Is COVID-19 “the forever plague”?

We here at SBM have been very critical of the Great Barrington Declaration (GBD) ever since it was first published in October 2020. The GBD, as you might recall, was a document published as a result of a meeting held in Great Barrington, MA at the headquarters of the right-wing libertarian free market think tank American Institute for Economic Research (AIER). The reason that we at SBM have been so critical of the GBD—calling it right from the beginning “magnified minority” and eugenics—is because it advocated a “natural herd immunity” approach to the COVID-19 pandemic; i.e., what we referred to as a “let ‘er rip” approach in which SARS-CoV-2, the coronavirus that causes COVID-19, should be allowed to spread through the “low risk” young and “healthy” population, in order to produce “natural immunity” in enough people to reach herd immunity, meanwhile using “focused protection” (never well defined) to shield the elderly and those with chronic health conditions that rendered them susceptible to death and the worst complications of the virus. (Remember, this was a couple of months before the mRNA-based COVID-19 vaccines received emergency use authorization.) It’s an approach that never would have worked, given the practical difficulties and the observation (predicted even in October 2020) that “natural” post-infection immunity was not likely to be durable, given the rise of immune-evading variants like Omicron. Even with the history of the last two years, GBD adherents still claim that “herd immunity” would be a mere 3-6 months away if we just followed their plan. Worse, GBD authors like Martin Kulldorff and Jay Bhattacharya have pivoted to help spread antivaccine disinformation, along with the “spiritual child” of the GBD, the Brownstone Institute (for which Kulldorff is the scientific advisor), which has apparently never seen a public health intervention that it liked—although it does very much like comparing public health to fascism and Communism.

Which brings us to an article going the opposite direction of Brownstone Institute propaganda that’s gone viral. You’d think that I would approve. You’d think wrong, simply because the article lacks nuance and supports positions to which I’m sympathetic with a maximalist fear mongering argument that ends up proposing a solution to the pandemic that is a fantasy, just the opposite fantasy advocated by the “natural herd immunity” proponents.

Dueling fantasy worlds

The article to which I referred that is going around, while appropriately noting the disastrous consequences of abandoning non-pharmaceutical interventions (NPIs, such as masks and social distancing) and other tools to slow the spread of COVID-19 too quickly, goes so far in the opposite direction of the GBD that it needs to be called out as well. It was published on July 4 by journalist Andrew Nikiforuk entitled “Get Ready for the Forever Plague” and has the tagline, “Public health officials’ COVID complacency has opened the door to new illnesses and devastating long-term damage”. It also features a suitably ominous image:

There’s nothing like the image of a medieval plague doctor to instill fear and alarm, is there?

In any case, the image chosen for the article tells you much of what you need to know about it. There is zero nuance, and the concept is that, thanks to the Omicron variants, the only strategy to halt the pandemic is something that’s become known as “zero COVID”. I’ll skip to the conclusion first, the better to go back and demonstrate how data and information were—shall we say?—carefully chosen to support a predetermined conclusion. I’m also going to refer to an Archive.org copy of the article from July 4, because on Friday the author responded to some criticisms and edited the article to its current form, which, while less objectionable than the original, is still pretty maximalist in its fear mongering. I also realize that by writing this post I might be perceived as some as being the same side as the cranks at the Brownstone Institute. Nothing can be further from the truth, and to support that, I’ll quote Gavin Yamey, my coauthor on our BMJ article criticizing the GBD, who Tweeted:

Now, before addressing the claim above that each Omicron reinfection confers “no immunity” (which is nonsense) let’s jump to Nikiforuk’s conclusion:

We could have avoided this deteriorating situation, as The Tyee repeatedly advised, by eliminating COVID in our communities more than a year ago.

Elimination remains the only long-term and bottom-up strategy that makes any sense in terms of risk reduction. It is also imminently doable with adequate testing, masking, tracing, supported sick leave and targeted goals for reducing transmission.

But our public health officials gambled with the future and chose a fantasy world instead. Now COVID has become a runaway train with unknown biological consequences.

I’ll give Nikiforuk the last point (I’ve said similar things in the past.) I’ll also give him this point elsewhere in the article:

By abandoning the critical goal of stopping or reducing viral transmission about a year ago, authorities have given viral evolution an incredible edge.

We’ve been saying much the same thing, particularly in our criticisms of the fantasy world inhabited by GBD proponents, in which immunity to COVID-19 is lifelong, “natural herd immunity” is achievable, and it’s relatively easily to implement “focused protection” of the elderly and those with chronic illnesses. We’ve also pointed out that it’s not so much vaccines driving new variants nearly as much allowing a novel virus to circulate mostly unchecked in an immunologically naïve population.

Even so, however, I’d argue that Nikiforuk is also living in a fantasy world, just a different one than the one that he accuses public health officials of inhabiting. Public health officials in much of the world did give up too early, but much of that was based on political pressure as a result of the unholy fusion of conspiracy theorists, the far right, and antivaxxers that political leaders could not resist or that some political leaders harnessed because they, too, viewed public health interventions (particularly mask and vaccine mandates) as unacceptable assaults on “freedom”. Remember, for the elimination of COVID-19 to be even theoretically possible now would require at least the possibility of every nation on earth implementing the suggested NPIs. Given how huge swaths of the US have become totally resistant to anything resembling mask mandates (as just one example), I have a hard time wondering how Nikiforuk’s vision isn’t every bit as much of a fantasy world as that of the GBD authors. I’ll give Nikiforuk credit, though, in emphasizing that the GBD fantasy of “natural herd immunity” is utterly detached from reality; unfortunately he goes too far in the other direction.

The claim that getting to “zero COVID” is “imminently doable” struck me immediately as so out of touch with reality that I was tempted to add one of my usual facepalm images here with a sarcastic caption, as I am wont to do when I come across claims this overblown. It might have been possible—even feasible—to achieve “zero COVID” early in the pandemic with such measures, as well as with massive international cooperation of the like unseen during the pandemic. Theoretically, elimination might even have been possible to achieve even in January 2021, when the linked article was published. However, to achieve it now, after repeated waves of infection and the rise of ever more transmissible and immune-evading variants, would require international cooperation that only happens in fantasy land, and even then that ignores the fact that there is an animal reservoir for these coronaviruses that would make elimination in the human population, if not outright impossible, damned near impossible. It is not “surrender” to admit this, but if the Twitter reactions to the criticisms of this article are any indication that’s exactly the sort of accusation I’ll soon see in the comments, with some people expressing extreme “disappointment” with me or even outright anger. Assuming that happens, I’ll shake my head, given my long history dating back to before COVID-19 was even declared a pandemic of countering claims from COVID-19 contrarians and antivaxxers that COVID-19 isn’t that deadly and explaining why “natural herd immunity”-based strategies were disastrous.

I suspect that I might regret having written this post. It wouldn’t be the first time, even when I’m right. So let’s look at some specifics.

Unsupported and exaggerated claims

In examining the claims made in this article, one has to go straight for its central claim that is used to justify all the other conclusions, namely that Omicron variants have become so transmissible and immune evading that reinfections with them confer “no immunity” to future infections, leading to a horrific scenario:

New science shows that Omicron and its variants are getting better at evading immune defences induced by vaccines or by natural infection. BA.5, for example, is more transmissible than any previous variant.

As a consequence it is now possible to be reinfected with one of Omicron’s variants every two to three weeks.

The data also shows that each reinfection confers no immunity. A summer infection, for example, will not protect you against a fall infection. But each and every infection will damage your immune system regardless of how mild the symptoms.

Interestingly, the article by Eric Topol to which Nikiforuk links, although it does describe how much more transmissible and immune evading Omicron BA.5 is than previous variants, also points out that, even with the new Omicron variants, existing vaccines are still very effective at preventing death from COVID-19. I mention this because another central theme of Nikiforuk’s article is that the vaccines are increasingly useless because of how Omicron variants are becoming increasingly good at evading immunity, for example:

So the virus is getting better at thwarting vaccines and evading immunity. Although vaccine protection against hospitalization and death remains strong, it is being steadily eroded by Omicron’s subvariants. Meanwhile protection against severe disease has declined as the effectiveness of our vaccines progressively wanes.

So Nikiforuk admits that the vaccines still work quite well at preventing serious disease and death, but pivots to paint a dire picture of future horror. In doing so, he completely ignores evidence showing that the vaccines are still quite effective at preventing severe disease and death, even from Omicron variants. Is it reasonable to be concerned that future variants will erode the ability of existing vaccines to prevent severe disease and death? Of course. Is it reasonable to portray this erosion as inevitable? Not so much, given that vaccines targeting newer variants are in development. I will admit, though, that Nikiforuk has a point when he laments that SARS-CoV-2 is evolving faster, seemingly, than our ability to develop new vaccines to cover variants that are emerging.

At this point, I’ll also note that in his response to critics, Nikiforuk basically admits that he overreached here:

But to be accurate (and avoid semantic disputes) I should have said that new infections confer so little immunity — because the immune system is unable to remember them — that we must seek every other protection available. The Tyee has made that correction to the original story.

Of course, semantics matter. Perhaps the most succinct criticism of Nikiforuk’s original wording came from a pseudonymous Twitter account, and I liked it enough to quote it directly:

Interestingly, if you look at the New York State reinfection data cited above, you’ll see that reinfection, while not rare, is nowhere near as common as Nikiforuk’s fear mongering would suggest. Indeed, the study states:

These data demonstrate low levels of reinfection, compared to first infections. This did not change after the Omicron variant emerged in December 2021, although the number of reinfections increased.

Data on this page also suggest that people with a prior diagnosed COVID-19 infection have had some protection against future infections. This is similar to lower levels of infection among vaccinated people (‘breakthrough infection’), compared to among unvaccinated people, which is used to demonstrate vaccine effectiveness.

Our in-depth study measured the relative protection afforded by vaccination and/or prior infection, during 2021, before the Omicron variant emerged. Both may offer protection against future infections and COVID-19 hospitalizations.

Of course, each infection carries the risk of severe disease, death, and long COVID-19; so the authors conclude that vaccination is the safest means of preventing these dire outcomes and should be the strategy employed. In any event, Nikiforuk’s take incorrectly and deceptively conflates the possibility of being reinfected with a variant once as early as two to three weeks after a COVID-19 infection with the likelihood of being reinfected multiple times every three weeks and then uses that to paint a picture of a horrific “forever plague” whose only end will be COVID elimination. It is a picture that is at odds with reality, as described here:

A few recent studies have shown it’s possible to get reinfected with another variant (or even another omicron subvariant) in as little as 20 days; back in January, Slate ran an account of a woman who was likely infected with delta one month and omicron the next. But these rapid reinfections still seem to be rare, and there are, as best as I can tell, no documented cases of people getting reinfected again one month, and then again the next, and then again the next. And while getting COVID “just” twice inside of a year might feel like a horror take on Groundhog Day, the “Forever Plague” author seems to be painting a picture of a nightmare world where the default human state is a constant state of SARS-CoV-2 infection. This is simply not the case.

To support his claim, in his original article Nikiforuk cites a VA study on reinfections, although, interestingly enough, he doesn’t directly cite the study itself (which has not been peer reviewed and is still a preprint) but rather a post on Eric Topol’s Substack. It examined findings from over 257,427 people with one COVID-19 infection, 38,926 people with 2 or more infections, and nearly 5.4 million uninfected controls, and compared risks and 6-month burdens of all-cause mortality, hospitalization, and a set of pre-specified incident outcomes, including adverse health outcomes in the pulmonary and several extrapulmonary organ systems (cardiovascular disorders, coagulation and hematologic disorders, diabetes, fatigue, gastrointestinal disorders, kidney disorders, mental health disorders, musculoskeletal disorders, and neurologic disorders) and concluded:

Compared to non-infected controls, assessment of the cumulative risks of repeated infection showed that the risk and burden increased in a graded fashion according to the number of infections. The constellation of findings show that reinfection adds non-trivial risks of all-cause mortality, hospitalization, and adverse health outcomes in the acute and post-acute phase of the reinfection. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.

Since this is the first study of its kind, we don’t know whether it will be replicated. Even if one accepts its findings at face value, the main people whom I’ve seen arguing that infections tend to be mild are GBD proponents and antivaxxers, and they tend to dismiss the possibility of reinfection because to acknowledge reinfection would be to acknowledge that a “natural herd immunity” strategy for the pandemic is disastrous.

Progressive destruction of the immune system by SARS-CoV-2

Ironically enough, I agree with Nikiforuk that a “let ‘er rip” approach rooted in a faith in “natural herd immunity” is disastrous, even as I have a serious problem with his cherry picking and exaggeration. Where Nikiforuk goes beyond what data will support is his picture of each COVID-19 infection and reinfection progressively damaging the immune system. To that end, he cherry picks certain studies:

So the virus is getting better at thwarting vaccines and evading immunity. Although vaccine protection against hospitalization and death remains strong, it is being steadily eroded by Omicron’s subvariants. Meanwhile protection against severe disease has declined as the effectiveness of our vaccines progressively wanes.

Immunologist Anthony Leonardi, a specialist in T cells, which play a complex role in immune function, predicted such a development nearly two years ago. That’s when he speculated that COVID was destabilizing the immune system by subverting T-cell function.

And that is exactly what many researchers are now finding.

So, based on a video, Nikiforuk is arguing that variants are steadily eroding the ability of vaccines to protect against hospitalization and death, and then cites one study. So I looked at the study. Interestingly, the study isn’t quite what Nikiforuk portrays. Yes, it shows that SARS-CoV-2 can cause T-cell apoptosis (programmed cell death). It also suggests a strategy to blunt or prevent that apoptosis, namely inhibition of an enzyme involved in the process known as a caspase. However, this study looked at apoptosis of T cells during severe and fatal acute infection, specifically 11 patients “in the Intensive Care Unit (ICU) for acute respiratory distress syndrome” and 30 patients “admitted to the Infectious Diseases Department (non-ICU) for symptoms of dyspnea and/or deterioration in their general condition”. It also looked at sera from 18 other hospitalized patients. It says nothing about less severe COVID-19 and representing it as generalizable to all COVID-19, as Nikiforuk does, is an example of the lack of nuance in this paper.

Elsewhere Nikiforuk cites a paper that examined infection Omicron B.1.1.529, a variant that carries multiple spike mutations with high transmissibility and partial neutralizing antibody escape, in healthcare workers with different COVID-19 infection histories and concluded:

B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.

What this study suggests is that “Omicron infections after vaccination recall the same antibodies that vaccines triggered against earlier strains, instead of eliciting all new responses to Omicron” and, as the authors concluded, “Some imprinted combinations, such as infection during the Wuhan Hu-1 and Omicron waves, confer particularly impaired responses”. Is this a potential problem with vaccine development? Yes. Is it, as Nikiforuk seems to suggest, slam-dunk evidence that the continued evolution of Omicron variants will result in a “forever plague” in which much of the population keeps getting sick because each wave of new variants progressively impairs the immune response? No. That’s an overgeneralization based on one study.

If you think that’s bad, buckle up, as Nikiforuk claims that COVID-19 will progressively destroy society, claiming that what we see now is worse than we’d see with a virus with much more than an order of magnitude higher mortality that passes through the population once and then disappears:

So letting the virus run unchecked is pretty much a strategy for creating a tsunami of neurological impairment and chronic illness in the general population. It is also a nihilistic prescription for sowing chaos in western societies already dancing a tango with political collapse.

Letting the virus rip also supports a nightmare scenario where initial infections disarm and sabotage immune systems leaving them more vulnerable to future infections and new pathogens such as monkeypox.

A pandemic that progressively weakens its host population with each successive wave is ultimately more dangerous than one that dispatches 10 per cent of the population and then vanishes.

Thanks to bad public policy, the frightening reality of a forever pandemic is becoming more probable day by day.

This, too, is exaggerated fear mongering and not how immunity works. Again, I refer to this article:

The empirical data coming in right now supports these basic immunological principles. If a previous omicron infection conferred little or no immunity against future omicron infections, then you’d expect that each subvariant’s surge would reach similar or even greater heights—because each subvariant is increasingly more contagious—than the original early 2022 omicron peak. But testing data from New York shows that the BA.2 wave fell far short of the original omicron wave—both in terms of total infections and reinfections. The same patterns held in Portugal, France, and Italy. The U.K. testing data followed a similar pattern (though testing data with randomized sampling, which better controls for testing rates, suggests the BA.2 peak was higher, a separate analysis from the U.K. Health Security Agency suggests reinfections were relatively rare, and not driving the spike). Testing in South Africa, where the BA.4/BA.5 surge has already peaked, showed much lower levels of infections. This is consistent with a population fortified by prior immunity.

As I like to say, when GBD proponents and antivaxxers argue that scientists and skeptics claim that natural immunity is useless, they misrepresent our position. I like to point out that postinfection immunity to some diseases is indeed lifelong; for others, like COVID-19, it’s far from it. Indeed, as I’ve pointed out, postinfection immunity to COVID-19 likely lasts a bit longer than post-vaccination immunity but is far from lifelong, one point on which Nikiforuk and I agree.

I also like to point out that vaccine efficacy will likely appear to wane just as more and more infection spreads through a population. Remember, estimates of vaccine efficacy (VE) compare infection rates in unvaccinated population to those in the vaccinated population. However, as the level of infection produces more “natural immunity” in both populations, the apparent difference between the risk of infection in the unvaccinated and the vaccinated will decrease just because the “unvaccinated” population will include a greater and greater proportion of people with prior infection and some degree of postinfection immunity.

Finally, wending its way through the entire narrative is long COVID-19. “Long COVID,” the syndrome of persistent symptoms and residual organ dysfunction after a COVID-19 infection is a real and concerning phenomenon. We’ve even said so a number of times on this very blog and that it will take years to determine the true burden of long COVID, not to mention to work out fully mechanisms and outcomes, and our resident neurologist, Steve Novella, has discussed the link between COVID-19 infection and neurodegenerative disorders. We actually agree that long COVID is likely to be a serious problem going forward. Indeed, concern about long COVID is the one of the germs of a good point in Nikiforuk’s article. Unfortunately, it is buried in all the fear mongering.

When allies go too far

Oddly enough, I was late to recognize a new phenomenon on “our side” that Nikiforuk’s article embodies, the so-called “zero COVID” movement. Pathologist Dr. Ben Mazer actually noted this a week and a half ago, a few days before Nikiforuk’s article was published:

This brings me to back to the response by my co-author Dr. Yamey:

And this one, by immunologist Angela Rasmussen, that includes points made by Nikiforuk that I agree with:

And:

I’d also amplify Dr. Rasmussen’s point about how odd it is that Nikiforuk seemed to ignore vaccination as part of the strategy to reach “zero COVID”. Has there ever been a disease eliminated without the use of an effective vaccine? I think you know the answer to that. In an earlier article, Nikiforuk declared confidently:

Yet as The Tyee has consistently warned, vaccines are imperfect tools that have severe limits. Moreover no vaccine has ended any outbreak without the help of other public health tools including masks, quarantines and reductions in mobility. The assumption that a vaccine or drugs can end a novel evolving pathogen in real time without the strategic use of other interventions to bring transmission to zero has made society more fragile and not less so.

But vaccines did vastly decrease the burden of many endemic diseases, such as measles and polio. They also ended smallpox. It’s not wrong that a vaccine-only policy is likely to be less than optimally effective (not almost completely ineffective, as Nikiforuk claims), but it’s clear that Nikiforuk doesn’t think much of vaccines, which are, contrary to his seeming belief, an essential part of any strategy to minimize death from a pandemic. In his response to criticism, Nikiforuk argues that he said that vaccines are important, just not enough, a position that is reasonable. Unfortunately, given all the loaded language and relative lack of discussion of this aspect of vaccine, his original article most definitely did not leave me with that impression. Quite the opposite, in fact. Go back and read his article and see if you don’t agree.

Also, in his response, Nikiforuk more or less doubles down on everything in his original article, admitting the error mentioned above, but in essence pointing to the same data cited in the paper and appealing to unknowns:

Last April the U.S. Centers for Disease Control and Prevention issued a field report on reinfections. It documented ten cases of reinfection — all during the Omicron wave — the majority among children and health-care workers. The shortest interval between one infection and a subsequent reinfection with a different lineage of COVID was 23 days — hence the basis for my sentence.

The researchers added that “antigen tests are increasingly performed at home, resulting in specimens being unavailable for strain testing. Thus, most early reinfections are likely not identified.” So the actual numbers of people having reinfections within 30 or 90 days is unknown but probably much greater than what the CDC picked up. (It is important to note that reinfections may also represent relapses whereby persistent infections reappear.)

None of this actually answers the entirely valid criticism that there is no evidence that anyone can be continually reinfected every few weeks with new COVID-19 variants, or that Nikiforuk provides no evidence that he’s doing anything more than JAQing off.

I also laughed out loud at this passage:

Rasmussen, like many critics, then professed ignorance about experts downplaying COVID infections as inevitable and even beneficial. Skeptical critics implied there was no evidence of this. Let me provide two links to articles in the Wall Street Journal representing this kind of harmful thinking. One article promised a good chance of herd immunity by April.

Another said taking measures to speed the spread of Omicron would produce the best long term outcomes.

The first article cited by Nikiforuk? It’s the infamous article from 2021 by Marty Makary claiming “we’ll have herd immunity by April”. Let’s just say that we at SBM have…not been kind…to that article, and rightly so. Nor have we been kind to claims that a let ‘er rip approach to the pandemic, as advocated in the second article cited, is a valid approach to the pandemic, noting that it is, in essence, eugenics. I also note that both articles cited were op-eds published in The Wall Street Journal, which has been a font of pandemic denial, COVID-19 minimization, and antivaccine fear mongering. Tellingly, Nikiforuk seems to be implying that these doctors represent mainstream public health thought in their COVID-19 minimization and advocacy of “natural herd immunity” approaches to the pandemic. They’re not, and those who have criticized his article have been harshly critical of these academics as well—even more critical, given that, while we have some common ground with Nikiforuk, common ground between us and pandemic minimizers like Marty Makary is almost nonexistent.

Let me conclude with an observation, namely that it is possible to acknowledge more than one thing at once about the pandemic without being a “COVID minimizer”, as some “zero COVID” advocates are claiming, and acknowledging these multiple things does not validate the complaints of the real COVID-19 minimizers (e.g., Marty Makary) at having the label applied to them. COVID-19 and long COVID are very bad. COVID-19 is not just a flu-like illness caused by a different virus, and SARS-CoV-2 does more bad things than previously suspected. Not nearly enough is being done any more (if it ever was) to protect vulnerable people, particularly the immunosuppressed, for whom the cessation of NPIs to slow the spread of COVID-19 has led to a feeling of abandonment and a recurrent fear of infection and death. It is also possible to be concerned about the rise of variants that are more transmissible and can evade prior immunity, both vaccine-induced and infection-induced. None of this means that those of us criticizing views espoused by Nikiforuk and others think that COVID-19 infection or reinfection is “good”.

I wish that zero COVID-19 were actually attainable. I would love to go back to a world before late 2019, when a novel coronavirus caused an outbreak of a mysterious pneumonia in Wuhan, China. Nikiforuk cites Japan as an example of how to do it, but even Japan has not achieved zero COVID. Moreover, although we too lament how quickly most countries have abandoned effective NPIs, we also lament that most countries in the world are not like Japan in how they are combatting COVID-19. Expecting them to be, as desirable as that might be, is just not realistic. As a result, COVID-19 is unlikely to be eliminated any time soon, if ever, which means that the best that we can do is to promote better ventilation, more masking, get vaccinated and boosted, avoid crowded indoor spaces, develop better vaccines, and in general continue to try to minimize the harm from COVID-19. Saying that is not “hopium”. It is realistic, far more realistic than GBD-like strategies or “zero COVID”. Public health during a pandemic has to be based on a realistic assessment of the situation, the tools available to combat the pandemic, and the political will to use those tools. Unfortunately, the world appears to lack the last of these, something about which we agree with Nikiforuk.