We continue from Johnson & Johnson, Explanations for Clotting ?

Most immunizations are into the deltoid muscle of the upper arm.  In recent years, there has been increased interest in subcutaneous injection. This can result in more immune response with less antigen, or the reverse.  That tissue is more delicate, more susceptible to damage.  And there have been some tragic failures, when the immunization did not “take”. So whatever site is used in the clinical trials is baked into the usage.

The deltoid muscle is resistant to damage, and there is a simple “finger rule” to avoid hitting a nerve with the needle. Some muscle fibers die as a result of the injection, but they are replaced in days. The muscle has strong blood supply and high metabolic rate, which protects it from occasional bacterial pathogens.

A fraction of active material of the injection stays in muscle to “transfect” muscle cells, causing them to produce spike protein, which in turn induces immunity. Most of the injected material does not remain in place.  Muscle is so well supplied with circulation that most of the active material drains out. Another fraction drains through the lymphatic system, reaching the axial lymph nodes, in the armpit, where it may still make a contribution to immunity, if it can find suitable cells to transfect.

The remaining fraction enters the blood circulation. With a classical vaccine, consisting of inert materials, this fraction is lost; it makes no contribution to developing immunity and has no further effect on the body. The bulk of it is caught by the liver, degraded into less suspicious substances, and excreted.

We are going to accumulate Tinkertoy pieces that may be useful in building a hypothesis bridge from a place called Mystery,  to another called Prospect, spanning the River Doubt. If and when the bridge is complete, it will be a theory that can be tested. Cast a wide net at first. Keep  Occam’s Razor always within sight. Back in August 2020, I had some suspicion. There are some Tinkertoys in (CNN) More European nations pause AstraZeneca vaccine use as blood clot reports investigated, but I’m not eager to pick them up. If in the future, they make an Occam contribution, well and good; let them lie for now.

An adenovirus vaccine is not inert. Even though the vector cannot reproduce, it pries its way into cells. The fraction that enters the blood may not be benign. Adenoviruses are generally toxic to the liver; (BMJ) The promise and potential hazards of adenovirus gene therapy. Quoting,

What’s toxic about adenovirus vectors?

Much concern has focused on the direct toxic effects of adenoviruses, particularly as intravenous administration of the virus can induce acute liver injury, as shown in animal models. It is this effect which may have triggered the cascade of events leading to the death of the patient with OTC deficiency—

AstraZeneca/J&J know this well, and think they have their bases covered, with a comparatively minute quantity of vaccine reaching the liver. Maybe, maybe not. It may depend upon prior infections, which often leave live viruses, jailed, in the liver. Until something comes along with the key.

You’re probably wondering what this has to do with CVST.  We’ll get to that. To be continued shortly.

In what follows, J&J and Astrazeneca are considered identical. The eventual explanation may fork into separate ones for each vaccine, but nothing’s showing now.

Let’s define some terms. The scientific method names two classes of explanation:

• Theory –an explanation that has a test, and can be proven false.
• Hypothesis — a good idea, with clues that point in a direction, with plenty of imagined glue to tie it together.

(BioSpace) COVID-19 Brief: Theories on the COVID-19 Blood Clotting and More Top Stories blurbs an incomplete theory, first described for  AstraZeneca  in this paper: Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. It’s  better than a hypothesis but not a complete explanation either. Quoting from the blurb:

The leading theory appears to be an unusual and rare immune response similar to heparin-induced thrombocytopenia (HIT), where the immune system makes antibodies to a complex of heparin and a protein known as platelet factor 4 (PF4). This causes platelets to form dangerous clots throughout the body. Some research has found that patients with clots had antibodies to PF4.

Antibodies were observed. They were created by the immune system in response to antigen which mimics portions of PF4 with pathological features. This antigen remains unidentified.

It was almost a complete theory. If part of the spike antigen made by these vaccines were shown to be the antigen by cross-reaction with PF4, it would be complete. An unreviewed preprint with good methodology, (ResearchSquare, pdf) Anti-SARS-CoV-2 Spike Protein and Anti-Platelet Factor 4 Antibody Responses Induced by COVID-19 Disease and ChAdOx1 nCov-19 vaccination, shows that it does not cross-react.

So to be complete,  this “leading theory” requires that some other antigen, made by some other action of the vaccine, reacts with PF4. The BioSpace blurb offers this:

A research team out of the University of Griefswal…Their theory is that there are about 50 billion virus particles in each dose of the vaccine, and some might break apart and release their DNA. Like heparin, DNA has a negative charge that might help bind it to PF4, which has a positive charge. That bound complex might trigger antibodies’ production, which could signal the body to increase blood coagulation.

This is not a theory. It’s a completely legitimate hypothesis.  To describe it as a theory in a specialty website does no service to the subject. It erodes clear thinking.

Next: A few more hypotheses, which you may elaborate with your own imaginative, well-founded logic.

The law is a blunt instrument, but sometimes, justice is done. The problem of Black Lives Matter runs so  deep that the guilty verdict serves as an admission and a statement — but not as a solution. Previous articles:

• Police Brutality, Derek Chauvin, and the Death of George Floyd Part 1
• Police Brutality, Derek Chauvin, George Floyd, Rousseau’s Social Contract Part 2
• U.S. protesters call to Defund the Police.

Police brutality and racial discrimination have ample precedent in U.S. history, though we thought we had banished the worst of the past. Why has the social climate in the U.S. has deteriorated so much since 9/11?

• Delayed effect of external pressure from terrorism?
• Modest expansions of liberality by the Obama presidency, or awakening of latent racism by a Black president?
• Decline of the standard of living, bringing illegal immigration to the fore?
• Or is it the Web, which has spawned millions of tiny hate channels?

How much has changed!, since JFK’s inaugural (YouTube):

(click for full text) And so, my fellow Americans: ask not what your country can do for you — ask what you can do for your country. My fellow citizens of the world: ask not what America will do for you, but what together we can do for the freedom of man.

The U.S. is not a failed state. It is a troubled state, with generosity and compassion under siege.

The argument for leaving is laid out in Trump Wants to Fire U.S. Commander in Afghanistan, in which I explained that the unsolvable part of the Afghan problem is civil, not military. Quoting,

The bare-bones boiled-down essence of modern government is just a few things:

• • Raise revenue by taxation.
  • Use at least some of the taxes to provide services.
  • Facilitate commerce.
  • The services provided justify the taxes enough for popular acquiescence.

You can add all the bells and whistles. But it’s the irreducible minimum. Anything less, and it becomes a protection racket.

Afghanistan has no legitimate economy.

Hence there is no way for the legitimate government to differentiate itself from the Taliban, save social values, which are not enough. We could stay there forever, as Lindsay Graham advised Trump. But when forever is over, the result would be the same. Liza Minnelli: Money makes the world go around.

(The Hill) Top general: Counterterrorism strikes in Afghanistan after withdrawal ‘harder’ but ‘not impossible’ Quoting ,

On Tuesday, [Gen. Frank] McKenzie also said he continues to have “grave doubts” about the Taliban’s reliability in upholding its commitments under the deal signed last year.

I have grave certainty that they won’t uphold. This will be a slaughter of the good. The   future reeks of the fall of Saigon, when our friends were falling off helicopter skids as they begged for rescue. I suspect that the slaughter of innocents bothers H.R. McMaster even more than the strategic retreat.

To remain would only delay the inevitable. Afghanistan is caught in the gyre of a primitive cultural ocean.  Eventually, China, and perhaps India will, in exploitation, bring some measure of humanity.

A legacy of attitude promotes Indefinite commitment. In 2001, the U.S. was the unchallenged superpower. Now it is challenged. We are not quite through that era, but we can see the sunset. Now, we must prioritize.

With the withdrawals, ceding large territories to the Taliban, costs are down. The cost of regaining control of the country approximates the $100BN/ year peak costs. But the budget bleed is not the deciding factor.

Afghanistan is not supplied by a sustainable air bridge. For gross tonnage, we rely on Pakistan, which has strong ties to China. The other bordering states are potential, if not actual, adversaries. U.S. troops could be isolated as hostages if hostilities occur elsewhere. Our presence in Afghanistan interferes with credible deterrence elsewhere.

This is not hawk versus dove. Most military, particularly those who are familiar with the hard truths of simulations, know this: A superior military can be destroyed by over-extension.

To those who idealize the U.S. posture without thought of strategic balance, there’s always common sense:

You don’t go into a gunfight with your nuts hanging out.

John Avlon takes on the medical establishment in video: These unlikely events are still more likely than a blood clot after the J&J vaccine.

All news teams encounter a  universal problem when the issue goes beyond the general competence implied by a modern, liberal education. Avlon’s team has grabbed statistics for a way into the problem. But as I wrote in AstraZeneca, What to Do?,

Statistics needs mechanisms. If peculiarities of cases are not correctly weighted, the statistical  threshold, surpassing chance, could be missed. Mechanisms  focus statistics.

Without the mechanism of these clots, the stats of the video are useless as reassurance. The FDA and CDC are concerned about adverse effects that are buried in noise of the unknown future. With mechanisms, you know what you are looking for. With knowledge of mechanisms, you can rule things out, like future mass casualties.

If you were to time travel back 60 years, to the time of dark ignorance preceding molecular biology,  to a med school class in tropical diseases, the prof might remark, if not in writing,  “Eventually, if an individual receives enough immunizations, the recipient will probably die.”

The current state of knowledge is vastly greater. Nevertheless, it might surprise that it is still  not possible to predict with certainty whether a particular virus, for which the genome is completely known, can reproduce in a particular host. The viral landscape remains shrouded in twilight, with at least the possibility of long term effects that must be ruled out by rigorous investigation. Statistics  by itself does not suffice.

The chance of widespread harm, from a vaccine administered to a mass population, is the nightmare of vaccinology. Here presents a hazard, on a scale Hippocrates could not have imagined, which reminds us of the first principle of bioethics: “First, do no harm.”

News teams cannot be expected to have specialist knowledge. They may rely on individuals who have been misqualified as competent on the issue. What systematic could a news team find useful to plug this gap? It’s worth taking a look at the (Wikipedia) Delphi method. Quoting,

Delphi is based on the principle that forecasts (or decisions) from a structured group of individuals are more accurate than those from unstructured groups.^[6]…

CNN, you might find it fascinating to assemble a group to address John Avlon’s question, and watch them work. Just by watching, you get insights into the structure of knowledge of the field in question.

Suppose the  rare but multiple deaths/injuries, by cerebral venous sinus thrombosis, have been caused by the AstraZeneca vaccine. Although my suspicions date to August 2020, a blog like this is in no position to establish causality. As with the Havana Sonic attacks, the determination of causality/reality requires national resources to acquire and analyze data.

Statistics needs mechanisms. If peculiarities of cases are not correctly weighted, the statistical  threshold, surpassing chance, could be missed. Mechanisms  focus statistics. (CNN) More European nations pause AstraZeneca vaccine use as blood clot reports investigated offers a possible mechanism.

The dilemma may recapitulate the yellow fever vaccine. It saves many lives, and takes a few. Over generations, inhabitants of regions where yellow fever is endemic  have learned the penalty, and correctly weigh the two risks. If COVID goes on long enough, we might arrive at the same understanding.

It is possible the AstraZeneca vaccine saves many lives and takes a few. The choice would be clear, except that the alternatives save many lives and take no lives, or far fewer. With the push of AstraZeneca, justified in the race against time, public health planners should be aware of the primitive logic people use to get by:

• Random risk. Ever present and possibly avoidable, “if I am careful”, “if I have no risk factors”, and so forth.
• Severe risk. For example, advanced cancer.
• Assumed risk. From a choice you make.

We are willing to assume just a little risk to minimize random risk. With severe risk, we are willing to assume considerably more, as with a bone marrow transplant. All the sophistication of the human brain permits just this simple weighing of pros and cons. COVID straddles the border of random and severe.

Unless strong counter-evidence emerges, as opposed to “no evidence”, that AstraZeneca is blameless of CVST, a blow back may result, playing into the hands of the antivaxers, in a highly disruptive way.

There are less fortunate places than the developed countries, where life is cheap and death is plentiful, where the inhabitants will be more appreciative of AstraZeneca.

We begin with the reality of political murder in Russia; then to bilateral relations.

With implied reference to the attempted Novichok poisoning of Alexei Navalny, Biden called Putin a killer. Putin responded with “It takes one to know one”, which shows that snappy retorts are multicultural. Putin may occasionally view this blog. I will not convict him here. A crime detective would note that he has the means and motive to kill Alexei Navalny, but open source proof is unavailable. Proof from clandestine sources could exist, but such proof could never be revealed without endangering the sources.

In Western law, conviction of a crime requires proof beyond reasonable doubt. Since this is unlikely to ever be available in Russia for a particular individual, only the Court of Public Opinion can convict. The proof exists for the Kremlin as a whole. (Guardian) Russian FSB hit squad poisoned Alexei Navalny, report says.

Motive: Navalny really is a mortal danger to Putin’s Russia. In Alexei Navalny, Poisoned Again? The Russian Poison Trick, I wrote

But why must Navalny be silenced now? Navalny has recently positioned himself as a pro-Western democrat, but his history includes association with the ultra-right. While his impulsive rants are harmless to the Kremlin, Navalny-the-strategist is the ultimate of danger…

(New Yorker, paywall) How Putin Controls Russia interviews Masha Lipman, a Moscow-based political analyst. Quoting one of the few points I actually agree with,

There’s reluctance to organize, as I mentioned earlier, around a political cause, a political leader, or form a political party or a movement. And this protest being limited to a particular cause or a locality is beneficial for the government…

Navalny is pan-Russian, attempting to forge a coalition of disparate and contradictory groups: Western, liberal, fascist, racist, nationalist-excluding the Caucasus, et. al., united only in opposition.

State execution by poisoning dates back to at least December 17 1916, when Prince Felix Felixovich Yusupov fed Grigori Rasputin cakes and wine laced with cyanide. Nothing happened; the Russians had adventitiously discovered the protective effect of sucrose.  The Bolsheviks got better; they established a  lab to make reliable poisons. This has been going on a long time. As with Navalny, failures occasionally happen. We don’t hear much about the successes.

Having committed the sin of surviving state-executed poisoning, Navalny is now in Penal Colony No. 2. How do you kill someone without making a martyr? It would not be surprising for Navalny to be murdered by well-paid convicts, guards, or plants. It would be tragic, since Navalny, the unrealistic idealist, is in many ways a man too good for today’s Russia. History is full  of deconstructions of governments that lead to renaissances. Russia desperately needs a renaissance.

As Putin himself has remarked, Russia ‘s government is historically paternal. In the West we think our way to our own destinies. In Russia,there is an almost universal, quasi-religious faith in rulers. So resulted the initial denial, in emotional terms, by Vladimir Kara-Murza Sr.,  that his son had been poisoned. (RFE) Kremlin Critic Emerges From Coma. Vladimir Kara-Murza Sr. died in 2019 at age 59. In Russia, you have to wonder.

We now have a circular sustaining loop. You can start at any point and work your way around:

• Paternal government, sustained by popular attitudes which deny misdeeds of government, such as political murder.
• Opposition, rejecting paternal tradition, who seek to overthrow the paternal government by political means, via the existing facade of democracy.
• Political murders of the opposition, with  effect to sustain the paternal government.
• Loop to the top.

Putin might say that the paternal government must be maintained because there is no bridge to something better. This was explored in:

• Fiona Hill, Putin’s Apology; Analysis Part 2
• Fiona Hill, Putin’s Apology; Analysis Part 3
• Fiona Hill, Putin’s Apology; Analysis Part 4; KGB Culture
• Putin’s Job Works on Him; His Apology; Navalny Detained

Takeaway: Political murder is organic in Russia. It has a long tradition, it is not rooted in a single individual, and we have zero chance to keep Navalny breathing if the Kremlin wishes otherwise.

To be continued shortly.

(CNN) More European nations pause AstraZeneca vaccine use as blood clot reports investigated. Quoting,

Denmark, Iceland and Norway have suspended the use of the Oxford-AstraZeneca Covid-19 vaccine while the European Union’s medicines regulator investigates whether the shot could be linked to a number of reports of blood clots.

Please refer to:

• Why I Would Not Take the Russian or Oxford – AstraZeneca Vaccines – Part 2
• (CNN) AstraZeneca pauses coronavirus vaccine trial after unexplained illness in volunteer
• (CNN)NIH ‘very concerned’ about serious side effect in AstraZeneca coronavirus vaccine trial, which offers a plausible mechanism.

An adenovirus vaccine uses an adenovirus vector to  transport a transgene cassette, a complete set of  instructions for making spike protein, into cells at the injection site.

The manufacturing process  of an adenovirus based vaccine uses a live “helper virus” to grow the vector virus, which cannot replicate. The proposed mechanism exploits the inability to completely purify the vaccine product of trace amounts of helper virus.  There is more to this, which is explained in (CNN)NIH ‘very concerned’ about serious side effect in AstraZeneca coronavirus vaccine trial.

It is frequently stated that adenoviruses are stable against recombination. This has been found to be false. For this mechanism to generate an actual adverse event would depend upon random recombination, and the particular strain of adenovirus used as a helper.

J&J’s vaccine uses similar technology, adenovirus-as-a-vector, but a different adenovirus strain. This may be why, for unknown reasons of detail, adverse events have not occurred with a frequency that suggests causality.

(CNN) Vaccinated Americans allowed to taste freedom. The article also contains an interview with Dr. Wen, who thinks CDC should have loosened more. In the past 12 hours, (Nature) Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 has brought The Outer Limits to your browser. It becomes suddenly urgent to do another napkin calculation. 

A napkin calculation was presented in Misplaced Hopes for COVID Herd Immunity; Napkin Calculation, with the implication that classic herd immunity, when COVID would drop down to occasional events, is not likely to happen any time soon.

(Reuters) ‘When will it end?’: Reuters vs. CNN vs. Intel9 explores why COVID reportage seems mired in platitudinous wishful thinking. Part of it stems from the difficulty for news teams of qualifying experts.  Dr. Wen of the video, former Health Commissioner for the City of Baltimore, has proven competence  at executing public health policy.

A keen intuitive connection with numbers is another affair. Not working spreadsheets and designing budgets, but the kind of innate, intuitive sense that the best modelers, mathematicians, engineers, and scientists have. When you have a serious disease, you look for a specialist.  The same goes for numbers. Clinical and administrative experience does not imply expertise in epidemiology, which is a highly mathematical sport.

Let’s do another napkin calculation, which will solidify (The Lancet) An action plan for pan-European defence against new SARS-CoV-2 variants.When you’re done, don’t wipe your chin with it.  Hold onto the napkin and show it around.

R_o, the basic reproduction number, is  the average number of new infections caused by a single infected individual, in a naive population, before public health interventions.  R (without the 0) is the number after interventions. From (NCBI) Time-Varying COVID-19 Reproduction Number in the United States,

… For the entire United States, the reproduction number declined from 4.02 to 1.51 between March 17 and April 1, 2020. We also found that the reproduction number for COVID-19 has declined in most states over the past two weeks which suggests that social isolation measures may be having a beneficial effect.

Why the sudden drop of R ? People got scared,  stopped  “going in your face”, and shaking hands.  That’s how variable it is.  R_o and R are weak concepts, useful to conceptualize, useless for prediction. The numbers vary too much with social activity. February tends to be an unsocial month.

Some conservative statements:

• No matter what, vaccination is personally beneficial.
• Vaccination benefits society. Only how much is in question.
• If, having been vaccinated, you still catch COVID, vaccination could reduce your infectivity.
• Then again, it might not. Asymptomatic cases are infectious.

The CDC goal is to reduce R to less than 1. Then, according to the prevailing bullshit, COVID will almost vanish. The goal is supposed to be accomplished by vaccination. Now try to swallow this pill, which assumes a worst-case vaccine efficacy of 60%, which avoids the assumption that vaccines are perfectly on target:

• The current value of R = 1.51
• Vaccination is 60% effective at preventing disease. 40% experience vaccine failure and contract COVID.
• Assume that this is equivalent to reduction of R to R*0.4 which isn’t supported by anything. If this looks sloppy, too bad. This is what hope looks like when you put it under the microscope.
  
• After the public has been vaccinated, R becomes (1-0.6)*1.51 = 0.4*1.51 = 0.604,  less than 1. COVID goes away!

Hold onto that napkin, even if the pill didn’t go down. In March 2020, R was 4.02. All it takes to be there again is bars, restaurants,  sports, choirs, and all the things we love to do.  It doesn’t even need French kissing. Then R after vaccination becomes 0.4*4.02 =   1.608, disaster!  Would a 75% effective vaccine fix this? To avoid catastrophe requires more than 75% protection against clinical disease. It requires the same number for infectivity.

We didn’t cook the numbers by use of  an efficacy 95% for “original COVID.” U.K. B.1.1.7 has been deemed manageable, but the South African variant,  B1.351,  is already here. Darwin’s selection decrees that B1.351 will become dominant; all the strains for which effective vaccines exist will vanish. See (The Lancet) An action plan for pan-European defence against new SARS-CoV-2 variants. Quoting,

…epidemiological data suggest they have a higher admissibility than the original variant…These viral properties could increase the effective reproduction number R in the population. In the case of B.1.1.7, estimates suggest R could increase from 1 to about 1.4 with no change in population behavior. If true, many countries that have succeeded in reducing R to 1 or less will be confronted with a novel wave of viral spread despite the current measures.

When B1.351 is vanquished, other variants will compete for dominance, with each other, and with vaccine makers.  Ad infinitum.  Ground Hog Day. Is this certain?  No, but to assume otherwise is wishful thinking.

Now you know why CDC doesn’t want you to fly. Statements from government are colored by awareness that many Americans have reached  the brink of madness. There seems little appetite in the press to dig. In normal times, the Reuters article  would not be exceptional. Now it is.

Now march your two napkins around the office, or show them on Instagram.  If someone tries authority,

(Reuters) ‘When will it end?’: How a changing virus is reshaping scientists’ views on COVID-19. Quoting,

 “I couldn’t sleep” after seeing the data, Murray, director of the Seattle-based Institute for Health Metrics and Evaluation, told Reuters. “When will it end?” he asked himself…

…data in recent weeks on new variants from South Africa and Brazil has undercut that optimism. They now believe that SARS-CoV-2 will not only remain with us as an endemic virus, continuing to circulate in communities, but will likely cause a significant burden of illness and death for years to come.

Murray’s thoughts align with mine. Quoting from Misplaced Hopes for COVID Herd Immunity; Napkin Calculation,

With anticipation of widespread SARS-CoV-2 501Y.V2 and other mutations, the factor of 1/2 could imply we are currently, not at 40%, but  20% immunity. … The implies herd immunity in November/December, not August….This is possible, not factual, if COVID doesn’t have more tricks up its sleeve. It takes influenza A about 25 years to cycle through its range of antigen permutations.

Even with the not-quite promise of herd immunity, COVID-19 is likely to remain a nasty, prevalent disease,  sparing only those with lucky genes,  and those who are exposed as children.

Contrast with (CNN) US could reach herd immunity by summer through vaccinations alone, CNN analysis finds. Quoting,

But experts generally agree that somewhere between 70% and 85% of the population must be protected to suppress the spread, a range that Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases has recently cited.

You have enough to compare the two predictions, by Chris Murray at University of Washington, Intel9, and CNN. Look at these points:

• Which argument has the most visible logic?
• Which article asserts a consensus of experts?
• Of the two predictions, how many supporters? How many dissenters?
• Which article cites an authority figure for support?
• Which article lays claim to authority as an argument in itself? Hint: Look at the title.
• Which articles emphasize COVID variants? Which mentions in  a minor closing remark?
  

Your comparison could be completely subjective, in which case, ask yourself, “What kind of a thinker am I?” Or you could apply (Decision Science News) Benjamin Franklin’s rule for decision making.

What do you come up with? You could just “pass”, but it’s a good exercise.