In early 2021, Nick Wilson was feeling hopeful. For months, New Zealand had been reporting zero or just a few daily cases of COVID-19. To Wilson, a public-health physician and researcher at the University of Otago in Wellington, eliminating the disease in New Zealand — and possibly across the globe — didn’t feel out of reach. “The success of public-health and social measures without the vaccine gave us confidence that when the vaccine became available — if it had sustained high efficacy and was rolled out everywhere — and was combined with public-health and social measures, we could eradicate COVID-19,” he says. In July 2021, he and his colleagues wrote a commentary saying just that (N. Wilson et al. BMJ Glob. Health 6, e006810; 2021).

But around the same time, the Delta variant of the coronavirus SARS-CoV-2 started upending the world once again. Within a few months, the New Zealand government abandoned its idea of eliminating COVID-19, at least in the near term.

Today, New Zealand is a microcosm of much of the rest of the world, where rapidly evolving variants of the virus continue to spread, causing illness and death. Wilson’s hopes for a future free of COVID-19 aren’t dashed completely, but they certainly aren’t as high as they were in mid-2021. “It’s disappointing,” he says. He maintains that eradication is still possible, but it would require that almost everyone on the planet receives a highly effective vaccine that could provide more or less lifelong immunity. “So yeah, basically it’s looking very unlikely,” he says.

For an infectious disease to be considered eradicated, there cannot be a single case of it worldwide. So far, the only human infectious disease to be eradicated is smallpox, in 1980. Other diseases, such as polio and the parasitic disease dracunculiasis teeter on the edge of eradication — two of the three strains of wild poliovirus have been eradicated, with the third eliminated from most of the world (although vaccine-derived poliovirus has, in the past year, been detected in a number of countries, including the United States).

Ridding the world of any infectious disease is a difficult task. Societal factors and the intrinsic characteristics of a given pathogen can conspire to make it harder still. Understanding those factors, and how they should affect the response to a pandemic, could make it easier to eradicate the next pandemic-causing pathogen.

Stroke of luck

Before its eradication in 1980, smallpox had been around for thousands of years. It killed more than 300 million people in the 1900s alone, and left many survivors with severe scarring and blindness. Smallpox was by no means easy to do away with, but a variety of factors made its eradication possible.

One such stroke of luck was that smallpox passes only between people — there is no animal reservoir in which the virus can hide. This is not the case for many diseases. SARS-CoV-2 probably made its way into people from animals at a market where wildlife was being sold. Now, SARS-CoV-2 has been detected in a range of species in the wild, as well as in household pets and zoo animals. Influenza viruses also reside in non-human hosts, including birds, cats, dogs, bats and sea lions. And malaria is shuttled between people by mosquitoes infected with the parasite responsible for the disease; dracunculiasis is similarly transmitted by parasite-infected water fleas.

As well as being points of potential spread to people, animal reservoirs can be breeding grounds for mutations, giving rise to variants that might evade the immune protection provided by vaccines or previous infection. Whether animal reservoirs are responsible for the more-recent SARS-CoV-2 variants is debated, but it is clear that current vaccines are less effective against these variants than against earlier forms.

The rate at which a virus accrues mutations can also affect efforts to eradicate it. Although many pharmaceutical companies are able to pivot and adapt their vaccines to target emerging variants, there’s always the chance that a virus will move faster and that the pathogen can spread unhindered once again. SARS-CoV-2 mutates faster than many viruses, including smallpox, says Rhea Coler, an infectious-disease researcher at the Center for Global Infectious Disease Research at Seattle Children’s Hospital in Washington. However, it still mutates more slowly than do many other infectious diseases, including influenza. Because of this, Coler says, she wouldn’t be surprised if an influenza virus were responsible for the next pandemic.

Another variable is how easy it is to tell that someone is infected. “From a microbiologist standpoint, you always ask, ‘Is the disease really easily recognizable?,’” says Coler. If a disease can be diagnosed by eye, she says, then that makes tracking its spread simpler, and measures such as quarantining more likely to succeed. “The more sophisticated the methods that are necessary for diagnosing a disease, quite frankly, the less likely it is that the disease will be eradicated,” Coler says.

Aerial view of a very long queue of people waiting outdoors for a vaccination.

Thousands of people in New York waiting to have a smallpox vaccination. Smallpox was eradicated in 1980.Credit: Bettmann/Getty Images

The symptoms of smallpox were impossible to miss. They began with a fever and body aches, followed by a distinct rash on the tongue and mouth that turned into sores. Then, a couple of days later, a similar rash and sores would appear on the face, before spreading to a person’s limbs. COVID-19 symptoms, by comparison, can seem similar to those of pneumonia or influenza, or hardly be present at all, meaning that someone can know if they are infected only by getting tested.

A person infected with SARS-CoV-2 can also be contagious even though they are asymptomatic, whereas smallpox was spread only by people with symptoms. This meant health workers could quickly deploy a ring vaccination strategy, in which anyone in close contact with a person showing smallpox symptoms — and therefore more likely to spread it to other people — was immediately vaccinated. This targeted delivery of vaccines was crucial to eradicating smallpox in places where mass vaccination — as used against COVID-19 — was falling short.

Team effort

The eradication of smallpox would not have been possible without a global effort. The same will be true of future campaigns to eradicate disease, Coler says. If political support within and between countries falters, these efforts will not succeed.

In the initial period of COVID-19, many countries formed a united front. “I was impressed that, very early on in the pandemic, there was a lot of sharing of information and collaboration,” says Coler. “We would not have gotten the sequences for the virus, for example, if scientists in Asia weren’t willing to share them with us.” Those genetic sequences allowed researchers around the world to begin developing vaccines immediately.

But as time went on, many of those international collaborations broke down, which harmed the chances of eradicating the pathogen. “With smallpox there were US and Soviet scientists working together. You had that level of cooperation,” says Wilson. “I just don’t think that’s feasible, unfortunately, in the current climate.”

A rise in vaccine nationalism over the course of the pandemic has also had a negative effect, Wilson says, with some countries hoarding vaccines, and so limiting vaccination efforts elsewhere. He’s also disappointed by the alleged actions of some nations to spread disinformation, discrediting highly effective vaccines developed by other countries. Behaviour such as this could undermine the use of these vaccines across the globe.

The spread of disinformation that has damaged efforts to eradicate COVID-19 has been aided, in part, by the lack of adequate funding for pandemic response. According to one report (see go.nature.com/3ddkg05), in the United States, thousands of public-health departments continue to be underfunded and understaffed. Emily Gee, a health-policy advocate at the Center for American Progress in Washington DC, says that not only does this make it more difficult to implement health measures that could aid eradication, such as contact tracing, vaccination and testing, but it also puts pressure on officials’ ability to engage with the public.

To react swiftly and effectively enough to eradicate a future pandemic-causing pathogen, Gee says, it will be important to consider not just how to manufacture and deliver vaccines to where they are needed, but also how to build the trust required for people to have them. She thinks that being more transparent — for example, about how scientists’ understanding of a virus will evolve as more research is done, and why certain public-health measures are being used — is an important tool to combat disinformation during a pandemic, as well as more generally.

Tougher tasks ahead

The possibility of eradicating COVID-19 might now be considered slim, but it could be the catalyst to do better the next time a pandemic strikes. Passing legislation such as the PREVENT Pandemics Act in the United States — a bill focused on improving public health, medical preparedness and pandemic-response systems — could put countries in a better position to eradicate future pathogens, Gee says.

Studying where we went wrong over the past two years is also important, Wilson adds. “We should be learning everything we can about every intervention that was tried on COVID-19 and how to optimize it for a much more severe pandemic,” he says. His concern that the next threat could be worse than SARS-CoV-2 is shared by Coler. “Even though it has been so devastating, we have been lucky,” she says.

“When you think about the viruses that infect humans, a lot of them are less well understood, and harder to control, than coronaviruses,” Coler says. The severe acute respiratory syndrome (SARS) outbreak in 2002, and the Middle East respiratory syndrome (MERS) outbreak in 2012, were both caused by coronaviruses. And although SARS and MERS research efforts pale in comparison with those of the past two years, by the time COVID-19 hit, scientists had already studied some essential components of coronaviruses. For example, valuable information about the spike protein allowed for the rapid development of vaccines and insight about key enzymes led to antiviral treatments.

The next pandemic threat might be less well understood and pose an even greater challenge than SARS-CoV-2. Simply preparing to deal with another pandemic of a similar threat level to COVID-19 might not be enough. “We have to be forward thinking,” Coler says. “While there are a lot of lessons to be learned from COVID-19, we can’t fall into the trap of being prepared for yesterday’s disaster.”