Tag Archives: Antibodies

Effective Immunity Means IF YOU CATCH IT, You Won’t Get Sick

12 Thursday Aug 2021

Posted by in Coronavirus, Uncategorized, Vaccinations

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Listen very carefully: immunity does NOT mean you won’t get COVID, though an infection is less likely. Immunity simply means your immune system will be capable of dealing with an infection successfully. This is true whether the immunity is a product of vaccination or a prior infection. Immunity means you are unlikely to have worse than mild symptoms, and you are very unlikely to be hospitalized. (My disclaimer: I am opposed to vaccine mandates, but vaccination is a good idea if you’ve never been infected.)

I emphasize this because the recent growth in case numbers has prompted all sorts of nonsensical reactions. People say, “See? The vaccines don’t work!” That is a brazenly stupid response to the facts. Even more dimwitted are claims that the vaccines are killing everyone! Yes, there are usually side effects, and the jabs carry a risk of serious complications, but it is minuscule.

Vaccine Efficacy

Right out of the gate, we must recognize that our PCR testing protocol is far too sensitive to viral remnants, so the current surge in cases is probably exaggerated by false positives, as was true last year. Second, if a large share of the population is vaccinated, then vaccinated individuals will almost certainly account for a large share of infected individuals even if they have a lower likelihood of being infected. It’s simple math, as this explanation of base rate bias shows. In fact, according to the article at the link:

“… vaccination confers an eightfold reduction in the risk of getting infected in the first place; a 25-fold reduction in risk of getting hospitalized; and a 25-fold reduction in the risk for death.”

The upshot is that if you are vaccinated, or if you have acquired immunity from previous exposure, or if you have pre-existing immunity from contact with an earlier COVID strain, you can still “catch” the virus AND you can still spread it. Both are less likely, and you don’t have as much to worry about for your own health as those having no immunity.

As for overall vaccine efficacy in preventing death, here are numbers from the UK, courtesy of Phil Kerpen:

The vertical axis is a log scale, so each successive gridline is a fatality rate 100x as large as the one below it. Obviously, as the chart title asserts, the “vaccines have made COVID-19 far less lethal.” Also, at the bottom, see the information on fatality among children under age 18: it is almost zero! This reveals the absurdity of claims that children must be masked for schools to reopen! In any case, masks offer little protection to anyone against a virus that spreads via fine aerosols. Nevertheless, many school officials are pushing unnecessary but politically expedient masking policies

Delta

Ah, but we have the so-called Delta variant, which is now dominant and said to be far more transmissible than earlier variants. Yet the Delta variant is not as dangerous as earlier strains, as this UK report demonstrates. Delta had a case fatality rate among unvaccinated individuals that was at least 40% less than the so-called Alpha variant. This is a typical pattern of virus mutation: the virus becomes less dangerous because it wants to survive, and it can only survive in the long run by NOT killing its hosts! The decline in lethality is roughly demonstrated by Kelly Brown with data on in-hospital fatality rates from Toronto, Canada:

The case numbers in the U.S. have been climbing over the past few weeks, but as epidemiologist Larry Brilliant of WHO said recently, Delta spreads so fast it essentially “runs out of candidates.” In other words, the current surge is likely to end quickly. This article in Issues & Insights shows the more benign nature of recent infections. I think a few of their charts contain biases, but the one below on all-cause mortality by age group is convincing:

The next chart from Our World In Data shows the infection fatality rate continuing its decline in the U.S. The great majority of recent infections have been of the Delta variant, which also was much less virulent in the UK than earlier variants.

Furthermore, it turns out that the vaccines are roughly as effective against Delta and other new variants as against earlier strains. And the newest “scary” variants, Kappa and Lambda, do not appear to be making strong inroads in the U.S. 

Fading Efficacy?

There have been questions about whether the effectiveness of the vaccines is waning, which is behind much of the hand-wringing about booster shots. For example, Israeli health officials are insisting that the effectiveness of vaccines is “fading”, though I’ll be surprised if there isn’t some sort of confounding influence on the data they’ve cited, such as age and co-morbidities. 

Here is a new Mayo Clinic study of so-called “breakthrough” cases in the vaccinated population in Minnesota. It essentially shows that the rate of case diagnosis among the vaccinated rose between February and July of this year (first table below, courtesy of Phil Kerpen). However, the vaccines appear only marginally less effective against hospitalization than in March (second table below).

The bulk of the vaccinated population in the U.S. received their jabs three to six months ago, and according to this report, evidence of antibodies remains strong after seven months. In addition, T-cell immunity may continue for years, as it does for those having acquired immunity from an earlier infection. 

Breakthroughs

It’s common to hear misleading reports of high numbers of “breakthrough” cases. Not only will these cases be less menacing, but the reports often exaggerate their prevalence by taking the numbers out of context. Relative to the size of the vaccinated population, breakthrough cases are about where we’d expect based on the original estimates of vaccine efficacy. This report on Massachusetts breakthrough hospitalizations and deaths confirms that the most vulnerable among the vaxed population are the same as those most vulnerable in the unvaxed population: elderly individuals with comorbidities. But even that subset is at lower risk post-vaccination. It just so happens that the elderly are more likely to have been vaccinated in the first place, which implies that the vaccinated should be over-represented in the case population.

Conclusion

The COVID-19 vaccines do what they are supposed to do: reduce the dangers associated with infection. The vaccines remain very effective in reducing the severity of infection. However, they cannot and were not engineered to prevent infection. They also pose risks, but individuals should be able to rationally assess the tradeoffs without coercion. Poor messaging from public health authorities and the crazy distortions promoted in some circles does nothing to promote public health. Furthermore, there is every reason to believe that the current case surge in Delta infections will be short-lived and have less deadly consequences than earlier variants.

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 Cases Decline Despite New Variants

19 Friday Feb 2021

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For weeks, even months, we’ve been hearing about dangerous new mutations of the coronavirus, and they’ve been identified in cases in the U.S. There’s a UK strain, a South African strain, a Brazilian strain, and still others, which differ in seemingly minor ways. Nevertheless, these variants are said to be more infectious. It’s also been reported that the South African and Brazilian strains might resist antibodies from prior infections from earlier strains.

Kyle Lamb has provided the following charts to put things in perspective:

Just to round things out, here is the trend in cases worldwide:

There is a great deal of concern about the new variants. A search for “COVID-19 variants” turns up plenty of scary articles. However, there is some evidence that the new variants are not as dangerous as alarmists contend. The resistance to specific antibodies does not necessarily imply resistance to protection by T-cells. As Youyang Gu points out, even if a new strain becomes “dominant”, that does not imply that cases will reverse their decline. This study indicates that the Pfizer vaccine is protective against both the UK and South African strains, and there is evidence that other vaccines offer adequate protection as well (and see here).

The charts demonstrate that the new strains haven’t arrested or reversed the declines in infections witnessed worldwide since early January. That doesn’t mean the mutations haven’t made a difference: perhaps the declines would have been faster in their absence. And we don’t know what the future will hold as the virus in various forms becomes endemic. Still, it’s reassuring to see that the increased transmissibility of the new strains hasn’t overcome factors that have contributed to the recent declines, which in all likelihood are related to increasing immunity in the population with a minor assist from vaccinations (thus far). As Lamb wryly notes about the recent declines in transmission: “Just saying”.

Predicted November COVID Deaths

08 Sunday Nov 2020

Posted by in Pandemic, Public Health

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Reported COVID deaths do not reflect deaths that actually occurred in the reporting day or week, as I’ve noted several times. Here is a nice chart from @tlowdon on Twitter showing the difference between reported deaths and actual deaths for corresponding weeks. The blue bars are weekly deaths reported by the COVID Tracking Project. The solid orange bars are the CDC’s “provisional” deaths by actual week of death, which is less than complete for recent weeks because of lags in reporting. Still, it’s easy to see that reported deaths have overstated actual deaths each week since late August.

I should note that the orange bars represent deaths that involved COVID-19, though a COVID infection might not have actually killed them. This CDC report, updated on November 4th, shows the importance of co-morbidities, which in many cases are the actual cause of death according to pre-COVID, CDC guidance on death certificates.

Leading Indicators

Researchers have studied several measures in an effort to find leading indicators of COVID deaths. The list includes new cases diagnosed (PCR positivity) and the percentage of emergency room visits presenting symptoms of COVID-like illness (%CLI). These indicators are usually evaluated after shifting them in time by a few weeks in order to observe correlations with COVID deaths a few weeks later. Interestingly, @tlowdon reports that the best single predictor of actual COVID deaths over the course of a few weeks is the sum of the %CLI and the percentage of ER patients presenting symptoms of influenza-like illness (%ILI). Perhaps adding %ILI to %CLI strengthens the correlation because the symptoms of the flu and COVID are often mistaken for one another.

The chart below reproduces the orange bars from above representing deaths at actual dates of death. Also plotted are the %Positivity from COVID tests (shifted forward 2 weeks), %CLI (3 weeks), the %ILI (3 weeks), and the sum of %CLI and %ILI (3 weeks, the solid blue line). My guess is that %ILI contributes to the correlation with deaths mainly because %ILI’s early peak (which occurred in March) led the peak in deaths in April. Otherwise, there is very little variation in %ILI. That might change with the current onset of the flu season, but as I noted in my last post, the flu has been very subdued since last winter.

What About November?

So where does that leave us? The chart above ends with our leading indicator, CLI + ILI, brought forward from the first half of October. What’s happened to CLI + ILI since then? And what does that tell us to expect in November? The chart below is from the CDC’s web site. The red line is %CLI and the yellow line is %ILI. The sum of the two isn’t shown. However, there is no denying the upward trend in CLI, though the slope of CLI + ILI would be more moderate.

As of 10/31, CLI + ILI has increased by almost 40% since it’s low in early October. If the previous relationship holds up, that implies an increase of almost 40% in actual weekly COVID deaths from about 4,000 per week to about 5,500 per week by November 21 (a little less than 800 per day).

FiveThirtyEight has a compilation of 13 different forecast models with projections of deaths by the end of November. The estimate of 5,500 per week by November 21, or perhaps slightly less per week over the full month of November, would put total COVID deaths at the top of the range of the MIT, UCLA, Iowa State, and University of Texas models, but below or near the low end of ranges for eight other models. However, those models are based on reported deaths, so the comparison is not strictly valid. Reported deaths are still likely to exceed actual deaths by the end of November, and the actual death prediction would be squarely in the range of multiple reported death predictions. That reinforces the expectation an upward trend in actual deaths.

Third Wave States

States in the upper Midwest and upper Mountain regions have had the largest increases in cases per capita over the past few weeks. Using state abbreviations, the top ten are ND, SD, WI, IA, MT, NE, WY, UT, IL, and MN, with ID at #11 (according to the CDC’s COVID Data Tracker). One factor that might mediate the increase in cases, and ultimately deaths, is the possibility of early herd immunity: in the earlier COVID waves, the increase in infections abated once seroprevalence (the share of the population with antibodies from exposure) reached a level of 15% to 25%.

Unfortunately, estimates of seroprevalence by state are very imprecise. Thus far, reliable samples have been limited to states and metro areas that had heavy infections in the first and second waves. One rule of thumb, however, is that seroprevalence is probably less than 10x the cumulative share of a population having tested positive. To be very conservative, let’s assume a seroprevalence of four times cumulative cases. On that basis, half the states in the “top ten” listed above would already have seroprevalence above 15%. Those states are ND, SD, WI, IA, and NE. The others are mostly in a range of 12% to 15%, with MI coming in the lowest at about 9%.

This gives some cause for optimism that the wave in these states and others will abate fairly soon, but there are a number of uncertainties: first, the estimates of seroprevalence above, while conservative, are very imprecise, as noted above; second, the point at which herd immunity might cause the increase in new cases to begin declining is real guesswork (though we might have confirmation in a few states before long); third, we are now well into the fall season, with lower temperatures, lower humidity, less direct sunlight, and diminishing vitamin D levels. We do not have experience with COVID at this time of year, so we don’t know whether the patterns observed earlier in the year will be repeated. If so, new cases might begin to abate in some areas in November, but that probably wouldn’t be reflected in deaths until sometime in December. And if the flu comes back with a corresponding increase in CLI + ILI, then we’d expect further increases in actual deaths attributed to COVID. That is only a possibility given the weakness in flu numbers in 2020, however.

Closing Thoughts

I was excessively optimistic about the course of the pandemic in the U.S. in the spring. While this post has been moderately pessimistic, I believe there are reasons to expect fewer deaths than previous relationships would predict. We are far better at treating COVID now, and the vulnerable are taking precautions that have reduced their incidence of infections relative to younger and healthier cohorts. So if anything, I think the forecasts above will err on the high side.

False Positives, False Cases, False Deaths

14 Monday Sep 2020

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The tremendous increase in testing for COVID-19 (C19) this summer was associated with an increase in cases. Most of these tests were so-called PCR tests with samples collected via deep nasal swabs. More testing did not fully explain the increased case load, but false positives (FPs) still accounted for a substantial share. That’s especially true in light of the decline in positivity rates, which reflected a decline in the actual prevalence of active infections. FPs also account for a substantial share of the deaths attributed to COVID, which are obviously cases of false attribution. If a test for C19 is positive, it will be listed on the death certificate.  

COVID Case Inflation

The exaggeration of confirmed cases due to FPs is more substantial as the prevalence of active infection declines. That’s because the share of true positives in the tested population declines, while the share of false positives must rise due to the greater share of uninfected individuals in the population.

Now, as the contagion is waning in former hot spots, there is a danger that FPs create the impression of persistence in the case counts. That’s costly not just for those incorrectly diagnosed, but also in terms of medical resources, for communities subject to excessive public intervention, such as inappropriate lockdowns, and in terms of the fear promoted by these inaccuracies.

FPs are extremely disruptive when testing is relied upon in critical situations such as health care staffing, or even among sports teams. For example, at the University of Arizona, out of 25 positive tests on September 3, only 10 were confirmed as positives in later tests. The NFL has also had its share of false positives. 

Lax Testing Standards

There is evidence that testing standards under CDC guidance are so broad that a large number of inactive, non-infectious cases are being flagged as positives (see the chart above for the intuition, as well as the graphic at the bottom of this post). The tests sometimes amount to a coin flip when it comes to evaluating positives; some of the positives might even come from non-novel coronaviruses such as the common cold! This paper by Andrew N. Cohen, Bruce Kessel, & Michael G. Milgroom – CKM) questions the guidance of public health authorities on testing more generally. From the abstract (my emphasis):

“Unlike previous epidemics, in addressing COVID-19 nearly all international health organizations and national health ministries have treated a single positive result from a PCR-based test as confirmation of infection, even in asymptomatic persons without any history of exposure. …  positive results in asymptomatic individuals that haven’t been confirmed by a second test should be considered suspect.”

False Positive Math

When I wrote about “The Scourge of False Positives” in July. I noted that a test specificity of 95% implies that 5% of uninfected individuals will falsely test positive. Unfortunately, that still produces a huge number of FPs when testing is broad. That’s NOT a good reason to avoid broad testing; it just means that positive tests should be confirmed by another test. (In this case, two tests with the same specificity reduce a 5% false positive rate to 0.25%. That’s why fast, cheap tests are necessary for confirmation.

Again, exaggerated case counts due to FP’s become more severe as a contagion wanes. That’s because FPs become an increasingly large share of positive test results and overstate the persistence of the virus. If active infections fall to 1% of 750,000 daily tests, or 7,500 true cases, the 5% specificity implies 37,125 FPs: true positives would be only 17% of positive cases. Much worse than a coin flip! And again, which cases are infectious?

How Bad Are FPs, Really?

This recent research, also authored by CKM, explains the reasons why FPs are usually an issue in the real world, despite the tests’ reportedly perfect reactivity to anything other than the virus’ genetic fragments. CKM find that the median FP rate in their sample of “tests of tests” was 2.3%. That means 23 out of every 1,000 uninfected people tested will test positive.

If that seems small to you, suppose the true prevalence of active infection in a population is 4%. If 1,000,000 people are tested and there are no false negatives (unlikely), then 40,000 infected people will be identified by the test. However, another 22,000 uninfected people will also test positive ((1,000,000 – 40,000 infected) x 0.023). That means the number of positive tests will be inflated by 55%. They’ll all receive some form of treatment or ordered into quarantine. Expanded Testing and FPs This summer, the volume of daily tests increased from about 150,000 a day in early April to more than 750,000 a day in July. That’s a 400% increase, but the true prevalence of active infection in the expanded test population during the summer was almost certainly lower than in the spring. Suppose active infections fell from 10% of the test population in the spring to 5% in the summer. That means the daily number of “true positives” would have risen from 15,000 to 35,000 in the expanded test population (and again I assume no false negatives for simplicity). The number of FPs, however, would have risen from 3,105 to 16,445. Therefore, FPs would have accounted for 40% of the increase in “confirmed” cases between spring and summer.

False COVID Deaths

FPs are also inflating COVID death counts. PCR tests are routinely given at hospital admission for any cause, and even after sudden death, especially as the availability of tests increased late in the spring. This subset of the tested population will certainly have its share of FPs. If such a patient dies, regardless of underlying cause, it might well be attributed to COVID-19 as it will still appear on the death certificate. The same has occurred in the case of traffic fatalities, suicides, and other sudden deaths.

Antibody Tests

The FP problem also plagues tests of seroprevalence, which determine whether an individual has had the virus or is cross-protected against the virus by antibodies acquired via non-novel coronavirus infections. The consequences of these antibody FPs can be serious as well, because it means a positive test might not ensure immunity. As the exposed share of the population increases, however, the FP share of antibody tests is diminished.

Conclusion

As long as testing is required, dealing with FPs (and false negatives, of course) requires repeated testing, as CKM state unequivocally. And the tests must be fast to be of any use. The current testing regime must be overhauled to prevent false positives from costly impositions on the lives of uninfected patients, consuming unnecessary medical resources, making unrealistic assessments of cases and deaths, and unnecessary suspensions of normal human social activity and liberty.

Not News: Infections and Long-Term Complications

06 Sunday Sep 2020

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At 15 years of age I was diagnosed as a Type I diabetic — 49 years ago. I had a genetic predisposition, but I’ve been told by several endocrinologists over the years that an “event” likely triggered the antibody response for which I was predisposed. The event was, in all probability, a viral or bacterial infection. The autoimmune response to that infection attacked the islet cells in my pancreas and destroyed my body’s ability to produce insulin. I’ve been dependent on external delivery of insulin ever since. Life goes on.

I relate this information to emphasize that it is not “novel” for a virus to trigger long-term “complications”. Recently, certain media factions have been shrieking about the long-term complications that might be triggered by the coronavirus (C19) even in those with otherwise light symptoms. Those are unfortunate, but again, this aspect of viral and bacterial infection is not uncommon.

We know, for example, that bacterial and viral infections often trigger autoimmune diseases like diabetes. Other examples are chronic fatigue syndrome, fibromyalgia, rheumatoid conditions, celiac disease, Graves’ disease, Guillain-Barré syndrome, Sjogren’s Syndrome, multiple sclerosis, and many others.

One condition that’s been cited as an especially dangerous complication of C19 is myocarditis, or inflammation of the heart muscle. This has been invoked as a reason to cancel sports competitions, for example. (See here for a denial of one rather hyperbolic claim regarding this condition.) Myocarditis has a long history as a side effect of influenza. Most people recover with no long-term complications, and others manage to live with it and remain productive. While C19 is “novel”, infection-induced myocarditis is not.

If you catch a virus or a bacterial infection, you might experience other complications with varying severity. Get used to the idea. It’s an unfortunate fact of life.

COVID Immunity, Herd By Herd

01 Tuesday Sep 2020

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Too many public health authorities remain in denial, but epidemiologists are increasingly convinced that heterogeneity implies a coronavirus herd immunity threshold (HIT) that is greatly reduced from traditional models and estimates. HIT is the share of the population that must be infected before the contagion begins to recede (and the transmission ratio R falls below one). Traditional models, based on three classes of individuals (Susceptibles, Infectives, and Recovered – SIR), predict a HIT of 60% or more. However, models that incorporate variation in susceptibility, transmissibility, and occupational or social behavior reduce the HIT substantially. Many of these more nuanced models show that the HIT could be in a range of just 15% to 25%. If that is the case, many regions are already there!

For background, I refer you to the first post I wrote about heterogeneity in late March, more detailed thoughts from early May, examples and more information on the literature later in May. I’ve referenced it repeatedly in other posts since then. And now, more than five months later, even the slow kids at the New York Times have noticed. The gist of it: if not everyone is equally susceptible, for example, a smaller share of the population needs to be “immunized via infection” to taper the spread of the virus.

Some supporting evidence appears in the charts below, courtesy of Kyle Lamb on Twitter. The first chart shows a seven-day average of C19 cases per million of population for ten states that reached an estimated 10% antibodies. These antibodies confer at least short-term immunity against C19. Most of these states saw cases/m climb at least through the day when the 10% level was reached, though Rhode Island appears to have been an exception.

The second chart shows the seven-day average of cases/m in the same states starting seven days after the 10% immunity level was reached. I’d prefer to see the days in the interim as well, but the changes in trend are still noteworthy. All of these states except Louisiana had a downturn in the seven-day average of new cases within a few weeks of breaching the 10% infection level (Louisiana had distinct and non-coincident outbreaks in different parts of the state). These striking similarities suggest that things turned as the infection level reached 15% or more, consistent with many of the epidemiological models incorporating heterogeneity.

Next, take a look at the states in which C19 surged most severely this summer. The new cases are not moving averages, so the charts are not quite comparable to those above. However, the peaks seem to occur prior to the breach of the 15% infection level.

Speculation about early herd immunity has been going on for several months with respect to various countries and even more “micro” settings such as cruise ships and military vessels, where populations are completely isolated. Early on, this “early” herd immunity was discussed under the aegis of “immunological dark matter”, but we know now that T-cell immunity has played an important role. In any case, anti-body expression (or seroprevalence) at around 20% has been linked to reversals in C19 cases and deaths in several countries. As Yinon Weiss notes, New York City and Stockholm were both C19 hotspots in the spring, both have seen deaths decline to low levels, and they have little in common in terms of public health policy. London as well. The one thing they share are similar levels of seroprevalence.

An important qualification is that herd immunity is not relevant at high levels of aggregation. That is, herd immunity won’t be achieved simultaneously in all regions. The New York City metro area might have reached its HIT in April, but Florida (or perhaps only Miami) might have reached a HIT in July. Many areas of the Midwest probably still aren’t there.

In the absence of a new mutation of C19, the final proof of herd immunity in many of the former hotspots will be in the fall and winter. We should expect at least a few cases in those areas, but if there are more intense contagions, they should be confined to areas that have not yet seen a level of seroprevalence near 15%.

COVID Seasonality and Latitudes

23 Sunday Aug 2020

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The coronavirus (C19), or SARS-CoV-2, has a strong seasonal component that appears to closely match that of earlier SARS viruses as well as seasonal influenza. This includes the two distinct caseloads we’ve experienced in the U.S. 1) in the late winter/early spring; and 2) the smaller bump we witnessed this summer in some southern states and tropics. 

COVID Seasonal Patterns and Latitude

The Ethical Skeptic on Twitter recently featured the chart below. It shows the new case count of C19 in the U.S. in the upper panel, and the 2003 SARS virus in the lower panel. Both viruses had an initial phase at higher latitudes and a summer rebound at lower latitudes.

 

 

 

 

 

 

 

 

 

 

I particularly like the following visualizations from Justin Hart demonstrating the pandemic’s pattern at different latitudes (shown in the leftmost column). The first table shows total cases by week of 2020. The second shows deaths per 100,000 of population by week. Again, notice that lower latitudes have had a crest in the contagion this summer, while higher latitudes suffered the worst of their contagion in the spring. Based on deaths in the second table, the infections at lower latitudes have been less severe.

Viral Patterns in the South

Many expected the pandemic to abate this summer, including me, as it is well known that viruses don’t thrive in higher temperatures and humidity levels, and in more direct sunlight. So it is a puzzle that southern latitudes experienced a surge in the virus during the warmest months of the year. True, the cases were less severe on average, and sunlight and humidity likely played a role in that, along with the marked reduction in the age distribution of cases. However, the SARS pandemic of 2003 followed the same pattern, and the summer surge of C19 at southern latitudes was quite typical of viruses historically.

A classic study of the seasonality of viruses was published in 1981 by Robert Edgar Hope-Simpson. The next chart summarized his findings on influenza, seasonality, and latitude based on four groups of latitudes. Northern and southern latitudes above 30° are shown in the top and bottom panels, respectively. Both show wintertime contagions with few infections during the summer months. Tropical regions are different, however. The second and third panels of the chart show flu infections at latitudes less than 30°. Influenza seems to lurk at relatively low levels through most of the year in the tropics, but the respective patterns above and below the equator look almost like very muted versions of activity further to the north and south. However, some researchers describe the tropical pattern as bimodal, meaning that there are two peaks over the course of a year.   

So the “puzzle” of the summer surge at low latitudes appears to be more of an empirical regularity. But what gives rise to this pattern in the tropics, given that direct sunlight, temperature, and humidity subdue viral activity?

There are several possible explanations. One is that the summer rainy season in the tropics leads to less sunlight as well as changes in behavior: more time spent indoors and even less exposure to sunlight. In fact, today, in tropical areas where air conditioning is more widespread, it doesn’t have to be rainy to bring people indoors, just hot. Unfortunately, air conditioning dries the air and creates a more hospitable environment for viruses. Moreover, low latitudes are populated by a larger share of dark-skinned peoples, who generally are more deficient in vitamin D. That might magnify the virulence associated with the flight indoors brought on by hot and or rainy weather.   

Mutations and Seasonal Patterns

What makes the seasonal patterns noted above so reliable in the face of successful immune responses by recovered individuals? And shouldn’t herd immunity end these seasonal repetitions? The problem is the flu is highly prone to viral mutation, having segments of genes that are highly interchangeable (prompting so-called “antigenic drift“). That’s why flu vaccines are usually different each year: they are customized to prompt an immune response to the latest strains of the virus. Still, the power of these new viral strains are sufficient to propagate the kinds of annual flu cycles documented by Hope-Simpson.

With C19, we know there have been up to 100 mutations, mostly quite minor. Two major strains have been dominant. The first was more common in Southeast Asia near the beginning of the pandemic. It was less virulent and deadly than the strain that hit much of Europe and the U.S. Of course, in July the media misrepresented this strain as “new”, when in fact it had become the most dominant strain back in March and April.

What Lies Ahead

By now, it’s possible that the herd immunity threshold has been surpassed in many areas, which means that a surge this coming fall or winter would be limited to a smaller subset of still-susceptible individuals. The key question is whether C19 will be prone to mutations that pose new danger. If so, it’s possible that the fall and winter will bring an upsurge in cases in northern latitudes both among those still susceptible to existing strains, and to the larger population without immune defenses against new strains.

Fortunately, less dangerous variants are more more likely to be in the interest of the virus’ survival. And thus far, despite the number of minor mutations, it appears that C19 is relatively stable as viruses go. This article quotes Dr. Heidi J. Zapata, an infectious disease specialist and immunologist at Yale, who says that C19:

“… has shown to be a bit slow when it comes to accumulating mutations … Coronaviruses are interesting in that they carry a protein that ‘proofreads’ [their] genetic code, thus making mutations less likely compared to viruses that do not carry these proofreading proteins.”

The flu, however, does not have such a proofreading enzyme, so there is little to check its prodigious tendency to mutate. Ironically, C19’s greater reliability in producing faithful copies of itself should help ensure more durable immunity among those already having acquired defenses against C19.

This means that C19 might not have a strong seasonal resurgence in the fall and winter. Exceptions could include: 1) the remaining susceptible population, should they be exposed to a sufficient viral load; 2) regions that have not yet reached the herd immunity threshold; and 3) the advent of a dangerous new mutation, though existing T-cell immunity may effectively cross-react to defend against such a mutation in many individuals.

 

Case Fatality, Stale Ratios and Exaggerated Loss

14 Tuesday Jul 2020

Posted by in Analytics, Pandemic

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I hope someday I won’t feel compelled to write or worry about the coronavirus. However, as the pandemic wears on, it seems to take only a few days for issues to pile up, and I just can’t resist comment. Today I have a couple of beefs with uses of data and concomitant statements I’ve seen posted of late.

People are still quoting case fatality rates (CFRs) as if those cumulative numbers are relevant to the number of deaths we can expect going forward. They are not. Just as hair-brained are applications of cumulative hospitalization and ICU admittance rates to produce “rough and ready” estimates of what to expect going forward. Or, I’ve seen people express hospitalizations as ratios to CFR, as if those ratios will be the same going forward. Again, they are not. Let me try to explain.

The chart below shows the course of the U.S. CFR since the start of the pandemic. It’s taken from the interactive Covid Time Series site. My apologies if you have to click on the chart for decent viewing (or you can visit the site). The CFR at any date is the cumulative number of deaths to-date divided by the cumulative number of confirmed cases. It is a summary of past history, but it is not well-suited to making predictions about death rates in the future. The CFR began to taper a little before Memorial Day, and it is now at about 4% (as of July 13).

Out of curiosity, I also generated CFRs for AZ, CA, FL, GA, and TX, which now average about half of the national CFR. There’s an obvious lesson: if you must use CFRs, understand that they vary from place to place.

Again, CFRs are cumulative. Their changes over time can tell us something about recent trends, but even then they are flawed. For example, case counts have risen dramatically with more widespread testing. Those testing positive more recently are concentrated in younger age cohorts, for whom infections are much less severe. Treatment has improved dramatically as well, so there is little reason to expect the CFR’s of recently diagnosed cases to be as high as the latest CFRs shown above.

There is no easy way to calculate an unflawed “marginal” CFR for a recent period, though an effort to do so might improve the predictive value. Deaths lag behind case counts because the progression from early symptoms to death can take several weeks. Even more vexing for constructing a valid, recent fatality rate is that reporting of deaths is itself delayed, as I explained in my last post. Each day’s report of deaths captures deaths that may have occurred over a period of several weeks in the past, and sometimes many more.

Finally no CFR can capture the true mortality rate of the virus without ongoing, ubiquitous testing. As the state of testing stands, the true mortality rate must reflect undiagnosed cases in the denominator. The CDC’s latest “best” estimate of the true mortality rate is just 0.3%, and 0.05% for those aged 50 years or less. Those figures are based on serological tests for the presence of antibodies to C19 in more random samples of the population. Those findings reflect the extent of undiagnosed and/or asymptomatic cases.

The point is one shouldn’t be too blithe about throwing numbers around like 4% mortality based on the CFR, or even 1% mortality as a “nice, round number”, without heavy qualification. Those numbers are gross exaggerations of what we are likely to see going forward.

The same criticisms can be leveled at claims that hospitalizations will proceed at some fixed ratio relative to diagnosed cases, or some fixed ratio relative to deaths. Again, new cases tend to be less severe, so hospitalizations are likely to be a much lower ratio to cases than what is reflected in cumulative totals. Because of improved treatment, the ratio of deaths to hospitalizations will be much lower in the future as well.

CFRs are not a useful guide to future COVID deaths. The true mortality rate is a much better baseline, particularly for subsets of the population matching the current case load. Finally, and this is the only disclaimer I’ll bother to provide today, we all know that suffering is not confined to terminal cases, and it is not confined to the hospitalized subset. But don’t exaggerate the extent of your preferred interpretation of suffering by applying inappropriate cumulative calculations.