COVID-19 has us all thinking about public health, but looking back, there have been many pandemics before, and we persist in spite of them.

As of April 15, the Centers for Disease Control (CDC) has reported 605,390 cases of COVID-19 in the United States. These have occurred across all 50 states and have resulted in 24,582 deaths. We are all feeling the effects of the pandemic. Schools are closed, businesses have shut their doors, and nobody knows what’s coming next.

While COVID-19 is one of the largest pandemics of the 21st century, you might be wondering how it stacks up to the terrible pandemics of the past. Let’s look at the 10 worst pandemics in human history.

10. The Great Plague of Milan: Italy (1629-1631)

Death Toll: 1 million

The Great Plague of Milan was a series of outbreaks of the bubonic plague (featured later in this list) that happened between 1629 and 1631. While numerous plague outbreaks occurred in Europe during the 17th century, this was one of the worst. The disease is thought to have been brought into the city of Mantua by French and German soldiers in the Thirty Years’ War, and it spread from there.

While the plague ravaged the country, some towns were spared. Ferrara in northern Italy did not experience a single death from the plague because it implemented strict border controls, sanitation laws, and personal hygiene practices. It even built state-funded plague hospitals outside the city’s walls to prevent larger outbreaks from single cases (although the disease was thought to be caused by corrupted air rather than a bacterium).

This is a rare example of effective disease control in history and is eerily reminiscent of what the world is going through with COVID-19. The Great Plague of Milan was so deadly, it is thought to be a major contributor to the decline in power of the Republic of Venice, which had risen to prominence during the Renaissance.

9. Hong Kong Flu: China (1968-1970)

Death Toll: 1-4 million

Influenza A pandemics have occurred multiple times throughout history when new, deadly strains of the influenza A virus evolved. The adaptability of the flu is why flu shots change each year.

The Hong Kong flu (H3N2) originated in China and was the second-worst flu pandemic of the 20th century, behind the famous 1918 Spanish flu featured later on this list. While this pandemic was much less deadly than the one in 1918, the virus was especially infectious, contributing to its spread around the world. Within two weeks, the virus had moved throughout southeast Asia, and within two months it had made its way across the ocean into the Americas, later spreading to Europe, Africa, and Australia.

Although we are no longer in the midst of a flu pandemic, H3N2 has stuck around as one strain of seasonal flu we see every year.

8. Cholera: India/Indonesia (1817-Present)

Death Toll: 95,000/year (more than 1 million historical total)

The cholera pandemic consists of a series of smaller pandemics that have been occurring on and off since 1817. We are now within the seventh cholera pandemic. Six of the seven major cholera pandemics have originated in India. However, the current pandemic originated in Indonesia. Trade and military routes over the years have contributed to spreading this disease throughout the world.

Although cholera today does not majorly affect developed nations due to their access to clean water, the disease thrives in developing areas that lack reliable water sources and solid sanitation systems.

Cholera is caused by the bacterium Vibrio cholerae. The virus causes severe diarrhea and is spread through raw sewage, which creates a vicious cycle of infection in areas experiencing an outbreak.

7. Antonine Plague: Rome (165-180)

Death Toll: 5 million

This ancient pandemic swept through the Roman Empire in the late second century. While it’s not certain which disease caused this pandemic, it’s thought to be measles, smallpox, or a combination of both.

At that time, the Roman Empire spread far beyond Italy into the Mediterranean region, as well as parts of Africa and Asia. Active trade and military movements contributed to the disease’s quick spread.

The plague was so deadly that today it is thought to contribute to the eventual fall of the Roman Empire, making this plague one of the major events of Western history.

6. Third Plague: China (1885 – 1950s)

Death Toll: 12 million

The Third Plague refers to the most recent pandemic outbreak of bubonic plague, which began in 1885 in the Chinese province of Yunnan. This pandemic lasted many years. By the beginning of the 20th century, there were cases on all six inhabited continents, although its most devastating effects were in China and India.

Interestingly, this pandemic led to much quality scientific research about this and the previous plagues. Because this outbreak occurred in the modern era (at least relative to the original Black Death), scientists had access to better research tools and methods. For example, studying this plague led to the discovery of the bacteria responsible for historical plagues, Yersinia pestis.

5. HIV/AIDS: Sub-Saharan Africa (1981-Present)

Death Toll: 25-35 million

Human immunodeficiency virus (HIV) first emerged in the Democratic Republic of the Congo in the late 1970s. The accepted hypothesis is that the virus jumped from chimps to humans through bush hunting in central Africa.

The virus causes acquired immunodeficiency syndrome (AIDS), a disease in which the immune system gives out, causing people to die not from HIV itself, but from a variety of secondary infections such as pneumonia.

Unlike many of the pandemics on this list, HIV is not transmitted from casual contact. HIV can spread through blood, sexual transmission, and from mother to child through birth or breastfeeding. In the United States, the virus ravaged the gay community and IV drug users.

Historically, the prevalence of the virus among disenfranchised groups contributed to the explosion of the pandemic because it was not as quickly addressed as other pandemics, including modern ones such as COVID-19. Today, HIV can be well managed in developed nations so it doesn’t progress to AIDS, but AIDS is still incredibly deadly in developing nations without access to adequate health care and preventative measures.

4. Plague of Justinian: Eastern Roman Empire (541-750)

Death Toll: 30-50 million

The Plague of Justinian is the first known outbreak of the plague that would later become the famous Black Death, as well as the Third Plague in the late 19th century. The bacterium, Yersinia pestis, is thought to have originated in Africa and then migrated to Europe through fleas on rats.

By the year 541, the plague was killing up to 10,000 people a day. There were so many victims that citizens of Constantinople could not keep up with burying them, so bodies were crammed into buildings or simply left in the open.

While the bulk of the deaths occurred between 541 and 542, this pandemic was stubborn, and did not fade entirely until 750. Until then, there were periodic outbreaks throughout the Mediterranean world.

3. Spanish Flu: Unknown (1918-1920)

Death Toll: 40-50 million

A number of deadly flu outbreaks have occurred over the years, but the 1918 Spanish flu is among the worst in history. Despite the common name of the pandemic, scientists are not entirely sure where the virus originated, though they do know it was caused by an H1N1 virus (similar to swine flu) that originated in birds.

It is estimated that 500 million people, or one-third of the global population at the time, were infected with the virus. Like all flus, this virus was easily transmitted from person to person, causing it to spread rapidly throughout the world. Another deadly characteristic of this flu was that it had high mortality in a variety of age groups, not just the very young and old we expect to have weaker immune systems.

While scientists have synthesized the 1918 flu virus in the lab, they are still not certain exactly why this particular flu was so deadly. It remains one of the great medical mysteries of all time.

2. New World Smallpox: Americas (1520 – 1600s)

Death Toll: 56 million

The Columbian Exchange, or the exchange of animals and plants between Europe and the Americas as a result of the voyages of Christopher Columbus, led to one of the great world pandemics of all time. Because native populations of South America had none of the immunities to Eurasian diseases that Europeans had developed over the centuries, they were highly susceptible to these diseases upon first contact.

Among the worst of these diseases was smallpox, caused by the variola virus. The disease swept through South and Central America, as well as the Caribbean, killing millions.

Smallpox remained a problematic disease for centuries, with the last natural outbreak occurring in the United States in 1949. However, nowadays people do not get smallpox. Smallpox remains the only disease that has been successfully eradicated worldwide as a result of intense international vaccination and isolation efforts between the 1960s and 1980s.

1. The Black Death: Europe and Asia (1347-1351)

Death Toll: 200 million

By far the deadliest pandemic of all time, the Black Death radically shaped the course of human history, plunging Europe into the Dark Ages. The bacterium that caused the plague, Yersinia pestis, is thought to have originated in Asia more than 2,000 years ago and eventually moved into Europe through trade ships.

The bacteria moved quickly through rats and fleas feeding on the rats. When infected rats died, leaving the fleas hungry, fleas switched to feeding on human blood, spreading the plague they had picked up from the rodents. Trade ships moving these rats around only perpetuated the spread throughout Europe and Asia.

In addition to its high death toll, what made the Black Death so remarkable was the speed with which it occurred. For example, at the start of the pandemic, 60 percent of Florence’s population died within a few months.

Today, bubonic plague is much rarer. However, well after the Black Death, the plague continued to cause periodic pandemics throughout Europe and Asia, including the Great Plague of Milan.

Final Thoughts

COVID-19 has us all thinking about public health, but looking back, there have been many pandemics before, and we persist in spite of them. While the devastation is real, eventually humans manage to press on. It’s easy to forget that after the Dark Ages following the Black Death, Europe entered its Renaissance, one of the great periods of creativity and ingenuity in human history.

For now, we are social distancing, isolating, and worrying about ourselves, our families, and communities. But it certainly won’t last forever. History tells us we don’t get to choose what happens to us or what period of history we are born in. All we can do is prepare and persist.