Ebola and Coronavirus Update

—Ebola again, because it’s quick.  No new cases.  A few hundred contacts still being followed, only about 80% of whom have been vaccinated.  A little under 100 are especially high risk, having come in contact with body fluids from one of the recent known patients.  So it continues to go.  The only new aside worth mentioning is that vaccine pipelines are expected to be “constricted” due to COVID-19.  Unclear if that accounts for the less than 100% vaccination of the known contacts.

Coronavirus:

—Again, hitting the high points.

—I know there are many parents on this list, so let’s address the Kawasaki-like syndrome being reported in association with COVID-19.  A major pediatric hospital in Italy just published a case series (with cohort comparison) in the Lancet today.

First, what the hell is Kawasaki disease?  Kawasaki disease is an over-exuberant reaction of the immune system, typically following some form of viral disease, that occurs almost exclusively in children.  Basically, the immune system gets so excited pulverizing the virus that it starts attacking medium sized blood vessels too.  The most consistent symptom of Kawasaki disease is a persistently high fever (often quite high, over 101.3) that Tylenol and Ibuprofen barely touch.  The fever will last 5 or more days.  That’s important. A fever of less duration than that is not likely to be Kawasaki disease, so don’t go running your kids to the pediatrician just because you are reading about this!  At least call the pediatrician first if you’re that concerned.  But if it’s a high fever, for 5 straight days, yeah, get ye to the doctor’s office with the quickness.  Most patients will also develop red, itchy eyes (conjunctivitis) without the mucus/pus of pink eye.  This will typically leave a ring of the “white” of the eye right around the iris.  This occurs within a few days of the fever.  So too will the cracked red lips and “strawberry tongue” (that’s the detail they pop onto medical exams to get us doctors to think “Kawasaki”).  You can google a picture of the strawberry tongue, because I am not going to do it justice with my descriptive prose.  A rash will often be present, but takes enough different forms that describing a specific kind of rash as THE Kawasaki rash is counter-productive.  The last manifestations are swelling in the hands and feet, and palms and soles get red, typically well after the fever has started and other symptoms are present.  There are very few things that will give a red rash on the palms and soles—this is one of them.

The swelling hands and feet speak to some of the uncommon (especially if caught and treated in time) complications of Kawasaki disease.  Classically, and especially common on your medical school exam, is dilation and even aneurysm of coronary arteries, but plain old poor functioning can happen too.

Kawasaki disease is -very- treatable.  The mainstays are a medication I will not name because only a doctor should be giving it to children (especially in the setting of flu-like illness, which often precedes or accompanies Kawasaki) and intravenous immune globulin (IVIG).  IVIG within the first 10 days of symptoms reduces the risk of developing coronary artery aneurysms by 75%.  Glucocorticoids are also used in the setting of especially severe manifestations of Kawasaki disease, known as macrophage activation syndrome (where the immune system is chewing up platelets and red blood cells too).  

I want to be clear that every patient in the Italian paper with Kawasaki disease in the setting of COVID was successfully treated with these medications.

So, in the Italian experience, they noticed a nearly 10 fold increase in Kawasaki cases presenting to their pediatric hospital since the COVID-19 outbreak in Italy.  Most, but not all, had known exposure to or proven COVID-19 disease.  They were generally older than Kawasaki patients presenting over the months immediately before COVID-19—these COVID-19 associated cases were 8 years old, plus or minus about 4 years.  They were also much more likely to have diarrhea as a symptom, which is consistent with other reports about how SARS-CoV-2 tends to manifest in kids.  A much higher percentage of them showed up with more severe Kawasaki disease, including macrophage activation syndrome.  Again, all of them were successfully treated with the typical Kawasaki regimens.  

The Italy paper stresses that even though appearing more often with SARS-CoV-2, Kawasaki disease is still quite rare, and they estimate fewer than 1 in 1000 children in their area with COVID-19 developed it.  Again, all of them were successfully treated with typical Kawasaki regimens.

This is yet another bit of evidence to a growing body of observations that the real threat of SARS-CoV-2, if you do get infected, is not necessarily the damage the virus itself causes.  Some patients’ immune systems just go haywire responding to the virus (so called “cytokine storm,” which can turn into sepsis and septic shock, and including acute respiratory distress syndrome).  This massive immune response may be what is doing the real damage in patients.  Think of it as that scene in the Arnold Schwarzenaeggerishardtospell oeuvre “Predator”, where the squad of commandos hears a twig snap and immediately fire at sustained full auto for what feels like 10 minutes, leveling a couple acres of jungle.  For a twig.  That’s basically what the immune systems of some patients are doing.  If you’re young and healthy, with a lot of jungle to spare, your body can handle all the damage the immune system is also doing.  If you have co-morbidities, where damage from age or other diseases have left some of your organs as a sparse copse of trees, you are probably one of the patients who is more likely to have problems.  

And indeed, all the clinical prediction models for morbidity (likelihood of trip to ICU) and mortality depend heavily on age and co-morbidities.  Lab tests associated with worse outcome include markers of liver damage, elevated inflammatory markers (c-reactive protein, ferritin [also high in macrophage activation syndrome]), and hypercoagulation (easy blood clotting—you have probably read articles about increased incidence of clots with COVID) like d-dimer and prothrombin.  D-dimer and prothrombin will show hypercoagulation changes in cytokine storms and excessive immune reaction too.

So that’s a lot of medicalese for “lab evidence that the commandos are firing sustained full auto at anything that moves” and “patient does not appear to have too many trees capable of soaking up all the stray rounds”.  

Yes, this may have treatment implications.  You may need to find a sweet spot between controlling the virus enough (to keep its actual damage to a minimum) while keeping the immune system from going full Ah-nold.  Maybe?  We’ll find out.  Lots of strategies being employed across the spectrum right now.

—We’ve got some good prevalence data in Indiana that is worth discussing.  It may be applicable beyond our borders.  First, PCR on less than symptomatic patients shows that about 1.7% of people walking around, feeling normal and healthy, have SARS-CoV-2 on board.  

That is the lower bound.  As we have mentioned, if you don’t have symptoms, the PCR is less likely to pick up the virus even if you have it, because less virus is there to be detected.  We still don’t know how MUCH less likely that is.  

So at least 1.7% of Indiana has SARS-CoV-2.  They found antibodies (using an assay that appears to be reasonably accurate) in another 1.1%.  These are people who had SARS-CoV-2 at one point in the recent past.

So at least 2.8% of Indiana has or has had SARS-CoV-2.  This implies at least 11 times as many people have had SARS over and above the current reported number positive.  

So you can back-of-envelope where you are, assuming Indiana’s numbers are approximately accurate.  Take the number of reported positives where you are at, multiply by 11, and that’s how much virus is/has been actually around.  Minimum.  It’s probably a little more.

That sets a more accurate denominator for the case fatality rate in Indiana.  Based on that, Indiana looks to have a 0.58% CFR (right between the flu and 1% I have been estimating).  I think it’s closer to the flu given that PCR is underestimating the number of “walking asymptomatic” patients, who don’t know they have SARS-CoV-2, and will never develop clinical symptoms.

Again, most people who encounter the virus will not have major problems.  

This reinforces that the issue with SARS-CoV-2 is NOT the CFR (unless you are a high risk group).  It really is that SARS-CoV-2 is good at spreading, and good putting people in the hospital for at least a little, probably because whatever twig it snaps makes some peoples’ (we don’t know how to identify who ahead of time yet) immune systems go Ah-nold.

—Other Indiana trends to watch.  We are in the window where if there was going to be a generalized spike in new cases as the state goes through phases of re-opening, we should see it.  So far, so good there.  The curve remains flat, at least.  However, specific places within Indiana continue to struggle.  There has been an outbreak in a county jail, and we will occasionally have several hundred cases show up from food pantries or food processors with suspected outbreaks.  So either don’t get arrested in Indiana right now, or, if you must, go big enough they file Federal and put you in a Federal pen (just joking).

–And that said, Texas’ case rate is creeping higher after re-opening.

—This speaks to a question I got last week.  “So if there is reason to believe there may not be a second wave in the fall, does this mean this could be over by late July/August?”

All my predictions are wrong, or your money back.  But if I were handicapping, the overwhelmingly most likely outcome is a long, slow simmer like this.  A flat curve, with occasional spikes that may happen in your workplace/town/city/county/state and cause at least temporary more aggressive measures.  Otherwise, maintaining your social distancing and precautions will be the key to preventing a more general outbreak and keeping the curve flat.

Next most likely, a second pandemic wave in the fall, mostly because enough people somewhere think “all clear” and quit washing their damn hands, and its not quite recognized and curtailed quickly enough.

Lowest odds, especially given the disappointingly low % prevalence for antibodies, is enough folks have been exposed and enough transmission chains broken that the virus peters out through the fall.  Odds of this, frankly, are not good.  But at least they are not zero.

—Lastly, keep in mind that some tests are better than others.  Abbott got dragged this week when a head to head comparison of ultra-rapid PCR tests (Abbott has a platform there) showed Abbott’s testing may have been missing a third to one half of positive cases.

—Yes, one third to one half is a lot.

—They have an antibody test that seems to be working much better though, so not all bad news for Abbott.

—BusinessInsider wrote the article that Tyson absolutely deserved this week, if you get a chance.  

—Food distribution remains a challenge, mostly because you are getting these almost rolling outbreaks at various canning plants, meat packers, and cold chain storage.  In terms of production, not a challenge at all.  If anything, articles this morning suggest the US has planted a record amount of corn, and the new concern for farmers is that escalating trade tensions between China and the US will leave them with more corn (and other food) than they can export.  Prices may be going up now, but at least on a supply/demand basis, should at least level off once the virus works its way through and isn’t closing processing/distribution hubs a few weeks at a time.

When trillions in additional spending to keep stawks high, bro, catch up to the purchase power of the dollar is another question…  And likely a when one.

Keep in mind though—it’s not like these plants are getting bombed.  They will be able to get back to work once the incubation period is passed and decontamination is complete.  As long as enough of them don’t go down at the same time, the US will be fine, and distribution will get back to normal.

If you are in a place that relies heavily on imported food, that is a little more difficult to predict.  Definitely keep durable supplies handy.

—Epsilon Theory’s “A Truth That Is Told With Bad Intent” this week is worth a read when you get a moment.

Your chances of catching Ebola are equivalent to the chances you can tell me if  “Schwarzenegger” is the correct spelling without looking it up.

Your chances of catching SARS-CoV-2 remain excellent.  Keep your precautions in place.

<Paladin>