Who's afraid of the big bad COVID?

 kw: analysis, epidemiology, immune system, vaccination, herd immunity

The magic number is 7. We'll get back to this. 

The first thing to understand about a pandemic disease is the ratio of infection to symptomatic illness. Only then can you understand the progress of the disease through time in a population. This ratio is the first thing a national disease-monitoring organization such as CDC should determine. However, they have not, or if they did, they are not telling. I have sought other sources.

Dr. Anthony Fauci, without citing sources, claimed a few times that of the total number infected with SARS-CoV-2 virus, about 40% have no symptoms. An estimate out of South Korea claims 30%. But both of these are actually talking about asymptomatic carriers, those who have no overt symptoms but can still spread the disease. A few test surveys that I have been able to find showed a different picture. In a test survey, everyone in some population is tested, such as residents in a dormitory. Reports popped up, were public for a few weeks or less, and then vanished. They had a narrow range of numbers of the ratio of infection to illness. From these I got the magic number above. Stated a better way:

For every 7 persons whose test showed they were infected, one was ill and the rest had no symptoms.

 The range of magic numbers was between 5 and 9. For one test survey it was 10. Therefore, in the earlier stages of the COVID-19 pandemic, when there were no accurate tests, the numbers of known cases was only 1/7th of the actual number of infections.

If we combine that with the 30%-40% "claimed asymptomatic carrier" rate, we can surmise the following, for a total of 1,000 infected persons:

• 143 will be ill at some point (we're not counting deaths yet; some of these will die).
• Between 61 and 95 will be "carriers" who have no symptoms, for a total of 204 to 238 who can infect others.
• The remaining 762 to 796 who are infected will recover without consequence, for themselves or for others.

Now to re-examine the first bullet point above: How many of the 143 will die? Spoiler: less than 2, and maybe much less than that.

I am going to use data from the charts supplied at Worldometer, as faulty as it is. The definition of a "Case" has changed over time. Early on, people with certain symptoms were "presumed positive". Later, testing was implemented. To date, in the U.S. about twice as many tests have been performed as there are persons in the country. However, there are those who get a test every week, some (like myself and my wife) who have been tested 3-4 times, and well over half of U.S. residents have never been tested. At the present time, the number of "cases" includes test results, which depends on the accuracy of record-keeping (We all have heard stories of people who were in line to get a test, had "signed in at the door", and then before getting tested, opted out and left; later they got a letter in the mail stating that they had tested Positive. Maybe the person in back of them in line was the one really tested, or something. We'll never know).

There is the further problem with "no Flu season in 2020-21". Really? Is that believable? Reasonably accurate tests for SARS-CoV-2 were just coming into use during the winter of 2020. COVID "cases" were among the "presumed positive". I contend that between 30,000 and 60,000 U.S. residents who are counted as "COVID deaths" actually died of Influenza. There are also those who died while they were infected with the virus, but they did not die OF the virus (car accidents, suicide, etc.). News of such events is being suppressed, so it is hard to gather statistics. Let's hope the number is small. With all those disclaimers, let's look at this chart, taking it (mostly) at face value.

The blue and brown curves are 7-day averages, as calculated at Worldometer. Blue is cases reported each day, however such cases were determined. This is for the U.S., and the axis to use is labeled "100k" and so forth. Five waves of infection can be seen; they peaked in April 2020, late August 2020, January 2021, April 2021 and late August 2021.

Each peak has a corresponding peak in daily deaths, the brown curve. The axis is labeled "2k" and so forth. These curves are scaled to have visible parity during the third wave. Note that the peaks in deaths and the curves for daily deaths are offset from the peaks and curves for cases…except for the first wave. At the beginning, people didn't get help until they were at death's door, so many of those who died did so within a day of being admitted to a hospital, and they had been reported as a "case" on the day of admittance. Thus, let's look at the same chart, with cases shifted 15 days back, which makes the third wave overlap as well as possible. 

This presentation makes the dates harder to discern. I presented a similar chart on August 1, just 2 months ago, when the fifth wave was just beginning, stating "Herd immunity has arrived." This conclusion was based on the anomaly about Wave 4: there was no peak in the death rate, and during the summer of 2021 case rates were lower than at any time since mid-March 2020.

The 5th wave is the Delta wave. It is smaller than Wave 3 because it is occurring primarily among the unvaccinated (in which I count those formerly infected: "vaccinated by God"). It also appears to have about a 15-day delay between discovery and death. However, look at the subtle vertical shift over time. The death rate is lower in proportion during Wave 5 than it was previously. And the gorilla in the room is the very high death rate during Wave 1.

What happened during Wave 1? Firstly, we had no clue what was going on. There were no effective treatments. President Trump ordered certain companies to ramp up the production of ventilators. It turned out that ventilators caused more deaths than they prevented. They aren't supposed to be used for weeks at a time. But even more, many of these deaths occurred in nursing homes where the virus ran rampant. This was aggravated in five states whose Governors ordered COVID patients moved from hospitals back to the nursing homes they came from, creating the first super-spreader events. 

Secondly, there were no effective medicinal interventions yet. Now there are two for early use (coded IVM and HCQS), and also monoclonal antibody treatments such as Regeneron, which was used to treat President Trump. Thus, the blast of early deaths represented the "low hanging fruit". A large proportion of the most vulnerable Americans died in Wave 1. Most variants of the virus that have arisen later cause fewer deaths, and we have medicines that work better. So let's look at another couple of charts.

For these I used the 7-day averaged number of cases or deaths at the peak of each wave. These are not totals for each wave, be clear on that. For a few cases in one state or another, and in the U.S. during Wave 4, where there was no peak in the death rate, I used a date 15 days delayed from the peak in cases.

The chart on the left has the data for the U.S. along with the five states whose governors forced COVID patients into nursing homes. Each bar represents the ratio of peak death rate divided by peak case rate, in each wave. The chart on the right has data for seven states I found of interest, including some in which I have lived. The one I find of particular interest is South Dakota (I lived there 8 years), which seems to have had a better handle on this disease than the rest, particularly in Waves 1 and 5.

The "easy take-away" is this: During Wave 1, D/C was about 7% nationwide, ranging from 4.5% to 9.5% for the five states shown on the left, and (except for NH) between 1.7% and 4.5% for the seven states shown on the right. The death rate has continued downward since then.

While state numbers hop around a bit, the national averages for the five waves are

7%, 1.7%, 1.4%, 1.0%, 1.1%

Let us return to the magic number, 7. On average, for 7 infections, there is one illness. Is all the testing finding every infection, whether ill or not? Not really. The vast majority of tests are done by those who either think they are sick, are feeling sick, or fear/think they have been exposed. So, if there are 6 people out there with no symptoms for everyone who has symptoms, and very few of those 6 are getting tested, they are still not known.

We were told that we needed to achieve 70% "fully vaccinated" to gain herd immunity. That was based on an infectivity rate for the Alpha variant, which is pretty much out of the picture by now. Back to variants in a moment. To date (Oct 1, 2021), just over 185.25 million Americans are recorded as fully vaccinated. This is called 56.1% of the population in news reports, but of course no children under age 12 have been vaccinated, and it isn't certain that they ever ought to be, at least with today's vaccines. That's 48 million, or 14.4% of the population. So the proportion of those12 and older who are fully vaccinated is about 65%. Getting close! But let's remember, the 2-shot "vaccines" are claimed to be 95% effective, while the one-shot version is 65% effective. We can expect about 90% overall effectiveness, so the "actually immune" adults in the U.S. total about 58.5%. One more factor must be considered.

The number of past infections that have resulted in recovery is 33.7 million, or 11.8% of persons 12 and older. 58.5+11.8 = 70.3%. By the criterion set by the CDC, we have achieved herd immunity. More vaccinations and more recoveries happen every day, so we are moving farther and farther into "herd immunity" territory.

So what's with Wave 5? I call it the Delta Wave. A word on variants.

There are many "serotypes" of the SARS-CoV-2 virus. A year ago it was reported that about 30 were circulating in the U.S., and more than 100 were known in China. It's practically impossible to get useful data out of China any more, so we don't know how many serotypes exist. A Serotype is a minor variation in the RNA of the virus. Not all have any practical effect. But a few do. The serotypes are grouped into families by RNA similarity and by clinical measures including infectivity and virulence. So far, there are 12 such Variants.

Infectivity is a measure of how many virus particles one must ingest to cause an active infection, for a person of "average immunity" (a quantity that has never been quantified). Those 5%-10% of vaccinated persons for whom the vaccine "didn't take" have lower immunity, didn't respond strongly enough to the mRNA agent in the vaccine, and so didn't develop a useful antibody defense. They were easier to infect before, and remain easier to infect. For most of us, there is some number, perhaps 1,000 particles, that are sufficient to swamp our early immune response and trigger active infection (whether we ever get symptoms or not, and I picked 1,000 "out of the hat"). We may be exposed to 100 particles several times, and out body fights them off, all the while getting more "wise" to the virus. That produces natural immunity without infection.

Reversing the logic, we have the case spreading rate. For a virus of average infectivity, someone who is infected might infect two other persons during his or her period of active infection. The 70% figure for achieving herd immunity was based on a case spreading rate of 3. I have read claims that the Delta variant is more infective (a smaller number of particles are sufficient to cause active infection), such that the case spreading rate is 6. 

Some claim that if this rate is greater than 5, herd immunity is no longer possible. That is nonsense. Those who state such things have their math wrong. They are using a simple ratio, but the math actually requires inverting a Weibull distribution, and never goes to 100%, meaning that herd immunity is always possible. However, it does get harder to achieve when infectivity is greater. For example, polio has a very high infectivity, as does measles, but we rely on herd immunity in both cases by striving for vaccination rates of 95% of the population, primarily by requiring all school children to be vaccinated for measles and polio (and a bunch of others).

Virulence refers to the likelihood of serious illness or death. If we look at Wave 1 above, it appears that virulence was such as to cause a 5% death rate, before we found effective treatments, and now it is about 1%. Untreated, AIDS and Ebola have a near-100% death rate. Influenza has a virulence about 1/10th as great as SARS-CoV-2, with a great range depending on the yearly variant.

So, although there are hundreds of serotypes out there, we hear of only Variants ranging from Alpha to Mu, the 1st and 12th letters of the Greek alphabet. Waves 1 through 5 were due to Variants Alpha and Lambda (11th). A Variant is a collection of similar serotypes. Delta was the fourth variant identified, but was kept out of the U.S. until late this summer. Now it is dominant.

If the Delta variant were to arrive in a totally naïve population, a big, big Wave of infections would occur. The comparatively smaller size of Wave 5 shows that it is occurring among the non-immune, which presently comprise 30% of adults in the U.S. All the variants so far known cause only mild infection in the vaccinated. Yes, there have been a number of vaccinated people who caught the disease and died. They are among the 5%-10% identified earlier. The mRNA vaccine didn't produce a useful response in them.

Now, a final word about the magic number, 7. For at least Waves 1 through 4, reduce the death rate by a factor of 7 to get a true death/case ratio. It is likely also true for Delta, so we find that actual death rates for the five waves are:

1.0%, 0.25%, 0.2%, 0.14%, 0.16%

That's a low death rate, and I repeat, we have achieved herd immunity for Alpha and Lambda, and we're on the way to achieving it for Delta.

Vaccines or epidemics - do we really have a choice?

kw: book reviews, nonfiction, medicine, vaccination, polemics

Lewis Thomas wrote an essay that I well remember, probably thirty years ago. He described the three kinds of medicine. The first is palliative, where all you can do is try to help the patient feel better, when the best you can do is comfort someone and "let nature take its course." In cases of chronic disease, this can be incredibly costly, both financially and emotionally. The second is corrective, which includes surgical procedures such as heart bypasses, though it also includes syndromes that you can medicate. The cost may be low for some conditions, but for many it can also be quite costly. Finally, there is effective prevention, and Thomas held up vaccines as examples of effective prevention. By contrast to the other two kinds of medicine, prevention is very inexpensive, and usually saves many more lives than any corrective medical method.

I remember the incredible relief of all the parents when the Salk vaccines for Polio were announced. We lived in Utah at the time, and I had, unknowingly, been one of Dr. Salk's experimental subjects. Among thousands of names of children published in the newspaper that day, I found mine. I have never been mentioned in the newspaper since! The funny thing is, when I was a teenager an orthopedic doctor measured my bones and told me I had had polio. I went to the doctor to get his advice about learning to walk straight. I had grown up with a slightly gimpy leg and one foot much smaller than the other. Now we knew why. The infection occurred when I was one year old, about seven years before Dr. Salk's experimentation on the children in my school (and many other schools). I was probably not the only child who had already had polio before being in the vaccination experiments.

Fast-forward about forty years. It came time to have our son vaccinated for quite a variety of diseases, and polio was on the agenda. I had heard that the oral vaccine, named for Dr. Sabin, very rarely causes polio, because the serum contains living but weakened virus. I learned that about ten children yearly contract polio from the vaccine. I wrote a letter to our doctor, telling him I'd had polio as an infant and preferred that our son receive the Salk vaccines (there are three). They are made from killed viruses. Though injection costs more, I was willing to pay extra for a reliably safe vaccine. Here is the bottom line, though. If I had not had a choice, if the Salk vaccine were no longer available, for example, I would have allowed my son to receive the Sabin vaccine, though breathing a prayer for him.

So our son received them all: Salk for polio, plus vaccines for DTP, MMR, Hepatitis (I don't recall how many kinds), and maybe another one or two. He had a bout of chicken pox before they finished developing the vaccine. When I was a kid, I received the DTP vaccine, but there was no MMR so I had measles and mumps at a young age. Fortunately not rubella.

I didn't hear at the time about the flap over Pertussis vaccine that began in the 1960s. There was a lot of other stuff going on. I didn't know about anti-vaccination organizations that were formed during that time, some of which still exist. I learned quite a lot about it in the opening chapters of Deadly Choices: How the Anti-Vaccine Movement Threatens Us All by Paul A. Offit, M.D. In fact, there was much too much there to learn. I do believe Dr. Offit would have done better to select a smaller set of cases to discuss. Before I was halfway through, I was overwhelmed, and stopped reading. Also, it is a bit of a downer. The story is not over, and the forces of ignorance are winning.

Unlike many vaccines, the early pertussis (whooping cough) vaccine contains whole, killed bacteria. That means it also contains thousands of their metabolic proteins, because in 1906 it was not known which proteins or other biochemicals were causing the problem. They just knew that you could prime the immune system with dead bacteria and nearly anyone would then be immune to the infection. This is one key point: nearly anyone, but not exactly everyone, not quite 100%. Because of allergic reactions, the vaccine has a lot of side effects. Many kids get feverish, or feel sore, and some cry for a long time; a few even had fever-induced seizures. Some kids died within a few months or years, and the vaccine was blamed. It took more than twenty years for scientists to determine that there were no "extra" deaths, nor "extra" cases of epilepsy or other brain damage. The dead and injured children were going to die or be harmed anyway. But that twenty years was plenty long enough for a powerful political movement to arise and drive all but one or two vaccine makers right out of business.

Sadly, it also led to hundreds of thousands of people declining to have their children vaccinated. Even at the time, this didn't make sense. At most, less than one hundred children were thought to have been killed over the years that the 1906 vaccine was used (It has since been shown that the vaccine did not kill anyone). In the 1970s and 1980s, there were epidemics of pertussis that caused tens of thousands of cases of permanent harm and took several thousand lives. And remember that the vaccine isn't 100% effective? A few of those who died had been vaccinated years before! In a population that is 95% immune to a disease, a few people will get it, but it won't be able to spread. When the immune portion drops to 80%, 70%, or less, epidemics can occur.

Well, doctors didn't just learn about the vaccine's effects. They also improved it. A lot was learned about pertussis infections, and modern pertussis vaccine just contains those proteins the body needs so it can recognize the germ and destroy it. But people are still declining DTP for their children. The word hasn't gotten through to them.

It was in the middle of the book's discussion of the Salk and Sabin vaccines that I ran out of steam. I had learned that the anti-vaccine movement is still with us. I suspect there is a closing chapter or two about combating the misinformation the movement delivers. But I am not a political animal. It does no good to call me to arms; I don't bear arms, literally or figuratively. The closest I can come to political action is a statement such as this one:

Take advantage of every vaccine available. Without it, the chances of death or permanent disability are 100 to a million times greater than any harm the vaccine might cause.

When Franklin blew it

kw: book reviews, nonfiction, medicine, vaccination, variolation, religion

Before the discovery of vaccination, there was variolation. The Variola virus causes smallpox, the most dreaded disease of antiquity. The Vaccinia virus causes the related zoonosis cowpox. Someone who survives infection by either virus is thereafter immune to both.

Centuries before Edward Jenner observed that milkmaids were immune to smallpox, it had been observed in Asia that people who caught smallpox by direct contact with someone who was mildly infected were much more likely to survive their infection. They also became immune to future infection. Asians developed the practice of infecting people with smallpox and caring for them during their illness. By 1700 the practice had spread to Africa and the Mideast. In 1716 in England and America, this became known to two people with the intelligence to understand its implications, and the influence to initiate the practice. In England, the proponent was Lady Mary Wortley Montagu, and in America, specifically Boston, it was Cotton Mather.

Lady Montagu's story is told elsewhere. The Pox and the Covenant: Mather, Franklin, and the Epidemic That Changed America's Destiny by Tony Williams tells of Cotton Mather and the "inoculation" controversy that sundered the Boston polity in 1721, created a turning point in the acceptance of the scientific method, and broke the power of the century-old Puritan Covenant.

Early in 1621, Cotton Mather had just turned 58 years old, and was at the peak of his powers as a Puritan preacher of great influence, both civil and religious, and also as a scientist—he was elected to the British Royal Society in 1713. He is often considered the finest mind of his generation in colonial America. He had been told by an African slave boy about the African method of preventing smallpox by making cuts in the skin and rubbing in pus from the pustules of a smallpox victim. The person thus inoculated would suffer a fever and break out with a relatively small number of pustules, and recover, now immune to smallpox infection.

Mather searched for earlier accounts of this practice, and soon found them. He might have saved himself a world of trouble by immediately discussing this with his British colleagues and the local physicians and scientists and fellow-ministers, but he kept the matter close for five years, expecting a smallpox epidemic to occur, as they did about once per generation; then he could reveal the matter and instigate a program to save the population from a severe plague.

There was a bit of vanity in this view, and he was blinded by simplistic thinking. When a smallpox epidemic began early in 1721, brought by the ship Seahorse from Barbados, Mather wrote a letter to all the local doctors explaining inoculation and referencing the literature (he knew better than to quote a slave). There was no reply. He waited, prayed, waited, and finally wrote again, and this time there was a response. One doctor, Zabdiel Boylston, responded favorably, by beginning to perform inoculations. He experimented with a small number and saw how they were only mildly affected, in contrast to longer fevers, greater pains, and a 30% death rate among those who acquired smallpox the ordinary way.

Shortly after this, the other doctors responded, with fierce opposition. They stirred the Selectmen to prohibit inoculation. Mather and Boylston took the fateful decision to quietly defy the authorities. Possibly due to the stature of Mather and Boylston, the authorities did not arrest them, but dithered. A withering flurry of publications ensued, primarily of the doctors of Boston against inoculation. Soon another pair of actors entered the fray. James Franklin and his young apprentice, his 16-year-old brother Benjamin, began to print the New England Courant, a weekly paper in which they pushed the limits of attacking convention, authority, and religion in particular. This paper quickly became the focus of anti-inoculation fervor.

The drama took months to play out, and in the main, the disease ran its course until it had infected nearly everyone who was not already immune. Among the immune were those who were inoculated. By the end of the epidemic, it was found that nearly 900 Bostonians had died of smallpox, of about 5,000 who were infected. This doesn't quite square with the 25% and 30% death rates quoted throughout the book, but 18% is still terrifying odds. By contrast, of 242 persons inoculated, only six died, a death rate of 2½%. This was enough for Mather and others to publish a tract showing statistically that inoculation was superior to letting nature run its course.

Curiously, within nine years, Benjamin Franklin became a proponent of inoculation. After the epidemic burned itself out, in 1722 Mather had extended an invitation to young Franklin, author of so many diatribes against him, to visit him at his home. It is not known what they discussed, but Franklin subsequently became, scientifically at least, a man much like Cotton Mather: very well-read, with wide scientific interests, and a keen desire not just to win an argument but to win over an opponent. Though Franklin as a youth was on the wrong side of history, as he matured he had the flexibility of mind to learn where he had been wrong and correct his course.

While science took a great step in the West at this time, the change in religious polity was equally profound. From 1630 to 1721 the Puritan Covenant in Boston and the Massachusetts Bay Colony had prevailed, and the people were generally in agreement with the spiritual rigors it entailed, and with the hegemony of religion in civil affairs. Dissension and heresy were censured, and in a few cases, dissidents were hanged. By the early 1700s this Covenant seemed to be weakening as "worldly" influences became stronger, but the intense opposition directed primarily at Mather in 1721 broke the back of the Covenant.

Some years earlier the Crown had mandated religious tolerance in the Colonies, in the wake of the Glorious Revolution in England in 1688. This hardly weakened the committed Puritans, and their ministers continued to be held in very high esteem, much the way Catholics today esteem Archbishops and Cardinals. This was shaken in 1721-1722, and came to an end by the time of the American Revolution. The powerful sermons of Jonathan Edwards in the 1740s were pretty much the last gasp of Puritan influence, although even in the mid-20^th Century "banned in Boston" was a common joke.

There is something we can learn from Cotton Mather, however. He risked everything for a scientific principle, as all his life he had risked everything for the sake of his faith. He saw "natural philosophy" and "natural theology" as handmaidens to one another. He understood the scientific method as well as any of his day, and believed that understanding the glories of nature and the worship of God went hand-in-hand. In contrast to the modern view of science and faith, best expressed by Steven Jay Gould as "non-overlapping magisteria", the Puritans embraced both. Without this embrace of science by the chief Puritan of his day, among those 242 inoculated Bostonians, another forty might have died.

Cotton Mather had dreams of saving the whole of Boston from the epidemic. He could save only a handful, but to that handful, that made all the difference. And indirectly, he brought in a turn toward a better attitude toward the men and women of God among us; that they are after all human, and deserve common respect, but are much better served by that alone than by the inflated esteem the "clergy" are often accorded. We would do well today to learn this of the Puritans: science and faith can work together. For myself and many others who are both scientists and people of faith, the "magisteria" overlap quite a bit.