Tag Archives: Immune Response

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.

Long COVID: a Name For Post-Viral Syndrome

15 Friday Jan 2021

Posted by in Coronavirus

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I see references to “long COVID” or “long-haul COVID” almost every day. No, it’s not an extended COVID infection or an extra scary version of COVID. It’s about lingering or new symptoms after recovery from the infection. Reportedly, these symptoms range from fatigue or anxiety to joint pain. Sometimes they are rather unusual afflictions such as “COVID toes”, described as rashes or red spots on toes. Sebastian Rushworth notes that there is “no hard evidence that long COVID is a distinct entity”. It was essentially invented on social media by groups of individuals who connected to discuss various post-COVID symptoms. Rushworth says:

“The most common symptoms in people with long covid (defined in the study as still having symptoms after four weeks) were fatigue (98%) and intermittent headache (91%). … symptoms of long covid are extremely unspecific, so it is probable that long covid is actually a whole bunch of different things, of which I would think post-viral syndrome is likely a significant part.”

Post-viral syndrome should not be a big surprise, since COVID is, well, a virus! PVS can last for months and commonly has the following symptoms:

Those sound familiar. PVS symptoms are thought to be a consequence of the body’s effort to fight off a virus, including the lingering effects of a strong immune response and the inflammation it can induce. Such an immune response can lead to even greater problems for those with a genetic predisposition for autoimmune diseases like diabetes. It happens. But none of this is new or unique to COVID.

While PVS and autoimmune diseases are very real, the unbridled panic over COVID has led to a few false claims. “COVID toes” is one of them. Moreover, the pandemic precipitated an avalanche of poor-quality academic research, rushed in an effort to produce useful findings. Some of that research is implicated in the COVID myths we’ve heard. An example discussed at the last link is the incidence of heart inflammation or myocarditis in COVID patients. This was all over the media in the months leading up to the college football season, as young athletes were said to be vulnerable. In fact, it’s incidence among COVID patients is fairly rare, and it’s not unique to COVID.

COVID can be a nasty infection, primarily for the aged and those with pre-existing conditions, including obesity. PVS is an unfortunate reality for many patients. But “long-COViD” is merely a varied collection of post-viral symptoms. Many of them are vague and usually self-diagnosed. Long COVID is, as Rushworth says, “basically whatever the person who thinks they have it says it is.” That the media has promoted long COVID and its varied manifestations as something wholly new, including a few probable “imagifestations” (to coin a term), is one more example of the “panic porn” to which we’ve been subjected during the pandemic.

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.