9 Scariest Plagues In Games, Ranked

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.

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The Best Games About Diseases And Outbreaks, RankedIn 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.

9 GUILT: Trauma Center

Trauma Center: Under the Knife could be famous for using the – at the time – newly released Nintendo DS’s stylus to its full advantage, but is instead famous for introducing a series of neigh-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.

8 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.

7 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.

6 Cordyceps Fungus: 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.

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The Most Dangerous Types Of Video Game Zombies, RankedThe 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.

5 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.

4 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.

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.

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Games To Play If You Like A Plague Tale: InnocenceThe Bite might not pack as much punch as some of the made-up diseases on this list, 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.

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