Ebola:

–Largely more of the same.  Up to 109 known cases now.  Contact tracing remains inadequate, but they are still attempting ring vaccination of known cases.  Several Ebola treatment centers remain overcapacity, which is probably why multiple cases are still being treated out in the community.  Geographic spread within the affected province of the DRC continues to grow, but so far, still confined to just that province.  The WHO report response staffing is inadequate, and some responders are up to 18 days and counting on strike due to non-payment of salaries and wages.  The only good news is that a lot of people have been vaccinated, accounting for the largely linear, and not exponential, growth in new cases and mortality thus far is about 40%–which for Ebola is the low end.

Coronavirus:

–Quite a bit, but we have, believe it or not, covered most of it already.  So this will be a little link happy to keep me from repeating myself–as much.

–First, state of spread.  Europe and parts of Asia continue to climb delayed first waves.  Yet, global new daily cases have plateaued.  Finally.  Your local results may still vary of course.

–In the US, a little more pink on the 7 day trailing positivity map from Johns Hopkins I have copy/pasted so often.  This is driven by the Dakotas and Iowa which have seen big spikes lately, but healthy chunks of the midwest, including Indiana, are stuck on a current plateau.  In fact, if you look at the map, you see two major patterns.

You see true flattened curves in states like Wisconsin, Indiana, Kentucky, Virginia and Pennsylvania, with a slight rise that just runs, and runs, and runs.  Or you see one enormous spike in the state at one point, which is there for a few rough weeks, and then crashes like a rock.

–Out here in the middle, my suspicion is that most of the action in the Dakotas and Iowas is rural (even for THEM) places are finally getting the ol’ corona rolling into town.  In Indiana, this is still the driver of new cases, and I suspect it is the same there.

–“Wait, wasn’t there a massive bike rally of hundreds of thousands of non-socially distancing people in South Dakota a few weeks ago?  Couldn’t these spikes be that?” I hear you say.  Well, anecdotally from people I know who went, yes, there were a lot of people there (between 250-400,000), no, none of them were doing any kind of social distancing, and no, I don’t think these spikes in the Dakotas and Iowa are attributable to the bike rally so far.  And they have looked.  As it stands, only 200 cases and one death are attributable to SARS-CoV-2 caught at the Sturgis rally.  Even if we assume the low end of attendance, 250,000 people, with no social distancing, that is not a lot of spread. 

They also went back and tested all the locals in Sturgis after the rally rolled out.

That sounds like a lot of tests–I assure you it is not.  This is Sturgis, South Dakota we are talking about. 

But the positivity rate was only 5%, well below the state’s average positivity rate.

–Even if we double the amount of cases attributable to Sturgis (and we’re at the end of incubation period, so that will be tough), the number of directly attributable cases bodes VERY well for our base case that herd immunity is close in many places.  The number of cases, given the proximity and poor social distance habits of the attendees, should be MUCH higher if herd immunity was not close.

–That said, along with a slightly more pink week on the map above, the Rt has crept back up for several states.  South Dakota is at an Rt of 1.29, meaning each case in South Dakota is currently transmitting to approximately 1.29 other people.  Considering how far one has to travel in South Dakota to even run into 1.29 other people, that’s impressive.  And cannot long continue there.  Similarly, know the end of the virus is near when it has finally infected all 1.33 people in Wyoming.

–Other major stories that have been making the rounds this week:

–First, OMG, did you hear that CDC found that only 6% of deaths with COVID on the certificate listed COVID as the sole main cause?!?!?!  Plandemic was right!

Yeah, we’ve covered this guys.  In fact, in the “Plandemic” update.  You can skip straight to the section on “How A Death Certificate Is Filled Out” here.

The 94% of cases with COVID and another condition causing the death were mostly conditions like “pneumonia”, “ARDS”, “sepsis”, “multi-organ failure”.  All conditions caused by the virus or the Ah-nold reaction to the virus.  They are all still very much accurately called, and counted, as “COVID deaths.”

–Second, OMG, did you read that article in the NYT?  “Your Coronavirus Test is Positive.  Maybe It Shouldn’t Be.” 

I glanced it over.  There was much eye rolling.

The main points of that article are:

1)  PCR for SARS-CoV-2 detects shockingly small quantities of the virus, and cannot tell if that virus is “alive” and infectious or “dead” and neutralized by your immune system.  PCR merely tells you that the virus is there and is really good at finding it if it is there.

In fact, we said this on May 8th:

“—Both our RT-PCR and these rapid amplification systems are best for symptomatic patients in this setting.  This is because they detect nucleic acid of the virus.  The limitations are that the assay only works when the virus is there (and picked up by the swab), and it does not tell you if the virus is living or dead.  You will detect the viral nucleic acid from happy intact virus or antibody coated and now non-infective virus or the RNA remnants of destroyed viral particles equally well.  But, you find the viral RNA, symptoms fit, and you probably have your diagnosis.”

2)  So even if you are positive by PCR, that doesn’t mean you have COVID (the respiratory disease caused by SARS-CoV-2).  We’ve covered this.  Most people who get exposed to this virus -won’t- get sick.  Some will though.  They have symptoms of the virus–flu-like symptoms, to be exact.  The information for patients and caregivers for the CDC’s PCR assay, our PCR assay, everyone’s PCR assay all states in some way that “detection of the virus by PCR is only proof the virus is there, and clinical signs and symptoms, plus history, are necessary to make a diagnosis of COVID.”

3)  Asymptomatic patients in particular don’t seem to have a whole lot of virus, and the tiny amount being detected by PCR (“low viral load”).  We even discussed how patients who were symptomatic, but are no longer, were reported to have low levels of detectable virus that did not appear to be infectious.  You can go straight to that section here, from the May 21st update.

4)  The New York Times quotes at length an epidemiologist who talks about how PCR should be seen as quantitative.  The implication is that a certain amount of virus detected by PCR is all we should care about.  We do have quantitative PCR for viruses.  We do.  In blood samples though.  NOT in the kinds of samples we get for SARS-CoV-2.  The viral load from these swab samples is not as accurate quantitatively.  You can easily infer that from studies like this one and this one.

In both of those studies, patients with a virus (ranging from flu A through common cold coronavirus cousins of SARS-CoV-2) were tested from multiple locations at the same time.  So they would get a nasal swab, an oral swab, and in the flu study, one additional oral/nasal passageway swab.  Up to a third of the patients in both studies would test flat out negative by PCR in one of their simultaneously obtained samples. 

If positive/negative, yes/no qualitative testing is that dependent on the swab finding the lucky spot where the virus is, what makes you think the count of the virus particles there is close to the average amount of virus present in the patient?

To see why counts are better for blood and not so great for respiratory swabs, you can do a little experiment.  Take out a vial and fill it with water (milk would be closer, but you can see through water).  Then pour a bunch of salt in it.  The salt is the virus–the water is blood.  Now, we know the heart pumps constantly, so rock your vial back and forth constantly.  Notice how the salt is mixed in, and the vial gets cloudy from top to bottom?  If you get a dropper and sample the water to count the salt grains, the salt grains in the dropper will be close to the average amount of salt grains throughout the vial.  Put another way, you don’t need to get lucky with your dropper.  Any dropper you take from that vial once it’s mixed by the “heart” will have about the same number of salt grains as any other.

Now get out some honey and smear it on a plate.  That’s close to your respiratory tract.  Sprinkle salt over it–again, that’s the virus.  As you breathe in and out, your respiratory tract mucus will mix a little, so you can brush the top of the honey with the salt on it back and forth a few times.  What you will notice is that the salt will be much more “clumpy” in the honey.  Now, it will matter where you put the swab.  Some places will have more salt stuck in them than others.  This is because the respiratory mucus is more tacky–by design!  That stickiness traps viruses and bacteria better than blood.  And there is no action of the heart to mix it really well like the vial of water/blood.  

In pathology, we call this a “matrix effect” and “pre-analytical variable.”  Unless you’ve run a lab, it’s not common to understand just how big an impact matrix and pre-analytical variables can be.

There has been a tendency when talking about viral load in SARS-CoV-2 to think that the ease and accuracy of quantitation from blood translates over directly to respiratory samples.  It doesn’t. 

That said, -directionally-, you get some information.  For example, patients who are asymptomatic tend not to have much virus detected at all.  But, rare patients have a really luck swab and an asymptomatic patient will rarely have a decent amount of virus detected.  Similarly, a really sick patient generally has more virus present than someone who is not all that sick.  But sometimes, the swab goes into the wrong part of the honey, and not as much salt is present at that particular place, and you can get an underestimate of how much virus is there really easily.

5)  The article joins the chorus arguing for less sensitive (“less accurate”) but more rapid testing because this is the breakthrough that will finally halt SARS-CoV-2.

Look, it’s September now.  Hard to believe.  It feels like it’s 2028 already.  But no, merely September according to my calendar.  That means you are about a month or two from the start of flu season.

Remember how COVID, the respiratory disease caused by SARS-CoV-2, has symptoms that overlap with the flu?  Remember how we talked about the serious possibility (since disproven) that California’s unusually severe influenza season in the winter of 2019 might have been SARS-CoV-2 arriving earlier than suspected?Because the symptoms of COVID and flu overlap that much?

Yeah.  Now is probably NOT the time to be using a less sensitive and certainly less specific assay for COVID.  It will make a medical difference if you are flu positive versus COVID positive when you pop into urgent care with flu like symptoms.

Instead, if the New York Times and the quoted epidemiologists want to focus detection on severe, higher viral titer infections that are more likely to spread SARS-CoV-2 as well, I have a happy solution.  One recently endorsed by the CDC, if only for a hot minute.

Test only patients who have symptoms.  That’s what the PCR was designed for, and where it makes most medical sense via the Golden Rule of lab testing.

If you really want to test asymptomatic patients for SARS-CoV-2, sure, the less sensitive assays may be the way to go.  Even less specific if your plan is to screen with the fast but crappy assay, and confirm any positives on the crap assay with PCR.  As we discussed on August 16th, reducing the sheer number of tests coming in for PCR is what will improve turnaround time the most.  You could save the PCR tests for symptomatic patients, confirming crappy COVID screening test results, and shortly, flu vs COVID testing.  With less tests going to less informative (asymptomatic) patients, more PCR tests would be run where they count, and faster.

–I despair of common sense winning this battle though.  Mostly because of the miasma of the times.  And this is where I wish I was a better writer, because I am not going to do this section justice.  I mean “miasma” when I write it.  I know it is an election year, but politics permeates everything in 2020.  When Ben Hunt wrote that he worried the 2016 election would “break us,” as the shift from co-operation games to zero sum competition would go into hyperdrive, I was not sure I agreed.  I get it now.  The CDC made the exact same argument about testing asymptomatic people for COVID, and had to walk it back in less than 24 hours.  We will never get good data on hydroxychloroquine and SARS-CoV-2 for the same reason the CDC had to walk back its recommendation.

Politics is everything.  Everything.  And it is so suffocating.  Even worse, somehow, politics came with this shift to zero sum competition that is everywhere.  One party could say the sky is blue; the other must immediately refute it, or at least agree conditionally while explaining how only they can really see the true, actual blue of the sky because the other team is NEVER right, never, about anything. 

We were never at war with Oceania.  We were always at war with Oceania. 

We make moral judgments based on politics.  If someone has the termity to post on social media a take clearly from the other side, they are a bad person.  For only bad people, with bad motives, or at best (best!) fools who have been taken in by the lies of bad people and believe them support the other side.  You must always be at war with Oceania.  Even if they were friend, family, and you have known them for years to be sane and reasonable people.  Well, clearly they are not now!  You saw what they posted!  You read what they forwarded!  Their sins, yes sins can be overlooked no longer.  For you must always be at war with Oceania.

If we truly receive forbearance and forgiveness in proportion to the forbearance and forgiveness we show others, God help us all these days.

Even science has become a pawn in this.  Each side accuses the other of inventing or ignoring science.  Everything, everything now it seems is judged on which side it is helping in an election.  There is no private life anymore.  Only politics.  2020 wasn’t bad enough–we have chosen to suffocate ourselves and each other.

The Civil Rights Act was passed in the United States in the 1960s, amidst riots over social and racial justice.  The only thing missing was the ol’ corona.  That Act was passed by a Democrat majority congress, but it was a truly bipartisan bill.  Although fewer in number, a greater percentage of Republicans voted for the bill than the percentage of Democrats.  How does that happen in the current miasma?  It has been years, and yes, long before the current administration since there was bipartisanship like that.  Not in the Obama years.  Not even really in the W years, except maybe some of the 9/11 acts.  You have to go back HW Bush and Clinton years.  Now, it’s a “bipartisan” bill if a single R or D crosses the aisle, and never more than a handful. 

If politics is downstream from culture, it is that culture which has spread from the zero sum competition of tribes of politicians, jockeying for sheer power, as politics infected everything.

That, clearly, has not been for the better, has it?

No one assumes that the other side has a reason for their view.  No one tries to hear the other side out, to learn that reason.

Which is a shame.  Because most people are not evil.  Some are not fools. 

Some of those reasons might be good ones, and lead to better solutions.

But we don’t allow this anymore. 

We are at war with Oceania.  We are always at war with Oceania.

–Now, I know what some of you are thinking as you read this.  “Clearly, that is the work of the other side.  Those bad people with evil aims.  It all started with [Politician X, who is from whatever side is Oceania to you]…”That thought, my friends, however fleeting, is the mirror.

Sorry.  Let me capitalize that for you:  The Mirror.

In The Mirror, you will notice yourself looking oddly like a rhinoceros.

Don’t become a rhinoceros.

–In better news, recent studies have confirmed that treatment with any of several common, generic steroids (not those steroids) in the Ah-nold stage of the disease is associated with a significant reduction in mortality.  This is pretty well known in the hospitals right now, and part of the reason the virus is a different animal in terms of ICU occupancy and mortality than it was in March and April.

–The US confirmed its first recurrent case of SARS-CoV-2.  The patient is out West, and was pretty sick in March and April.  After recovering, the same patient recently popped positive, but was not especially symptomatic at all.  Sequencing of the virus in the March vs. recent samples showed this person did, indeed, catch a slightly different genetic strain of SARS-CoV-2.  Considering the US is up to over 6 million confirmed cases, and I am pretty confident that re-infection events will be pretty rare.  1 in millions kind of events.  And this re-infection fits the pattern of the other rare events reported so far, where the second infection is either not symptomatic at all (and picked up on a screening test) or much, much less severe than the first round.

–Lastly, the United States’ biggest, baddest supercomputer crunched all the pathways implicated by various studies to see if it could predict what is going haywire to cause severe COVID disease.  A good write up is here.  In short, bradykinins, a major signal for blood pressure regulation and an “emergency” signal to the immune system, may be the snapping twig that leads to Ah-nold and the commandos leveling acres of forest.  Vitamin D may be protective.  High levels of hyaluronic acid, a fancy name for “joint oil” (reduces friction in your joints and found in many supplements for joint pain), may lead to bad outcomes.  The virus may be triggering a reaction in hyaluronic acid in the lungs which causes it to congeal.  The article linked memorably describes this congealing as “trying to breathe through jello.”  To be clear, this is hypothesis generating work, but is in broad agreement with what we know so far about the virus, and suggests a few other avenues for existing treatments that work along the bradykinin axis as possible treatments for early COVID disease.  Yes, there may also be some tie ins to T-cell mediated immunity versus antibody mediated immunity choices by the immune system too. 

–Your chances of catching Ebola look about as good as your chances of finding 1.33 people in Wyoming.

–Your chances of catching coronavirus remain good in some parts of the world, and, frankly, falling in lots of others.  Continue to be prudent with your local situation.

<Paladin>