Without durable individual immunity you cannot even talk about herd immunity

 In the early days of the covid 19 pandemic there was much speculation about what percent of the population would have to be vaccinated in order to achieve herd immunity )(HI). It seemed to be a matter of not if but when HI would be accomplished.

Writers made analogies to  measles and smallpox for which vaccination programs achieved herd immunity and in the case of smallpox, eradication. If HI could be achieved  for a  very infectious disease such as measles spread by aerosols, why not covid 19?

Theoretical considerations regarding HI center on the basic reproduction number (R naught or Ro which is the average number of people that one infected person will infect.  The number of people needed to be immunized in order to reach HI is 1-1/Ro.For example-if the Ro is 2 then 50% would have to become immune (either through vaccination or infection) for a Ro 0f 3 we see 1-1/3 equals 2 thirds or 67% 

Several simplifying assumptions underlie the formula for HI including that all individuals have an equal opportunity to become infected. Epidemiologists disagree as to what exactly HI is and as to what the necessary assumptions are in estimating a HI vaccination level.

However the key-typically implicit- assumption is that being vaccinated ( or recovering from an infection) results in long lasting immunity.(1)

We now know that this major assumption does  not conform with reality. We now know that fully immunized individuals can become infected and can transmit the disease and also  that recovery from covid 19 infection does not preclude becoming infected again. 

The idea underlying HI is that as individuals become vaccinated ( or recover from infection) they are removed from the susceptible pool. With covid vaccination or infection  both groups seem to be removed from that pool only for a time , perhaps as short a time as 6-8 months. While infection blocking immunity (nasal mucosal immunity) wanes quickly the disease reducing immunity seems to be more durable.

When cases of abreakthrough infection became recognized as a real thing,some in the public health sector  said  " well, the vaccine was only intended to prevent serious disease and death".But if that were the case why was there so much  talk about achieving herd immunity a concept that IMO only makes sense if the vaccine prevents spread.

Dr Jennie S Levine has been quoted that she and her colleagues talk about transient herd immunity.

My thought on that is perhaps we are seeing a transient HI for example now In Louisiana and Texas .Both states had a major Delta surge with a surge of cases and hospitalization and death and now the surge seems to have abated.Possibly as more and more people were vaccinated and more infection plus mandatory NPIs (in Louisiana ) the number of susceptible individual decreases to reach some level of transient herd immunity like condition. However, as immunity wanes again in states with a large number of unvaccinated individuals serving as a covid reservoir some level of spread could occur again  for another round of surges . Are we likely to continue to see regional whack a mole events .

A much more optimistic scenario is that the booster shots will bring about a sufficiently long period of immunity so that more than a transient herd immunity could be achieved. In other words- the covid 19 mRNA vaccine should have been a three shot vaccination  program all along.  

1)Core Concept: Herd immunity is an important—and often misunderstood—public health phenomenon | PNAS

How big will the US covid winter surge be?

The epidemiology  predictors at IMHE made their prediction for the 2021 winter on a tweet published November 5.

Based on three factors they predicted there will be a winter surge but, of course its magnitude is unknown.

The factors are : 1) seasonality 2) waning vaccination immunity 3)less caution by the public,We think we know the direction of these vectors but what about their magnitudes?

As time goes on not only vaccine immunity will fade but so will the immunity of previous covid 19 infection  both of which seem to fade in about six months.   Countering that direction is the number of people receiving the booster shots.Countering that is the relentless barage from right wing media claiming that the vaccines are either dangerous or worthless.

Meanwhile in France and Germany a new surge seems underway and travel restrictions to to the US have been lifted. What could possibly go wrong?

Dr. Michael Osterholm is quoted: "Any effort to predict future course beyond 30 days relies on pixie dust for its basis" and we all remember what Yogi said about predictions particularly for the future.

Cardiac fibrosis in endurance athletes

 There have been a number of reports of cardiac fibrosis in endurance athletes. It turns out that these reports pertain to areas of late gadolinium enhancement in right ventricular insertion points.Some explanation is required . To begin with-all forms of fibrosis are not the same.

Gadolinium is the contrast agent  used in MRIs.It accumulates in the extracellular space and lights up on a cardiac MR and is called Late Gadolinium Enhancement (LGE)

LGE is seen in myocardial infarctions in necrotic areas with scars consisting of replacement fibrosis.LGE has also been reported in hypertrophic cardiomyopathy (HCM) ,pulmonary hypertension and more recently in a number of long time highly trained endurance athletes.In these three conditions the underlying pathology is not replacement fibrosis  (as is seen in a myocardial infarction scar) but rather plexiform fibrosis and myocardial fiber disarray and is typically seen at the insertion points or hinge points where the right ventricular wall inserts on the interventricular septum. 

Sato et al (1) proposed  that paradoxical motion of the interventricular septum is a primary mechanism for late gadolinium enhancement (LGE) at the ventricular insertion or hinge points.

LGE at ventricular insertion points has been described in pulmonary hypertension and in a number of highly trained endurance athletes .It is unlikely that paradoxical septal movement explains the LGE at hinge points in these athletes although it may be  true in the cases described by Sato.

DeBosscher et al (2) found LGE at the hinge points in young and older highly trained endurance athletes but found no evidence that LGE was associated with any structural,functional or electrical problem with LGE at the insertion points which they found  28% of the 233 athletes studied.

LGE was first described in  older endurance athletes   but now this data demonstrates that younger runners may also have that finding and that it is not a uncommon findings in highly trained runners and its long term significance remains to be determined. I suppose the fact that the LGE does not represent replacement fibrosis  with its associated risk of reentrant ventricular tachycardia  is good news.However,data is lacking as to the long term consequences (if ANY) of LGE at the RV insertion points in long time endurance athletes regarding reentrant rhythms or other clinical problems. 

1) Sato,t et al Paradoxical motion of the interventricuar septum as a primary mechanism of ate gadolinium enhancement at ventricular insertion points. Int J Cariol 2012;158 (1) 156-7 

2)De Bosscher, R et al Hinge point fibrosis in athletes is not associated with structural, functional or electrical consequences;a comparison between young and middle aged elite endurance athletes. Euro Heart Journal, 41,supp 2, Nov 2020 

What is the threshold for exercise induced cardiac remodeling (EICR)

 It has been known for over 100 years that physical exercise  may cause heart enlargement.A study of Harvard rowing team members described cardiac enlargement in an 1899 issue of the Boston Medical Surgical Journal.  

There have been numerous cross sectional and longitudinal studies documenting the structural changes in the heart associated with high levels of aerobic exercise.These  are enlargement of all four chambers and mild to moderate increase in the left ventricular wall thickness and an increase in left ventricular mass index- a condition referred to as eccentric hypertrophy to be distinguished from the concentric hypertrophy characteristic of strength building exercise. 

How much exercise is required to bring about that remodeling? Is  eccentric remodeling observed in runners whose activity  level is far less that that required  to be competitive in a full triathlon ?

Dawes and associates  (1) have provided some answers.They performed cardiac mri s on 1096 volunteers and linked  the mr results with their self reported exercise habits over the previous 12 months. They divided the exercise histories into four categories with category 1 being essentially no regular aerobic exercise and category 11 defined as less than or equal to 3 hours per week. They found that there was no statistical difference between category I and category 11 in regard to cardiac MR findings/

So one 'take- home" from their study might be  that exercise less than 3 hours per week is not likely to be associated with any exercise related structural cardiac changes. 

Moreover they found that increasing activity levels were significantly associated with increased ventricular end-diastolic volumes and left ventricular mass index

However, minutes exercised is not the only variable related to EICR which is likely related to some summation or interaction between intensity, frequency and duration. One could speculate that someone doing 3 hours of high intensity interval training per week  might well induce a bit of EICR and that someone doing 8 hours of slow walking in the park per week may probably would not

1) Dawes TJW Moderate physical activity in healthy adults is associated with cardiac remodeling.Circ Cardiovascular imaging 2016  se004712  

Has the conservative- libertarian "fusion" been severed by Trumpian authoritarianism ?

 Aaron Ross Powell from Cato Institute writes about the  always fragile "fusion" of conservatives and libertarians becoming increasingly severed. He refers  back to Robert Nozik's observation that  " Liberty disrupts patterns" as at least a partial explanation. 

Conservative- preferred social patterns are disrupted by liberty  So to maintain those patterns conservatives turn to authoritarian means , if not they loose their conservative values. 

What are these conservative values? They generally include family values which mean a man-woman stable relationship,opposition to gay unions,opposition to abortion and a tending to endorse traditional female roles in society, allegedly based in and supported by biblical principles. Additionally conservatives  endorsed  a society that is  largely managed and controlled by white anglo saxon men with opposition to encroachment by black and brown immigrants, preferring things as they once were or  were thought to be at some vaguely defined prior time.

Progressive big government with its ever growing body of liberty limiting regulations is a common foe for conservative and libertarians with conservatives bristling  at bureaucratic rules antithetical  to conservative's preferred social norms and libertarian obviously promoting liberty.

Decisions once made by families and local governments have been shifted to state and then federal government as the locus of decision making, a development well described and critiqued by Thomas Sowell in his book "Knowledge and Decisions ". This central decision making  shift is another common foe for conservatives and libertarians.

Arnold Kling offered a framework for considering the differences between the languages used by progressives,conservatives and libertarians Progressives tend to frame things as there being a battle between the oppressed and the oppressors, while conservatives see things as between civilization and barbarism while libertarians view matters as between liberty and coercion.

In answer to the title question-No Trumpian authoritarianism   did not break the conservative-libertarian fusion as it was a fragile union to begin though arguably useful regarding  certain issues   but his rhetoric may have provided a effective rallying cry (MAGA) and gave the nativists' core of conservatism a person around whom  to rally.

I believe the key insight in Powell essay is that liberty disrupts patterns and conservatives hold certain societal patterns to be important which are put at risk by liberty so conservatives have to jettison liberty to protect their values. In the terminology of Kling the issue  framed for conservatives is barbarism versus civilization and sometimes liberty must be sacrificed to fight off barbarism.Quoting Powell " conservatives have to restrict liberty to retain their social and economic patterns.".

Korean study shows a positive and graded association between physical activity and coronary artery calcification

 A large prospective study (1) from Korea demonstrated a positive relationship between self-reported physical activity and coronary artery calcification (CAC) scores.

There is overwhelming epidemiological evidence that regular exercise is associated with decreased risk of cardiovascular and all-cause mortality.Data indidcate that small amount of exercise is beneficial in that regard and that more seems  better.A panel in 2018 recommended as a minimum 500 met hours per week which is equivalent to 2.5 hours of moderate exercise or 1.25 hrs of vigorous ( greater than 7 Mets) exercise.

Eijesvogel in his comprehensive analysis of the " extreme exercise hypothesis" noted  that the maximum reduction in CV morality was noted at 41 Met hrs per week which is five times the minimum recommended level.  So there is a well defined linear relationship between exercise volume and CV mortality and so far data have not indicated a J shaped curve in that regard.

Defina et al (2) demonstrated that high levels of physical activity ( 3,000Met min per week which is five times the minimum 2018 recommended level) was associated with  prevalent CAC but was not associated with increase in CV disease mortality..Other publicaions have  also demonstrated an increase in coronary calcification in long time endurance athletes .

Sung's article now provides a "positive , graded association between physical activity and progression of coronary calcification, regardless of CAC scores". 

Quoting Sung ;"The standard Agatson CAC scores are calculated as a combination of calcium density and the volume of plaque burden. Higher calcium density,which suggests a more stable calcified plaque, produces a higher CAC score, however it is associated with lower CAD risk."

Both long time endurance exercise and long term use of statins are associated with increased coronary artery calcification  but  lower CV morality.

1)Sung,K et al Physical activity and the progression of coronary artery calcification. Heart 2021;0:1-7,

2) Defina,LF at al Association of all-cause and cardiovascular mortality with high levels of physical activity  and concurrent coronary artery calcifications,JAMA Cardiology, 2019 42 (2) p 174 

Anti Hubris thoughts for medical students-- "our ignorance is boundless"

Sixteen years ago I posted an entry on this blog in which I suggested an anti-hubris courses ( or at least a few lectures) for medical students.

I did not have all the content of this course prepared  (and still have not) but I do have the sense of it and some great quotes which I will sprinkle below.

 The following is a lightly re-edited version of that entry.
 

Most of the  sense of it is from the writings of Norton Hadler and much of it can be found in his article on various European backache compensation systems (JOM,vol 31, pg 823, 1989). In it he speaks of clinical truth which he distinguishes from scientific truth-although scientific truth must be utilized in obtaining clinical truth-and from legal "truth"-which is incidental to settling the dispute at hand. Clinical truth is or is derived from a contract between a physician and a patient and is based on trust.He said it better than I can and his article would be required reading in this "anti-hubris" course.

Our approaches are provisional and based on fragmentary information and when I think about the algorithms and paradigms that are in our tool boxes, Boris Pasternak's quote appears as an emphatic "yes..but", "What is laid down, ordered, factual, is never enough to embrace the whole truth:Life always spills over the rim of every cup". Karl Popper said " we know a great deal but our ignorance is sobering and boundless...all things are insecure and in a state of flux".


All of this does not mean that we can't pull out the latest guidelines from whomever on our smart phone and see if that does or does not apply to the case at hand.But the operative words there are "see if it applies to the case at hand." The experienced physician has one- at least one-advantage over the younger one, he has seen the 180 degree changes in a given algorithm or clinical guideline. Plaintiff attorneys are fond of saying to the expert witnesses ,"Doctor,were you wrong then or are you wrong now" in the situation where there is an apparent contradiction.

Medical students need to know-in regard to the "factual knowledge" imparted to them- that while that material may be the very best that the very best of minds can determine at this time that they need to stay tuned because all of that may change at any time and the physician will have to decide what to do for the patient even before the next authoritative pronouncement is prepared.In that decision she will have to call upon her knowledge,expertise and judgement and the patient's values and views and do her job the way physicians have for many years before guidelines were part of medical language and work with the patient for their particular clinical truth.

"Life is short,the art long and judgement fallacious." is a hard quote to beat.
 .

Still another variation of conduction system pacing -left posterior fascicular pacing

 The right ventricular apex was the preferred site for ventricular activation for pacemakers for several decades.After the realization that apical pacing was associated with an increased risk of heart failure and atrial fibrillation his bundle pacing was rediscovered.Although two cases series of his bundle paced patients were published  in the 1970 s it was not until over forty years later that his bundle  pacing finally began to become established and it was claimed by some electrophysiologists that the era of physiological pacing had  arrived. 

Although his bundle  pacing was considered to be physiologic,it was more technically daunting and typically required a higher ventricular capture voltage.There was also  some frequency of delayed lead displacement  and a shortened battery life paralleled the higher capture voltages.

In 2017 Huang et al described the next development in conduction system pacing-left bundle branch area pacing.  In this technique the sheath is advanced about 1.5 centimeter from the site of His signal recording towards the apex and deeply inserted into the ventricular septum.It is less technically demanding than is His bundle pacing  and requires a lower capture voltage and in some EP centers it has replaced His pacing as the go to conduction system pacing of choice.

 In 2020 Ponnusamy et al (1)described a case in which they were unable to obtain a satisfactory left bundle branch area lead placement and  then maneuvered the lead  2 cm lower and positioned the lead in the area of the left posterior fascicle. A similar case had been described by LJ Zen et al in 2019(2)

The 12 lead EKG with Left posterior fascicular pacing demonstrates a pattern of left anterior hemiblock. 

1) Ponnusany, SS et al. Left posterior fascicular pacing. J Innov Cardiac Rhythm Manage 2021 12 (5) 4493

2)Zeng, l, et al Permanent left posterior fascicular area pacing through the interventricular septum in a patient with infra-Hisian block, Heart rhythm Reports, 2019, Aug 5 (8) 411-413

Long time endurance athletes long time outlook looks good less so for "power" sport advocates

 Dr Runacres (I am not making that up) et al published a meta-analysis of 165000 long time athletes and found , as have other studies, that endurance athletes have lower  cardiovascular mortality and all cause mortality but that does not hold true for long devotees  of power sports. See here 

September 2021- US in another surge in spite of excess vaccine and plenty of masks

 Here we are in another covid surge in the US even though there are no shortages of masks or vaccines.Neither is there a shortage of people who oppose the use of vaccines and masks nor is there a shortage of people seemingly ignorant of the seriousness of the Delta variant driven surge and stress placed on the health care system. 

Neither is there the  previous  official ignorance about the basic transmission mechanisms of Sars Cov2 spread. 

It was not until April/May 2021  that the CDC and WH0 finally abandoned  the primacy of the 100  year old dogmas put forth by Charles Chaplin which said that the basic mechanisms of respiratory disease spread were by droplets and fomites. 

By September  2021 it is well established that Sars Cov 2 can spread in pre symptomatic and asymptomatic people by the aerosol route and that measures directed at droplets and fomites will not suffice. Well fitted high grade masks ( eg.N95s) are needed as well  as mitigation efforts directed along the lines of ventilation, and air flow,  air filtration and air exchange  in indoor settings to complement a vaccination and testing program.

So we know more and should be better  prepared and yet in some parts of the country we are seeing high deaths and hospitalizations. We see parts of the country in which mask wearing is much less than it was in the 2020 surges.Parts of the country that had mask mandates in 2020 now have "anti mask mandates" that prohibit local authorities from imposing mask mandates. Anti mask and anti covid  19 vaccine advocacy flourish on social media and right leaning radio and tv. We know what to do to mitigate the spread of covid 19 but many are defying those measures and apparently many others seem indifferent.

Watching the Astros on TV play at home on in Dallas the optics are the same, virtually no one in the stands wear a mask. even though Covid is surging in Texas.

Whatever effect anti mitigation efforts may or may not be having on the magnitude of the spread  of the Delta variant, its  increased infectiousness has to be considered a primary cause of the latest surge.Delta is clearly more infectious and there is growing evidentiary support for the claim that it is more capable of causing serious disease than were earlier variations. At a time when a more contagious variant is surging we are also seeing surges in ignorance, indifference and political ambition all of which make the  magnitude and speed of spread  even worse. 

Why the US Covid Delta surge may not burn out as quickly as it did in England.

 The rapid uptick and downtick of Delta observed in England has been thought by some to predict  a similar course for the US but the opening of schools may b ae wild card and the Delta surge may not end as quickly as it did in England.

Both Dr. Michael Osterholm and  Dr.Larry Brillant offer a more pessimistic prediction because of their concern that the opening of schools across the country will provide fertile ground for spread and also  offers a platform for virus mutation.

In numerous areas of the country students will not be masked and only a small percentage of high school and primary school kids will be vaccinated. In several states there  has been a concerted effort by the governors and sometimes that state legislatures to issue executive orders and pass legislation  the effect of which is to limit the use of masks and certain other virus mitigation measures in schools and to restrict the right of a private company to  use  " vaccine passports".  

Osterholm in, a recent interview said that a multi layered approach is necessary ..Ventilation is important ( i.e 5-6 air exchanges per hour),as are HEPA air filters and use of proper masks ( e,g, N95 or KN95). Testing students,staff and teachers  several  times a week and removal of positive cases. The importance of airborne transmission makes the popular plexiglass barrier not very effective and may be more for show than efficacy.

The CDC and the American Academy of Pediatricians recommended  masks for school kids.Governor Abbott and Governor Desantis have issued executive orders forbidding local school boards to issue mask mandates.

Another reason that the US might not echo the path taken in England may relate to the different sequencing of vaccination doses.England had a longer period between shot one and shot 2 which has been offered as an explanation for the greater time related decreased in vaccine efficacy in the US versus England and Canada who also opted for the longer time between the 2 doses of the mRNA vaccine.

CDC realizes the vaccinated can spread covid 19 delta variant-now what

 CDC has now seemingly realized that fully vaccinated people can harbor large amounts of the delta variant in their noses and are able to transmit the disease to others. This is a conclusion that could have been reached upon analysis of the Houston Wedding event in which 6 fully vaccinated attendees develop covid  although admittedly there are alternative  less likely explanations for the Houston wedding cases.

In May 2021  when CDC seemed to set people free from mask use the data it had indicated that the likelihood of spread  from the fully vaccinated was low enough to recommend that masks were no longer necessary for vaccinated people under many circumstances.

But by July 29 with access to new data CDC concluded  that fully vaccinated people could  actually spread the disease and that the data they relied on for that conclusion would soon be released. That data is now available Further the greater infectivity of the Delta virus prompted CDC to express a much greater concern.

It now seems that the following should be considered the  operational reality on the ground.

1. Fully Vaccinated people can develop and spread covid 19 delta variant.In the vast majority of cases the disease is either mild or asymptomatic.

2.Some very small  percentage of fully vaccinated people can develop serious and fatal covid 19

3.Delta variant infection results in significantly higher viral loads and infectivity and possibly 

more serious disease. (data from Canada ,Singapore and Scotland  show Odds Ratio for ICU admission range from 3.87 to 4.9 ) 

4.Large areas of the US have relatively low levels of full vaccination 

So practically what does all of this mean.

If you are vaccinated you still  may need to wear a mask.

Why?

Since fully vaccinated people can spread covid wearing a mask protects others. There are two sets of others, the vaccinated and the unvaccinated.  A vaccinated person can contract covid and bring it home to infect children and the elderly. 

If you are not vaccinated you need to wear a mask.Masks should be N95s and ideally covered by a blue procedure or surgical mask.After exposure the mask could  be stored in a container so that they can be used after a several days period of "decontamination "  Adding a face shield to the mask may add another layer of protection although strong supporting data to that point seems not to exist The double mask has not been recommended this time by the CDC but that was recommended for a surge from a Covid version that was less contagious and perhaps less lethal than the delta strain.. Now the CDC advises that the vaccinated should wear masks if they live in a area with a high test positivity rate and a low rate of vaccination.

5.At least some of the geographic  areas cited in item 4 have governors and/or legislators who resist or oppose the standard public health measures used to control epidemics of contagious respiratory disease specifically mask and vaccine mandates. Quantification of the harm that is causing awaits the scrutiny of epidemiologists.

Breakthrough Covid cases-how many vaccinated ? Unvaccinated ?

 In the pre Delta variant era the vaccines were thought to be the answer. The expectation and hope were that a vaccine could provide immunity, stop spread and push us all to the elusive herd immunity and life would return to the pre Pandemic norm.

And for while it  appeared that was the case.As cases numbers dipped lower and lower by the spring 2021 it appears that the worse was over at least in the US and by May  2021 the CDC believed it was time for the fully vaccinated to no longer wear masks with a few exceptions noted ( eg the immunocompromised, in health care setting etc)

But then the Delta variant spread rapidly mainly in the southern states whose vaccination numbers lagged behind. Data from Israel and the US now seemed to indicate that fully vaccinated (FV) people could not only contract Delta but they could spread it.A wedding outbreak in Houston seemed to indicate that fully vaccinated people could spread it to each other. We were learning that Delta was definitely more contagious and data from Canada and Scotland suggested it was also more virulent. 

So while the vaccine promises were not met in some regards it was believed and regularly quoted by the public health and vaccine experts that the vaccine really worked well in that serious disease -the type requiring ICU care,was quite rare. 

Even with or  perhaps because of the unpresented avalanche of covid data published it has been difficult to determine how common are breakthrough cases, how frequent are the serious cases and who does it mainly attack ( is it only a disease of the unvaccinated?) ?  

Data from Israel is instructive. Israel is like an experimental lab for the world.Israel has 78% of its citizens who are over age 12 years fully vaccinated. Most if not all of the citizens are members of one of the HMOs which collect individualized  data which seems to be quickly available for analysis.

Israel is in a Delta surge . A 78% vaccination level is not high enough to prevent Delta surges. 

As of data from August 15 2021 there are 514 patients in hospital. Of those 59% are fully vaccinated  and 87% are over age 60 years. See foot note 1

In Israel serious breakthrough Covid 19 due to delta variation is not rare.

Is serious breakthrough really rare in the US or do we just have not the data to know what is going on with Delta?  Eric Topol and Dr L Wen have been critical of CDC for our flying blind predicament.

Antibody levels have been shown to be decreased at 6 months for both Moderna and Pfizer. Antibody responses in the elderly have been shown to be lower  Does that explain the preponderance of older patients in the Israel ICUs. Increased infectiousness of Delta and decreased antibody levels in patients immunized 6 month or more ago are suspects in regard to delta breakthroughs.intensified by less public attention to masking and distancing.

The case is strong for older folks both vaccinated and unvaccinated to wear masks in congregate settings and the CDC has recommended that as they walked back their May proclamation of no masks for most of the vaccinated.It seeems as if the public heard and remembered the CDC May advice but not their retraction or so it seems based on my personal observation of how few people in Harris County Texas are wearing masks. 

Will the booster fix the covid surge? Well, already Israel has reported 37  breakthroughs  after the booster shot but also have reported strong neutralizing antibody response to a booster mRNA jab. 

 foot note1)

Jeffery Morris (1) offers a illuminating discussion of the Israeli data in which  he demonstrates that when  the overall aggregate data are used the vaccine efficacy is calculated to be lower than it is in either group when the population is stratified  into two groups by age which we are told is an example of Simpson's paradox. His argument is that the "real" VE for serious disease is not as suggested by computing a VE based on the aggregate  data. My take is that  yes  the loss of efficacy for severe disease is not as great as a simple data display would suggest but my main point ,ie the breakthrough cases are not rare, seems solid .

1)Morris,J.  Israeli Data- how can efficacy versus severe disease be strong ... www.covid.data science

Will the current non-plan of "Maybe delta will have a rapid downturn " really work?

 As the delta wave continues to surge steeply upward some optimistic public experts project that US will see the rapid downturn in attack rate noted in England It is nice to think so but...

The US differs from England in at least the following ways:

1.England gave their second dose later than in the US perhaps giving the vaccinated a higher antibody level when Delta landed onshore  

2.  Some or many Brits continued to wear masks even after the controls were lifted.Arguably to a higher degree than in US.

3) England did not have powerful  elected regional leaders actively opposing mask wearing as governors of several  states in the US are now doing.

Dr Eric Topol is critical of the CDC current performance. First CDC was premature in their announcement in May that masks were no longer necesary for the fully vaccinated. The next mistake, in his view and in that of Dr. Leana Wen was to discontinued surveillance of breakthrough cases that were not serious enough to require hospitalization. Further according to Topol they should be doing genomic analysis on breakthrough cases and studying their antibody levels and noting  when and what kind of vaccine they received.  Basically Topol is saying we are flying blind  regarding the delta surge.Additionally CDC is admixing breakthrough case numbers from the pre delta times frame with those of the post delta period giving a falsely optimistic estimate of the fatality rate which in turn tends to negate the impact of their "wear mask again" advice.

From my admittedly limited personal experience in Texas  people just do not seem to be taking the surge seriously. This should not be surprising   One elderly  family friend eats out serval times a week and is now to attend a mini high school reunion Another elderly couple is planning a family union. A large local church is still living by the May CDC recommendations ignoring the most recent CDC advice as well as a recommendations by the county commissioner.Looking over the crowds at the  Astros game, only a few masks are seen. Local  authorities  have been forbidden by executive order to issue mask mandates even though delta is clearly more contagious and arguably more virulent  than the version of covid dominant in earlier surges.

Why does the Pfizer vaccine seem to work significantly less well In Israel

 Data (1) are available regarding effectiveness of   the Pfizer 2 dose mRNA vaccine in Israel,Canada and England/Scotland.

As regards the vaccine effectiveness  (VE) against the Delta variant  there is a wide difference  in the  values for VE for symptomatic disease .For Canada and England/Scotland there are  values of 87 % and 89% versus 64% for Israel.

Both Canada and England/Scotland administered the vaccine not according to the time frame used in the clinical trails for  Pfizer. Due as in part to a  shortage of vaccine in Canada a decision was made to give the second short 4 months after the first .

 In England/Scotland  a similar decision was made to postpone the second shot to maximize the number of  people who received the first shot as the alpha variant was surging at that time.This was done with the realization that they using a dosing schedule different from that used in the clinical trials which is inconsistent with standard method of applying clinical trial results to clinical practice. The British decision was controversial. Some suggested that a partially immune population ( i.e many folks with only a single jab) along with a surge in cases was a set up for a  perfect storm of super surging.

  In Israel, which was not facing a vaccine shortage,the decision was made to give the vaccine according to the time schedule that was carried out in the clinical trials.Also in the US The mRNA vaccines were given according to the time schedule used in the trials.So, will the data for the US show a pattern more like Israel or\more like Canada?

One explanation for the international disparity in vaccine effectiveness  is that the longer delay between doses of the mRNA vaccine results in a more robust  protective response. Could this be another example of "sometimes it is better to be lucky than good"? Perhaps confounding the comparison is the fact that the degree to which Delta was prevalent in the populations varied, i.e.  possibly more Delta at the time of the Israel data compilation. 

1) I based this blog  in part on a slide presented by CDC on or about July 30, 2021 which I believe in turn was derived from several sources including Sheikh,  a. SARs-COV 2-Delta in Scotland.Lancet vol 397 p 2461,June 26 2021 

and an article by B Lopez et al Effectiveness of Covid 19 vaccines against the B.1.617.2 (Delta) variant NEJM July 21, 2021 

Is the US into the 4th ( or 5th) surge of Covid

 Is the US already into the 4th surge of covid pandemic?

Cases and hospitalizations and ICU admission are definitely trending upwards.

Physicians in Alabama,Mississpii,Arkansas and Louisiana are pleading with the public to get vaccinated as they see cases in their hospitals surge and young people are being intubated.

In California, mask mandates are back while in other states governors deny the need and at least one governor (Colorado) said no restriction or mask mandates are necessary until  it is clear that hospitals are being over whelmed. 

It is time already for masks to come back .The CDC mask lifting in May was premature and widely misunderstood and IMO has been  in part, perhaps in large part,responsible for the rise in cases caused by the Delta variant.

The public experts interviewed on TV appropriately emphasize the importance of the unvaccinated getting the jab but if miraculously everyone rushing to the largely empty vaccination sites today it would be over a month before immunity would be obtained. Meanwhile the vaccinated as well as the unvaccinated need to wear mask indoors and in congregate settings. 

The Israeli data and British data differ significantly regarding the effectiveness of the Pfizer vaccine as regards preventing infection (33 %- 88 %) but agree as to a 90 Plus %value for prevention of death or serious illness. But in the worse case scenario many vaccinated persons can contract disease and likely spread the disease making in the short and intermediate term masks and social distancing a high priority. Fully vaccinated parents can contract the disease and spread it to their under 12 year old children who are currently not eligible for vaccination.

Unfortunately until the CDC makes important revisions in its mask recommendations businesses are not as likely to reinstitute mask mandates and masking is essential  until a sea change occurs in the large segment of the population who continues to be vaccine "hesitant". 

Dr. Scott Gottlieb tweeted "CDC has consistently been through,meticulous and late" and that they are not suited to provided quick solutions to emergent problems. He also said CDC's decision to tell the vaccinated that they could unmask was based in part on the demonstrated low risk of a fully vaccinated person to  contract or spread  the earlier variants of covid. That advice clearly does not apply to the Delta variant. 

 

Heavy viral loads with Delta results in greater infectivity setting up 4th US surge

 The 4th covid  wave is already in the US. It is  fueled by the much greater infectivity (1) of the Delta variant  arriving at a time of nationwide reduction in masking and social distancing in part driven by what a increasing number of public  health officials  believe to be a premature and widely misunderstood lifting of the mask mandate\by the CDC.

Some virologists are estimating the R naught of Delta variant to be as high as five. Anecdotal report from Australia indicates that viral transmission occurred with simply passing an infected person in a mall.That seemed to me unlikely until I read of the Chinese study demonstrating a viral load in Delta infected persons greater  than one thousand times that of the original Wuhan strain. Their report found that high viral loads persisted up to 4 days in asymptomatic patients. Asymptomatic spread from  persons with high viral load is pretty  good if not perfect storm for spread in a population who just recently were officially relieved of need to mask or distance.

The report of  transmission of the Delta variant among fully vaccinated people at an outdoor wedding event  in Houston seems to strongly indicate that transmission can happen in fully vaccinated people which should mean that not just the unvaccinated should wear masks in public but so should the vaccinated.

The vaccinated should wear masks in public for two reasons; 1) they can spread the disease to the unvaccinated which includes children who are too young to be currently eligible for vaccine  and of course the elderly and immunocompromised 2)there are "break through" cases  i.e cases in the vaccinated These are usually described as "mild" but some are not and there have been deaths largely in the elderly. 

Israel quickly reacted to increased Delta cases by reinstituting  a mask mandate  as did Los Angles County in California. The medium term answer is more vaccination but the short term answer is masking and social distancing .Already governors in Colorado,Florida  and Texas have said they will not mandate masking for the public and will not "allow"  mask mandates for kids returning to school although that is the recommendation of the American Academy of Pediatrics.

 

With this wave it looks like there will be fewer deaths in the elderly ( mainly because of the higher vaccination rate in the old folks) but reports from Alabama, Arkansas and Louisiana hospitals indicate that ICU admissions and some  deaths are occurring in the younger group. Whether  that indicates a greater lethality  from Delta is not determined at this time.

 

 

1)Viral infection and transmission in a large well-traced outbreak caused by the Delta SARS-CoV-2 variant - SARS-CoV-2 coronavirus / nCoV-2019 Genomic Epidemiology - Virological

More covid lessons from Israel and Houston Wedding

 Recent data from Israel. Of 61 patients hospitalized because of covid , 24 were unvaccinated  and 37 were fully vaccinated, Of the 37- 36 were over age 60 and one was in their fifties.

Clearly being fully vaccinated does not provide 100% protection against being seriously ill. Older people are not immune to developing serious covid 19 illness even after 2 shots of the mRNA vaccines.

Earlier the Israeli Health Ministry released the following summary without the detailed data on which the conclusions were made:

 The effectiveness of the Pfizer vaccine for prevention of disease was said to be 64% and the effectiveness as regards prevention of serious disease was 93% . Both values were in in the 90s from the randomized clinical trials for Pfizer.  

Why are they so different. Perhaps the antibody levels induced by the vaccine have decreased over time to a point at which the disease protection ability has also decreased. The other likely explanation is increasing number of cases due to the Delta variant.Both could be operative.

From the Houston wedding case report we have to conclude that serious covid 19 disease can occur with spread of the virus from vaccinated person(s) to another vaccinated person. 

An important question is:

1)Can a fully vaccinated person transmit the virus to another person? The Houston wedding  story makes it apparent that the answer is yes. While we do not know with a solid level of certainty the chain(s) of transmission in that spreader event  it seems most likely that at least one fully vaccinated person gave it to at least one other fully vaccinated  person.For that conclusion to be valid we have to assume there were no unvaccinated individuals, perhaps a service  person or a valet parking attendant  who could have transmitted the virus to all six of the infected attendees. 

Those type epidemiologic details would be important because if the fully vaccinated can transit the disease to the fully vaccinated and of course to the unvaccinated than the CDC advice for the vaccinated to do whatever they were doing before the pandemic without masks needs to be revisited and revised particularly as the Delta variant spreads

Further if vaccinated persons can spread the virus and since we know there can be asymptomatic spread and we know that there is aerosol spread then vaccinated persons should not go mask less in congregate settings such as grocery stores and churches to mainly protect others as well as themselves.

What about protection of children too young to be eligible for vaccination? Vaccinated parents should wear masks in public to minimize the risk of bring a covid virus home to infect the child.The vaccinated parents are very unlikely to get seriously ill from the Delta variant but may be  able to transmit the virus to their unvaccinated child. 

Mask wearing became a political issue earlier on in 2020 and when the discussion turns to why do folks oppose mask reading one purposed reason is "libertarian thought".

There is nothing libertarian about the vaccinated tossing the masks away if there is asymptomatic spread even among the vaccinated. One does not have the right to put others at risk. The foundational libertarian principle is that of non aggression i.e. one does not have the right to initiate force against another, Libertarian thinking is sometimes blamed for mask aversion but if someone believes he can spread a potential fatal disease to others  and if he does not wear a mask that is not libertarian exercise of a right  but rather a hostile act. 

So what are the lessons from recent Israel data and the Houston wedding story.

1) If and when the Delta variant is increasing in a community ( particularly  in a community with low level of complete vaccination ) people who have been vaccinated should not believe themselves to immune to covid They can spread the disease and there are break through cases..The CDC proclamation was poorly understood  or taken to mean to be no mask at all under most all circumstances. More troublesome is the obvious fact that everyone who is mask less is not fully vaccinated. Less than 50% of residents of Harris county Texas,home of Houston, have been vaccinated but try and find more than one or two people with masks when a crowd shot is shown at a Astros home game.Further, one shot of either of the two mRNA vaccines does not protect against the Delta variant.

2)Vaccinated people can get seriously ill from Covid and  some will  die.

3)With the increasing spread of a many time more contagious everyone should wear a mask in congregate setting to as was true in the beginning of the pandemic to protect others and yourself.

 The CDC said that masks may still have to be worn when government regulation (Federal or state or local) so indicates. Unfortunately in some states the legislature and or the governor have decreed that business may not demand a "vaccine passport" and/or that public schools cannot mandate vaccination or masks regardless of what the level of risk may be.

As cases again begin to spike, CDC needs to revise its mask guidelines and when a virus is on the ascending limb of spread time is of the essence.

 

Documented cases of Delta variants in fully vaccinated patients

 The setting was an outdoor wedding near Houston Texas for which only vaccinated persons were allowed to attend. Fully vaccinated and outdoors-and yet six cases with 2 hospitalized and one death. 

See here for the pre print .

Of particular interest in patient 1 who had received the Pfizer vaccine and had no comorbidities.He required hospitalization and was treated with Regeneron antibody with recovery.

Patients 0a and 0b traveled  to the wedding from India and tested negative before the flight.Patient 0a was hospitalized and died from covid19 complication one month after the event. Both of the visitors from India had received the Indian covid vaccine.

The planners of the wedding were careful-having the event outdoors and required the quests to all be fully vaccinated. The report does not mention whether masks were worn but according to CDC recommendation masks are not required for outdoor events for fully vaccinated people.

Eight fully vaccinated health care workers apparently contracted covid 19 at a swimming party.All were mildly ill with upper respiratory symptoms and self quarantined. See here for link.These cases were much milder than some of Houston wedding guests who contracted covid and also seemed linked to the Delta variant. 

Clearly fully vaccinated does not mean fully protected from the Delta variant.

Should the CDC's mask advice be fine tuned in view of the increasing number of Delta variant cases and its apparent increased infectiousness and possibly capability to evade the vaccine's protection.Another element in the argument is that Israel's Health Ministry has stated that the Pfizer now appears to have effectiveness in the 60% range for protecting against infection but still has protection against serious illness and death in the 90% range. 

Masks and social distancing in the vaccinated elderly

 The CDC, when it lifted its mask recommendation, stated that- in general- people who have been fully vaccinated do not  need to wear masks except in certain situations such as planes,trains and hospitals and contact with the elderly and immunocompromised  They further said that one " should consider" wearing a mask if you have a condition that weakens your immune system" or if you lived in an area of the country where the infection rate was high.(High was not defined by the CDC).The "not wearing masks" was heard and little else was remembered and the take home message was the long awaited "take off your masks".

Remembering back to the early days of the pandemic in 2020 we were told that it was a priority to protect the vulnerable which was taken to mean the immunocompromised and the elderly. 

Were the elderly ignored in the surprise turn around from the CDC's mask guidance? They did not seemed to be specifically mentioned.

In an earlier blog posting I commented about two studies that addressed the immune status of the elderly following Covid vaccination and I wrote the following:

"Muller et al (1) conducted a cohort study on subjects less than 60 years of age and those over the age of 80 who received the Pfizer vaccine. Specific IgG antibody tiers against SARS-COV-2 spike protein were lower in the elderly and 31 %  the elderly had no detectable neutralizing antibodies. In the younger group 2.2% had no detectable antibodies."

A large Danish Cohort study (2) compared vaccine effectiveness in health care workers and long term care patients. After the second dose the effectiveness in the patients was 64% ( 95% CI  14-84) while in  health care workers the   effectiveness was 95% (95% CI  82 -95. The median age of the 39 040 patients was 84 and there were 488 PCR confirmed cases of SARS-COV 2 cases. If this study can be generalized the widely quoted 90 % plus vaccine efficacy does not apply to the elderly. It should be noted that may well represent the worse case in that the eldely in long term care are a less resilient group that 80 years old independently lived in the community. Note  also sometimes  I am saying effectiveness and sometimes efficacy, they sound alike but in epidemiology they are terms of art and mean different things. More on that below. Also see footnote 1 for explanation of efficacy.

More data on that topic of how well vaccines really work. has  become available.

Jablonska et al (3) published a pre print estimating the " real life " impact of vaccination on covid mortality using data from 31 European countries and Israel from the period from Jan 2020 until April 2021. They found the vaccine effectiveness  in terms of  protection against death was equal to 72%.

Note: The Jablonska article seemed careless  ( it is a preprint after all) in the use of the words "effectiveness" and "efficacy" in that sometimes the authors said effective and sometimes efficacious in reference to their study. In the jargon of epidemiology "effectiveness " refers to real world data , i.e. how a medical intervention in used outside of a randomized clinical trial (RCT)  .The results of a RCT are expressed in terms  of efficacy.   The results of the  RCTs for the Covid vaccines are expressed as efficacy.`

The Danish cohort study and the Jablonska paper were non RCT data and expressed them major metric as effectiveness,

For prevention of severe disease Pfizer,Moderna as well as AstraZeneca and Novavax reported a 100% 

efficacy. 

Why is there such a difference.As the authors suggest age of the populations studied varied.

Only 24.7 % of subjects in the Moderna trial were equal to or older than 65 years of age and 42% of Pfizer trial subjects were over 55 years  of age and only 12.2 % were over  55 in the AstraZeneca trial.

In regards to a medical intervention the disease reducing ability as indicated from the results of a RCT is  always better and correctly expressed as efficacy than that observed when the intervention is utilized outside of the confines  of a RCT and which is correctly expressed as effectiveness. This is very well known .

A number of the public health experts appearing on TV  may have forgotten that when they emphasized  the 100% efficacy against death  that was reported in the randomized trials. It was extrapolation beyond the data to claim or at least hint  that everyone who would be vaccinated would be protected from serious illness  and death. Whether this was intended or not I believe many people were lead to believe when fully vaccinated they were almost guaranteed not to have serious or fatal covid 19 regardless of how old they are on to what degree there may be covid spreading in the community and whether or not that spread may be driven by covid variants such as the Delta variant. 

When I heard repeatedly that the mRNA vaccines were 100% effective against death after the several month duration trials were published I shuddered because I assumed that at least some of those experts knew that the effectiveness of a medical intervention is never at high as the efficacy demonstrated in a clinical trial.  

In early July the Health Ministry of Israel announced that the Pfizer vaccine now seem 65% effective in decreasing symptomatic and asymptomatic disease and 93% effective in preventing hospitalization and death.Several deaths were reported in fully  immunized patients.

From personal experience involving  acquaintances  and family it seems that the  many of the over 75 year old crowd have eagerly accepted the need- no- mask advice since they have been vaccinated and are not known to be immunocompromised and believe that masks and avoiding crowds are no longer necessary.It is not that simple although it was very easy to take away that impression from the CDC announcements.

 

I would have preferred that  the CDC at least  recommend that the immunocompromised consult with their  oncologist or hematologist, a number of which, I believe, are recommending that their patients have their antibody levels checked and in some cases take a third shot. One group in France has taken that approach with their solid organ transplant patients and given third shots which had generally demonstrated a significant increase in antibody levels which were typically low after the standard two doses of the mRNA vaccines.  As for the elderly perhaps they should have been advised to consider the level of vaccination in their community as well as the number of cases of the Delta variant before they go mask free to do things like dining out in inside eateries and attend indoor sporting events.

Of course  the fully vaccinated can gather together for food or singing or whatever and be very unlikely to get sick. This quite different from singing and drinking in bar or a crowded restaurant  in a locality  with 20% vaccination rate and increasing cases of  covid19 from a variant. 

Cases still soar world wide and more have died in 2021 from covid than in all of 2020,India and South America  are hot beds  and cases are increasing in Japan preventing live spectators in the upcoming Olympics  and for lack of vaccine much of Australia is in some form of lockdown.In parts of the world with low or zero vaccination rates variants will develop and air travel links everyone with everyone in the world. The more contagious Delta variant is already over 50% of cases in US and increasing particularly in areas with low vaccination rates.

1)Muller,L et al Age-dependent immune response to Biotech/Pfizer BNT 162b2 COVID-19 vaccination Clin infect Dis 2021 Apr 27

 2)Moustsen-Helms,IR et al Vaccine effectiveness after 1st and 2 nd dose of the BNT162b2 Covid-19 Vaccine in long term care facility residents and healthcare workers A Danish cohort study. Pre Print from Medrxiv 09 March 2021.

3)Jablonske,K et al The real-life impact of vaccination on covid-19 mortality in Europe and Israel. MedRxiv ( this is a pre print and at the time of publication had not been subject to peer review.

 Footnote 1.

Efficacy refers to the proportional reduction in disease attack rate between ARV and ARU, where ARV is the attack rate of the vaccinated group and ARU is the attack rate in the unvaccinated group.

Risk ratio is the ratio of ARV/ARU

Vaccine efficacy is 1-RR expressed as a percentage.

For example if in a given time frame 100 of unvaccinated get the disease and 5 in the vaccinated  group get the disease  we have 1-5/100 = .95 or expressed as a percentage of 95%. 

To put vaccine efficacy in some context we see that in  the 2018-2019 season the flu vaccine has a 29% efficacy .Measles vaccine is about 97% efficacious. 

Addendum 1/4/22 A correction was made in regard to the Muller article. It was 31% of the elderly not having neutralizing antibodies not none.