Did Vaccine Apartheid Cause Omicron?

A few days after South Africa alerted the world to the emergence of the rapidly spreading new variant and the United Nations named it “Omicron,” the normally reserved former British prime minister Gordon Brown did not mince words when he denounced what he called the “neo-colonialism of the European Union.”

Brown, who is also World Health Organization (WHO) ambassador for global health financing, was livid to discover that in August, at the very moment when in countries like Zimbabwe morgues were running out of room amid the deadliest wave of the disease to hit Africa yet, the EU was disrupting efforts to vaccinate Africans by commandeering ten million single-shot Johnson & Johnson jabs that had been filled and finished in South Africa. With 70 percent of Europeans having been fully vaccinated by then, one can only conclude that this requisition was intended so that Europe could ready itself for boosters even as nations like Burundi have yet to administer a single dose.

There was immediate pushback from some quarters, suggesting that this was ill-informed moral grandstanding, as South Africa was, in fact, overflowing with vaccines and instead suffering from widespread vaccine hesitancy. If only it were so simple, the reply went, as waiving intellectual property rights and funding technology transfer and Global South regional manufacturing capacity! The EU, which opposes vaccine patent waivers, used the opportunity ahead of a World Trade Organization (WTO) conference in Geneva to reiterate its position that such relaxation of intellectual property rights would do nothing to enhance vaccination distribution in the developing world.

However, Brown is correct to say we should not be surprised. (And the fact that this WTO confab about vaccine patent waivers would subsequently be postponed due to the spread of Omicron, itself in part a product of the lack of such patent waivers, is an irony we can be sure is not lost on him.)

It’s important to note that while South Africa was first to alert the world about the spread of the new variant, identified among diplomats who had traveled to Botswana, it doesn’t follow that either country was the site of its origin. Instead, we should thank the region for its superb infectious disease surveillance and genomic sequencing infrastructure, a response to Africa’s history of struggles with illnesses such as HIV, tuberculosis, and Ebola. Subsequent data showed that Omicron was already spreading in the Netherlands a week earlier, suggesting the variant had been circulating widely before the alert was issued.

Nevertheless, circulation beyond southern Africa doesn’t mean it did not first emerge there either. We simply don’t know. And if we do assume that the variant evolved somewhere in South Africa, we should note that, while it is true that the South African government asked Pfizer and Johnson & Johnson to delay vaccine deliveries in November due to a slowing down of uptake, it was only in August that supplies to the country finally stabilized.

Phylogeneticists and allied researchers can track the evolution of strains of SARS-CoV-2 by sharing and comparing their genomes via online data sharing hubs, notably Nextstrain, an open-source project put together by University of Washington epidemiologist and computational biologist Trevor Bedford and his colleagues. The scientists working through Nextstrain monitor in real time minor changes to the virus’s genetic code, and in so doing, they build a family tree showing the evolutionary relationship between different lineages. Bedford points out that Omicron’s closest relatives on this tree are not recent variants but strains that were in circulation around the middle of 2020. At the same time, even though its closest relations are from last year, its mutations since then still make it substantially different from those 2020 strains.

How is this feasible? There are three possible scenarios, say phylogeneticists. The virus could have infected other animals some time ago and then escaped them to infect humans. Or the strain could have been in circulation in a region of low surveillance and recently spread to Botswana and South Africa, where it was finally spotted. But the most likely scenario is that Omicron evolved within the body of an immunocompromised person, such as someone with untreated HIV. Such a person’s immune system attacks the virus but is unable to completely defeat it. The remaining virions (individual virus particles) will be those least susceptible to the immune system. This occurs repeatedly in the same person, driving multiple iterations of mutation, and thus evolution, otherwise hidden from disease surveillance.

The upshot of all of this is, first, that greater support for HIV treatment is not a parallel process to that of tackling Covid-19 but part of it. Indeed, one might point out that the processes that have delimited access to such treatment over the years are not unlike those that perpetuate vaccine apartheid. And second, with respect to the claim made by Brown and others of vaccine apartheid playing a role, the time line for Omicron’s emergence (somewhere between mid-2020 and a few weeks ago) beyond this hypothesized immunocompromised individual plainly includes a lengthy period of many months in which vaccines could have been widely distributed but weren’t.

South Africa was only able to begin its vaccination program in May. This is not to say that, had there been comprehensive vaccine distribution in the country and wider region alongside limited vaccine hesitancy, Omicron could not still have emerged, but rather that such distribution would have reduced its likelihood.

Supply and hesitancy are also not the only issues in South Africa and elsewhere on the continent. Distribution can be as much of a challenge, with many people unable to access the vaccine due to the cost of traveling to clinics. Distribution bottlenecks are as much a part of vaccine apartheid as questions of intellectual property, technology transfer, and regional manufacturing.

It remains more than reasonable, then, to maintain the pressure on elites to overcome vaccine apartheid. There has been no moral grandstanding.

Vaccine Hesitancy in the Global South

This doesn’t mean that we do not have to worry about growing vaccine hesitancy in South Africa or the rest of the Global South. Vaccination rates in the country have struggled to climb much higher than 55 percent for those over age fifty, and barely 20 percent of those under fifty have been fully vaccinated.

In their ultimate effect, vaccine apartheid and vaccine hesitancy are the same: they produce a large cohort of people in which the virus can continue to mutate and pose a threat to those who are vaccinated, as well as potentially to the nonvaccine medical interventions we have developed. Both situations must be overcome.

But one is harder than the other. As difficult as transcending vaccine apartheid is, due to the financial interests of pharmaceutical companies being orthogonal to universal vaccination and the abetting of such inhumanism by their diplomatic defenders, in principle, at least, it could be ended with a snap of the fingers. Vaccine hesitancy has historically, for the most part, been considerably less of a problem in the Global South than in the developed world, but the evidence suggests it is now increasingly established here, too. And there is no easy solution.

Surveys in recent years tracking the strength, spread, and reasons behind both vaccine hesitancy and anti-vaccination sentiment around the world have shown such attitudes to be, with a small handful of exceptions, substantially less entrenched in developing countries compared to their richer counterparts. The reason for this, the authors of these surveys report, is that thanks to vaccines, antibiotics, modern hygiene, and sanitation, most of the common infectious diseases that we confronted throughout history have been declining in the developed world. The knowledge of what it is like to live in a grim, dark world where pestilence awaits behind almost every corner had, until the advent of COVID-19, all but disappeared. But in the developing world, many of these diseases, and others endemic to such regions, remain a part of everyday life. They can see the immediate benefit from vaccine jabs.

Vaccine hesitancy, for the most part, has been a malady of the rich world, not the poor.

And South Africa is something of a liminal state, with extremely uneven levels of development. Here, hesitancy is greatest among whites with comparably better income levels. A survey of almost eight thousand people in the country published in August and performed by researchers from the Human Sciences Research Council and the University of Johannesburg found that while three-quarters of all black adults were willing to receive a COVID-19 shot, a mere 52 percent of white adults felt the same way. Most often, concerns among this latter group focused on possible side effects or lack of effectiveness.

Furthermore, hesitancy is growing among white South Africans but declining among their black counterparts. (And yet, despite there being greater hesitancy among whites, they are still more likely to have been vaccinated, probably due to access to superior health facilities.)

While vaccine hesitancy on a global level is more commonly a vice of the affluent, the problem remains a growing problem in the developing world, even if the uptick in hesitancy is starting from a low level. And within the developed world, vaccine hesitancy occurs not just among alternative-medicine-gobbling-and-crystal-bothering yoga moms but also among poorer and racialized communities who have, for good historical reasons, developed a lack of trust in health authorities.

In South Africa, there is a similar distinction in rationales for fear of the vaccines. A France 24 news article from the early summer, just as the inoculation campaign was beginning, may not be as quantitatively rigorous as the University of Johannesburg survey, but its quotes from clinicians and the vaccine hesitant give us a useful qualitative background. In one example of this, a doctor who regularly confronts vaccine resistance tells of the impact of recent press revelations that cardiologist Wouter Basson, who had headed Project Coast — an apartheid-era chemical and biological warfare program that, among other activities, researched a “vaccine” contraceptive that could be clandestinely applied to blacks to reduce their birth rate — was still practicing medicine.

And the radical global disparity of COVID-19 vaccine manufacture and distribution itself is only contributing to this distrust. Given vaccine apartheid, Western governments and companies must only be handing over rejects to the developing world, thirty-five-year-old Mbali Tshabalala told the reporter: “What if most people get a third-grade kind of vaccine?”

Thus, defeating vaccine apartheid contributes to defeating vaccine hesitancy in the developing world; or rather, allowing vaccine apartheid lets vaccine hesitancy in the Global South continue to fester.

End of the Pandemic?

But does any of this matter? Preliminary data from South Africa suggests that the case fatality rate in Gauteng province — epicenter of the Omicron outbreak there — has dropped to 1 in 200, lower than it has ever been during the outbreak and some ten times lower than September 2020, when the country had the tenth highest number of cumulative cases in the world. The first study, based on three weeks’ worth of investigation since Omicron was identified and yet to be peer-reviewed, suggests that hospitalization rates are sharply down, dropping to 38 admissions per 1,000 people infected from a rate of 101 per 1,000 infected by Delta. Those who have been hospitalized have had far milder illness and enjoyed a much-reduced length of stay. Meanwhile, effectiveness of the Pfizer-BioNTech vaccine against infection declined to just 33 percent.

And the vaccines are not the only intervention that have taken a hit. AstraZeneca’s antibody cocktail Evusheld, a pre-exposure prophylaxis treatment for those severely immunocompromised individuals whose immune systems do not mount a strong response to vaccination, is holding up well against Omicron, as is GlaxoSmithKline’s antibody therapy. But those of Eli Lilly and Regeneron are less effective. Omicron is limiting treatment options for those who do catch the disease.

Despite the apparent mildness and the vaccines’ reduced effectiveness against infection, this still does not argue in favor of forgoing vaccination: effectiveness of the Pfizer jab against severe illness and hospitalization remains relatively robust at 70 percent. Of those who needed oxygen, the majority were unvaccinated, as were those requiring intensive care. Other researchers report that Moderna’s shot has also lost effectiveness, although a booster restores effectiveness to the level of that against Delta.

If the variant turns out to be super transmissible but super mild, and outcompetes the previously dominant Delta variant, could we achieve global herd immunity without having to overcome vaccine hesitancy and vaccine apartheid? Will this be the best-case scenario, and, as one reporter asked, will Omicron turn out to be the “perfect variant,” the “light at the end of the tunnel”? Is this the end of the pandemic?

It is certainly to be hoped that Omicron, which the WHO confirmed this week is spreading far more easily than the highly transmissible Delta or any other previous variant, will prove to result in much milder illness in those infected. But we should be cautious about assuming this to be the case. It may be that the data from South Africa showing milder illness simply reflect a high rate of previous infection in the region and its younger age demographics rather than that this variant is less virulent (disease-causing), and so other regions mileage may vary. It’s important to note as well that higher immune escape should lead to greater spread, even without there being any greater inherent transmissibility.

Omicron’s greater immune escape is due to its multiple mutations — like a character in a movie being hunted by the police and then changing jackets or hair color to avoid detection, the mutations mean that while the immune system’s “security camera” may still be able to spot the virus, it will be harder for it to do so.

Since the beginning of the pandemic, there has been an explosion of public interest in viral evolution. Lots of people have done a remarkable job of educating themselves about the subject. We should not be sneering at this wave of virology and phylodynamics autodidacticism. At the same time, alongside this, there has been a good deal of misinformation and “armchair epidemiology.”

Typical of this is the notion that there is some sort of law that all viruses tend to become more transmissible but milder over time as host and pathogen evolve toward a mutually benign relationship. (On the other hand, there is also the fear of any mutations at all, with the very word “mutation” prompting visions derived from horror movies of super-deadly, super-contagious civilization slayers.)

Enhancing the spread of such misinformation can be a frustration at how, due to the complexity of the interaction of pathogen evolution with a great many other factors that impact the progression of a pandemic, most experts will stress that precise predictions of how a particular virus will evolve are impossible. At the same time, as evolutionary biologist Elisa Visher and her colleagues argue in a recent review paper attempting to clarify what we can say amid the swirl of misunderstandings about viral evolution during the COVID-19 pandemic, this does not mean that we have zero idea about how they evolve in general.

The authors note that it doesn’t help that the tendency toward milder disease (“avirulence”) as the spread of a pathogen progresses was, for a long time, what scientists believed occurred. The pioneering nineteenth-century epidemiologist Theobald Smith developed what he called a “law of declining virulence.” It certainly makes intuitive sense. If a virus hijacks and kills lots of host cells in the process of making copies of itself, alongside producing a great deal of toxins and its very form being toxic, it will cause severe disease (high virulence), in turn causing the host to remain bedridden and thus not spread the virus to many other new hosts. The host may even die quickly, again making it harder for the virus to spread. But if the virus is “smarter” and evolves to be less virulent, the host is less likely to be bedridden or die, and so will continue to spread copies of the virus to many more hosts, who will themselves spread more copies, and so on.

But since the 1980s, this conventional wisdom has been rejected by the scientific community. It is not what contemporary theory of viral evolution, or the evidence, tells us.

Instead of a tendency toward avirulence, the contemporary “trade-off model” of viral evolution describes an “optimal virulence” that balances virulence and transmission, depending on the relationship between host and pathogen, and this optimum can change over time if that relationship changes. For example, low virulence could result in fast recovery, which, just like rapid fatality, could hinder the spread and replication of the virus. Or a faster replicating virus could cause more damage to the host but also produce a greater population of virus particles, and with a larger virus population size, there could be an increased transmission rate. Thus, there could be increased transmission alongside high virulence.

Something like this can occur within families or in other situations where there is a high density of people. This is because, even if a highly virulent pathogen kills its host, family members who are potential hosts are still nearby. A pathogen with the same level of virulence might not, however, achieve similarly high levels of transmission if the conditions it found itself in were a sparsely connected group of people. And so the optimum virulence for a pathogen in one set of conditions may not be the optimum virulence should those conditions change. Indeed, while Dengue fever has been with us since the eighteenth century and had evolved over time to a relatively low level of virulence (however painful the illness may be), changes to the size and mobility of the human population may have driven an increase in its virulence over the last five decades.

Visher and her colleagues also note that, at the outset of any zoonotic spillover (when a pathogen spreads from its animal host to a human host for the first time), the pathogen usually has very little experience of humans and so is not likely to be well adapted to transmission among us. In turn, this could mean that, at the start of any epidemic or pandemic, any mutations that improve upon transmission will be of enormous benefit. But at these early stages, this increase in transmission rate might not come with a cost; there may not yet be any trade-off in virulence.

This is all very general, and not specific to the nuances of the biology of SARS-CoV-2 and the evolutionary regime in which it finds itself. We don’t know where we are with SARS-CoV-2. Are we well advanced along this trajectory?

In addition, as Trevor Bedford has pointed out, Omicron’s increased transmissibility doesn’t mean that it will automatically displace Delta the way that Delta displaced other lineages. If Omicron’s substantial number of mutations mean that it is well suited to a slightly different ecological niche (a different set of human conditions) than Delta, they could coexist rather than competing with each other. Bedford gives the historic example of the flu, where displacement does tend to be the rule. However, he notes that a pair of influenza B lineages (which only infect humans and seals) that descended from the same source and diverged from each other around 1980 have since circulated alongside each other without displacement,

So while it is plausible that SARS-CoV-2 will evolve toward producing a milder form of illness, much like the coronaviruses that (alongside rhinoviruses) cause the common cold, it’s not an inevitability. In addition, even if it does evolve to a milder form, this is no guarantee that such mildness is permanent, or that the milder variant will displace the more virulent one.

Perhaps Omicron, or some other variant in the future, will turn out to bring an end to the pandemic, but we cannot bank on it. The fight to end vaccine apartheid and to try to win people away from vaccine hesitancy must continue — and with respect to the latter goal, so as to avoid backfiring, perhaps with more carrot and less stick. We must reduce the opportunity for “Houdini” variants to develop that have evolved still greater immune escape than Omicron while bearing virulence capable of collapsing health systems.

If we fail, all that we have had to bear for the last two years will have been for nothing, as our public health efforts would be set back almost to square one. Good luck convincing citizens to obey lockdowns and submit to new vaccines when that happens.