Will We Ever Get Rid of COVID-19?

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No matter how much we’d like to eradicate SARS-CoV-2, it may be better to settle for other forms of control.

Will We Ever Get Rid of COVID-19?

Maggie Chiang for Quanta Magazine

As the end of the year approaches, we are nearing the two-year anniversary of the COVID-19 pandemic. Globally, over 5 million have died, and that’s almost certainly an undercount, especially in countries that still lack the resources to properly test and vaccinate their populations. The U.S. has reported more than 750,000 COVID-19 deaths, and we’ve seen four surges of cases since early 2020, hoping that each would be our last. Just last week, scientists detected a heavily mutated new variant, Omicron, which may end up leading to another rush of cases — or have no lasting effects. We still don’t know enough to tell.

Everyone is ready for the pandemic to be over, but it’s still unclear what that would look like. How likely are we to eradicate the virus? What would that really mean, and what will the world look like if we can’t? 

While there is much we still don’t know about SARS-CoV-2, the virus that causes COVID-19, we have learned enough to answer some of these questions. 

Can we eradicate COVID-19? 

Some people think so. Advocates of a campaign to eradicate the virus cite the high costs of an endemic SARS-CoV-2 virus, both in terms of health and as an ongoing economic issue. To date, over 250 million infections have been confirmed globally with over 5 million deaths, and absent any intervention, economists have estimated that COVID-19 infections would cost the U.S. $1.4 trillion by 2030. Even with the vaccines, COVID-19 will still be exceedingly costly in the coming years on multiple fronts.  

And it’s true that once a pathogen is eradicated, mitigation measures can be reduced or eliminated. We no longer vaccinate the general public for smallpox (though we do maintain a military smallpox vaccination program due to the potential for bioterrorism). One medical journal has suggested that eradication of SARS-CoV-2 should not be ruled out, and that it could be about as challenging as our ongoing polio eradication efforts

I disagree. The epidemiology of the virus makes eradication unlikely. Investing in a campaign to do so would be a misuse of limited resources, and the failure of a high-profile eradication campaign could make other levels of control more difficult.

What’s the difference between eradication, extinction and elimination of a virus?

Eradication means that the virus is completely extinguished in nature. We’ve actually achieved this with smallpox in humans and rinderpest in animals. Extinction goes further and includes the destruction of any samples in laboratory stocks as well. This has not yet happened for any pathogen, for many reasons that are primarily political rather than scientific: above all, the mutual distrust between the U.S. and Russia, who each hold remaining stocks of the virus.

Eradication is sometimes confused with elimination. While eradication refers to the global extermination of the virus (except in labs), elimination refers to a more limited form of control, where new infections within particular countries are reduced to zero. In the U.S., we have done this with other viruses including the ones causing measles, rubella (German measles) and polio. While we have had recent outbreaks of measles, the original cases for each outbreak came from an outside source — generally a traveler who was infected abroad before going to an area where measles remains endemic. 

Maintaining elimination is difficult. The U.S., which eliminated measles, almost lost that status due to a 2019 epidemic that sent cases surging globally (primarily because of outbreaks among the unvaccinated). 

What makes COVID-19 so resistant to eradication?

A candidate for eradication will typically possess three qualities: an effective intervention that can stop transmission, readily available diagnostic tools that can rapidly detect infection, and a lack of the disease among nonhuman animals. COVID-19 fails on all three counts. 

We think approximately 35% of COVID-19 infections are asymptomatic. That complicates control of spread and diagnosis. For every symptomatic case, many other infections have almost certainly occurred that went unnoticed. To find them, we would need to build up extensive surveillance programs (as we’ve done in the campaign to eradicate polio), examining human cases as well as samples of sewage to determine if the virus is circulating in a community. It’s hard to interrupt transmission if you don’t even know the disease is there. 

And even for symptomatic cases, diagnosis is fraught. Unlike smallpox, which had very distinct symptoms that could readily distinguish it from other rash-causing viruses, COVID-19 causes symptoms that can be similar in presentation to those of influenza and other respiratory viruses, meaning rapid, accurate, widespread and affordable testing are critical to confirm cases.   

Finally, the disease is currently circulating among multiple species of animals besides humans, with no end in sight.

What do other animals have to do with our eradication efforts?

Smallpox, measles and polio are all caused by human-specific viruses; they do not infect other animals, and so they’re easier targets for eradication. SARS-CoV-2, by contrast, is a zoonotic pathogen that originated from an as-yet-unknown species, probably a bat. This means there is already a nonhuman reservoir of the virus in nature. Following its spread to humans, researchers have identified SARS-CoV-2 in many other animal species, including ferrets, otters, white-tailed deer, gorillas, mink and more

These animal infections complicate eradication efforts, because there will always be sources of the virus that could reintroduce it into humans. Animal-to-human transmission may be infrequent (though mink-to-human transmission has already been documented), but it only takes a single event to bring the virus back into an area where it has been eliminated. Each new chain of transmission needs to be stopped if eradication or elimination is the long-term goal.

What about vaccines? 

Vaccines have been a great method of interrupting transmission, but the current vaccines for COVID-19 simply aren’t as effective as vaccines for smallpox, measles and polio. COVID-19 vaccines reduce transmission if vaccinated individuals are infected, but they do not completely eliminate it. Again, this makes eradication much more challenging.

An additional issue is variants. The viruses that cause measles, smallpox and polio have less genetic diversity, so variants can generally be neutralized by vaccine-induced immunity. With SARS-CoV-2, we’re not yet sure how much of an impact variants will have, but it is at least theoretically possible that a variant will emerge that can completely escape the immunity brought on by vaccination or previous infection. (Tests are currently underway with the Omicron variant to determine if it has the ability to escape from antibodies generated against prior variants.) Mutations in the virus’s spike protein, which binds to the host’s cells and is what the immune system recognizes, could result in changes to the protein’s amino acid sequence. If these changes hit in the right places, they could alter the protein to such a degree that our antibodies will bind to it less tightly or no longer recognize the protein.  

There’s also the issue of waning immunity over time. Vaccination for polio, smallpox and measles results in long-term, potentially lifelong, immunity. With coronaviruses in general, we know that immunity can wane rapidly, leaving individuals susceptible to reinfection. We are already witnessing this now with SARS-CoV-2, in both vaccinated and previously infected individuals. 

The solution to these issues is simply additional vaccinations, but that requires a regular, global vaccine campaign that would have to surpass vaccination efforts in 2021, which themselves only came about with emergency funding and have still left many unvaccinated, either because they declined the vaccine or because it’s not yet available to them. 

Are there other reasons to be skeptical about SARS-CoV-2 eradication? 

While discussion of the pathogen’s biology may dominate when we look at eradication potential, that is only one aspect of the issue. Potentially more difficult are political and economic considerations. 

Eradication is a global enterprise. Interventions must be globally available and affordable, and there must be agreement among nations that eradication is not only possible but necessary. Reaching such an agreement would be facilitated by the World Health Assembly, the World Health Organization’s decision-making body. It is here that any campaign must begin, as delegates are the first to decide if eradication is feasible, if it’s a good use of resources, if all countries would value it enough to contribute, and so on. Even assuming everyone is interested in working toward the goal — which is assuming a lot — countless logistical issues would delay and hinder the project.

What do we do instead?

While eradication is unlikely, we have other options. Elimination of infections — reduction to zero within defined geographic areas — may be possible, but even that would require many years of sustained work. Elimination would be easier if we had second-generation vaccines that could provide long-term immunity and better protection from “breakthrough” infections, but it’s unclear if any coronavirus vaccine can do this, given that even infection does not. 

As we consider the loftier goal of elimination, in the short term we must aim simply for control: reduction of incidence to an acceptable level, due to deliberate efforts. This will come at a cost, probably a higher one than many public health experts are comfortable with, of thousands of COVID-19 deaths each year and additional chronic outcomes, such as long COVID. Luckily, the combination of vaccination, infection-induced immunity and novel treatments should reduce the risk of serious infection and death from COVID over time. Annual vaccination may be necessary to keep immunity high and to respond to any variations in circulating virus, as with influenza. Some individuals may also choose to wear masks in times of increased infections. 

We need to be honest about what to expect moving forward. The specter of COVID-19 will likely always be here, but with interventions it can be defanged. Achieving this is unlikely to herald the “return to normal” so many desperately desire — but neither will illusions of eradication.

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