Ebola–

Now up to 25 confirmed cases, although data is lagging a bit.  There are 865 known contacts of confirmed cases, with a little over 90% being effectively followed up.  Only about 43% of the contacts have been vaccinated, despite 6,000+ people having now been vaccinated.  Arguably, they might already have it as they were close contacts of a known case, but one would suspect that successful ring vaccination should -start- with known contacts and spread out to their known close contacts.  5 patients with Ebola are still being cared for in their communities (and not a BSL 4 hospital ward, which is suboptimal) and one suspected case has disappeared into the general population.  No new geographic spread this week at least.  They also confirmed that this outbreak is not only NOT related to the one across the country that just officially wrapped (for the second time), but the virus strain is NOT related to the outbreak in this same region just a few years ago.  Appears the fruit bats have been migrating again, or someone ate infected bush meat.  Again, expect this one to continue for a little bit, but at least it is comparatively muted for now.

Coronavirus– A lot again.

–In the US, the positive test rate is leveling off at around 7.2% nationally.  That’s a bit of a rise from last week, but again, has stabilized.  Just four states (the ones most frequently in the news for their new nominal highs in cases per day) account for 24% of new cases in the last week.  These are all states hitting their late peak, or, in the case of FL, in the throes of a second definite peak.  In states with robust outbreaks, even if they are not as “surface of the sun” hot as FL, AZ, TX or CA, have a higher % positive than the national average.  For example, SC has a % positive rate that is at least as high as the March/April peak.  GA looking very brisk too.

–Recent moves to re-close bars and gyms in some of the hotspot states (and beyond), or slow re-opening plans in other states, should not be unexpected.  We have discussed frequently how such measures were likely on a city/county/state level.

–Some cities are also running into hospital capacity warnings.  Houston is already at 105% ICU capacity, meaning patients are being diverted to emergency ICUs.  I have been hearing similar rumors for parts of Arizona. 

–That said, mortality from SARS-CoV-2 in the US is down.  Hospitalization rates continue to level off.  The median age of a SARS-CoV-2 positive in March/April was like 58 in the US; right now, it’s closer to 38.  In Houston, for instance, even though ICU capacity is starting to activate emergency wards, average duration of hospital and ICU stay per SARS-CoV-2 patient is down from March/April.

–So it’s a younger patient population, with generally fewer comorbidities, and less risk for severe complications for SARS-CoV-2.  That explains the largely stable hospitalization rate, and falling mortality rate, despite SCARE HEADLINE SIZE DAILY NEW CASES (ALWAYS IN RAW NUMBERS ONLY OR AS A PERCENT INCREASE IF THE NEW NUMBER IS NOT NOTICEABLY HIGHER THAN YESTERDAY’S).  While it could be evidence of adaptation by the virus to become less severe over time as it gets more used to humans.  This makes the virus more likely to be transmitted if it makes people less sick, and thus, less noticeable.  A virus would prefer to be sneaky like that if it can. 

–However, while a change in the biology would be nice, that “less severe disease” adaptation is unlikely given the time frame and SARS-CoV-2 mutation rate.  What is far more likely is that younger people were going to the bars and gyms again (and yes, Virginia, were more likely to be at protests or on the beach over Memorial Day) as the states reopened.  Enough of those younger people were still vulnerable, and enough of those younger people were actually in the early stages of being sick to be infectious in public, in places that had not had their big wave yet and re-ignition happened.

–So let’s make that explicit.  Yes, protests (and Memorial Day) likely contributed to new cases as June came to an end.  No, they are not the sole explanation.  But it means that in many places in the country, there was not sufficient penetration yet to achieve herd immunity.  Yes, testing more is finding more positives (hence the high nominal new cases, but flattening percent positive well below March/April highs for the nation as a whole).  No, this does not, by itself, account for the new nominal highs.  As we have mentioned, at the state level at least, you are seeing continued climb of the initial first wave.

Depending on where you get your news, you have heard one side or the other of those possibilities.  They are not mutually exclusive, as they are often presented.  Ignore the bark of the sheep dogs.  Don’t become a rhinoceros.

–Yes, I am aware there are publications claiming that protests were magically protected from transmission of SARS-CoV-2.  I haz some doubts about their methods.  Because I also know, in many if not most testing locations, no one asks and no one tracks if you were at a protest–which is exactly how it should be for both first and fifth Amendment purposes. 

You can’t find an association to protests if you don’t ask if they were at a protest.

I’m also old enough to remember published interviewers in the news with people who had participated in some of the larger, peaceful daytime marches (actual rioters were apparently unavailable for on the record ,attributed comment).  In those interviews, some of them said yes, they and friends of theirs who marched had a few days of flu symptoms afterwards.  And we all saw headlines of people at pools and bars in the news on Memorial Day who popped positive.  No way to know if those were above the baseline positive rate; you’ll never collect accurate enough data for it now; but common sense says packing that many people in close proximity during an outbreak of something that spreads just like it’s a relative of the common cold probably didn’t help reduce transmission.

Regardless, the national rate is what it is.  Unless we can get that lady from “Plandemic” back in the lab, we cannot alter space and time now to change the mass possible exposure events of Memorial Day and protests.

–We can, however, be prudent.  Including wearing a mask, when applicable.  The virus is likely to slow burn for awhile still (we are now past the “over by August” possibility) until some semblance of herd immunity is reached.  Or a vaccine miracle occurs.  Or you get a treatment that keeps people out of the hospital and ICUs entirely, and the last vestige of threat to heatlhcare systems is removed.

–It is also worth mentioning last week’s “influenza like illness” data, suggesting that more people got SARS-CoV-2 in March/April than got a test in March/April.  That is the best explanation for the clear data that in many states, despite reopening, protests, Memorial Day weekend experimentation etc., there has not been nearly the liftoff as in the new hot spots–slight upticks if any, as June draws to a close. There was a very good chance there was higher penetration of less severe SARS-CoV-2 in at least some, if not many, of these locations and thus fewer “eligible”, unexposed hosts left to the virus in them.  That’s a good thing.  That means herd immunity is close in some places.

–Internationally, song is pretty much the same.  Europe is re-opening, but I would lay money that you will see a Beijing/Australia/Singapore/Florida like re-ignition somewhere locally in the continent before too long.  Those nations with the best chance of hunkering down and waiting for successful treatment/vaccine are small islands that have quashed internal transmission and can enforce a strict 14 day quarantine to keep the virus from re-surfacing.  If you are not Taiwan or New Zealand though, you’ll have some trouble.

–Many nations in South America and Africa are just starting to reach first wave peaks too, so SARS-CoV-2 is still very much active globally.  The WHO is not wrong in saying that you are still in middle innings.

–Speaking of “Plandemic”, there was a little more conspiranoia floating around about connections of HIV and SARS-CoV-2 on some otherwise reputable websites this week.  In short, severely affected SARS-CoV-2 patients can often show a decrease in white blood cells.  SARS-CoV-2 also has mechanisms to remove MHC-1 proteins from the surface of infected cells.  MHC-1 is the “ID Card” of the body.  All your cells make it, and use it to prove to immune cells that they are you.  In a cell that has been infected by a virus, MHC-1 is also used to show parts of the virus to the immune system, provoking the immune system to react to the virus.  Thus, LOTS of viruses (including HIV) have ways to cause cells they infect to make less MHC-1, so they can hide from the immune system for longer.  Some cancers play similar games.  Note that even this is imperfect, as your immune system has a special class of cell that Hulk up and Hulk SMASH if they are not shown enough MHC-1 by a cell.  So yes, your immune system is wise to that whole “virus tries to hide by making less MHC-1” trick, and the trick only delays the inevitable for the virus.  But some of these sites have seized on the “decrease in white blood cells” in severe SARS-CoV-2 and downregulation of MHC-1 “just like HIV” to raise the whole “bioengineered with HIV” canard again.  Just keep in mind that a drop in white blood cells happens frequently in sepsis (or any time Ah-nold and his commandos level an acre of forest, no matter what virus/bacteria/fungus etc. snapped the twig).  Causing an infected cell to make less MHC-1, to help the virus hide, is not limited to HIV and SARS-CoV-2.  Influenza A does it, EBV and our old friend CMV do too, just to name a few off the top of my head.  There is still no conclusive proof that I have seen that would suggest SARS-CoV-2 is an engineered bioweapon.

Perhaps an accidental release of a lab virus.  Perhaps.  But as we mentioned before, releasing a bioweapon you don’t have the cure for already is a special kind of stupid, and an awful lot of people got sick and died in China too.

–Couple pre-publication papers worth mentioning.  The first is Pfizer and BioNTech’s SARS-CoV-2 vaccine safety and immunogenicity data from the first part of its Phase 1/2 study:  https://www.medrxiv.org/content/10.1101/2020.06.30.20142570v1.full.pdf   Because neither one is my employer, I will keep my comments brief, but I will make a few since we do have the paper.  First, this is a mRNA vaccine, which is an increasingly popular strategy.  A traditional vaccine takes an inactivated or weakened whole virus, while the HBV vaccine uses a purified surface protein from HBV, injects it, and the immune system reacts to proteins on the virus or the purified injected protein.  But the virus has to be grown, inactivated or attenuated, or the protein has to be made and purified.  An mRNA vaccine lets your cells make the viral protein target for the vaccine.  It works like this.  If you recall your biology classes, at some point, you learned the Central Dogma of molecular biology:  1)  DNA encodes proteins as genes, and stores them as a giant library of “blueprints” for all of these proteins.  2).  When your cells need a particular protein to do stuff, they make a copy of that gene (blueprint) as RNA.  Specifically, mRNA (messenger RNA).  3).  The mRNA blueprint is taken to ribosomes in the cytoplasm, which are protein factories.  The ribosome “reads” the mRNA to build the protein according to the “blueprint” on the mRNA. 

So what Pfizer and BioNTech have done is made a mRNA of a SARS-CoV-2 protein.  That is injected into the body, and transported to the cells of the body.  The ribosomes get a brand new “blueprint” for SARS-CoV-2 protein delivered direct to them, and dutifully make this piece of the virus.  Since it’s just a piece, and not the entire viral genome, the vaccine does NOT inject a working virus.  Just the instructions to make this one specific viral protein.  Your cells display this protein on MHC-1 (remember that from a few paragraphs ago?) and a similar molecule named MHC-2 (which helps trigger antibody production).  The immune system recognizes the viral protein encoded on the vaccine mRNA as foreign, and mounts a SARS-CoV-2 specific response.

That’s the plan.  How’d it do?

Well, keep in mind this is JUST safety and immunogenicity.  They are only looking for safety and side effects, and they want to see the antibody they are hoping to stimulate the body to produce (immunogenicity) if the mRNA is getting the right viral protein made and to MHC-2.

There were no show stopping side effects in the 45 patients reported in the paper.  At the highest dose of mRNA, there is a lot of fever, chills and muscle/joint pain, all suggesting the immune system is being triggered.  They do indeed see a lot of the antibody they hoped to produce, which is identical to antibodies found in patients recovered from SARS-CoV-2.  In fact, they see as much of it at a lower dose than at the dose that caused all the fever/headache/joint pains etc., so they may be able to avoid some of those side effects and still be an effective vaccine.

As they themselves mention in this paper, the main limitations are that the patients they tested are all much younger and more healthy in general than high risk SARS-CoV-2 demographics.  They are testing older patients now though.  Further, no one really knows if that antibody is enough to stop infection from SARS-CoV-2, and in this phase of drug study, they don’t look for efficacy in terms of demonstrated reduction in SARS-CoV-2 infection rate quite yet.  That’s coming next.  But the good news is that, unless this paper needs HEAVY revisions in its data, the efficacy study will be coming soon.  “VACCINE SHOWS EFFICACY!” headlines were a little TOO optimistic (over interpretation of the antibody production data), but they have a vaccine with a shot (no pun intended).  That’s all you ask for at the phase of testing in this paper.

–The second pre-publication paper comes to us from one of our California readers:  https://www.medrxiv.org/content/10.1101/2020.04.10.20053207v1.full.pdf+html  We were pleasantly surprised to see this was not a large print edition, given the recent birthday of that correspondent–glad to see those readers got delivered by Amazon in time!  Cheap pot shots at someone younger than me aside, the paper makes an interesting in silico comparison of key proteins of SARS-CoV-2 with the viruses in the measles, mumps and rubella vaccine.  There is enough structural homology between some of them that the MMR vaccine could theoretically cross react with SARS-CoV-2.  They raise the possibility that the significant age disparity in mortality from the virus could be due to lapsed MMR immunity, and younger patients, more likely to have just received the vaccine or a booster, may have more resistance to the virus as a result.  They did the smart thing and looked at least rubella titers and how that correlated to disease severity.  Quite frankly, they don’t have nearly enough patients and did not do titers of all three viruses, nor do we have any information as to where the SARS-CoV-2 patients were in their disease course to know if they were in the Ah-nold leveling trees phase and how much SARS-CoV-2 was on board at the time (or asymptomatic but positive and uninfected patients for comparisons).  So their titers are unconvincing, and actually look higher in more severe disease–but again, they don’t have nearly enough patients to know if that is statistical artifact yet or not.  Like blood type and SARS-CoV-2 infection rate, this should be easy enough to check though.  They just need someone to get approval to do this serology for MMR on a whole bunch of well characterized patients, and you might even be able to get a bunch of MMR boosters together and do a prospective randomized double blind to see if MMR vaccine does reduce the risk of SARS-CoV-2 infection and/or COVID-19 disease severity.

–Speaking of ABO blood type and SARS-CoV-2, have not seen a follow up yet, but possible I missed it.  If you come across one, send it along.

–Enough testing capacity is now up and running in Indiana that we have been able to step back from testing for the state, and focus on our own clinical trials.  Nice to have weekends back again.  I’m winding up with a little over 62,000 SARS-CoV-2 tests signed out since mid-March.

–Your chances of catching coronavirus, in most places in the world, remain equivalent to Ghislaine Maxwell, recently arrested co-conspirator of Jeffrey Epstein, finding herself on suicide watch in prison sometime soon.

–Your chances of catching Ebola are approximately the chances that Jeffrey Epstein killed himself AND the chance that the security cameras outside Ghislaine’s cell will be working should she, too, find herself “contemplating suicide.”

<Paladin>