Tag Archives: T-Cell Immunity

Herd Immunity To Public Health Bullshitters and To COVID

16 Monday Aug 2021

Posted by in Coronavirus, Herd Immunity, Uncategorized

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My last post had a simple message about the meaning of immunity: you won’t get very sick or die from an infection to which you are immune, including COVID-19. Like any other airborne virus, that does NOT mean you won’t get it lodged in your eyeballs, sinuses, throat, or lungs. If you do, you are likely to test positive, though your immunity means the “case” is likely to be inconsequential.

As noted in that last post, we’ve seen increasing COVID case counts with the so-called Delta variant, which is more highly transmissible than earlier variants. (This has been abetted by an uncontrolled southern border as well.) However, as we’d expect with a higher level of immunity in the population, the average severity of these cases is low relative to last year’s COVID waves. But then I saw this article in ScienceAlert quoting Sir Andrew Pollard, a scientist affiliated AstraZeneca and the University of Oxford. He says with Delta, herd immunity “is not a possibility” — everyone will get it.

Maybe everyone will, but that doesn’t mean everyone will get sick. His statement raises an obvious question about the meaning of herd immunity. If our working definition of the term is that the virus simply disappears, then Pollard is correct: we know that COVID is endemic. But the only virus that we’ve ever completely eradicated is polio. Would Pollard say we’ve failed to achieve herd immunity against all other viruses? I doubt it. Endemicity and herd immunity are not mutually exclusive. The key to herd immunity is whether a virus does or does not remain a threat to the health of the population generally.

Active COVID infections will be relatively short-lived in individuals with “immunity”. Moreover, viral loads tend to be lower in immune individuals who happen to get infected. Therefore, the “infected immune” have less time and less virus with which to infect others. That creates resistance to further contagion and contributes to what we know as herd immunity. While immune individuals can “catch” the virus, they won’t get sick. Likewise, a large proportion of the herd can be immune and still catch the virus without getting sick. That is herd immunity.

One open and controversial question is whether uninfected individuals will require frequent revaccination to maintain their immunity. A further qualification has to do with asymptomatic breakthrough infections. Those individuals won’t see any reason to quarantine, and they may unwittingly transmit the virus.

I also acknowledge that the concept of herd immunity is often discussed strictly in terms of transmission, or rather its failure. The more contagious a new virus, like the Delta variant, the more difficult it is to achieve herd immunity. Models predicting low herd immunity thresholds due to heterogeneity in the population are predicated on a given level of transmissibility. Those thresholds would be correspondingly higher given greater transmissibility.

A prominent scientist quoted in this article is Paul Hunter of the University of East Anglia. After backing-up Pollard’s dubious take on herd immunity, Hunter drops this bit of real wisdom:

“We need to move away from reporting infections to actually reporting the number of people who are ill. Otherwise we are going to be frightening ourselves with very high numbers that don’t translate into disease burden.”

Here, here! Ultimately, immunity has to do with the ability of our immune systems to fight infections. Vaccinations, acquired immunity from infections, and pre-existing immunity all reduce the severity of later infections. They are associated with reductions in transmission, but those immune responses are more basic to herd immunity than transmissability alone. Herd immunity does not mean that severe cases will never occur. In fact, more muted seasonal waves will come and go, inflicting illness on a limited number of vulnerables, but most people can live their lives normally while viral reproduction is contained. Herd immunity!

Sadly, we’re getting accustomed to hearing misstatements and bad information from public health officials on everything from mask mandates, lockdowns, and school closings to hospital capacity and vaccine hesitancy. Dr. Pollard’s latest musing is not unique in that respect. It’s almost as if these “experts” have become victims of their own flawed risk assessments insofar as their waning appeal to “the herd” is concerned. Professor Hunter’s follow-up is refreshing, however. Public health agencies should quit reporting case counts and instead report only patients who present serious symptoms, COVID ER visits, or hospitalizations.

Note: This post also appears at The American Reveille (or will soon!).

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.

Note: This post also appears at The American Reveille.

COVID Immunity, Herd By Herd

01 Tuesday Sep 2020

Posted by in Coronavirus, Herd Immunity

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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

Posted by in Pandemic

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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.

 

Some Cheery COVID Research Tidbits

16 Thursday Jul 2020

Posted by in Pandemic, Public Health, Uncategorized

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Here’s a short list of new or newish research developments, some related to the quest to find COVID treatments. Most of it is good news; some of it is very exciting!

Long-lasting T-cell immunity: this paper in Nature shows that prior exposure to coronaviruses like severe acute respiratory syndrome (SARS) and even the common cold prompt an immune reaction via so-called T-cells that have long memories and are reactive to certain proteins in COVID-19 (SARS-CoV-2). The T-cells were detected in both C19-infected and uninfected patients. This comes after discouraging reports that anti-body responses to C19 are short-lived, but T-cells are a different form of acquired immunity. Derek Lowe says the following:

“This makes one think, as many have been wondering, that T-cell driven immunity is perhaps the way to reconcile the apparent paradox between (1) antibody responses that seem to be dropping week by week in convalescent patients but (2) few (if any) reliable reports of actual re-infection. That would be good news indeed.”

The herd immunity threshold (HIT) is much lower than you think: I’ve written about the effect of heterogeneity on the HIT before, here and here. This new paper, by three Oxford zoologists, shows that the existence of a cohort having some form of prior immunity, innate or acquired, reduces the number of infections required to achieve the HIT. For example, if initial transmissibility (R0) is 2.5 and 40% of the population has prior immunity (both reasonable assumptions for many areas), the HIT is as low as 20%, according to the authors’ calculations. That’s when the contagion begins to recede, though the final infected share of the population would be higher. This might explain why new cases and deaths have already plunged in places like Italy, Sweden, and New York, and why protests in NYC did not lead to a new wave of infections, while those in the south appear to have done so.

Seasonal effects: viral loads might be decreasing. From the abstract:

“Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation. Mucosal barrier and mucociliary clearance can significantly decrease viral load and disease progression, and their inactivation by low relative humidity of indoor air might significantly contribute to severity of the disease.”

The BCG vaccine appears to be protective: this is the bacillus Calmette-Guérin tuberculosis vaccine administered in some countries, This finding is not based on clinical trials, so more work is needed.

Is there no margin in plasma? No subsidy? This is the only “bad news” item on my list. It’s widely agreed that blood plasma from recovered C19 patients can be incorporated into an immune globulin drug to inoculate people against the virus. It’s proven safe, but for various reasons no one seems interested. Not the government. Not private companies. Did Trump happen to mention it or something?

C19 doesn’t spread in schools: this German study demonstrates that there is little risk in reopening schools. One of the researchers says:

“Children act more as a brake on infection. Not every infection that reaches them is passed on…. This means that the degree of immunization in the group of study participants is well below 1 per cent and much lower then we expected. This suggests schools have not developed into hotspots.”

Also worth emphasis is that remote learning leaves much to be desired, as acknowledged by the National Academies of Science, Engineering and Medicine, which has recommended that schools reopen for younger children and those with special needs.

Can angiotensin drugs (ACE Inhibitors/ARBs) reduce mortality? This meta-analysis of nine studies finds that these drugs reduce C19 mortality among patients with hypertension. The drugs were also associated with a reduction in severity but not with statistical significance. These results run contrary to initial suspicions, because ACEI/ARB drugs actually “up-regulate” ACE-2 receptors, to which C19 binds. Researchers say the drugs might be working through some other protective channel. This is not a treatment per se, but this should be reassuring if you already take one of these medications.

Tricor appears to clear lung tissue of C19: this research focused on C19’s preference for an environment rich in cholesterol and other fatty acids:

“What they found is that the novel coronavirus prevents the routine burning of carbohydrates, which results in large amounts of fat accumulating inside lung cells – a condition the virus needs to reproduce.”

Tricor reduces those fats, and the researchers claim it is capable of clearing lung tissue of C19 in a matter of days. This was not a clinical trial, however, so more work is needed. Tricor is an FDA approved drug, so it is safe and could be administered “off label” immediately. Tricor is a fibrate; the news with respect to statins and C19 severity is pretty good too! These are not treatments per se, but this should be reassuring if you already take one of these medications.

Hydroxychloroquine works: despite months of carping from media and leftist know-it-all’s dismissing the mere possibility of HCQ as a potential C19 treatment, evidence is accumulating that it is effective in treating early-stage infections after all. The large study conducted by the Henry Ford Health System found that treatment with HCQ early after hospitalization, and with careful monitoring of heart function, cut the death rate in half relative to a control group. Here’s another: an Indian study found that four-plus maintenance doses of HCQ acted as a prophylactic against C19 infection among health care workers, reducing the odds of infection by more than half. An additional piece of evidence is provided by this analysis of a 14-day Swiss ban on the use of HCQ in late May and early June. The ban was associated with a huge leap in the C19 deaths after a lag of less than two weeks. Resumption of HCQ treatment brought C19 deaths down sharply after a similar lag.

Meanwhile, a study in Lancet purporting to show that HCQ was ineffective and posed significant risks to heart health was retracted based on the poor quality of the data.

Remdesivir also cuts death rate: by 62% in a smaller controlled study by the drug maker Gilead Sciences.

Pet ownership might confer some immunity: this one is a little off-beat, and perhaps the research is under-developed, but it is interesting nonetheless!

I owe Instapundit and Marginal Revolution hat tips for several of these items.