Ebola–

There are two active outbreaks of Ebola now. The one most recently mentioned, Guinea, is now up to at least 17 cases with 7 deaths. The most recent confirmed case was on 28 Feb, and of just under 500 known contacts, all but 3 have been successfully followed up. They have been aggressive with both vaccine and treatment, and so far, none of the cases are reported to be outside of known transmission chains.

The other outbreak is back in Butembo in the Democratic Republic of the Congo. Yes, the DRC again, and yes, that city should also sound familiar. This was part of the DRC outbreak two outbreaks ago. Butembo has about a million people in it, and currently has 8 cases with 4 deaths. The first case of this one back dates to about 4 Feb.

There is no obvious connection between outbreaks, before you ask.

This is either re-activation of the previous outbreak (less likely) or a new outbreak in outbreak-prone DRC (more likely). There are just under 800 known contacts, but of those, only 89% have been successfully followed up and there is a decent slug of those that have never been contacted and may not even known they are a known exposure. The WHO reports “considerable” community resistance to both containment and vaccination, which is par for the course there from the last outbreak. The DRC should have a whole lot of vaccine in country–the question for them, again, is effective distribution and more effective contact tracing.

Coronavirus–

–Trends in the vast majority of the world continue to look very promising. In the US, the rate of decline was slowing late last week. I thought about mentioning that, but wanted to see if the trend held–it did not. Most likely, that was an artifact of delayed reporting during the heavy snow and other adverse weather that smashed a good part of the US during the middle and end of February. The rate of new cases continues to drop, despite variants of concern continuing to be identified around the country. In Indiana, for example, the daily percent of tests positive has not been this low in a year, including the between wave periods of the late spring and late summer.

This is consistent with getting perilously close to herd immunity, although not quite there juuuust yet.

Results vary across the world, with Czechia, for example, starting to plateau a recent wave. And sports, still a good back of the envelope indicator of disease activity, continue to have positive cases forcing game cancellations and postponements. The UFC continues to lose a bout or three per card to positive tests. Even sumo has not been unaffected, as yokozuna Hakuho was unable to participate in the January tournament with a positive test (and symptoms) and the other yokozuna caused some anxiety yesterday with a noticeable cough and cold symptoms during interviews ahead of the March basho.

Hakuho was not hospitalized and largely sailed through, before you go “wait, aren’t sumo wrestlers kind of big, and obesity a major risk factor for severe COVID?” He’s also 35. From what I can gather, he was back in top form during practices in the run up to the March tournament starting soon.

–Turns out most athletes recover well and quickly. JAMA Cardiology has a study out this week of 785 professional athletes, with only around 1% showing any signs of myocarditis as a result of positive COVID testing, and all of that well managed. That said, the “COVID fog” is a real thing for some. One of the rising UFC stars kicked off some headlines this week after an especially distressing practice session, and announced his retirement blaming lingering effects of COVID contracted months ago. He’s Chechen, though, and got a lot of support from their, um, duly elected Head of the Chechen Republic who has generously offered to fly the guy back to Chechnya and get his head right. Our UFC friend has apparently taken him up on the probably not in any way coerced offer.

–Speaking of COVID fog, over the past couple of months there have been some interesting bubbles from autopsy studies in COVID patients. My father once told me that the four most dreaded words in medicine are when the pathologist calls you up and says “What a great case!”

Which, admittedly, is pretty fair. Typically, it’s only a great case to us when something rare, bizarre, rare AND bizarre, or bizarrely rare has happened. The reason that’s dreaded is because often no one has a good clear way to treat whatever happened, and you’ll be off the edge of the map a bit.

Well, SARS-CoV-2 has managed to become a great case. On these autopsy cases, the virus is now associated with something I have never heard of before, and am struggling to come up with a good way of how it’s even happening.

This is the finding:

I’m going to pause here and speak medical to the other docs among our regulars real quick, and then I will try to translate back to the King’s English: So what you’re seeing there is embolization, in brain capillaries, of otherwise normal megakaryocytes. Note this is not extramedullary hematopoiesis, but instead true mobilization of megakaryocytes from the bone marrow followed by (predictable) embolization in distant capillary beds after the megs somehow transmigrated into the circulation. How and why are obviously questions, and I don’t have great answers. But this follows reports of megakaryocytes seen in capillaries in the liver and lungs in previous autopsy studies. To quote from the source article for that image, “Prior to this pandemic, the study neuropathologists (D.W.N. and I.H.S.) had not seen megakaryocytes in brain vessels, and we find no reference to this in the literature.” I’ve never heard of it either. In the case series for the ones in the brain, they have the patient platelet counts over the course of illness, and unlike most COVID patients, there is no associated thrombocytopenia. In fact, they’re all within the reference range during the entire time course. Aside from the mechanistic questions of what the virus is doing to provoke this, either from a signal it is somehow creating, changes it is making to endothelial cells it infects, or something truly special and previously undescribed in the inflammatory reaction to cause transmigration of megs, is the question it raises about the clinical correlation. The assumption has been that “COVID toes” and other vascular misadventures were part of an inflammatory storm leading to a consumptive thrombocytopenia and intravascular coagulation. However, these findings suggest that embolization of megakaryocytes, which is somehow happening, may play at least some role in the vascular symptoms of SARS-CoV-2 infection. Yet, at least in those images above, there is not immediately obvious ischemic changes in the surrounding cortex–although I would not rule ischemic changes further downstream. However, in the supplemental materials, only one case mentions distinct hypoxic-ischemic changes in the brain. So you’re cramming something the size of a normal meg into a capillary–without obvious ischemic change? How is that possible?

Anyways, the nice thing about being a pathologist is I can get my mind blown by that being unexpectedly part of the pathology. What, if anything, to do about it, I have no idea…. I mean, how do you move something the size of a normal megakaryocyte out of the bone marrow vasculature without significant disruption of the endothelium? And if it’s that disrupted, why isn’t there third spacing of fluid everywhere? Very weird.

What a great case!

Alright, why this is weird for those of you that don’t speak medicalese… Look at the top row of pictures in that image up above. See the big purple smear in the middle? That is a giant cell, one of the largest in your body, in a place where it should not be. Specifically, that is a megakaryocyte. As you can guess from “mega” and “cyte”, it’s a big, big cell (“karyo” refers to its nucleus, which is also huge). The place where they ordinarily live is the bone marrow, where camp out next to the many blood vessels running through your bones and do their primary job–making platelets.

Think of a megakaryocyte as the “Snorlax” of the bone marrow–a jovial giant, just hanging out, shedding new platelets into the blood stream.

In an emergency, the immune system will poke the Snorlax/megakaryocyte, which will release MOAR platelets. Think of situations like massive bleeding, where platelets are getting used up fast forming clots, trying to plug holes. The megs will roar to life trying to replace the platelets being used up.

But they don’t move to do that. They just start spraying out more new platelets.

In the rare times when you do see something like a megakaryocyte out of the bone marrow, it’s usually in what we call “extramedullary hematopoiesis”. This is where normal bone marrow cells are out in a different tissue and making new blood cells there. The liver is popular, because this is where some blood cells are made when you were a fetus, and sometimes the cells doing it did not get the memo to stop. But the key there is they are in the tissue, not just in the capillaries in that tissue. Ordinarily, the Snorlax/meg will spend its entire life in the bone marrow, not moving from a spot beside the capillaries it uses to shed platelets.

SARS-CoV-2 is apparently NOT ordinary times though.

Remember those purple smears that we said were megakaryocytes in the first picture up there? And how they look a like super smushed version of the cells with the arrows in the middle picture?

That’s because, and we have no idea -how- or -why-, something the size of a Snorlax is now trying to move through a capillary in the brain in that top picture. Same in the liver and the lungs among other organs where this has been seen. And yeah, it’s going about as well as you would expect moving something the size of 50-100 red blood cells through a tube designed to fit 1 red blood cell at a time.

The point of all this is we had no idea before SARS-CoV-2 that megs could even move through the blood stream like this. Obviously, it’s not a real great idea for them to do that, as they will clog capillaries, which -may- impair blood and oxygen flow. That may be related to the COVID toes and “brain fog” that may be a generalized lower amount of oxygen reaching the brain, but we’re not sure. And simple abnormal blood clotting as you sometimes see when the immune system goes Ah-nold as we’ve discussed before may be the lion’s share of COVID toes (and probably is). The point is that the virus has done what we previously did not know could happen–convince a Snorlax/meg to leave the bone marrow, hop into the blood stream, and then inevitably get stuck in a tube too small to fit it. We don’t know why. We don’t know how. We don’t know what this means for symptoms or duration.

But we do know something is now possible that we didn’t know could happen before–and that’s the start of new scientific discoveries.

–Alright, onto the more practical. JNJ’s vaccine got approved. There is some angst over the lower headline efficacy. I want to be clear–that’s just efficacy in terms of stopping ANY form of COVID (about 66-72% for JNJ’s one shot vaccine). Many of those who did get COVID through the vaccine got only a very mild case that did not result in hospitalization.

Again, the goal is to keep you out of the hospital. Just like the flu vaccine, sometimes the virus breaks through–but the vaccine will generally stop it from being a bad flu, and shorten the duration of symptoms by a bunch.

You are better off getting the JNJ vaccine if that’s what they have the day you show up than being a brand snob and waiting 3 weeks to get one of the mRNA vaccines later.

Also, as we mentioned last week, in fairness to JNJ that efficacy is similar to the efficacy seen with just one shot of the Pfizer mRNA vaccine (no booster).

—Study out this week showing that in people who had caught COVID already, the first shot of the vaccine does indeed act like a booster and antibody levels rocket up to be around the same level as someone who did NOT catch COVID but has had the vaccine and booster. The authors suggest that this may inform a way to stretch vaccine supply, as patients who had PCR confirmed COVID before may ONLY need the one shot for booster-effective protection.

–Onto more social issues, yes, I heard Texas is being all Texas and dropping essentially all precautions. That -may- be a little early. I think end of month if there is no bump in new cases from some of the variants we have been talking about already, and especially if no wave of reinfections, you’ll see some of the more aggressive states really start to drop restrictions on businesses and social distancing. There are rumblings that the CDC will be out with recommendations for the pandemic end game and return to work here soon too. Certainly got a couple of direct questions on when you can start to loosen social distancing on employees, and I know the lawyers will be much happier if they can follow an “official” road map from CDC or other major health body.

Of course, cases in Indianapolis after March Madness wraps here over the next month will be worth watching for trends toward re-ignition.

Regardless, Texas is getting a lot of press because this is definitely on brand for Texas, but I can assure you, Florida has already been doing that in practice for months and just not advertising it.

Because it’s equally on brand that no one will out crazy Florida : )

–Got this NYT opinion piece sent by a reader, and it’s definitely worth a few minutes. Aside from surprise at the source, the reader mentioned how it goes through the damage to institutions, and how very, very few of them have acquitted themselves well through the pandemic, that we have discussed multiple times already: https://www.nytimes.com/2021/02/27/opinion/sunday/trump-cuomo-media-covid.html

–And if you are wondering what the dismal vaccine rollout across Europe mentioned in that piece really looks like, Europe is averaging about 2-3% of their entire population successfully vaccinated so far. Canada around 2% [they like to think they’re European anyways, right? : )].

Meanwhile, proving Churchill’s adage that you can count on America to do the right thing (after it has tried everything else), the US has fully vaccinated what will be 8.5% of its 300 million plus by the time I finish typing this, and has distributed more vaccine than anyone else in the world.

Now before we put up some ‘Murica picture of a bald eagle and a flag to really spike that ball for a healthcare system everyone shits on we should…

…I said before we post a spike the ball Murica picture, the US is not actually the global leader in terms of percentage of population successfully vaccinated so far. Instead, that list is topped by Israel, the UAE, and other obvious candidates like the Cayman Islands, the Seychelles, Gibraltar and Bermuda.

Wait, those last four especially -not- obvious, you say?

Well, they are small and relatively wealthy….

…And ask any accountant you know to just start listing some places with a reputation for banking systems with a certain moral laxity to recording who money coming in is from and where and to whom it might be going.

See if those names turn up.

But maybe the pandemic is just making me cynical. After all, Bermuda has made great strides on money laundering through its banks and registered corporations. And they might just be really well run. They’ll make interesting case studies for the who and how they have leapt out to such sizeable percentage of population vaccinated leads so far no matter what the answer really is.

–US state leading the charge in terms of percent of population successfully vaccinated?

Yep, you guessed it.

West, by God, Virginia at 18%.

American Samoa, Alaska, and North and South Dakota are not far behind though…

Your chances of catching Ebola this week are equivalent to the chances you knew there were two active yokozuna.

Your chances of catching coronavirus this week is equivalent to the chance you knew the other active yokozuna is named Kakuryu, even though I didn’t name him above, and that they are both originally from Mongolia.

<Paladin>