Deadly viruses throughout history
From the Ebola to COVID-19, diseases caused by viruses have killed humans throughout history. Viruses are much older than human beings, possibly even older than the first cellular life.
More than 600 viruses that can infect humans have been identified, according to a 2025 Virology report. Of those, several virus types commonly make the news for their widespread impact or unique symptoms.
Technological advances and public health efforts have made many of these viruses less deadly than before. In fact, one of the deadliest viral diseases, smallpox, has been eradicated through mass vaccination campaigns and public health containment efforts.
Viruses vary wildly in severity. Some barely cause symptoms, while others, like COVID-19, have devastating, worldwide effects and earn pandemic status. Read on to learn more about the deadliest viruses to humans.
Measuring virus severity
There are several ways to measure how deadly a virus is. Some viruses don’t infect many people, but have high mortality rates, meaning that they kill a high percentage of people who are infected. Other viruses spread easily and infect many people, but have lower mortality rates.
Mortality rates are a good estimate of how deadly a disease is, but they aren’t always very accurate.
“Sometimes people are infected, but they either have really mild disease so that they don’t even get tested, or they don’t even have any symptoms at all,” says Dr. Nicole Iovine, chief epidemiologist at UF Health Shands Hospital. “Sometimes the mortality rate can be overstated. That’s been said about COVID and about pretty much almost any infection you can name.”
Here are some of the deadliest viruses in history, by case fatality rate, number of people killed or the percentage of the global population that was infected.
Human immunodeficiency virus (HIV)
Human immunodeficiency virus, or HIV, has often been cited as the deadliest virus in human history. The World Health Organization (WHO) estimates that between 35.7 and 51.1 million people have died from HIV. An additional nearly 40 million people are living with HIV currently.
HIV is only passed through the exchange of bodily fluids, but once a person is infected, the HIV virus will remain in the body forever. Acquired immunodeficiency syndrome, or AIDS, is the furthest stage of HIV infection, and causes a person’s immune system to be unable to fend off otherwise low-risk infections, like a normal cold or flu.
Dr. Robert Gallo, who co-discovered the HIV virus and developed the HIV blood test, explains that at first, it was not clear that the cause of this horrible disease was a virus.
This is because HIV is actually a retrovirus, which uses an enzyme to integrate its own DNA into the host cell’s own DNA. When Gallo started looking for the cause of HIV, he believed it may have been a retrovirus. At the time, retroviruses had never been identified in humans.
“In the 1970s, when I started looking for human retroviruses, this was passe,” he says. Others “really felt that this was remote and maybe even impossible that humans were infected by retroviruses.”
Even in the midst of a major breakthrough in the discovery of the virus, which Gallo describes as his “eureka” moment, Gallo and his team were sobered by the severity of the moment.
“We never had any celebration or happiness with HIV,” he says. “Too many problems, too many headaches, too much pressure, too many things that we weren’t prepared for; political and non-political.”
Because of Gallo’s work, decades of supporting research and public health efforts, HIV is now much more survivable than it was when Gallo began researching it. PrEP, which stands for pre-exposure prophylaxis, is now available to help prevent infection in individuals who may be at higher risk.
Ebola and Marburg virus
Some viruses have aggressive symptoms and high mortality rates, including Ebola and Marburg virus. Both of these closely-related viruses are marked by sudden-onset high fevers, liver failure and severe bleeding.
Both have a case fatality rate that averages around 50%, which is extremely high for a virus. In some Ebola outbreaks, however, slightly different versions of the virus can have case fatality rates of up to 90%, according to the WHO.
There is one FDA-approved vaccine that is effective in preventing one of the Ebola-causing viruses, and early medical intervention can help improve survival rates.
The reason why Ebola, with such a high case fatality rate, hasn’t killed more people globally, comes down to how the disease itself progresses, says Iovine. Ebola and Marburg have short incubation periods, meaning that the time between a person getting infected and when they show symptoms is relatively short.
“If something has a short incubation period and it causes the quick onset of severe symptoms, those people typically don’t get on an airplane.” For this reason, she says, Ebola doesn’t easily become a worldwide pandemic.
In addition, both Ebola and the Marburg virus are primarily spread through direct contact with infected blood, body fluids or contaminated objects, not airborne transmission like some other highly contagious diseases. This limited mode of transmission restricts its ability to spread rapidly in the general population.
Rabies
Rabies is a virus that is virtually 100% fatal once symptoms appear, making it by one measurement, the most deadly virus. According to the WHO, the virus causes tens of thousands of deaths annually.
Rabies is transmitted to humans from animals mainly through bites and scratches, when the saliva of an infected animal gets into the open wound, or into a person’s eyes or mouth. Initial symptoms can mimic the flu, with fever, headache and pain or itching at the bite site. As the virus progresses, neurological symptoms like anxiety, confusion, hallucinations, and muscle spasms may appear.
The good news is that a person who believes that they’ve been infected with rabies can be treated with post-exposure prophylaxis, or PEP, which entails a series of shots over a 14-day period. This stops the virus from reaching the central nervous system.
Dog vaccination and other animal vaccination efforts can reduce rabies incidence, as can animal bite prevention efforts.
COVID-19
COVID-19 is the disease caused by the coronavirus SARS-CoV-2. According to the WHO, there have been 760 million cases and 6.9 million COVID-19 deaths recorded since December 2019.
While it isn’t the single deadliest virus in human history, it’s also important to consider the non-fatality impact of the virus. According to the Kaiser Family Foundation, approximately 43 million Americans have had long COVID symptoms, some of which include people who are permanently disabled due to the virus.
The COVID-19 pandemic may not be over yet. While the start of the pandemic has a clear date, experts disagree on the ending. The virus continues to infect people around the world, mutating into new strains that may cause worsened disease in the future.
Vaccination efforts have slowed down the infection rates and mortality, but COVID-19’s total death toll is yet to be determined.
Influenza and avian flu
Influenza, or the flu, causes pandemics every few decades.
The 1918 “Spanish flu,” one of the most severe instances of influenza, is estimated to have infected a third of the world’s population at the time, or about 500 million people, according to the Centers for Disease Control and Prevention (CDC). It’s been called the most severe pandemic in recent history because of its reach. In fact, the 1918 flu caused more casualties of people from the United States than than both World Wars, the Korean War and the Vietnam War combined. Worldwide, the 1918 flu is estimated to have killed about 50 million people.
At the time, there was no flu vaccine available, so preventing the spread of the disease was limited to public health methods like isolation, hygiene and quarantine.
Bird flu, or avian influenza, is another type of influenza virus, but it differs in origin, transmission and potential severity. Though both can cause similar symptoms, bird flu can be more severe and has a higher mortality rate in humans, though it doesn’t spread easily between people.
“What is so concerning about the avian influenza in some instances when people have contracted a particular type of bird flu, the mortality rate is exceedingly high,” Iovine says. “The first very well-reported outbreak of avian influenza occurred in 1996 in China. That outbreak only involved 18 people; however, six of them died.”
Iovine points out that a one-in-three case fatality rate, or 33% fatality rate, for an avian influenza virus is extremely high, given how transmissible respiratory viral infections are as well. For comparison, she notes, COVID-19’s case fatality rate was only about 2% pre-vaccine.
Deadly viruses of the future
Understanding how deadly an avian influenza outbreak could be is a major concern for Iovine. She says that the possibility of a more transmissible version of an avian influenza keeps her up at night.
So why haven’t we experienced that type of pandemic yet? The bird flu strains don’t yet transmit as well as COVID-19 did.
“People who get bird flu tend to get it from an infected animal, which is not always a bird, but often a bird,” she says. “So they’re catching it from another animal, but then they can’t transmit it to another human being. But these viruses mutate all the time,” and at some point, they could acquire that ability.
Additionally, many doctors and researchers have begun to sound the alarm about outbreaks of vaccine-preventable diseases, including measles and polio.
“I am concerned about those sorts of vaccine-preventable diseases,” says Iovine. “It’s just a pity that we have to even be talking about this when we have such effective vaccines.”
Preventing the next pandemic
The work that Gallo is doing now through the Global Virus Network may help us be better prepared for the next pandemic.
“With the help of the Global Virus Network here and the involvement of the USF (University of Southern Florida) with Tampa General Hospital, (we are) putting together a kind of playbook of what should be done (during a pandemic),” he says.
He hopes that this playbook, once distributed, would help other regions know what to do when the next pandemic begins, whenever that might be.
“No one should tell you that they can predict the next pandemic or when it’s going to come,” says Gallo.
Instead of spending time trying to predict when or what the next pandemic may bring, he recommends great public health preparation, and in particular, training virologists, which is a major goal of the Global Virus Network.
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Deadliest Viruses on Earth in the Past, Present and Future originally appeared on usnews.com
Update 06/27/25: This story was previously published at an earlier date and has been updated with new information.
