Tag Archives: T-Cells

Vagaries of Vaccine Efficacy

23 Sunday Jan 2022

Posted by in Coronavirus, Vaccinations

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There should never have been any doubt that vaccines would not stop you from “catching” the coronavirus. Vaccines cannot stop virus particles from lodging in your nose or your eyeballs. The vaccines act to prime the immune system against the virus, but no immune response is instantaneous. In other words, if you aren’t first “infected”, antibodies don’t do anything! A virus may replicate for at least a brief time, and it is therefore possible for a vaccinated individual to carry the virus and even pass it along to others. The Omicron variant has proven that beyond a shadow of a doubt, though the wave appears to be peaking in most of the U.S. and has peaked already in a few states, mostly in the northeast.

I grant that the confusion over “catching” the virus stems from an imprecision in our way of speaking about contracting “bugs”. Usually we don’t say we “caught” one unless it actually makes us feel a bit off. We come into intimate contact with many more bugs than that. The effects are often so mild that we either don’t notice or brush it off without mention. But when it comes to pathogens like Covid and discussions of vaccine efficacy (VE), it’s obviously useful to remember the distinction between infections, on the one hand, and symptomatic infections on the other.

Cases Are the Wrong Focus

Unless calibrated by seroprevalence data, these studies are not based on proper estimates of infections in the population. Asymptomatic people are much less likely to get tested, and vaccinated individuals who are infected are either much more likely to be asymptomatic or the test might not detect the weak presence of a virus at all. VE based on detected infections is essentially meaningless unless testing is universal.

We are bombarded by studies (and analyses like the one here) alleging that VE should be judged on the reduction in infections among the vaccinated. The likelihood of a detected infection by vaccination status is simply the wrong way to measure of VE. It’s not so much the direction of bias in measured VE, however. The mere presence of cases among the vaccinated has been sufficient to inflame anti-vax sentiment, especially cases detected in mandatory tests at hospitals, where the infections are often incidental to the primary cause of admission.

The typical evolution of a novel virus is further reason to dismiss case numbers as a basis for measuring VE. Mutations create new variants in ways that usually promote the continuing survival of the lineage. Subsequent variants tend to be more transmissible and less deadly to their hosts. Thus, given a certain “true” degree of VE, so-called breakthrough infections among the vaccinated are even more likely to be asymptomatic and less likely to be tested and/or detected.

There is the matter of immune escape or evasion, however, which means that sometimes a virus mutates in ways that get around natural or vaccine-induced immune responses. While such a variant is likely to be less dangerous to unvaccinated hosts, more cases among the vaccinated will turn up. That should not be interpreted as a deterioration in VE, however, because detected infections are still the wrong measure. Instead, the fundamental meaning of VE is a lower virulence or severity of a variant in vaccinated individuals than in unvaccinated individuals.

Interestingly, to digress briefly, while immune escape has been discussed in connection with Omicron, that variant’s viral ancestors may have predated even the original Covid strain released from the Wuhan lab! It is a fascinating mystery.

Virulence

In fact, vaccines have reduced the virulence of Covid infections, and the evidence is overwhelming. See here for a CDC report. The chart below is Swiss data, followed by a “handy” report from Wisconsin:

From the standpoint of virulence, there are other kinds of misguided comparisons to watch out for: these involve vaxed and unvaxed patients with specific outcomes, like the left side of the graphic at the top of this post (credit to Twitter poster aparachick). This thread has an excellent discussion of the misconception inherent in the claim that vaccines haven’t reduced severity: the focus is on the wrong conditional probability (again, like the left side of the graphic). Getting that wrong can lead to highly inaccurate conclusions when the sizes of the two key groups, hospitalizations and vaccinated individuals in this case, are greatly different.

Bumbled Messaging

The misunderstandings about VE are just one of many terrible failures of public health authorities over the course of the pandemic. There seems to have been fundamental miscommunication by the vaccine manufacturers and many others in the epidemiological community about what vaccines can and cannot do.

Another example is the apparent effort to downplay the importance of natural immunity, which is far more protective than vaccines. This looks suspiciously like a willful effort to push the narrative that universal vaccination as the only valid course for ending the pandemic. Even worse, the omission was helpful to those attempting to justify the tyranny of vaccine mandates.

Waning Efficacy

It should be noted that the efficacy of vaccines will wane over time. This phenomenon has been measured by the presence of antibodies, which is a valid measure of one aspect of VE over time. However, immune responses are more deeply embedded in the human body: so-called T-cells carry messages alerting so-called B-cells to the presence of viral “invaders”. The B-cells then produce new antibodies specific to characteristics of the interloping pathogen. Thus, these cells can function as a kind of “memory” allowing the immune system to mount a fresh antibody defense to a repeat or similar infection. The reports on waning antibodies primarily in vaccinated but uninfected individuals do not and cannot account for this deeper process.

Conclusion

Vaccines don’t necessarily reduce the likelihood of infection or even the spread of the virus, but they absolutely limit virulence. That’s why Jay Bhattacharya, one of the authors of The Great Barrington Declaration, says the vaccines provide a private benefit, but only a limited public benefit. Yet too often we see VE measured by the number of infections detected, and vaccine mandates are still motivated in part by the idea that vaccines offer protection to others. They might do that only to the extent that infections are less severe and clear-up more quickly.

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”.

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.