Guest post by Rud Istvan,
I have been following this closely for a number of previously explained reasons, while mostly self-isolating with my significant other in South Florida (groceries once a week0. This post updates global WUWT readers with new facts and maybe new ‘knowledge’, some for sure now as controversial as climate change stuff. Incorporates all past facts, plus some important stuff buried in previous comments to other’s related posts. There are a number of separate fact categories itemized below.
Post 1 explained my ‘qualifications’, explained virion shed via a lot of basic virology 101, and concluded a US pandemic was unlikely thanks to effective quarantine, unlike flu—WRONG.
Post 2 explained why #1 was wrong—conclusive proof of pre-symptomatic/asymptomatic ‘spreaders’, completely unlike SARS 2003 where there was NO asymptomatic spread and the peak virion shed was 4 days after symptoms appeared. Unlike SARS, there is no way for a CoViD-19 symptom (fever>100.4) test at borders to contain infection. Very Bad News.
Post 3 analyzed the two most hopeful therapeutics, including my Remdeisvir adenosine drug analog RNA nucleic alphabet ‘A’ brain cramp—each of those ‘alphabets’ is only 4 letters. RNA ACTU, DNA ACTG. Adenosine is “A” in both. Not the exactly 20 amino acids that build all proteins in all of life based on their four alphabet coding. Each RNA/DNA ‘ three letter word’ codes for a single ‘amino acid’ to build onto the eventual protein —the complexity comes with newly discovered non ‘coding’ DNA epigenetics (regulating gene expression frequency). See my illustrated musings on MesoAmerican dried beans over at Judith Curry’s Climate Etc some years ago if you want to ‘view’ the current roughly understood state of epigenetic ‘knowledge’.
Comments to other’s previous posts are also redeveloped here, using two continually revised related math models of fatalities, making them easier to find. The issues that new data shed insight on are: infectivity attack rate (seasonality?), asymptomatic infectives, mild/hospitalizations, S/C hospital ratio, number of C dying, and intervention efficacy. We deal with each changing factor in turn.
Attack rate
We previously derived a projected Korean viral attack rate (AR) of about 2.6% and a related projected case fatality rate (CFR) of about 2.0% with extreme contact tracing, massive testing, and a capable (un-overwhelmed) medical system. Now stable tested Korean attack rate is still 2.6%. and the resulting CFR is now 1.9%, and projecting forward will settle finally at ~1.7%. The final viral attack rate CFR in US is unknown, except that it must still be much worse than Korea now. Lets compare that to known common flu in US at about 0.1% CFR after variably effective seasonal vaccines. >10x Not Good.
This AR depends on R0. Which we do not know, because depends on how we societally ‘bend the curve’. Initial US valid estimates were 2.6-3.0. Very bad. Now, much less for sure but by how much we dunno because of ‘bend the curve’ measures that for sure temporarily also kill the economy.
But lets assemble and project some simple ‘math’ outcome models, previously derived only in comments. We know from their extensive Korea testing data (then about 39600k then to find about 9.6K then positives as of last weekend) that the Korean AR is about 2.6%. We also know now from Korea that the asymptomatic/total is about 20% AFTER 14 day positive test quarantine. Those are potential “Typhoid Mary’s”, which make the pandemic difficult to control absent an effective vaccine, still probably at least 18 months away. Two potential vaccines in US have now started initial human phase one trials.
And from NYC/NOLA last week we know that hospitalized ((serious~=oxygen/critical=~ICU and probably a ventilator) is about 0.12, while the hospitalized/critical ratio is about 0.3. The most recent figures this past Friday as opposed to last Friday, 0.14 and 0.26 — giving about the same end fatality result via more hospitalizations for supplemental oxygen but a bit less deaths in the ICU. And per a NOLA critical care pulmonologist, about 50% of ventilated ICU criticals eventually die. It was anecdotaly higher (~80%) in Wuhan. So the end fully diagnosed (by testing) US math plus Korean CFR will land somewhere between 1.7% and 1.9% based on current data.
That is real bad, as the US Surgeon General said earlier this week (4/5/20). Attack rate >2.6% * about 327.2 million legal US citizens (dunno illegals) * optimistic 1.7% CFR implies 145,000 deaths in next few months. The president is not exaggerating, as some conservative blogs have implied.
There is a second way to derive this death estimate without CFR. Asymptomatics 0.8. Hospitailzation of symptomatics 0.14 (this past Friday). Criticals of hospitalized 0.26 (this past Friday). Deaths among criticals 0.5 (could be higher). Then:
327000*0.026*0.8*0.14*0.26*0.5= 124 thousand deaths next few months.
Now overload the ICU (>0.26 spike), and/or increase the viral attack rate because US is NOT Korea with strict contact tracing and testing, and Dr. Fauci’s recent horrible projected worst case 240K deaths is plausible.
Viral Load
We know generally that infectivity depends on the viral load ingested. We do not know what that load is per unit time to symptoms.
When a person becomes originally infected, it could be from a single virion per day or from (say) a titer of 1000 per day. If the one virion infects a cell and eventually creates 10 viables (previous comment post RNA transcription error example) then it takes 1E3 replication times (whatever those are) to equal the other initial infection viral titer. Immune system has 1000x more time to respond to a minimal infection titer than to a high initial titer. That compounds if exposure happens equally each day, like in a hospital. Fully explains observational clinical asymptomatics, plus a mean incubation of 5.1 days and a 97.5% symptom display of 11.5 days.
If the initial viral load is E+3 in ‘one’ dose (an un-self-distanced cough), then in the same dimensionless time example the immune system has to respond in a E-3 time frame but cannot. Voila, fast symptomatic infection.
Seasonality
Dr. Fauci now says probably. I still say probably not, for reasons explained previously in guest posts and comments to others. Facts/logic before assumptions follow.
Fact: Common colds are still common in summer (albeit less common than in winter thanks to winter contact proximity); summer flu is almost non-existent.
Reason is simply explained by differential route of infection (See previous posts and comments, not worth explaining in detail yet again). In short, flu aerosols dry in dry winter indoor air, so remain circulating longer, so the main route of transmission is infected aspirate inhalation. In humid summers they remain wet, so heavy, so sink, so are not inhaled. Fu becomes winter seasonal. Colds are different, (including all three types: rhino, corona, adeno), because their main transmission route is contact (hands/face), so much less seasonal. Seasonal flu/cold data is incontrovertible.
Fauci thinks Wuhan virus may be seasonal– flu aerosol spread assumptions– based on ‘new’ science observations. I think not based on historic facts. An artificially high virus titer from his nebulizer experiment by NIH ALSO found a virus half life (not like nuclear, just remaining RNA independent of possible infectivity) of Wuhan (just remaining RNA found, not infective envelope found) of about 1.5 hours in air, 3.5 hours on cardboard, 5.5 hours on steel, and about 6.8 hours on plastic. Now, since the infective minimum viral titer is not yet known, this is all speculative. But strongly suggests low aerosol spread and much more close contact viral transmissivity, implying without much seasonality. Translation, social distancing and frequent hand washing works, DIY masks don’t.
And previous media reports on this same experiment of 3 days max viability on plastic did NOT cite the viral half life factors above bearing on minimum infectious titer, so overstate the unknown contact residual viral titer infection scare (heck, me too) (hand washing and face touching at 6 hours half life still says real important). All good for social distancing and frequent hand washing to ‘bend the curve’.
Second cited evidence, the WA massive spreader church choir event. Except, my late Dad was in a much smaller such church choir. They greeted each other weekly with hugs and handshakes. Aerosols not needed. Just usual church choir enthusiasm. Discounted ‘science’.
Basic observational Fauci seasonality
The common cold is caused by about ~100 naked rhinovirus serotypes (abut 75% of common colds), exactly four enveloped humanized coronaviruses (about 20%) and about 20 of about 60 enveloped DNA adenoviruses, of which about 20 (~5% infectivity because of immunity against DNA mutation) cause common cold symptoms. The other ~40 adeno serotypes are much worse (e.g. various forms of conjunctivitis).
There is no evidence that the common cold (4 coronas included) is seasonal. It is more common in winter simply because people are in more confined spaces so there is more contact transmission. Summer colds are common. Summer flu is rare.
So Dr. Fauci speculates a case based on flu analog aerosols, when his own epidemiological mask message says the opposite, as does the data on common cold coronas. He is publicizing a dubious message based mostly on tenuous non-observational science. We have seen that before in climate ‘science’.
This corona virus is unlikely to be seasonal, because its main route of transmission is not aspirate aerosols, just like other corona common colds.
Mask efficacy.
There is much present internet nonsense about face masks. Lets clarify. IF Wuhan coronavirus is spread by breath aerosols and therefore seasonal (defined as less than 5 micron droplets) (doubtful biologically, see above), then N95 will by definition intercept 95% (their definition is <=0.3 micron 95% stopped), and likely drop the viral load below infectivity. All else will not.
So IF Covid-19 is actually seasonal, then everything else except N95 masks is USELESS. So then why the new public home made cloth mask recommendations? Like climate change renewable deals, makes you feel good while being practically useless.
Now IF the route is cough sneeze, not aspirate aerosol, then nose/mouth coverings make sense—for the infected only. And the advice already is, if you have symptoms, stay home and self isolate. So either way the public face mask recommendations are mostly ‘feel good’ rather than effective
Interventional efficacy
There is much new data.
First is the viral attack rate. This number is not a constant. It depends on many other societal measures like contact tracing, testing, and social distancing: ‘bend the curve’ stuff. Korea is down to 2.6%. US must be worse despite current efforts.
The second and third factors are what happens to those identified as infected/hospitalized/criticals. There, we have real time updated data. To a first approximation last week based on NY and NOLA, we had the following: (.12*0.3*0.5)
This week we had on the same data basis 14% of cases would become serious/critical (s/c, serious defined as needing supplemental hospital oxygen, times 0.26 critical defined as ICU (ventilator)). Half of those in ICU die. Run the alternative last week /this week math math per 10000 infected, is 0.12*0.3*0.5 or 180 deaths per 10000 symptomatic. Or, 0.14*0.26*0.5 = 182 deaths per 1000. Close into the zone of Korea actuals noted above–Rough closure is a good enough approximation.
Therapeutics
On the HCQ/Z pac/Zinc ‘Trump cocktail,’ the Orthodox Jewish doctor’s successful NY treatment of his 699 patients has now explained his thinking and gives an alternative therapeutic pathway. X-pak antibiotic is only for opportunistic bacterial infections. His supplemental zinc enhances a possible secondary HCQ mechanism of action. I previously posted that the first was via the same liposomal enhanced pH mechanism as it’s use in RA, deforming the ACE2 receptor.
There may be a second. HCQ is a zinc ionophore—extra zinc into the intracellular metabolism inhibits RNA viral reproduction. Dunno for sure, but a cursory review of the medical literature says his idea is very plausible.
HCQ is also zinc ionophore for sure. Extra zinc transported into a cell’s interior is a known RNA Polymerase inhibitor (common colds). So, the azithromax antibiotic in the “Trump cocktail’ may be a secondary bacterial against Wuhan, and the doctor’s extra zinc loading is a primary agent. Maybe.
Now, why this is important is that there are two other known non prescription zinc ionophores, EGC in green tea extract, and the flavonoid quercetin in gingko biloba extract (both are in varying degrees in both, and in many other greens plus apples). Both are proven cellular zinc ionophores. So there may be OTC treatments cheaper than generic hydroxychloroquine for treating WuFlu.
Dunno. Do know green tea is good no matter what. Salud.
Rud – I enjoyed your article as always. I went to bed wiser, or at least more knowledgeable, than when I woke up. Regarding your views on masks. When one looks at the Worldometer daily stats both Japan and South Korea have very low death stats. And both countries, particularly Japan is known for mask wearing in a situation like this pandemic.
The inference would seem to be that masks are effective in both these countries. Could you – or others – comment on this please?
Found this interesting take on the virus, seems to answer a lot of questions.
https://medium.com/@agaiziunas/covid-19-had-us-all-fooled-but-now-we-might-have-finally-found-its-secret-91182386efcb
Any experts got an opinion?
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looks like the article you linked has been removed…
My little foray into personal research on this confirms that statement. The studies I have looked at use a lot of “may”, “could”, “more research needed”, “not well understood”, “might be less effective if”, ….
… you get the gist — ignorance framed in academic dressings and published, with final conclusions based on the hopeful side of “may”, without the actual confirmation of solid evidence.
Do you KNOW how small a coronavirus is?
Do you KNOW how reflexive most human behaviors are?
(e.g., vet tech looses mask off face in parking lot, picks it up, puts it back on her face, germaphobe client sees it, cancels appointment from fear of catching COVID-19 — true story)
(e.g. #2, lady in food market pulls mask from face, resting it on neck, touching items on shelf, presumably putting it back on her face later, with hands having touched stuff — I witnessed this)
(e.g. #3., lady in home improvement store walks about the isles with mask covering only her mouth, with nose over top of mask — I witnessed this also)
Oh, and let’s not forget our eyes — mucus membranes, ducts leading down inside our sinuses, aqueous humor acting like a water magnet for saliva droplets with SARS-Cov-2 riding on them. In other words, what about eye coverings? — oops! — guess we overlooked that. So, not only N95s, but also a good face shield might offer some real diverting of the little demons. And proper, meticulous care in sanitizing these and placing these correctly, both on and off your face to prevent contamination is a must. There’s that human-behavior issue again. Are people really going to do this? Can people reasonably be expected to do this? Even people who know and have trained how to do this are prone to reflexive behaviors in a split second.
Seen on French news TV channel: during “élections municipales”, 1st round (2nd was cancelled), a voting official has gloves, but at a point in time he has nothing to do, so he does what inactive people do: he rests his face on his gloved hand.
Solution: keep hands of voting official busy at all times.
No expert but this sounds reasonable, if so we need to adjust treatment accordingly and get back to work, problem solved.
https://medium.com/@agaiziunas/covid-19-had-us-all-fooled-but-now-we-might-have-finally-found-its-secret-91182386efcb
It sounds reasonable but it’s not actually the case.
It does seem to address the observation that patients with low blood oxygen levels do not benefit from ventilation as would be expected and further that HCQ is so effective at resolving the symptoms, how would you explain this away?
Oops, I see my original comment made it through.
https://cliffmass.blogspot.com/2020/04/flying-blind-on-coronavirus-why-random.html
Cliff Mass says “Epidemiological projection, like numerical weather prediction, is an initial value problem. You start with an estimate of the initial state and your model, which contains information about the processes of the phenomena in question, attempts to project the initial state into the future. If your initial state is uncertain, so is your forecast.” But testing is inadequate for this. “The current testing regime leaves decision makers poorly informed. How many individuals currently have active infections, with or without symptoms? How many people have had the virus and are now potentially immune? We don’t know. And without such information, it is nearly impossible to project the future.”
“Extraordinarily serious decisions are being made without key information
“Washington State is rapidly getting out of this terrible situation due to the combination of social distancing and the building immunity of the population. But we are pretty much ignorant about the magnitude of the herd immunity because we do not know how many have had and currently have the virus.”
Rud. Thanks again for your efforts on this.
I would note that even if homemade facemasks are probably ineffective, they probably aren’t dangerous for most people most of the time. (Inevitably, i imagine somebody somewhere will manage to get one tangled up with some massive machine and rip an ear off). And they are only a bit uncomfortable. So why not wear them until we are sure they are useless?
Something I haven’t seen much mentioned by anyone is parallels with the Spanish flu of 1918. That was, of course, an H1N1 influenza, not a coronavirus so it’s not exactly the same. But I came away from the lengthy Wikipedia article with two concerns.
1. There were two waves of Spanish Flu and the second was more lethal than the first. We probably shouldn’t blithely assume that can’t happen with COVID-19.
2. Apparently some of the deaths attributed to Spanish Flu might actually have been caused by the notion at the time that massive doses of Asprin were a cure/preventitive for the disease. It wasn’t. And Asprin can kill you if you ingest enough. Perhaps a bit of caution is indicated in gulping down large amounts of potentially toxic substances. At the very least, folks should probably look up recommended dosages and overdose symptoms for their home cures.
watch
Rud, thanks for this series you’ve done. That’s a lot of research to have done.
“N95 will by definition intercept 95% (their definition is <=0.3 micron 95% stopped)"
0.3 microns or 300 nanometers. This is the rating for N95 masks. However, this corona virus should be around 125 nanometers, which is significantly smaller. The N95 stops 95% of particles 300 nanometers or larger. With the virus being significantly smaller than 300 nanometers, relatively speaking, there's no way it would stop 95% of this virus when aerosolized. That's something to think about. It's my understanding that typical hospital surgical masks are ineffective with this virus, which makes sense. It seems like even with an N95, it's a significant risk of infection with exposure.
The virions are not generally thought to be floating free as a virion and nothing else.
And it is only one virion.
Rather, it is small droplets containing a large number of virions.
And with a mask, they are less likely to be breathed deeply into the lower airway…they are more likely to be deposited on surfaces of the mouth or the lining of the nasal epithelium, where the infective dose is far larger than the lower airway surfaces.
Dr. Istvan,
When I first read this essay I was immediately struck by your explication of the viral infective dose effect on the course of disease progression in a host.
Very few people have touched on the details of this aspect re why it is so.
I was going to post a comment I had made a few hours prior on another comment thread, in which I ran through a brief synopsis of one reason why viral dosage at first infection matters.
But it was stuck in moderation for several days, so I could not do so.
I had many of the same thoughts as you have expressed here, although lacking the quantitative aspect.
It has now appeared, and here it is:
“It is intuitively obvious that anything is better than nothing.
If you found yourself in a burning room with heavy choking smoke, would you put a cloth over your face?
The largest particles from a sneeze or cough carry enough virus to cause a flu infection in one single microscopic droplet.
And breathed into the lower airway, the infectious dose is far lower than the same virus spread onto the nasal epithelium.
In other words…you get sick far easier if you breathe more and large droplets, than if virions are on your nose.
Also it must be considered the possibly huge effect that the actual number of virions a person ingests by any route has on the course of the disease in that person.
This is a much unappreciated fact of the way our immune system works.
A large number of virus particles will necessarily infect a larger number of cells and begin replicating in far larger numbers, than a smaller number of such virus particle.
Our various layers of innate immunity can mop up a certain number of any invader, and dispose of a certain number of infected cells, per unit of time.
But the antibody response that is what allows us to eventually overcome any infection begins gradually and takes a certain amount of time to even get started, and then to ramp up. The more virions and the more infected cells cranking out more virions that the infection has in it’s head start in the process, can have a hugely consequential effect on how sick a person comes, how widespread the infection is at any stage, and hence on how many cells in the host are destroyed, and how vigorous a level an immune response must ramp up to and max out at to overcome it.
The two things that seems to make this disease so dangerous for so many…even those it does not ultimately kill outright…are the length of time a person spends being sick, and the reaching of a stage of immune activity that winds up being highly damaging in itself…the cytokine release syndrome like end stage of viral pneumonia
We have many layers of innate immunity to infectious organisms, no one of which can do the job by itself.
We help ourselves when we add more layers.
It makes the job much easier for the other layers.
Anything is better than nothing, and the protection offered by a mask may be poorly understood and understated in certain instances.
Besides for decades of studies demonstrating the effectiveness of barrier protection…there is the obvious example of the countries where they are wearing masks faring far better than the places that do not.”
https://wattsupwiththat.com/2020/04/08/boris-johnson-in-intensive-care/#comment-2959599
I did, as can be seen, come to a different conclusion regarding the usage of masks, that you yourself have done.
I think there is certainty room for differences of opinion on this.
The literature itself from the clinical trials on mask usage says as much, and many of the authors have found contradictory results, at least some of which related to how individuals adhered to best practice in their usage of masks.
But I think on balance the research indicated that masks can be beneficial, but that this benefit is directly related to the type of mask and how fastidiously they were used.
In a series of comment posts after the one I linked to above, I added links to several studies and article pertaining to the usage of masks, in particular during pandemics.
In any case, I have appreciated all you have done to keep this issue at our attention, and to inform us, keep us up to date, and move the conversation forward.
I am a big fan, and look forward to your next essay.
BTW…it does not seem to have made much in the way of headlines, so in case you missed it, Gilead has written up the first of the results from remdesivir compassionate use patients in the NEJM:
https://www.nejm.org/doi/full/10.1056/NEJMoa2007016
A careful read gives much cause for hope.
Mods, I have a comment gone to moderation, perhaps for including multiple links.
Thank you.
Just a note on the transmission: whether it’s a cold, the flu, or COVID-19, they’re all transmitted the same way. I looked it up on the CDC’s site. They’re ALL transmitted the same way. And guess what? You can have asymptomatic flu as well. https://twitter.com/4TimesAYear/status/1249839151756783619/photo/1