Category Archives: Vaccinations

Bottom-Line Booster Shots

17 Saturday Apr 2021

Posted by in Coronavirus, Public Health, Vaccinations

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The barrage of precautionary COVID missives continues, and with a familiar “follow-the-money” twist. The CEOs of both Pfizer and Moderna say that booster shots are likely to be needed a year after initial administration of their COVID vaccines, and almost certainly every year thereafter. Of course, this message is for those who felt compelled to be vaccinated in the first place, whether out of concern for their own health, high-minded community spirit, fear of social ostracism, or fear of possible vaccine passport requirements. It’s probably also intended for those who acquired immunity through infection.

There are reasons to believe, however, that such a booster is unnecessary. This case was made a few days ago in a series of tweets by Dr. Monica Ghandi, an infectious disease expert and Professor of Medicine at UCSF. Ghandi says immunity from an infection or a vaccine can be expected to last much longer than a year, despite the diminished presence of antibodies. That’s because the immune system relies on other mechanisms to signal and produce new antibodies against specific pathogens when called upon.

So-called B cells actually produce antibodies. Another cell-type known as T cells act to signal or instruct B cells to do so, but so-called “killer” T cells destroy cells in the body that have already been infected. Dr. Ghandi’s point is that both B and T cells tend to have very long memories and are capable of conferring immunity for many years.

While our experience with COVID-19 is short, long-lasting immunity has been proven against measles for up to 34 years, and for other SARS-type viruses for at least 17 years. Dr. Ghandi links to research showing that survivors of the 1918 flu pandemic were found to have active B cells against the virus 90 years later! The COVID vaccines cause the body to produce both B and T cells, and the T cells are protective against COVID variants.

A last point made by Dr. Ghandi is intended to dispel doubts some might harbor due to the relatively ineffectual nature of annual flu vaccines. The flu mutates much more aggressively than COVID, so the design of each year’s flu vaccine involves a limited and uncertain choice among recent strains. COVID mutates, but in a more stable way, so that vaccines and adaptive immunity tend to retain their effectiveness.

While I’m sure the pharmaceutical companies believe in the benefits of their vaccines, there are undoubtedly other motives behind the push for boosters. There is money to be made, and much of that money will be paid by governments eager to jump on the precautionary bandwagon, and who are likely to be very insensitive to price. In fact, the vaccine producers might well have encouraged those pushing vaccine passports to include annual booster requirements. This would be another unwelcome imposition. The very discussion of boosters gives government officials more running room for other draconian but ultimately ineffective mandates on behavior. And the booster recommendation gives additional cover to public health “experts” who refuse to acknowledge real tradeoffs between the stringency of non-pharmaceutical interventions, economic well being, and other dimensions of public health.

COVID Now: Turning Points, Vaccines, and Mutations

20 Wednesday Jan 2021

Posted by in Coronavirus, Pandemic, Vaccinations

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The pandemic outlook remains mixed, primarily due to the slow rollout of the vaccines and the appearance of new strains of the virus. Nationwide, cases and COVID deaths rose through December. Now, however, there are several good reasons for optimism.

The fall wave of the coronavirus receded in many states beginning in November, but the wave started a bit later in the eastern states, in the southern tier of states, and in California. It appears to have crested in many of those states in January, even after a post-holiday bump in new diagnoses. As of today, Johns Hopkins reports only two states with increasing trends of new cases over the past two weeks: NH and VA, while CT and WY were flat. States shaded darker green have had larger declines in new cases.

A more detailed look at WY shows something like a blip in January after the large decline that began in November. Trends in new cases have clearly improved across the nation, though somewhat later than hoped.

While the fall wave has taken many lives, we can take some solace in the continuing decline in the case fatality rate. (This is not the same as the infection mortality rate (IFR), which has also declined. The IFR is much lower, but more difficult to measure). The CFR fell by more than half from its level in the late summer. In other words, without that decline, deaths today would be running twice as high.

Some of the CFR’s decline was surely due to higher testing levels. However, better treatments are reducing the length of hospital stays for many patients, as well as ICU admittance and deaths relative to cases. Monoclonal antibodies and convalescent plasma have been effective for many patients, and now Ivermectin is showing great promise as a treatment, with a 75% reduction in mortality according to the meta-analysis at the link.

Reported or “announced” deaths remain high, but those reports are not an accurate guide to the level or trend in actual deaths as they occur. The CDC’s provisional death reports give the count of deaths by date of death (DOD), shown below. The most recent three to four weeks are very incomplete, but it appears that actual deaths by DOD may have peaked as early as mid-December, as I speculated they might last month. Another noteworthy point: by the totals we have thus far, actual deaths peaked at about 17,000 a week, or just over 2,400 a day. This is substantially less than the “announced” deaths of 4,000 or more a day we keep hearing. The key distinction is that those announced deaths were actually spread out over many prior weeks.

A useful leading indicator of actual deaths has been the percentage of ER patients presenting COVID-like illness (CLI). The purple dots in the next CDC chart show a pronounced decline in CLI over the past three weeks. This series has been subject to revisions, which makes it much less trustworthy. A less striking decline in late November subsequently disappeared. At the time, however, it seemed to foretell a decline in actual deaths by mid-December. That might actually have been the case. We shall see, but if so, it’s possible that better therapeutics are causing the apparent CLI-deaths linkage to break down.

A more recent concern is the appearance of several new virus strains around the world, particularly in the UK and South Africa. The UK strain has reached other countries and is now said to have made appearances in the U.S. The bad news is that these strains seem to be more highly transmissible. In fact, there are some predictions that they’ll account for 30% of new cases by the beginning of March. The South African strain is said to be fairly resistant to antibodies from prior infections. Thus, there is a strong possibility that these cases will be additive, and they might or might not speedily replace the established strains. The good news is that the new strains do not appear to be more lethal. The vaccines are expected to be effective against the UK strain. It’s not yet clear whether new versions of the vaccines will be required against the South African strain by next fall.

Vaccinations have been underway now for just over a month. I had hoped that by now they’d start to make a dent in the death counts, and maybe they have, but the truth is the rollout has been frustratingly slow. The first two weeks were awful, but as of today, the number of doses administered was over 14 million, or almost 46% of the doses that have been delivered. Believe it or not, that’s an huge improvement!

About 4.3% of the population had received at least one dose as of today, according to the CDC. I have no doubt that heavier reliance on the private sector will speed the “jab rate”, but rollouts in many states have been a study in ineptitude. Even worse, now a month after vaccinations began, the most vulnerable segment of the population, the elderly, has received far less than half of the doses in most states. The following table is from Phil Kerpen. Not all states are reporting vaccinations by age group, which might indicate a failure to prioritize those at the greatest risk.

It might not be fair to draw strong conclusions, but it appears WV, FL, IN, AK, and MS are performing well relative to other states in getting doses to those most at risk.

Even with the recent increase in volume, the U.S. is running far behind the usual pace of annual flu vaccinations. Each fall, those average about 50 million doses administered per month, according to Alex Tabarrok. He quotes Youyang Gu, an AI forecaster with a pretty good track record thus far, on the prospects for herd immunity and an end to the pandemic. However, he uses the term “herd immunity” as the ending share of post-infected plus vaccinated individuals in the population, which is different than the herd immunity threshold at which new cases begin to decline. Nevertheless, in Tabarrok’s words:

“… the United States will have reached herd immunity by July, with about half of the immunity coming from vaccinations and half from infections. Long before we reach herd immunity, however, the infection and death rates will fall. Gu is projecting that by March infections will be half what they are now and by May about one-tenth the current rate. The drop will catch people by surprise just like the increase. We are not good at exponentials. The economy will boom in Q2 as infections decline.”

That sounds good, but Tabarrok also quotes a CDC projection of another 100,000 deaths by February. That’s on top of the provisional death count of 340,000 thus far, which runs 3-4 weeks behind. If we have six weeks of provisionals to go before February, with actual deaths at their peak of about 17,000 per week, we’ll get to 100,000 more actual deaths by then. For what it’s worth, I think that’s pessimistic. The favorable turns already seen in cases and actual deaths, which I believe are likely to persist, should hold fatalities below that level, and the vaccinations we’ve seen thus far will help somewhat.

Let’s Do “First Doses First”

06 Wednesday Jan 2021

Posted by in Coronavirus, Vaccinations

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Both the Pfizer and the Moderna COVID vaccines require two doses, with an effectiveness of about 95%. But a single dose may have an efficacy of about 80% that is likely to last over a number of weeks without a second dose. There are varying estimates of short-term efficacy, and but see here, here, and here. The chart above is for the Pfizer vaccine (red line) relative to a control group over days since the first dose, and the efficacy grows over time relative to the control before a presumed decay ever sets in.

Unfortunately, doses are in short supply, and getting doses administered has proven to be much more difficult than expected. “First Doses First” (FDF) is a name for a vaccination strategy focusing on delivering only first doses until a sufficient number of the highly vulnerable receive one. After that, second doses can be administered, perhaps within some maximum time internal such as 8 – 12 weeks. FDF doubles the number of individuals who can be vaccinated in the short-term with a given supply of vaccine. Today, Phil Kerpen posted this update on doses delivered and administered thus far:

Dosing has caught up a little, but it’s still lagging way behind deliveries.

As Alex Tabbarok points out, FDF is superior strategy because every two doses create an average of 1.6 immune individuals (2 x 0.8) instead of just 0.95 immune individuals. His example involves a population of 300 million, a required herd immunity level of two-thirds (higher than a herd immunity threshold), and an ability to administer 100 million doses per month. Under a FDF regime, you’ve reached Tabarrok’s “herd immunity” level in two months. (This is not to imply that vaccination is the only contributor to herd immunity… far from it!) Under the two-dose regime, you only get halfway there in that time. So FDF means fewer cases, fewer deaths, shorter suspensions of individual liberty, and a faster economic recovery.

An alternative that doubles the number of doses available is Moderna’s half-dose plan. Apparently, their tests indicate that half doses are just as effective as full doses, and they are said to be in discussions with the FDA and Operation Warp Speed to implement the half-dose plan. But the disadvantage of the half-dose plan relative to FDF is that the former does not help to overcome the slow speed with which doses are being administered.

Vaccine supplies are bound to increase dramatically in coming months, and the process of dosing will no doubt accelerate as well. However, for the next month or two, FDF is too sensible to ignore. While I am not a fan of all British COVID policies, their vaccination authorities have recommended an FDF approach as well as allowing different vaccines for first and second doses.

Fauci Flubs Herd Immunity

03 Sunday Jan 2021

Posted by in Coronavirus, Herd Immunity, Public Health, Vaccinations

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Anthony Fauci has repeatedly increased his estimate of how much of the population must be vaccinated to achieve what he calls herd immunity, and he did it again in late December. This series of changes, and other mixed messages he’s delivered in the past, reveal Fauci to be a “public servant” who feels no obligation to level with the public. Instead, he crafts messages based on what he believes the public will accept, or on his sense of how the public must be manipulated. For example, by his own admission, his estimates of herd immunity have been sensitive to polling data! He reasoned that if more people reported a willingness to take a vaccine, he’d have flexibility to increase his “public” estimate of the percentage that must be vaccinated for herd immunity. Even worse, Fauci appears to lack a solid understanding of the very concept of herd immunity.

Manipulation

There is so much wrong with his reasoning on this point that it’s hard to know where to start. In the first place, why in the world would anyone think that if more people willingly vaccinate it would imply that even more must vaccinate? And if he felt that way all along it demonstrates an earlier willingness to be dishonest with the public. Of course, there was nothing scientific about it: the series of estimates was purely manipulative. It’s almost painful to consider the sort of public servant who’d engage in such mental machinations.

Immunity Is Multi-Faceted

Second, Fauci seemingly wants to convince us that herd immunity is solely dependent on vaccination. Far from it, and I’m sure he knows that, so perhaps this too was manipulative. Fauci intimates that COVID herd immunity must look something like herd immunity to the measles, which is laughable. Measles is a viral infection primarily in children, among whom there is little if any pre-immunity. The measles vaccine (MMR) is administered to young children along with occasional boosters for some individuals. Believe it or not, Fauci claims that he rationalized a requirement of 85% vaccination for COVID by discounting a 90% requirement for the measles! Really???

In fact, there is substantial acquired pre-immunity to COVID. A meaningful share of the population has long-memory, cross-reactive T-cells from earlier exposure to coronaviruses such as the common cold. Estimates range from 10% to as much as 50%. So if we stick with Fauci’s 85% herd immunity “guesstimate”, 25% pre-immunity implies that vaccinating only 60% of the population would get us to Fauci’s herd immunity goal. (Two qualifications: 1) the vaccines aren’t 100% effective, so it would take more than 60% vaccinated to offset the failure rate; 2) the pre-immune might not be identifiable at low cost, so there might be significant overlap between the pre-immune and those vaccinated.)

Conceptual Confusion

Vaccinations approaching 85% would be an extremely ambitious goal, especially if it is recommended annually or semi-annually. It would be virtually impossible without coercion. While more than 91% of children are vaccinated for measles in the U.S., it is not annual. Thus, measles does not offer an appropriate model for thinking about herd immunity to COVID. Less than half of adults get a flu shot each year, and somewhat more children.

Fauci’s reference to 85% – 90% total immunity is different from the concept of the herd immunity threshold (HIT) in standard epidemiological models. The HIT, often placed in the range of 60% – 70%, is the point at which new infections begin to decline. More infections occur above the HIT but at a diminishing rate. In the end, the total share of individuals who become immune due to exposure, pre-immunity or vaccination will be greater than the HIT. The point is, however, that reaching the HIT is a sufficient condition for cases to taper and an end to a contagion. If we use 65% as the HIT and pre-immunity of 25%, only 40% must be vaccinated to reach the HIT.

Heterogeneity

A recent innovation in epidemiological models is the recognition that there are tremendous differences between individuals in terms of transmissibility, pre-immunity, and other factors that influence the spread of a particular virus, including social and business arrangements. This kind of heterogeneity tends to reduce the effective HIT. We’ve already discussed the effect of pre-immunity. Suppose that certain individuals are much more likely to transmit the virus than others, like so-called super-spreaders. They spur the initial exponential growth of a contagion, but there are only so many of them. Once infected, no one else among the still-susceptible can spread the virus with the same force.

Researchers at the Max Planck Institute (and a number of others) have gauged the effect of introducing heterogeneity to standard epidemiological models. It is dramatic, as the following chart shows. The curves simulate a pandemic under different assumptions about the degree of heterogeneity. The peak of these curves correspond to the HIT under each assumption (R0 refers to the initial reproduction number from infected individuals to others).

Moderate heterogeneity implies a HIT of only 37%. Given pre-immunity of 25%, only an additional 12% of the population would have to be infected or vaccinated to prevent a contagion from gaining a foothold for the initial exponential stage of growth. Fauci’s herd immunity figure obviously fails to consider the effect of heterogeneity.

How Close To the HIT?

We’re not as far from HITs as Fauci might think, and a vaccination goal of 85% is absurd and unnecessary. The seasonal COVID waves we’ve experienced thus far have faded over a period of 10-12 weeks. Estimates of seroprevalence in many localities reached a range of 15% – 25% after those episodes, which probably includes some share of those with pre-immunity. To reach the likely range of a HIT, either some additional pre-immunity must have existed or the degree of heterogeneity must have been large in these populations.

But if that’s true, why did secondary waves occur in the fall? There are a few possibilities. Of course, some areas like the upper Midwest did not experience the springtime wave. But in areas that suffered a recurrance, perhaps the antibodies acquired from infections did not remain active for as long as six months. However, other immune cells have longer memories, and re-infections have been fairly rare. Another possibility is that those having some level of pre-immunity were still able to pass live virus along to new hosts. But this vector of transmission would probably have been quite limited. Pre-immunity almost surely varies from region to region, so some areas were not as firmly above their HITs as others. It’s also possible that infections from super-spreaders were concentrated within subsets of the population even within a given region, in certain neighborhoods or among some, but not all, social or business circles. Therefore, some subsets or “sub-herds” achieved a HIT in the first wave, but it was unnecessary for other groups. In other words, sub-herds spared in the first wave might have suffered a contagion in a subsequent wave. And again, reinfections seem to have been rare. Finally, there is the possibility of a reset in the HIT in the presence of a new, more transmissible variant of the virus, as has become prevalent in the UK, but that was not the case in the fall.

Fragility

Tyler Cowen has mentioned another possible explanation: so-called “fragile” herd immunity. The idea is that any particular HIT is dependent on the structure of social relations. When social distancing is widely practiced, for example, the HIT will be lower. But if, after a contagion recedes, social distancing is relaxed, it’s possible that the HIT will take a higher value at the onset of the next seasonal wave. Perhaps this played a role in the resurgence in infections in the fall, but the HIT can be reduced via voluntary distancing. Eventually, acquired immunity and vaccinations will achieve a HIT under which distancing should be unnecessary, and heterogeneity suggests that shouldn’t be far out of reach.

Conclusion

Anthony Fauci has too often changed his public pronouncements on critical issues related to management of the COVID pandemic. Last February he said cruises were fine for the healthy and that most people should live their lives normally. Oops! Then came his opinion on the limited effectiveness of masks, then a shift to their necessity. His first position on masks has been called a “noble lie” intended to preserve supplies for health care workers. However, Fauci was probably repeating the standing consensus at that point (and still the truth) that masks are of limited value in containing airborne pathogens.

This time, Fauci admitted to changing his estimate of “herd immunity” in response to public opinion, a pathetic approach to matters of public health. What he called herd immunity was really an opinion about adequate levels of vaccination. Furthermore, he neglected to consider other forms of immunity: pre-existing and already acquired. He did not distinguish between total immunity and the herd immunity threshold that should guide any discussion of pandemic management. He also neglected the significant advances in epidemiological modeling that recognize the reality of heterogeneity in reducing the herd immunity threshold. The upshot is that far fewer vaccinations are needed to contain future waves of the pandemic than Fauci suggests.

Allocating Vaccine Supplies: Lives or “Justice”?

29 Tuesday Dec 2020

Posted by in Pandemic, Public Health, Uncategorized, Vaccinations

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There are currently two vaccines in limited distribution across the U.S. from Pfizer and Moderna, but the number and variety of different vaccines will grow as we move through the winter. For now, the vaccine is in short supply, but that’s even more a matter of administering doses in a timely way as it is the quantity on hand. There are competing theories about how best to allocate the available doses, which is the subject of this post. I won’t debate the merits of refusing to take a vaccine except to say that I support anyone’s right to refuse it without coercion by public authorities. I also note that certain forms of discrimination on that basis are not necessarily unreasonable.

The vaccines in play all seem to be highly effective (> 90%, which is incredible by existing standards). There have been a few reports of side effects — certainly not in large numbers — but it remains to be seen whether the vaccines will have any long-term side effects. I’m optimistic, but I won’t dismiss the possibility.

Despite competing doctrines about how the available supplies of vaccine should be allocated, there is widespread acceptance that health care workers should go first. I have some reservations about this because, like Emma Woodhouse, I believe staff and residents at long-term care facilities should have at least equal priority. Yet they do not in the City of Chicago and probably in other areas. I have to wonder whether unionized health care workers there are the beneficiaries of political favoritism.

Beyond that question, we have the following competing priorities: 1) the vulnerable in care homes and other elderly individuals (75+, while younger individuals with co-morbidities come later); 2) “essential” workers of all ages (from police to grocery store clerks — decidedly arbitrary); and 3) basically the same as #2 with priority given to groups who have suffered historical inequities.

#1 is clearly the way to save the most lives, at least in the short-run. Over 40% of the deaths in the U.S. have been in elder-care settings, and COVID infection fatality rates mount exponentially with age:

To derive the implications of #1 and #2, it’s more convenient to look at the share of deaths within each age cohort, since it incorporates the differences in infection rates and fatality rates across age groups (the number of “other” deaths is much larger than COVID deaths, of course, despite similar death shares):

The 75+ age group has accounted for about 58% of all COVID deaths in the U.S., and ages 25 – 64 accounted for about 20% (an approximate age range for essential workers). This implies that nearly three times as many lives can be saved by prioritizing the elderly, at least if deaths among so-called essential workers mimic deaths in the 25 – 64 age cohorts. However, the gap would be smaller and perhaps reversed in terms of life-years saved.

Furthermore, this is a short-run calculation. Over a longer time frame, if essential workers are responsible for more transmission across all ages than the elderly, then it might throw the advantage to prioritizing essential workers over the elderly, but it would take a number of transmission cycles for the differential to play out. Yes, essential workers are more likely to be “super-spreaders” than work-at-home, corporate employees, or even the unemployed, but identifying true super-spreaders would require considerable luck. Moreover, care homes generally house a substantial number of elderly individuals and staff in a confined environment, where spread is likely to be rampant. So the transmission argument for #2 over #1 is questionable.

The over-riding problem is that of available supply. Suppose enough vaccine is available for all elderly individuals within a particular time frame. That’s about 6.6% of the total U.S. population. The same supply would cover only about 13% of the younger age group identified above. Essential workers are a subset of that group, but the same supply would fall far short of vaccinating all of them; lives saved under #2 would then fall far short of the lives saved under #1. Quantities of the vaccine are likely to increase over the course of a few months, but limited supplies at the outset force us to focus the allocation decision on the short-term, making #1 the clear winner.

Now let’s talk about #3, minority populations, historical inequities, and the logic of allocating vaccine on that basis. Minority populations have suffered disproportionately from COVID, so this is really a matter of objective risk, not historical inequities… unless the idea is to treat vaccine allocations as a form of reparation. Don’t laugh — that might not be far from the intent, and it won’t count as a credit toward the next demand for “justice”.

For the sake of argument, let’s assume that minorities have 3x the fatality rate of whites from COVID (a little high). Roughly 40% of the U.S. population is non-white or Hispanic. That’s more than six times the size of the full 75+ population. If all of the available doses were delivered to essential workers in that group, it would cover less than half of them and save perhaps 30% of minority COVID deaths over a few months. In contrast, minorities might account for up to two-thirds of the deaths among the elderly. Therefore, vaccinating all of the elderly would save 58% of elderly COVID deaths and about 39% of minority deaths overall!

The COVID mortality risk to the average white individual in the elderly population is far greater than that faced by the average minority individual in the working age population. Therefore, no part of #3 is sensible from a purely mathematical perspective. Race/ethnicity overlaps significantly with various co-morbidities and the number of co-morbidities with which individuals are afflicted. Further analysis might reveal whether there is more to be gained by prioritizing by co-morbidities rather than race/ethnicity.

Megan McArdle has an interesting column on the CDC’s vaccination guidelines issued in November, which emphasized equity, like #3 above. But the CDC walked back that decision in December. The initial November decision was merely the latest of the the agency’s fumbles on COVID policy. In her column, McArdle notes that the public has understood that the priority was to save lives since the very start of the pandemic. Ideally, if objective measures show that identifiable characteristics are associated with greater vulnerability, then those should be considered in prioritizing individuals who desire vaccinations. This includes age, co-morbidities, race/ethnicity, and elements of occupational risk. But lesser associations with risk should not take precedence over greater associations with risk unless an advantage can be demonstrated in terms of lives saved, historical inequities or otherwise.

The priorities for the early rounds of vaccinations may differ by state or jurisdiction, but they are all heavily influenced by the CDC’s guidelines. Some states pay lip service to equity considerations (if they simply said race/ethnicity, they’d be forced to operationalize it), while others might actually prioritize doses by race/ethnicity to some degree. Once the initial phase of vaccinations is complete, there are likely to be more granular prioritizations based on different co-morbidities, for example, as well as race/ethnicity. Thankfully, the most severe risk gradient, advanced age, will have been addressed by then.

One last point: the Pfizer and Moderna vaccines both require two doses. Alex Tabarrok points out that first doses appear to be highly effective on their own. In his opinion, while supplies are short, the second dose should be delayed until all groups at substantially elevated risk can be vaccinated…. doubling the supply of initial doses! The idea has merit, but it is unlikely to receive much consideration in the U.S. except to the extent that supply chain problems make it unavoidable, and they might.

Harbingers of COVID Fade, But Not the Pretense for Hysteria

17 Thursday Dec 2020

Posted by in Coronavirus, Pandemic, Vaccinations

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My pre-Thanksgiving optimism about a crest in the fall wave of the coronavirus has been borne out for the Midwest and Mountain states in the U.S. These regions were the epicenter of the fall wave through October and most of November, but new cases in those states have continued to decline. Cases in a number of other states began to climb in November, however, contributing to a continuing rise in total new cases nationally. Some of these states are still in the throes of this wave, with the virus impacting subsets of the population that were relatively unscathed up till now.

My disclaimer: COVID is obviously a nasty virus. I don’t want to get it. However, on the whole, it is not a cataclysm on the order of many pandemics of the past. In fact, excess deaths this year will add just over 10% to projections of total deaths based on a five-year average. That level puts us in line with average annual deaths of about twenty years ago. And many of those excess deaths have been caused by our overreaction to the pandemic, not by the virus itself. As my endocrinologist has said, this is the greatest overreaction in all medical history. Unfortunately, a fading pandemic does not mean we can expect an end to the undue panic, or pretense for panic, on the part of interventionists.

This post will focus largely on trends in newly diagnosed COVID cases. I have been highly critical of our testing regime and COVID case counts because the most prominent diagnostic test (PCR) falsely identifies a large number of uninfected individuals as COVID-positive. However, case numbers are widely tracked and it’s fairly easy to find information across geographies for comparison. Deflate all the numbers by 30% if you want, or by any other factor, but please indulge me because I think the trends are meaningful, even if the absolute level of cases is inflated.

I’ll start with the good news and work my way down to states in which cases are still climbing (all of the following charts are from @Humble_Analysis (PLC)). The first chart is for the Great Plains, where cases peaked a little before Thanksgiving and have continued to fall since then. That peak came about six weeks after it began in earnest and cases have faded over the last four weeks.

Next we have the Mountain states, where again, cases peaked around Thanksgiving, though Idaho saw a rebound after the holiday. You’ll see below that a number of states had a distinct drop in new cases during the week of Thanksgiving. There was somewhat of a pause in testing during that week, so the subsequent rebounds are largely due to a “catch-up” at testing sites, rather than some kind of Thanksgiving-induced spike in infections.

Back to the Mountain region, the peak came an average of about six or seven weeks into the wave, but the duration of the wave appears to have been longer in Montana and Wyoming.

Here are the Southern Plain states, where cases plateaued around Thanksgiving (though cases in Missouri have clearly declined from their peak). In this region, case counts accelerated in October after a slow climb over the summer.

The situation is somewhat similar in the Midwest. where cases have generally plateaued. There were some post-Thanksgiving rebounds in several states, especially Tennessee. The wave began a little later in this region, in mid- to late October, and it is now seven to eight weeks into the wave, on average.

Here are the Mid-Atlantic states, which may be showing signs of a peak, though North Carolina has had the greatest caseload and is still climbing. These states are about seven weeks into the wave, on average.

The Northeast also shows signs of a possible peak and is about seven weeks into the wave, except for Rhode Island, which saw an earlier onset and the most severe wave among these states.

And finally we have the South, which is defined quite broadly in PLC’s construction. It’s a mixed bag, with a few states showing signs of a peak after about seven weeks. However, cases are still climbing in several states, notably California and Florida, among a few others.

Oregon and Washington were skipped, but they appear as the Pacific NW in the following chart, along with aggregations for all the other regions. Maine is Part of the “Rural NE”, which was also skipped. The fall wave can be grouped roughly into two sets of regions: those in which waves began in late September or early October, and those where waves began in early to mid-November. The first group has moved beyond a peak or at least has plateaued. The latter group may be reaching peaks now or one hopes very soon. It seems to take about seven weeks to reach the peak of these regional waves, so a late December peak for the latter group would be consistent.

Justin Hart has a take on the duration of these waves, but he does so in terms of the share of emergency room (ER) visits in which symptoms of COVID-like illness (CLI) are presented. CLI tends to precede case counts slightly. Hart puts the duration of these waves at eight to ten weeks, but that’s a judgement call, and I might put it a bit longer using caseloads as a guide. Still, this color-coded chart from Hart is interesting.

If this sort of cyclical duration holds up, it’s consistent with the view that cases in many of the still “hot” states should be peaking this month.

Aggregate cases for the U.S. appear below. The growth rate of new cases has slowed, and the peak is likely to occur soon. However, because it combines all of the regional waves, the duration of the wave nationwide will appear to be greater than for the individual regions. COVID-attributed deaths are also plotted, but they are reported deaths, not by date of death (DOD) or actual deaths, as I sometimes call them. Deaths by DOD are available only with a lag. As always, some of the reported deaths shown below occurred weeks before their reported date. Actual deaths were still rising as of late November, and are likely still rising. However, another indicator suggests they should be close to a peak.

A leading indicator of actual deaths I’ve discussed in the past now shows a more definitive improvement than it did just after Thanksgiving, as the next chart shows. This is the CLI share discussed above. An even better predictor of COVID deaths by actual DOD is the sum of CLI and the share of ER patients presenting symptoms of influenza-like illness (ILI), but ILI has been fairly low and stable, so it isn’t contributing much to changes in trend at the moment. There has been about a three-week lead between movements in CLI+ILI and COVID deaths by DOD.

(The reason the sum, CLI+ILI, has been a better predictor than CLI alone is because for some individuals, there are similarities in the symptoms of COVID and the flu.)

The chart shows that CLI peaked right around the Thanksgiving holiday (and so did CLI+ILI), but it remained on something of a plateau through the first week of December before declining. Some of the last few days on this chart are subject to revision, but the recent trend is encouraging. Allowing for a three-week lead, this indicates that peak deaths by DOD should occur around mid-December, but we won’t know exactly until early to mid-January. To be conservative, we might say the latter half of December will mark the peak in actual deaths.

The regional COVID waves this summer and fall seem to have run their course within 10 – 12 weeks. Several former hot spots have seen cases drop since Thanksgiving after surges of six to seven weeks. However, there are several other regions with populous states where the fall wave is still close to “mid-cycle”, as it were, showing signs of possible peaks after roughly seven weeks of rising cases. The national CLI share peaked around Thanksgiving, but it did not give up much ground until early December. That suggests that actual deaths (as opposed to reported deaths), at least in some regions, will peak around the time of the winter solstice. Let’s hope it’s sooner.

Successive waves within a region seem to reach particular subsets of the population with relatively few reinfections. The 10 – 12 week cycle discussed above is sufficient to achieve an effective herd immunity within these subsets. But once again, a large share of the vulnerable, and a large share of COVID deaths, are still concentrated in the elderly, high-risk population and in care homes. The vaccine(s) currently being administered to residents of those homes are likely to hasten the decline in COVID deaths beginning sometime in January, perhaps as early as mid-month. By then, however, we should already see a decline underway as this wave of the virus finally burns itself out. As vaccines reach a larger share of the population through the winter and spring, the likelihood of additional severe waves of the virus will diminish.

Lest there be any misunderstanding, the reasons for the contagion’s fade to come have mostly to do with reaching the effective herd immunity threshold within afflicted subsets of the population (sub-herds). Social distancing certainly plays a role as well. Nearly all of that is voluntary, though it has been encouraged by panicked pronouncement by certain public officials and the media. Direct interventions or lockdown measures are in general counter-productive, however, and they create a death toll of their own. Unfortunately, the fading pandemic might not rein-in the curtailment of basic liberties we’ve witnessed this year.

Post-Script: Let’s hope the side effects of the vaccines are not particularly severe in the elderly. That’s a little uncertain, because that sub-population was not tested in very high numbers.

The FDA Can Put Virus Behind Us, Sans Vaccine

19 Wednesday Aug 2020

Posted by in Liberty, Pandemic, Vaccinations

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Most of the news about COVID vaccine development is positive, but there are still huge doubts about 1) whether an effective vaccine(s) will ever be available; 2) when it will be available; 3) in what quantities (supply chains for vaccines present issues that most lay persons would never imagine) ; 4) the best approaches to allocation across young/healthy vs. old/vulnerable; 5) how long it will provide protection (the news is good on lasting immunity as well); and 6) whether people will actually take it. Given all these uncertainties, it’s worth considering an approach to stanching the coronavirus that won’t require a vaccine while still allowing a return to normalcy: cheap, rapid tests available to consumers on a daily basis in their homes or in businesses.

The full benefits of cheap, rapid tests can take people a while to wrap their heads around. In fact, there are skeptics who’s views on any and all testing are colored by suspicions that increased testing is some sort of conspiracy to spread fear and keep the economy hobbled. It’s true that increased testing drove much of the increase in COVID cases this summer, which caused the mainstream media to delight in spinning alarmist narratives. Fair enough, but that misses the point, which I’ll try to elucidate below. I credit a John Cochrane post for bringing this to my attention.

A successful vaccine breaks the so-called “transmission chain”, but so does frequent testing to identify infectious individuals on an ongoing basis so they can self-quarantine. As Alex Tabarrok has emphasized, we should worry about identifying infectious individuals, as opposed to infected individuals. They are not the same. Cheap, rapid, and easy-to-administer tests have already proven to be fairly accurate during the infectious stage. The idea is for individuals to self-test every day and stay home if they are positive. Or, employers can test workers every day and send them home if they are positive. Frequent testing also makes it simpler to trace the source of an infection and may reduce the importance of tracing.

To those who say this represents an affront to personal liberty, and I’m very touchy on that subject myself, recall that even now people are being screened in their workplaces using thermometers, questionnaires, or on the basis of any frogginess perceived by supervisors and co-workers. Those “tests” are far less accurate in identifying COVID-19 contagiousness than the kinds of cheap tests at issue here, and they are certainly no less intrusive. Then there are the many businesses facing restrictions on their operations: how “accurate” is it to keep everyone at home by locking down places of business? How intrusive is that? Those restrictions are indefensible, and especially with the advent and diffusion of cheap, rapid tests.

Of course, people might cheat and not report positives. Tests could be administered at workplaces to avoid that possibility, or at points of admission to businesses and facilities, but a few minutes of delay would be necessary. I would not support a centralized database of daily test results. If nothing else, relying on the good faith of individuals in reporting their results would be a giant leap forward in breaking the transmission chain now, rather than counting on the possibility of a successful virus in the indefinite future. And we might then avoid the whole pro-vax/anti-vax imbroglio that already foments, which raises major questions bearing on individual liberty.

Then there is the question of positive tests within multi-person households. Should the entire family or household self-quarantine? I say no, not if the others are negative, but then the others should test twice before going out, which dramatically reduces the probability of a false negative, and they should probably test more frequently, perhaps several times a day.

There are other important details to address: Who will pay for the tests? Will workers be paid to stay home if they test positive? How long will they be required to stay home? How will repeated tests be treated? I don’t want to get into detail on all of these points, but cheap, fast tests can help overcome many of these difficulties, and I believe many of the details can and should be worked out privately.

Unfortunately, the FDA has approved only two rapid tests, and they are not very rapid and not cheap enough. Only one had been approved up until last weekend because the FDA found the accuracy to be lacking … compared to PCR tests! But the FDA finally issued an Emergency Use Authorization for a saliva-based test (SalivaDirect) developed at Yale, partly funded by the NBA and the Players Association. The test still requires processing at a lab, so it’s really not convenient enough and not fast enough. Here is Zach Lowe on the cost:

“The cost per sample could be as low as about $4, though the cost to consumers will likely be higher than that — perhaps around $15 or $20 in some cases, according to expert sources.”

Not bad, but it’s much higher than more rapid, paper tests developed by Harvard’s Wyss Institute for Biologically Inspired Engineering and a company called E25Bio. Both of those are expected to cost about $1 per sample and can be completed anywhere. That’s a price that can work. And there are other promising candidates.

The benefits of tests that are rough, ready, and cheap will be huge. Such tests will also enable retesting, which helps to overcome the dilemmas of false positives and negatives. False negatives might be of greater concern to the FDA, but again, false negatives are less likely during the contagious stage of an infection, and the tests will be accurate enough that transmission risk will be drastically reduced.

The FDA needs to move beyond its stodgy insistence on achieving laboratory levels of accuracy. It’s unlikely that a single test source will be adequate to stanch the transmission chain, so the agency should rush to approve as many cheap, rapid tests as possible, with as many advisories and patient warnings regarding test results and follow-up instructions as it deems necessary. Remember, these tests are much better than thermometers!

Statists Might Like To Vaccinate Against Many Things

25 Monday Nov 2019

Posted by in Vaccinations

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The vaccine debate illustrates a widespread misunderstanding about the meaning of an “advanced society”. It does not mean that difficult social problems must be dealt with always and everywhere in a uniform way, as supporters of vaccine mandates seem to assume. Instead, it often means that society can respect differences in the preferences of individuals by allowing varied approaches to problem-solving across jurisdictions, as well as across public and private institutions. This latter notion of advancement respects individual freedom and facilitates experiential social learning. But is that varied approach wise in a world of communicable diseases?

One standard of “community” protection assumes that vaccines work with a high degree of certainty within groups of individuals, especially with a second booster. The share of the population vaccinated against most common childhood diseases is fairly high. In fact, these shares mostly exceed their respective “community protection thresholds” — the percentage required to prevent a particular disease from spreading. That means achieving so-called “herd immunity”. Of course, that will not be true across many local subgroups. Nevertheless, if one accepts this standard, a runaway contagion in the U.S. is an extremely remote possibility, affording some flexibility for respecting preferences for and against vaccination.

My Friend, the Vaccine Resistor

One of my best friends is a passionate vaccine resistor (VR). I won’t say he’s “vaccine hesitant” because that doesn’t come close to his position. I won’t call him an “anti-vaxxer” because he doesn’t mind if others avail themselves of vaccines (and besides, the term has taken on such derogatory connotation. He’s a fine fellow, very smart, lots of fun to be with, and we have plenty of mutual interests. We’ve argued about vaccinations before, and a few other medical and nutritional issues, but we mostly stay out of each others’ ways on these topics.

But I recently witnessed my pal get into a “debate” on social media with a mutual acquaintance and some of her connections. She happens to be a nurse. She’d posted a photo of an attractive young woman in a t-shirt imprinted, “Vaccines Cause Adults”. My buddy spoke up and said “Not for everyone!’, and he posted a link to an article that he felt supported his position. Of course, a number of barbed responses came his way. Okay, some of those were fair debate points, though barbed, but others were quite derisive, ad hominem attacks on him. He responded by posting links to more articles and research, which might not have been productive. It’s usually a waste of time to argue with people on social media. But to his great credit he maintained his equanimity. The episode made me feel a bit sad. People can be such assholes on social media. I was put off by the nurse’s refusal to moderate . That’s a typical pattern: posters allow their other friends to hurl terrible insults at anyone who disagrees, even when it’s an old friend. Mind you, I stayed on the sidelines in this case, except that I originally “liked” the nurse’s meme.

Later, I had a private exchange with my friend. I’m on board with vaccinations. I believe that widespread immunization contributes to public health, but I told him there are certain points on which I can sympathize with VRs. Without knowing the details, he encouraged me to write a blog post on the subject. I’m not sure he’ll like the results. However, as noted above, I’m willing to make a few concessions to my buddy’s side of the argument, and I wish we could identify a path that would settle the debate.

My Standpoint

This is one part my pal won’t like. Are VRs anti-science? First, VR’s come in several varieties. Some might resist only some vaccines and not others. But VRs do not disavow empiricism, as they claim their own set of empirical findings to support their position, however one might regard the research quality. 

I believe many VRs are misled by a serious post hoc ergo propter hoc fallacy: after this, therefore because of this. For example, for many observers, the purported link between autism and the measles, mumps and rubella vaccine was put to rest when the British medical journal Lancet retracted the original article supporting that claim as faulty. That doesn’t wash with more radical VRs, many of whom seem to have someone on the autism spectrum in their own families. They are understandably sensitive, but please forgive me: that suggests a need to find some external explanation, a source of blame not related to genetics.

Radical VRs are selective proponents of the precautionary principle: any risk of harm from a vaccine delivered in any amount is too great a risk. They seem reluctant to acknowledge the reality of a dose-response relationship, which bears on the risks of exposure to certain compounds often present in vaccine formulations. VRs will not acknowledge that vaccines present a manageable risk. And then there are the misleading references to disease incidence counts, as opposed to disease incidence rates, that are all too common (though my friend is almost certainly innocent on this count).

Vaccine resistance is not a new phenomenon, as the cartoon above from 1802 illustrates. Certain people will always find the idea of injecting germs into their systems deeply unsettling. Of course, that’s a very natural basis of resistance. A person’s body is their own property, after all. My default position is that an individual’s control over their own body is inviolable, and parents should always be the first authority over decisions about their children. The real issue, however, is the question of whether unvaccinated children inflict external costs on others.

Points of Contention

The major objections of VRs fall into several categories: 1) preservatives; 2) multiple viruses; 3) vulnerable infants; 4) contra-indications; 5) inefficacy; and 6) free choice. There may be others, but I’ll go with those.

Preservatives: Some vaccines still use a form of mercury, but a much more innocuous variant than the one VRs found so objectionable a few decades ago. Still, they object. And they object to many other compounds used in minute quantities as preservatives, such as formaldehyde, which occurs naturally in our bodies. I think the following test is helpful: if it were proposed that VRs take new versions of the vaccines that had zero preservatives, many would still refuse, especially if they were asked to pay the additional cost of providing them in that form. Thus, preservatives are revealed to be something of a side show.

Multiple Viruses: VRs object to the administration of vaccines that inoculate against several viruses in one dose or within a short window of time. This objection has some plausibility, since an injection of several different “bugs’ at once might place excessive stress on the body, even if the risk is still small. But again, would VRs volunteer to take single strain vaccines in a schedule over a lengthier period of time? Probably not.

Vulnerable Infants: VRs say it’s too risky to vaccinate infants in their first few months of life. This too is a plausible objection, and it would seem like a relatively easy concession to make in the interests of compromise … except, it won’t ever be good enough. Radical VRs will not agree to having their children vaccinated at any age.

Contra-Indications: There are undoubtedly genetic factors that pre-dispose certain individuals to an adverse reaction to certain vaccines. These might be rare, so an effort to compromise by requiring a thorough genetic profile before vaccination would be costly. I believe profiling is a reasonable demand for individuals to make, however, provided they pay the cost themselves.

Inefficacy: My friend posted an intriguing article about the drastic declines that occurred in the incidence of various diseases before the introduction of vaccines to prevent those diseases. This might not be the same link, but it makes the same argument. That doesn’t mean vaccines don’t work, of course. There is a vast literature that shows that they do. Bing it! And in cases such as smallpox, the use of “folk applications” of puss to a small scratch in the skin were in use long before the vaccine was available. Nevertheless, the VRs contend that the historical rates of disease incidence provide evidence against vaccinating. They also contend that diseases like measles are not serious enough to warrant precautions like vaccines. Measles can be deadly, though not as deadly as the flu.

Free Choice: This is the point on which I’m most sympathetic to VRs. Again, we own our own bodies and should have authority over our own minor children, yet communicable diseases seem to be a classic case of externality. Susceptible individuals may inflict a cost on others by refusing vaccination or segregation. Other people own their bodies too, and they have a right to avoid exposure. They too can isolate themselves or take precautions as they deem necessary. If both parties wish to participate in society, then both hold rights they allege to be threatened by the other. That complicates the task of reconciling these interests in private, voluntary ways, and yet they often are reconciled privately.

Solutions?

The debate today often revolves around mandatory vaccination, which would be an extreme measure relying on the coercive power of the state. The rationale is that even a vaccinated majority would be subject to an unnecessarily high risk of infection when in frequent contact with an unvaccinated minority. It’s difficult to endorse such broad intrusiveness when we’re dealing with a negative externality of such minute probability. And such a policy is not at all defensible without exceptions for individuals for whom a vaccine is contra-indicated.

Tolerating differences in vaccination rules across cities, school districts, or even states, may be a reasonable approach to settling the debate in the long run. These variations allow empirical evidence to accumulate on the efficacy of different vaccine regimes. It also allows individuals and families to “vote with their feet”, migrating to jurisdictions that best suit their preferences. These are the basic foundations of federalism, a principle of great usefulness in preserving freedoms while addressing regional differences of opinion on contentious issues.

Michigan has a policy allowing unvaccinated children to attend schools, but a waiver must be obtained requiring the child’s parents to attend a vaccine education program. The policy is credited with increasing vaccination rates. The problem is that VRs tend to view this requirement as an infringement on their rights. Advocates of the policy might argue that the situation should be viewed as an arms-length, voluntary exchange between two parties, in this case a family and a public entity. The vaccine education program is just the price one must pay in lieu of vaccination. The exchange is not arms length, however, as it would be if the school were a private entity. The VR parents who refuse the waiver are not rebated for taxes paid for local schools. In fact, like all taxes, the payment is coerced.

It’s not always necessary to appeal to some form of government action, even at local levels. For example, private schools may require vaccination among enrollees, and private businesses, especially health care providers, may require staff to be vaccinated. Life and health insurers may wish to price risk differently for the unvaccinated. VRs might object that they are subject to discrimination by institutions requiring immunization, or who price discriminate in favor of the immunized, but VRs are free to form competitive institutions, even on small scales or as mutual companies. To the extent that such private rules are unjustified, the institutions who discriminate are likely to learn or lose eventually. That’s the beauty of market solutions. In these ways, non-coercive private governance is far preferable to action by the state.

Dr. Jeffrey Singer is an advocate of immunization who opposes mandatory vaccine laws, as he explained a few years ago in “Vaccination and Free Will“. He suggested elsewhere, in “Seeking Balance In Vaccination Laws“, that schools, instead of requiring immunization, could mitigate the risk of a contagion by insisting that unvaccinated children be held out of school when a particular threat arises and remain out until it passed. That’s a reasonable idea, but I suspect many pro-vax parents would fear that it doesn’t go far enough in protecting against the introduction of a disease by an unvaccinated child.

Conclusion

Recent increases in the incidence of diseases such as measles, mumps and whooping cough are extremely troubling. Whether these outbreaks bear any relationship to patterns of vaccination in the population is certainly a valid question. To the extent that more families and individuals wish to be immunized, and that private institutions wish to take action to increase vaccination rates within their sphere of influence, I’m all for it. Vaccination laws are a different matter.

Political action at the local level might mean that school districts and other public entities will require vaccinations or vaccine education programs. Alternatives exist for those refusing to vaccinate, but broad mandatory vaccination is too coercive. Such measures carry significant costs, not least of which is a loss of liberty and normalization of losses of liberty. It’s not clear that a vaccination mandate at the national level, or even a state vaccination mandate, can offer benefits sufficient to justify those costs. Nudges are irritating and may be costly, but forcible intrusions are way out-of-bounds. Unfortunately, there are parties that simply can’t resist the temptations of behavioral control, and that’s worthy of resistance. Let’s continue to muddle through with an essentially federalist approach to vaccination policy. I regard that as a hallmark of an advanced society.