The deadliest viruses in history

Humans have been fighting viruses long before our species had even evolved into its modern form. For some viral diseases, vaccines and antiviral drugs have allowed us to keep infections from spreading widely, and have helped sick people recover. For one disease — smallpox — we've been able to eradicate it, ridding the world of new cases. 

However, we're still a long way from defeating viruses. Several viruses have jumped from animals to humans in recent decades, causing large outbreaks and killing thousands of people. The viral strain that drove the 2014-2016 Ebola outbreak in West Africa kills up to 90% of the people it infects, making it the most lethal member of the Ebola family.

Related: 20 of the worst epidemics and pandemics in history

But there are other viruses out there that are equally deadly, and some that are even deadlier. Some viruses, including the novel coronavirus currently driving outbreaks around the globe, have lower fatality rates, but still pose a serious threat to public health as we don't yet have the means to combat them. 

Here are the 12 worst killers, based on the likelihood that a person will die if they are infected with one of them, the sheer numbers of people they have killed, and whether they represent a growing threat.

Marburg virus

The Marburg virus causes hemorrhagic fever in humans and non-human primates. (Image credit: ROGER HARRIS/SCIENCE PHOTO LIBRARY via Getty Images)

According to the World Health Organization (WHO), the Marburg virus was first identified by scientists in 1967, when small outbreaks occurred among lab workers in Germany who were exposed to infected monkeys imported from Uganda. Marburg virus symptoms are similar to Ebola in that both viruses can cause hemorrhagic fever, meaning that infected people develop high fevers, and bleeding throughout the body that can lead to shock, organ failure and death, according to Mayo Clinic.

The case fatality rate in the first outbreak (1967) was 24%, but it was 83% in the 1998-2000 outbreak in the Democratic Republic of Congo, and 100% in the 2017 outbreak in Uganda, according to the WHO. 

The first known Marburg virus outbreak in West Africa was confirmed in August 2021. The case was a male from south-western Guinea, who developed a fever, headache, fatigue, abdominal pain and gingival hemorrhage. This outbreak lasted for six weeks and, while there were 170 high-risk contacts, only one case was confirmed, according to Reuters.

Ebola virus

Microscopic image of an Ebola virus (Image credit: Shutterstock)

In 1976, the first known Ebola outbreaks in humans struck simultaneously in the Republic of the Sudan and the Democratic Republic of Congo. Ebola is spread through contact with blood or other body fluids, or tissue from infected people or animals. The known strains vary dramatically in their deadliness, Elke Muhlberger, an Ebola virus expert and associate professor of microbiology at Boston University, told Live Science.

One strain, Ebola Reston, doesn't even make people sick, according to Essential Human Virology (2016). But for the Bundibugyo strain, the fatality rate is up to 50%, and it is up to 71% for the Sudan strain.

The outbreak underway in West Africa began in early 2014, and is the largest and most complex outbreak of the disease to date, according to the WHO. 

In December 2020, the Ervebo vaccine was approved by the U.S. Food and Drug Administration. This vaccine helps to defend against the Zaire ebola virus and a global stockpile became available from January 2021. 

Rabies

This image of the rabies virus, taken through an electron microscope, shows particles of the virus itself, as well as the round structures called Negri bodies, which contain viral proteins. (Image credit: CDC/ Dr. Fred Murphy)

Although rabies vaccines for pets, which were introduced in the 1920s, helped to make the disease extremely rare in the developed world, this condition remains a serious problem in India and parts of Africa.

Infection from this virus develops after a bite or scratch from an infected animal. This can result in damage to the brain and nerves. Once symptoms begin to show, death almost always follows, according to the National Health Service (NHS).

"It destroys the brain, it's a really, really bad disease," Muhlberger said. "We have a vaccine against rabies, and we have antibodies that work against rabies, so if someone gets bitten by a rabid animal we can treat this person," she said.

However, she said, "if you don't get treatment, there's a 100% possibility you will die."

HIV

This scanning electron microscope image shows the human immunodeficiency virus (HIV, in green), infecting a cell.  (Image credit: Cynthia Goldsmith, Centers for Disease Control and Prevention)

In the modern world, the deadliest virus of all may be HIV. "It is still the one that is the biggest killer," said Dr. Amesh Adalja, an infectious disease physician and spokesman for the Infectious Disease Society of America.

An estimated 32 million people have died from HIV since the disease was first recognized in the early 1980s. "The infectious disease that takes the biggest toll on mankind right now is HIV," Adalja said.

Powerful antiviral drugs have made it possible for people to live for years with HIV. But the disease continues to devastate many low- and middle-income countries, where 95% of new HIV infections occur. 

Nearly 1 in every 25 adults within the WHO African region is HIV-positive, meaning that there are over two-thirds of the people living with HIV worldwide, according to the WHO. In 2020, there were 680,000 HIV-related deaths worldwide.  

Smallpox

Illustration of a smallpox virus (Image credit: Keystone-France/Gamma-Keystone via Getty Images)

In 1980, the World Health Assembly declared the world free of smallpox. But before that, humans battled smallpox for thousands of years, and the disease killed about 1 in 3 of those it infected, according to the BBC. It left survivors with deep, permanent scars and, often, blindness.

In populations outside of Europe, where people had little contact with the virus before visitors brought it to their regions, mortality rates were much higher. For example, historians estimate that smallpox, which was introduced by European explorers, killed 90% of the native population of the Americas. In the 20th century alone, smallpox killed 300 million people, the BBC reported.

"It was something that had a huge burden on the planet, not just death but also blindness, and that's what spurred the campaign to eradicate from the Earth," Adalja said.

Hantavirus

The hantavirus caused an outbreak in November 1993, in the Four Corners region of the U.S.  (Image credit: Getty)

Hantavirus pulmonary syndrome (HPS) first gained wide attention in the U.S. in 1993, according to the Centers for Disease Control and Prevention (CDC). A healthy, young Navajo man and his fiancée living in the Four Corners area of the United States died within days of developing shortness of breath. A few months later, health authorities isolated hantavirus from a deer mouse living in the home of one of the infected people. More than 600 people in the U.S. have now contracted HPS, and 36% have died from the disease, according to the CDC.

The virus is not transmitted from one person to another, rather, people contract the disease from exposure to the droppings of infected mice.

Previously, a different hantavirus caused an outbreak in the early 1950s, during the Korean War, according to a 2010 paper in the journal Clinical Microbiology Reviews. More than 3,000 United Nations troops became infected, and about 12% of them died.

While the virus was new to Western medicine when it was discovered in the U.S., researchers realized later that Navajo medical traditions describe a similar illness, and linked the disease to mice.

Influenza

Women working for the Red Cross make masks during the Spanish flu pandemic in 1918 (Image credit: Bettmann Archive/Getty Images)

During a typical flu season, up to 650,000 people worldwide will die from the illness, according to WHO. But occasionally, when a new flu strain emerges, a pandemic results in a faster spread of disease and, often, higher mortality rates.

The most deadly flu pandemic, sometimes called the Spanish flu, began in 1918 and sickened up to 40% of the world's population, killing an estimated 50 million people, according to CDC.

"I think that it is possible that something like the 1918 flu outbreak could occur again," Muhlberger said. "If a new influenza strain found its way in the human population, and could be transmitted easily between humans, and caused severe illness, we would have a big problem."

Dengue

Dengue viruses are transmitted to humans by the bite of an infected mosquito. (Image credit: Getty)

Dengue virus first appeared in the 1950s in the Philippines and Thailand and has since spread throughout the tropical and subtropical regions of the globe, according to Clinical Microbiology Reviews. Up to 40% of the world's population now lives in areas where dengue is endemic and the disease, according to the journal Nature — with the mosquitoes that carry it — is likely to spread farther as the world warms.

According to WHO, dengue infects 100 to 400 million people a year although dengue fever has a lower mortality rate than some other viruses, at around 1%, the virus can cause an Ebola-like disease called dengue hemorrhagic fever, which has a mortality rate of 20% if left untreated. "We really need to think more about dengue virus because it is a real threat to us," Muhlberger said. 

A vaccine for Dengue was approved in 2019 by the U.S. Food and Drug Administration for use in children 9-16 years old living in areas where dengue is common and with a confirmed history of virus infection, according to the CDC. In some countries, an approved vaccine is available for those 9-45 years old, but again, recipients must have contracted a confirmed case of dengue in the past. Those who have not caught the virus before could be put at risk of developing severe dengue if given the vaccine.   

Rotavirus

Rotaviruses particles are shown here under a very high magnification of 455,882X. (Image credit: CDC/ Dr. Erskine L. Palmer)

Two vaccines are now available to protect children from rotavirus, the leading cause of severe diarrheal illness among babies and young children. The virus can spread rapidly, through what researchers call the fecal-oral route (meaning that small particles of feces end up being consumed).

Although children in the developed world rarely die from rotavirus infection, the disease is a killer in the developing world, where rehydration treatments are not widely available.

The WHO estimates that worldwide, there are more than 25 million outpatient visits and two million hospitalizations each year due to rotavirus infections. Countries that have introduced the vaccine have reported sharp declines in rotavirus hospitalizations and deaths. 

SARS-CoV

(Image credit: CDC/ Dr. Fred Murphy)

The virus that causes severe acute respiratory syndrome, or SARS, was first identified in 2003 during an outbreak in China, according to the WHO. The virus likely emerged in bats initially, then hopped into nocturnal mammals called civets before finally infecting humans, according to the Journal of Virology. After triggering an outbreak in China, SARS spread to 26 countries around the world, infecting more than 8000 people and killing more than 770 over the course of several months, according to History.com. 

The disease causes fever, chills and body aches, and often progresses to pneumonia, a severe condition in which the lungs become inflamed and fill with pus. SARS has an estimated mortality rate of 9.6%, however, no new cases of SARS have been reported since the early 2000s, according to the CDC.  

SARS-CoV-2

This transmission electron microscope image shows SARS-CoV-2– the virus that causes COVID-19– isolated from a patient in the US.  (Image credit: NIAID-RML)

SARS-CoV-2 belongs to the same large family of viruses as SARS-CoV, known as coronaviruses, and was first identified in December 2019 in the Chinese city of Wuhan. The virus may have originated in bats and passed through an intermediate animal before infecting people, according to Nature. 

The initial outbreak prompted an extensive quarantine of Wuhan and nearby cities, restrictions on travel to and from affected countries and a worldwide effort to develop diagnostics, treatments and vaccines. Since its appearance, the virus has caused over five million deaths worldwide, according to Reuters.

The disease caused by SARS-CoV-2, called COVID-19, poses a higher risk to people who have underlying health conditions, according to WHO. Common symptoms include fever, cough, loss of taste or smell and shortness of breath and more serious symptoms include breathing difficulties, chest pain and loss of mobility. 

On Aug. 23 2021 the U.S. Food and Drug Administration approved the first COVID-19 vaccine, called Pfizer-BioNTech. In December 2020, this vaccine became the first to be approved after a large clinical trial, according to Nature.

MERS-CoV

An illustration of the MERS virus, a type of coronavirus. (Image credit: Shutterstock)

The virus that causes Middle East respiratory syndrome, or MERS, sparked an outbreak in Saudi Arabia in 2012 and another in South Korea in 2015. The MERS virus belongs to the same family of viruses as SARS-CoV and SARS-CoV-2. According to WHO, the disease infected camels before passing into humans and can trigger a fever, coughing and shortness of breath in infected people. 

MERS, which is most common in the Middle East, often progresses to severe pneumonia and has an estimated mortality rate of around 35%. There is no vaccine available to prevent this disease, according to the NHS. The best way to reduce the chances of infection is to wash hands regularly, avoid contact with camels and not consume products containing raw animal milk.