COVID-19 is not humanity’s first time staring down a seemingly unstoppable disease. Just in the past century, we’ve survived a few. Here’s a look at some of them — and how we might we get ourselves out of this one.

How it started: Unclear, but probably not in Spain. It was a particularly deadly strain of H1N1 influenza and first took root in the U.S. in Kansas.

If the flu did hit your town, it hit hard: A young person could wake up in the morning feeling well and be dead 24 hours later. Half the people who died of the flu in 1918 were in their 20s and 30s.

So how did we, as a species, beat the Spanish flu? We didn’t. We survived it. It torched through individual communities until it ran out of people to infect.

A third of the world’s population was believed to have contracted the Spanish flu during that pandemic, and it had a case-fatality rate as high as 10-20% globally and 2.5% in the United States. (Johns Hopkins University reports the COVID-19 case fatality rate in the U.S. is 1.6% as of December 2021.) Roughly 675,000 people in America died out of a population of 103.2 million.

Flu vaccines wouldn’t be developed until the 1930s and wouldn’t become widely available for another decade. Ultimately, the virus went through a process called attenuation. Basically, it got less bad. We still have descendant strains of the Spanish flu floating around today. It’s endemic, not a pandemic.

As a society, we accept a certain amount of death from known diseases. The normal seasonal flu usually kills less than 0.1% of people who contract it. Deaths have been between 12,000 and 52,000 people in the United States annually for the last decade.

The regular seasonal flu is both less contagious and less deadly than COVID-19. That people were washing hands, working from home and socially distancing in the winter 2020 flu season likely contributed to the fact that it was a comparably light flu season.

As places reopen and people feel more confident about socializing and traveling again, the flu could make a calamitous comeback.

How it ended: Endemic

How it started: The first documented polio epidemic in the United States was in 1894. Outbreaks occurred throughout the first half of the 20th century, primarily killing children and leaving many more paralyzed.

Polio reached pandemic levels by the 1940s. There were more than 600,000 cases of polio in the United States in the 20th century, and nearly 60,000 deaths — a case fatality rate of 9.8%.

Polio was highly contagious: In a household with an infected adult or child, 90% to 100% of susceptible people would develop evidence in their blood of also having been infected. Polio is not spread through the air — transmission occurs from oral-oral infection (say, sharing a drinking glass), or by “what’s nicely called hand-fecal,” said Paula Cannon, a virology professor at the USC Keck School of Medicine. “People poop it out, and people get it on their hands and they make you a sandwich.”

If you survived, polio could have devastating long-term effects. President Franklin D. Roosevelt was among the thousands of people who lived with permanent paralysis from polio. Others spent weeks, years, or the rest of their lives in iron lungs.

Precautions were taken during the polio pandemic. Schools and public pools closed. Then, in 1955, a miracle: a vaccine.

A two-dose course of the polio vaccine proved to be about 90% effective — similar to the effectiveness of our current COVID vaccines. Vaccine technology was still relatively new, and the polio vaccine was not without side effects. A small number of people who got that vaccine got polio from it. Another subset of recipients developed Guillain-Barre syndrome, a noncontagious autoimmune disorder that can cause paralysis or nerve damage. A botched batch killed some of the people who received it.

By 1979, polio was eradicated in the United States.

How it ended: Vaccination

How it started: The disease had been observed in the Eastern Hemisphere dating to as early as 1157 BCE, and European colonizers first brought smallpox to North America’s previously unexposed Native population in the early 1500s. A 2019 study suggested smallpox and other viruses introduced by colonizers killed as much as 90% of the Indigenous population in some areas. Globally, smallpox is estimated to have killed more than 300 million people just in the 20th century. The case fatality rate of variola major, which caused the majority of smallpox infections, is around 30%.

Outbreaks continued in North America through the centuries after it arrived here, at one point infecting half the population of the city of Boston. We fought back by trying to infect people with a weakened version of it, long before vaccines existed. An enslaved man named Onesimus is believed to have introduced the concept of smallpox inoculation to North America in 1721 when he told slave owner Cotton Mather that he had undergone it in West Africa. Mather tried to convince Boston doctors to consider inoculating residents during that outbreak, to limited success. One doctor who inoculated 287 patients reported only 2% of them died of smallpox, compared to a 14.8% death rate among the general population.

In 1777, George Washington ordered troops who had not already had the disease to undergo a version of inoculation in which pus from a smallpox sore was introduced into an open cut. Most people who were inoculated developed a mild case of smallpox, then developed natural immunity. Some died, though at a far lower rate compared with other ways of contracting the disease.

Edward Jenner first demonstrated the effectiveness of his newly created smallpox vaccine in England in 1796. Vaccination spread throughout the world, and deaths from smallpox became rarer over time: In a century, smallpox went from being responsible for 1 in 13 deaths in London to about 1 in 100.

But while early vaccines reduced smallpox’s power, it still existed: An outbreak hit New York City in 1947. It demonstrated that the vaccines were not 100% effective in everyone forever: 47-year-old Eugene Le Bar, the first fatality, had a smallpox vaccine scar. Israel Weinstein, the city’s health commissioner, held a news conference urging all New Yorkers to get vaccinated against smallpox, whether for the first time or what we would now call a “booster shot.”

The mayor and President Truman got vaccinated on camera. In less than one month, 6.35 million New Yorkers were vaccinated, in a city of 7.8 million. The final toll of the New York outbreak: 12 cases of smallpox, resulting in two deaths.

Our country’s final outbreak affected eight people in the Rio Grande Valley in 1949.

In 1959, the World Health Organization announced a plan to eradicate smallpox globally with vaccinations. The disease was declared eradicated in 1980.

Of all the diseases our species has tackled, “the only one we’ve ever been really successful to totally eradicating is smallpox,” said Dr. Georges Benjamin, executive director of the American Public Health Assn.

The only remaining smallpox pathogens exist in laboratories.

How it ended: Vaccination

How it started: In 1981, the CDC announced the first cases of what we would later call AIDS.

Roughly half of Americans who contracted human immunodeficiency virus in the early 1980s died of an HIV/AIDS-related condition within two years. Deaths from HIV peaked in the 1990s, with roughly 50,000 in 1995, and have decreased steadily since then. As of 2019, roughly 1.2 million Americans are HIV-positive; there were 5,044 deaths attributed to HIV that year.

The Reagan administration initially didn’t take HIV seriously. The virus spread for years before scientists knew for sure how it was transmitted.

Today, we know how to prevent the spread of HIV, and treatments for it have progressed to the point where early intervention can make the virus completely undetectable in an infected person’s system.

Around 700,000 people in the U.S. have died of HIV-related illnesses in the 40 years since the disease appeared.

How it ended: Endemic

How it started: SARS first appeared in China in 2002 before making its way to the United States and 28 other countries.

Severe acute respiratory syndrome — shortened to SARS in news coverage — is caused by a coronavirus named SARS-CoV, or SARS-associated coronavirus. COVID-19 is caused by a virus so similar that it’s called SARS-CoV-2.

Globally, more than 8,000 people contracted SARS during the outbreak, and 916 died.

One hundred fifteen cases of SARS were suspected in the United States; only eight people had laboratory-confirmed cases of the disease, and none of them died.

Fatality rates from SARS were very low for young people — less than 1% for people under 25 — and up to a more than 50% rate for people over 65. Overall, the case fatality rate was 11%.

Public anxiety was widespread, including in areas unaffected by SARS.

SARS and COVID-19 have a lot in common. But the diseases — and the way the government responded to them — weren’t the same.

The response to SARS was robust and immediate. The WHO issued a global alert about an unknown and severe form of pneumonia in Asia on March 12, 2003. The CDC activated its Emergency Operations Center by March 14, and issued an alert for travelers entering the U.S. from Hong Kong and parts of China the next day. Pandemic planning and guidance went into effect by the end of that month.

“There wasn’t asymptomatic spread,” Benjamin said. “Early on we had a functional test. We had a public health system that was in much better shape than it is today.”

The disease stopped spreading before a vaccine or cure could be created. Scientists knew another coronavirus could emerge that was more contagious. They laid the groundwork for developing the COVID-19 vaccines we have now.

How it ended: Died out after being controlled by public health measures

How it started: From 2014 to 2016, 28,616 people in West Africa had Ebola, and 11,310 died — a 39.5% case fatality rate. Despite widespread fears about it spreading here — including close to 100 tweets from the man who would be president when the COVID-19 pandemic began — only two people contracted Ebola on U.S. soil, and neither died.

So how did we escape Ebola? Unlike COVID, Ebola isn’t transmitted in the air, and there’s no asymptomatic spread. It spreads through the bodily fluids of people actively experiencing symptoms, either directly or through bedding and other objects they’ve touched. If you haven’t been within three feet of a person with Ebola, you have almost no risk of getting it.

Part of the problem in Africa was that families traditionally washed the bodies of the deceased, exposing themselves to infected fluids. And healthcare workers who treated patients without proper protective equipment or awareness of heightened safety procedures were at risk.

Once adequate equipment was delivered to affected areas and precautions were taken by healthcare workers and families of the victims, the disease could be controlled. People needed to temporarily change their behavior to respond to the public health crisis, and they did.

While this particular outbreak ended in 2016, it’s very possible we will see another Ebola event in the future. An Ebola vaccine was approved by the FDA in 2019.

How it ended: Subsided after being controlled by public health measures

Experts say the most likely outcome at this point is that COVID-19 is here to stay.

COVID has a lot going for it, as far as viruses go: Unlike Ebola and SARS, it can be spread by people who don’t realize they have it. Unlike smallpox, it can jump species, infecting animals and then potentially reinfecting us. Unlike polio, one person can unwittingly spread it to a room full of people, and not enough people are willing to get vaccinated at once to stop it in its tracks. It’s less contagious than swine flu, and less deadly than Ebola, landing it in a sort of perverse sweet spot where it infects a lot of people but doesn’t kill enough of them to run out of victims. For many people, it’s mild enough that it convinces others they don’t have to take the disease or precautions against it seriously. No one thought that about smallpox or Ebola.

If someone were designing a virus with the maximum capacity to succeed, it might look a lot like this coronavirus.

So what happens next? In some populations, enough people will get vaccinated to achieve something like herd immunity. In others, it will burn through the population until everyone’s had it, and either achieves naturally gained immunity (which confers less long-term protection than vaccination) or dies. People still die from influenza and HIV in the United States; a disease becoming endemic isn’t exactly a happy ending.

We’re still learning about the Omicron variant. Early reports out of South Africa suggest it may be a more contagious but milder version of the disease, though it’s too early to say for sure. In a perfect world, COVID would go away entirely; with that possibility almost certainly off the table, an attenuated strain that displaces the Delta variant and turns COVID into an illness that rarely requires hospitalization is perhaps the best we can hope for at this point.

How it ends: A combination of vaccine- and naturally gained immunity, attenuation, availability of rapid testing, and improvements in treatment for active cases could turn it into what skeptics wrongly called it to begin with: a bad cold or flu.