–Yes, we have added bubonic plague to the update too.  Over the weekend, Chinese media reported at least one confirmed case, a farmer in a region that borders Mongolia, and as of Monday, it appears there is another case in a teenager that ate marmot meat.

Again, and I cannot stress this enough folks, DO NOT TOUCH DEAD MARMOTS.

Yeah, those.  NEVER TOUCH THOSE WHEN THEY ARE DEAD. 

NEVER.

So this is also a reminder that Yersinia pestis, the bacteria that causes bubonic plague (aka The Black Death), is still very much around.  And very much endemic several places in the world.  Mongolia and those marmots in the picture there were the original spring board for the Black Death (if you remember that comparison in a previous update).  Y. pestis is still very much endemic in the region, and yes, centuries later, still gets carried by those very same marmots.  Madagascar, which had an unusual cluster not too long ago that we updated on, also has endemic plague.

And so does Colorado, believe it or not.  Yes, above a certain elevation in the American west, Y. pestis lives in prairie dogs, rats and other rodents.  If you visit the Rockies, DO NOT TOUCH DEAD RODENTS.  The US gets a few cases per year of bubonic plague, and some of them occasionally die, since the bubonic plauge is not recognized for what it is in time, since it’s so rare and not always suspected quickly enough.

The good news, despite the whole “Black Death” thing, is that Y. pestis is a bacteria.  One that is VERY responsive to modern antibiotic treatments.  If caught in time, bubonic plague is very treatable.  As a result, this current outbreak (which would not be especially newsworthy in that region, but for the global pandemic getting everyone hyper focused on exotic infectious disease) is likely to be contained quickly.

–Ebola:  Now up to 38 confirmed cases, and now with 3,596 contacts being followed.  Of those contacts, only 79% have been vaccinated thus far.  Contact tracing has gotten much worse though, and is inadequate for a ring vaccination strategy to be effective.  They need to tighten that up fast, or move quickly (quicker than they did across the country in that outbreak) to a “carpet bombing” vaccination strategy, or this will continue to climb an exponential curve.  The WHO is no longer reporting on the number of rings being vaccinated, so hopefully, the absence of that in the update suggests this strategy change is underway.  So far, the virus remains geographically restricted and away from the megacities downstream on the Congo river.  So far.  Two cases have been caught at traveller screening sites in the past week though. 

Coronavirus — Here we go again.

–Latest scare headline are reports of neurological complications associated with SARS-CoV-2 infection, of course provided with absolutely no context whatsoever, but make it sound as bad as they possibly can.  This all comes from a case series of 43 patients in the UK.  Of those, only 29 were actually proven positive for SARS-CoV-2.  The rest are merely suspected, but included anyways.  But in fairness, the virus need not be active for the symptoms described to present.  So a multitude of neuro symptoms appeared in these patients, running the gamut from Guillen-Barre syndrome to what was called in the lay news report I saw “psychosis.”  Now, most of you read “psychosis” and you think something like this:

“Psycho killer”, right?

And I assure you the news “reporter” writing the piece knows you think that too.  What the authors of the actual study meant was the definition of psychosis that I have in my medical textbooks.  In this case, auditory and visual hallucination +/- delirium (i.e. not knowing who or where they were).  Yep.  They saw and heard some things that weren’t there.  Not -quite- that picture above. 10 of these patients had these symptoms (not clear how many were proven SARS-CoV-2 positives, but I don’t have access to the full paper).  What the lay articles don’t mention is that as the scientific article went to print, 9 of the 10 had already recovered from “psychosis” or were well on their way–with no other treatment.  Odd detail to leave out, but maybe there was a word limit on the news write ups on this?

Anyways, the most common symptoms overall fit the category of acute disseminated encephalomyelitis, or ADEM.  That’s a fancy way of saying “the immune system is attacking the ‘insulation’ of the ‘wires’ of the central nervous system.”  It’s pretty similar to multiple sclerosis in that regard.  Think of it as Ah-nold and the commandos nuking an acre of myelin sheaths (the brain wire insulation) all over the brain.  The majority of cases of ADEM following a bacterial or viral infection.  Most of the time, the specific agent isn’t even identified.  You were sick with flu/bacterial thing, and then an average of 26 days later, you have some limbs and digits that randomly don’t work right.  Or your hearing goes suddenly–in one or both ears.  Or your eyes don’t move in one direction suddenly.

It’s actually more common in kids, but is still very, very rare.  The guys writing this paper are dedicated neurologists, where all of these cases are sent.  They see about one case a month–with COVID, they are up to one case a week.  Remember, though, there has been a lot of SARS-CoV-2 infections.  Like, a lot.  Again, they have 43 patients in this series, and only 29 of them with lab confirmed virus.

This is not, by any stretch of the imagination, a common complication, even of SARS-CoV-2.  Indeed, some or all of the other 14 cases without confirmed SARS-CoV-2 might have been caused by other viruses/bacteria entirely.

That said, there was a higher incidence than normal of so-called “hemorrhagic” ADEM among the cases broadly fitting this description (5 cases total with hemorrhage).  This is usually seen in association with severe headache, neck stiffness, and seizures on top of the other sudden neuro oddities of classic ADEM.  The “hemorrhagic” part comes from MRI of the brain, showing small, stroke-like hemorrhages along with ADEM.  Coma is pretty common with this.  If these are the SARS-CoV-2 positives (again, what I can get from the actual scientific report doesn’t say), that would be more evidence that Ah-nold is a little more likely to nuke blood vessels with this virus, as we have previously discussed.  

Now, in fairness, both forms of ADEM are a big deal, as the symptoms make them sound.  They are also both very rare.  At least in terms of total number of SARS-CoV-2 infections, also seems pretty rare too.  Mortality is about 4-12%; 1 in 3 will have some degree of permanent loss of function.  But, it typically responds very well to steroids (just like the Kawasaki-like syndrome in kids, and as reports keep mentioning in hospitalized patients in general).

In fact, by the time the scientific report was hitting publication, 1 of the 12 had died, 1 had recovered fully, and the other 10 were on their way with steroids +/- intravenous immunoglobulin (IVIG, also used to treat Kawasaki and Kawasaki-like).  That, too, was oddly left out of the news reports on this article.  Word count must just be brutal.

Next most common symptoms in the actual scientific paper were strokes.  Again, I would like to know how many were SARS-CoV-2 positive for sure (we’re not told)–some could just be people with coincidental strokes.  But again, suggests immune attack on blood vessels is a real possibility as a significant portion of the threat of SARS-CoV-2 to the individual patient. 

And lastly, you had some patients with Guillain-Barre syndrome.  This, too, can follow any number of infections (again, usually weeks later), and even rarely with vaccines.  In this case, Ah-nold and the commandos attack the insulation of the peripheral nervous system, causing a characteristic ascending paralysis.  This, too, responds to drugs that settle the immune system down.  Because Guillain-Barre can eventually interfere with muscles responsible for breathing, patients not infrequently wind up on a vent for a little bit.  Even so, the vast majority recover.  In this paper, 6 of 8 were already well on their way to recovery by the time it went to print.  That, too, apparently got sacrificed to the word count.

Funny how, in all the news reports on this I saw, they had all this space to describe the symptoms of all these patients, in as frightening a tone as possible, but didn’t mention that most were recovering or had already recovered.

Interesting editorial choice.

–Epidemiology.  Cases worldwide continue to climb, as select countries, most of Africa, and most of South America march up the first wave.  In the US, unfortunately, more and more states appear to be seeing at least a flatline in the number of new cases, or an outright increase.  Ohio, for example, now has a clear second peak.  Which means Indiana is probably not far behind, given the economic links between the two states.  The virus came in on the interstates; it will return to flare on the interstates.  The next two weeks will be critical for Indiana, but you can already see the start of lift off in our numbers.

Now, within each state, that will manifest as pockets of outbreak, probably depending on how much penetration into a particular county, town and city there was before the broad lock down.  States like California, Texas, Arizona and Florida have already taken additional measures like closing bars, gyms and beaches again.  That has been at the state level, and I suspect that state level measures will dominate.  A nationwide lock down is not in the cards (just look at all the Californians who told Governor Newsome to stuff it, and fired off fireworks anyways). 

And frankly, I am sure you have seen what I have too–there is mixed adherence to social distancing measures.  As states re-opened, people got back out, and traveled, there was a tendency to believe the threat had largely passed.  Sure, you social distance at home, but you’re at the beach on vacation.  Come on, do you really need that mask on vacation?

Memorial Day and protests (some of which are still on going) didn’t help, putting a little more active disease around.  I doubt the 4th of July did either.

–A part of that, at least in the US, is still because we are testing more cases, and many of these new positives don’t need the hospital.  In fact, avoid the temptation to compare to other countries, where testing is less available (either because they don’t have enough machines and medical labs or have stricter rules around who qualifies to be tested).  We were fighting with the army we had in March/April.  Just like every WW the US fights though, the Army you start with is not the Army you end with.  There is way more testing, and more being added, every day.

But that doesn’t explain away the current increase, especially as it creeps into more and more states (likely as people return from vacations etc.)

The positivity rate nationally continues to creep up (now around 8%).  Your LOCAL rate may vary significantly.  New England has an extremely low positivity rate.  Florida is setting records right now. 

Deaths are still low in the US, and have been even through the early phases of the CA/AZ/TX/FL breakout.  BUT deaths are a lagging indicator.  The sheer number of cases is starting to overwhelm ICUs locally in Arizona, Texas and Florida.  The overall US death rate crept up a bit this week, but is still not as high as the March/April time frame.  However, that again, is very local.  New England’s deaths are tiny.  Most affected states are creeping up more, particularly as ICUs fill.

I would give it another couple weeks, but a march of the death rate back to the highs of March/April seems less likely at the moment.  There is still good reason to suspect that the majority of these new cases are less severe disease in general.  There’s just a LOT of them right now.

That said, you still have the very real risk of an all cause mortality spike in those areas where ICUs are full.  Again, the biggest threat of the virus is overwhelming local healthcare systems like this, and ‘bed’s taken’ because a COVID patient is in it starts to weigh on all the other medical conditions that might require an ICU.

–So now the big epidemiology question, and it relates to a question I got from a reader this week about the % of the population that needs to be immune to halt the virus.  The magic number floating around out there is 60-70% of the population needs to be immune, either through prior exposure, natural resistance, or vaccination, for herd immunity to be reached.  At least in terms of keeping the number of cases that SARS-CoV-2 sends to the hospital from overwhelming the system.  That number is ?probably? accurate.  People better at calculating that than me came up with it, although I would ball park 50-70%, as starting around 50%, the virus is going to have a considerably harder time mounting a meaningful outbreak. 

So if a national re-lockdown is difficult to impossible, and even state/county/city measures will have scattered adherence and enforcement, how close are we to herd immunity?  That’s the big question.

Right now, the US is sitting on 3.1 million confirmed cases (~1% of the population).  Looks bad.  But that’s only confirmed.  Not everyone gets symptoms to know to get tested.  Not everyone is sick enough to choose to get tested.  Not everyone got sick when enough tests were available.  I have heard from people on this and the broader mailing list about symptoms they -had- that were suspicious, but were only in retrospect.  They got better–never got tested when a test would have been able to confirm COVID.

Go back to the ILI paper in Scientific American from just a couple coronavirus updates ago.  They make a pretty good argument that by March 28th, about 8.3% of everyone in New York had been exposed.  They cite antibody testing done in New York that suggests 14% of all New York had been exposed by April 23rd.  Even if that was an inaccurate antibody test (no idea which one was used or how accurate it is), that may still be close, because as we have mentioned, not everyone exposed seems to make detectable antibodies, but may still be immune.  So for the back of the envelope, we will accept these figures as true.  Thus, in an area with -rapidly- spreading coronavirus, despite heavier lockdown than now, about 1.5% of the population was getting infected, on average per week.

This despite the fact that on April 23rd, same cited study, only 0.3% of the population had been confirmed positive by PCR.  Remember, though, that PCR only detects ACTIVE infection, while the virus is there.  Antibodies, when done well, will tell you if you have SEEN the virus already–thus, can tell if you WERE infected at some point in the past.  PCR is a “are you infected right now, yes/no” question.  Antibodies–“were you, or are you now, infected yes/no” question.

So the true number of Americans who have, or have had, SARS-CoV-2 may be up to 46 times the current confirmed number, given the PCR proven rate in New York versus what antibody testing showed.

Now, I doubt it’s 46.  First, cases swooned as lockdown measures took hold and the ILI rate that paper used for their estimates of coronavirus that did not, for whatever reason, get PCR tested has come back to earth from March/April.  But their point that many more people got infected than were confirmed infected, especially in that time span, is probably true.  Second, if it was 46, we would not be seeing the creep in new cases we are seeing now.  But, it -is- higher than the current 1% of US population confirmed to date suggest, because the creep in new cases is just that–a creep. Previously heavily affected cities and regions are not seeing the same liftoff now, probably because they are already close to the herd immunity cut-off. 

There are other data points to estimate how many people per week, as % of population, are infected.  For example, there is the Indiana study on asymptomatic patients.  Not a huge number, but it suggested around 1.5% of the population or so of asymptomatic people were getting infected.  That was across multiple weeks though, but 1.5% in that study is broadly consistent with the rate of new cases per week calculated from the New York numbers antibody numbers above.

You also have the longest running continuous, multiple-consecutive-tests-per- patient study on asymptomatic people in the United States still going.

The UFC.

That’s right.  It has been the only live sport through the lock downs, by staging fight cards in empty arenas with mandatory testing of the fighter and their team frequently leading up to the fight.  Each fighter and their three cornermen are tested for COVID multiple times leading up to the fight.  Each card has lost 2-3 fighters due to a positive test in them or their corner and either replaced them or scratched their fight. 

And they have had fights nearly every week since the lockdown.

Now, with each card running between 13-15 fights, 2 fight teams per fight (1 fighter and 3 corners per team), that’s about 120 people tested per week.  They have to announce when the fighters/team are scratched for positive COVID (because it changes the line up–not so much any UFC employees, so they are an unknown), but I have yet to hear that any of the positives were symptomatic, let alone hospitalized.  Khabib’s father and coach recently died of COVID complications in Russia, but he hasn’t been on a card in this period.  So you have men and women young enough to cage fight, out and about, with at least close contact with their corners and training team.  While a small number of total people, the UFC numbers, with 2-3 scratches per week out of 120 fighters/corners per week, is also consistent with about 1.5% of the population exposed per week.

This is not a formal epidemiology analysis of the UFC data and there are limitations.  The fight camps are not randomly distributed across the US, and they are at more risk by being in sustained close contact for hours in gyms preparing for these events.  While continuous, that’s not a whole lot of patients tested, even among all the fight cards since March.  But it’s another data point in line with the other estimates above.

And honestly, where else but here are you going to get the COVID epidemiology estimate based on the UFC? Automatic for the people on these, I tell ya’.

–So, if we keep conservative on estimates and pencil in from all of that above an estimate of 1-1.5% of the population exposed, on average, per week how close are we to 50-70% expected for immunity?

Counting weeks from March 17th, and assuming March/April’s higher rates will balance lockdown heavy May/June a bit to a 1-1.5% average, we get:

17 weeks x 1-1.5% = 17-25.5% of the US population already previously infected.

Remember that is not evenly distributed, and is probably higher in places like NYC (which had a LOT of cases in March/April), and lower in places like Wyoming, which I am told has a population, even if no one has seen it and is so sparse there is probably not a lot of COVID penetration.  The current big population states with high re-ignition, like TX/FL/AZ/CA were probably below that average, certainly in those parts of them now getting swarmed by new cases.

So if we are all Sweden, and the rate stays about the same (1-1.5% per week), you are 25 to 53 weeks from natural herd immunity (latter is the difference between 70 and 17%, assuming 1% per week growth). 

Expect an unusual year?

And again, though, that is for national level herd immunity.  Your local results will vary, and you will get there either by a slow, flat curve march, or a sudden blow out of some type (if you haven’t had one of those already).  The further we march through the end of the year though, the more and more localized the disease activity is likely to get.

But yes, 53 weeks on the high end is mildly depressing.  On the plus side, there is a chance we are too conservative on the estimate, and the current rise now is the last meaningful hurrah for the virus this year.  We’ll have to see.

–Maintaining prudent social distancing is the best way to keep your local ICU beds available should you need them though.  Cannot stress that enough.

–Even then, you only reduce the risk.  I swear, just last night, I was reading an article I cannot now find again about how Japan had relatively fewer cases per capita than many countries (US included), with no big lockdown and less economic upheaval because “everyone there wears masks”
Here’s Japan’s daily cases:

Yes, that little blip over on the far right is Tokyo starting to have increased numbers of confirmed cases again.  Not everyone in Tokyo wears masks, it seems.

–Speaking of which, big headline earlier in the week was a group of scientists imploring the WHO to change the transmission of the virus to airborne, which is a terminology quibble that basically suggests stricter airflow engineering in hospital rooms and strict use of N95 respirators for work with patients.  I kind of assumed that airborne was likely given the sheer transmission rate.  Did not realize that wasn’t quite official yet.  So if you haven’t guessed, it’s about as infectious as the common cold.  Again, prudence in your measures to protect yourself and others.

–To wrap the coronavirus section on the treatment front, hydroxychloroquine continues its schizophrenia.  The WHO halted trials with it this week.  But studies were also published that show, if started early enough, hydroxychloroquine reduces the mortality rate.  Combination with zinc and azithromycin may be important for the effect.  So, I dunno man.

–Your chances of catching bubonic plague this week are directly proportional to how often you touch dead rodents, especially marmots in Mongolia.

–Your chances of catching Ebola are equivalent to the chance that Dr. Jane Goodall, having defeated the Army of the Bioterrorist Monkeys, takes a contract on short notice to fill in for a UFC main event when the originally scheduled fighter pops positive for SARS-CoV-2.

–Your chances of catching coronavirus this week, in most places in the world, are the chance that Jane Goodall would win that fight.