The Deadliest Diseases In Video Games

Key Takeaways

• Diseases in video games drive narrative and player motivation.
• Some games use diseases as a status effect, while others create horrifying plagues.
• Different fictional diseases in video games can instill fear and create unique gameplay experiences.

Diseases are one way that video games can push their narrative forward. Whether it’s giving your character motivation to move on in the plot or explaining an enormous change in the world they’re a useful tool in any developer’s belt.

In some games, disease is just one more thing in a long line of status effects that your character can heal. Others, though, like to ratchet up the horror, and create plagues that’ll give you nightmares. They’re fictional, sure, but the way games portray them is real enough for you to want to avoid them at all costs.

Updated on November 11, 2024 by Mackenzee Hardyk: Many games still utilize the fear of getting sick and being infected with something you cannot cure. It creates a heightened sense of awareness and fear for your character who is inevitably coming into contact with such bacteria. With that in mind, we’ve decided to update this article with a few new entries with other forms of plagues and pestilence for you to enjoy.

13

GUILT

Trauma Center

Trauma Center: Under the Knife could be famous for using the Nintendo DS’ stylus to its full advantage, but is instead famous for introducing a series of nigh-sentient diseases which are straight out of your childhood nightmares. These diseases, collectively called GUILT, are part parasite, part toxin, and part convoluted terrorist plot to destroy all of humanity.

Fortunately for the world, you are a doctor with magical powers derived from the ancient Greek god of medicine and an unlimited number of retries to get the touch controls right. Its manifestations are terrifying, but with a little divine help, the world-ending GUILT is nothing more than a footnote on humanity’s continued rise.

12

Radical-6

Virtue’s Last Reward

The Zero Escape series’ world-ending bug seems innocuous enough when compared to most viruses. There’s no hemorrhaging or even a cough. Instead, the virus slows down your brain function, causing you to perceive time as slower than it actually is.

While this might not seem like a big deal, the slowdown quickly overwhelms your senses and makes it unbearable to live. This means that most people who contract Radical-6 don’t die from the virus directly. Instead, they take their own lives. It’s dark.

11

The Gray Death

Deus Ex

You might think that cybernetic enhancements in Deus Ex are a fun way of getting good at something without having to practice, and for the most part, you’d be right. But while you can use them to make you sneakier than Corvo Attano and run faster than Usain Bolt, you’re also inviting the Gray Death into your body.

Originally created in a lab as a population control, the gray death infects people with mechanical augmentations, with limited vaccines only given to the people who can pay the exorbitant price for one. Sometimes, the price is a whole lot of money, but sometimes you have to give a world-spanning secret society your allegiance to stay safe. Maybe the real plague here is capitalism.

10

Hooligan Virus

Days Gone

The Hooligan virus was made in a lab in Oregon, though unfortunately, a curious intern got himself unknowingly infected with it and within two weeks it had spread to the entire world. It also infects animals, causing them to become not only stronger but feral.

The Hooligan turned everyone under 12, almost everyone over 60, and anyone with a weak immune system into freakers or zombies. They would become cannibalistic and violent, and the state of the person would depend on what they turned into. For example, a child would turn into a Newt.

9

Biophage

The Callisto Protocol

On the moon of Callisto, a colony of miners encountered a massive alien, and of course, the alien was killed. Scientists studied it and discovered the Biophage Pathogen, and they then began experimenting with it.

The scientists turned people into violent mutations, letting them get infected and change despite the consequences. It was the result of Callisto becoming overrun with these mutations, killing almost everyone on the moon. Biophage literally means life devourer or devourer of life. It’s definitely not something you would want to come in contact with.

8

Cordyceps Fungus

The Last Of Us

Everybody has their own zombie survival plan these days, but the Cordyceps fungus from The Last of Us throws them all out the window. Sure, you know to remove the head or destroy the brain, but now you have to avoid barely visible fungal spores, and sneak past mushroom-faced clickers? Holing up in your local mall doesn’t seem so great anymore after you discover that the zombies are seriously fast and can sense movement.

The scariest thing about Cordyceps, though, is that it’s sort of real. One species of Cordyceps is known to infect the brains of certain insects, and while it doesn’t infect humans, that doesn’t really make the idea any better.

7

Scarlet Rot

Elden Ring

Sure, you can technically walk through a lake of Scarlet Rot in Elden Ring without too many ill effects, but what the scarlet rot did to an entire corner of the Lands Between is nothing short of horrifying. Not only does it devastate the land of Caelid, it seems to corrupt anything it touches, causing some victims to descend into a mindless fury. Even the demigods aren’t immune.

You can live with the rot through magical means, like Malenia and Millicent, but getting there can’t be pleasant, especially since it seems to liquify limbs first, before going to the core.

6

E48K15

One Chance

One Chance is a flash game where you only get one chance to play it, so you only have one opportunity to get a somewhat desirable outcome. E48K15 came about from a group of scientists who made a cure for cancer, which the cure attacks cancer cells.

Unfortunately, the cure they created did not just attack cancer cells after it was released. It became airborne and started to attack every living cell. You only have six days to save the world, as the ‘cure’ is wiping out every living thing on Earth.

5

Kharaa

Subnautica

Most of the time that you’re exploring an alien world covered in water, you’re not concerned too much with getting sick. You’re probably focused on more pressing matters, like not getting eaten by the enormous leviathan class sea creatures that lurk in the depths.

But disease is exactly what you’ll find once you dive into the waters of Subnautica. Kharaa is an ancient organism, predating humanity, that apparently killed over 143 billion members of the Precursor race and seems at home in any organism that it touches. Thankfully, there is a cure, but the body count alone should give you pause on your next trip to the beach.

4

Manhattan Virus

Crysis 2

The Manhattan Virus is described as an engineered bioweapon that was created by the Ceph, who are a group of advanced alien species who appear to be determined to wipe out humanity. The Ceph released the Manhattan in New York and was spread through spores.

There are multiple stages of the Manhattan Virus, at first it was not obvious who is infected, but eventually, the virus began to attack internal organs and caused tumor-like masses to quickly form. People who are infected with the virus will die, there was no curing it as it rapidly evolved.

3

The Bite

A Plague Tale

The Bite is what folks in A Plague Tale call the Black Death, which, if you need a reminder, was really, really bad news. Not content to just show the devastation of a disease that killed over a third of Europe in four years, Asobo Studios re-imagined the plague as something even more sinister, spread by hordes of vicious rats driven by a dark power.

The Bite might not pack as much punch as some of the made-up diseases in other games, but it doesn’t need to. An entire continent is still getting over its collective trauma from the plague. Sometimes, just mentioning it is enough.

2

Genophage

Mass Effect

Probably one of the cruelest tricks in the Council’s war arsenal, Mass Effect’s Genophage made it almost impossible for the Krogan race to reproduce.

Sure, the Krogans warred without ceasing, but the Genophage essentially condemned an entire species to death without actually killing them. The scariest thing about the Genophage isn’t what it does to a single person, but that it throws an entire species into an existential crisis.

1

Just All Of This

Resident Evil

A lot of diseases in games cause people to turn into zombies, but very few of them are as absolutely wicked as the series of viruses that Umbrella Corporation rolls out in Resident Evil from day one.

Sure, they’ll make your run-of-the-mill zombies, but they’ll also turn you into a hulking monstrosity with multiple limbs or give you a huge blade for an arm, which would be pretty cool if it didn’t make it impossible to pick up a glass of water. The many viruses in the Resident Evil series have an X factor (or maybe a T factor) that makes their existence truly alarming.