet another wave.

All the more reason to avail yourself of a vaccine should one become available to you, and if it is appropriate for your personal medical situation. You should of course use this and any other medication under the supervision of an authorized medical professional and according to its product label. Thank you again for your understanding.

–In the US, cases continue to fall in general. However, the rate of decrease is noticeably slowing, and some places (i.e. Indiana) are looking pretty flat.

If you’ll recall our discussion on CDC models on impact of more contagious variants, this decrease in velocity is right on schedule for two scenarios that differ only by the ability of the variant(s) to get past existing vaccines. If they can, this pause will turn into another wave starting sometime in April. If they cannot, you will remain roughly level in terms of new cases per day through May, and then dwindle to nothing over the next several months. Hence, my recent emphasis on what happens to case numbers in Texas (good so far) and Indiana after the NCAA tournament starting this weekend over the next several weeks. Those -should- be bellweathers for any spike in cases, suggesting the variants are indeed escaping vaccines or previous infection. If that happens, July for the medical end is overly optimistic on my part. But I think based on what we know right now, the latter case is more likely. Pops will be small and not sustained, and as vaccination marches on across the world, the virus will be at the end of the road medically in the US by July.

Politically is another thing entirely : )

–Also a good sign that South Africa cases remain very stable right now. Continues to suggest that reinfection with the variant that was so prevalent in their last wave may not be enough to meaningfully shift the curve.

–Speaking of reinfection risk, data from the Danes this week suggesting that 80% of those previously infected will be immune to subsequent infection. This number is skewed a bit though because those over age 65 are only 50% likely to be immune following their first bout of COVID. Since they are also most at risk for severe disease, that’s not great. This does raise the possibility that the elderly will need boosters earlier and perhaps more frequently.

–Finally, social issues. At least one Indiana school district reports that attendance to virtual classes and online work has dropped at every grade level. On a typical day, 1/4th of its middle school and 1/3rd of its high school students do not show up to virtual classes at all or make up the day’s work. As you might suspect based on that attendance data, 1 in 4 of middle and high school students in this district are, indeed, failing every class.

I doubt this experience is unique.

Unwinding this inadvertent consequence of prolonged lockdown will be challenging. You don’t get time back, after all.

–Other knock on effects. Good read on a financial crisis from a firm that specialized in “supply chain finance” loaning money to large construction companies (among others) based on the value of their accounts receivable.

It may surprise you to know that the slowdown earlier in the year disrupting supply chains especially may have impaired the ability of those loans to be repaid. Since the rest of this firm’s business was pretty much shenanigans (as the article details), this has become a bit of a problem…

–Finally, social issues. If the contemplation of civilization’s possibility for mortality has been on your mind over the past year, one of history’s enduring mysteries is what caused the Bronze Age collapse in the Mediterranean between 1200 B.C. and ~1000 B.C. There’s a good lecture from an expert historian on the period (also wrote a book) on YouTube. This was the sudden decline and disappearance of several empires you have absolutely heard of, ranging from Greeks to the Hittites, to the Canaanites to the Egyptians. All those civilizations in the same region collapsed and went into a dark age at the exact same time.

But say you don’t have the hour in your car to listen to that. Why am I bringing it up? Well, for one, he’ll draw some parallels between a “globally” (since they were the entire world to one another) integrated and specialized economy, where supply disruption from one part of that world dominoed into sudden scarcity of needed goods and equipment elsewhere. You had climate change, with droughts of up to 50 years happening across the region. Significant increases in frequency and likely severity of natural disasters (earthquakes in particular). You had full on migrations, as the invasions of the “Sea People” into all of those empires are, by the archeological evidence, probably dislocations in response to worsening conditions back home. You had rebellions and insurrections as the local institutions, stable for hundreds if not thousands of years at that point, could not cope with the challenges. The historian will even state the only thing missing was a plague, and it’s actually surprising that didn’t happen.

Does all of that history sound like it rhymes a bit?

Yeah, just a touch.

So the historian will make a couple points worth emphasizing. First, when you are in a civilizational collapse period like that, it’s surprisingly hard to know. Just as the fall of the Roman Empire is really a period of hundreds of years, all of these bronze age civilizations collapsed (some cities would NEVER get their previous numbers back) over a period of about a 100 years of so. That’s a short time considering their history to that point, and unexpected given how much inertia, and how inevitable they must have seemed to people living at the time. But as much as we expect to wake up to zombies and the Walking Dead apocalypse one day, true full scale societal collapse is the work of decades if not centuries.

Second, our historian argues that it is not one smoking gun that got them all, but a confluence of serious stresses all coming in waves, one after another. The “perfect storm”, and the institutions that had stood for hundreds to thousands of years could not cope quickly enough (even though the change likely took decades).

But here’s the question I still have. Those empires had been around long enough that they had all been challenged by droughts, wars, earthquakes, migrations, sudden supply chain issues etc. before. Most likely, given how long some of them had been around, they had faced several of those problems simultaneously before as well. We can ask whether it was severity, or just all of those problems arriving at once, rather than say 2 or at most 3 at time before.

But the more interesting question is still why didn’t those same problems collapse them then?

What was the source of their previous resilience to those problems? Those are what you want to build on. You can also then look as to why they failed. Were they just not tried? Had they been weakened somehow? If so, by what (so we don’t make the same mistake again!)? Or was the problem so great that those previously reliable systems no longer worked–in which case, we had better find something better?

Then start looking for parallels to our time.

I mean, if I had to guess, I would say just for effect size a 50 year drought was their most significant problem. Most of their workers were agricultural workers at that point, and they did not have the ability to store, preserve, and transport food they way we do now. We also have more energy as a society (from renewable and non-renewable sources) to power machines that let us control conditions in greenhouses and pump water from one place to another to reduce drought impacts. The average US farmer now feeds 155 other people–around the world. Back then, the average farmer fed just a little more than themselves. 50 years of drought is a big problem for them.

On the flip side, we are now reliant on that abundant energy to maintain our civilization. One farmer feeding 155 others means those 155 others can do all sorts of other cool specialized stuff–that’s how we got an internet, for example. But as we mentioned during supply crunches during pandemic, our fragility is that 155 people are S.O.L. if the truck doesn’t show up at the grocery store a couple weeks in a row. In fact, I would argue the most compelling reason for things like renewable energy and electric cars is that the oil powering modern society took millions of years to form and a little over a hundred years to burn a big chunk of it. Once the oil runs out, one farmer ain’t feeding 155 others no mo’, and we have a problem. Conversion to more sustainable sources of energy while we still have cheap, abundant oil to provide the energy to build the infrastructure for truly sustainable energy at scale is not a bad idea. The worst that could happen is we run out of oil (or more realistically, cheap oil, and all we can get now costs hundreds of dollars to get out of the ground) and then try to build out a sustainable facsimile of our current civilization. Getting people to make the switch while there is still cheap oil around, and everyone is used to it, will be the major challenge.

But here’s the secret, and one of the other points of this rambling discourse here…

If you can net more energy than oil from sustainable sources, that’s the Goldilocks outcome, and humanity’s march continues unabated.

If the total sustainable energy is less than what we currently get from oil, though, that will look over the course of a century, like collapse.

Put another way, if you can feed 155 people per farmer on oil at its current price, but we can only get enough sustainable energy (without major revolution in power production and cost) that the new equilibrium is feeding 110 people per farmer, that standard of living may well look like collapse. Some large number of people will have to go back to farming, reducing the specialization in other goods and services–or you have to reduce total population. Either way, looks like a step back from a golden age as that happens over a century. Now, that new equilibrium will be extremely stable if the energy powering civilization is truly completely sustainable at that level. And over subsequent centuries, will compound technological advancement elsewhere to rival and eventually pass our current “Golden Age”–without the sudden collapse of a society that chose NOT to switch and waited until the oil suddenly ran out or become utterly uneconomical, but there was not enough total power left to build the infrastructure out to replace it.

And one day future historians will be on some future YouTube discussing the “sudden” decline of civilization during the switch from unsustainable to sustainable energy, the brief “Dark Age” as population reduced or more of it went back to agricultural work over a century, and only the next X hundred(s) of years saw it regain its previous high… : )

Your chances of catching Ebola this week are equivalent to the chance you actually watched the Bronze Age collapse YouTube video above.

Your chances of catching coronavirus this week remain equivalent to the chances that only here will you start with Ebola, and somehow wind up with Bronze Age civilization collapse turning into what our future will look like to historians based on how much total sustainable energy we can actually get versus how much total energy we already get from oil. Only here.

<Paladin>