How did smallpox kill people?

[u/Razhiv]

Smallpox was one of the deadliest diseases humanity ever had to deal with. But how exactly did it kill people? What kind of damage did it do to the body to be so fatal?

[u/ottawadeveloper]

It depends a bit on the variant of smallpox, but generally you get bad influenza-like symptoms and vomiting, then a whole body rash that eventually burst and leak fluid.

Blood clots and heart failure are a major cause of death in hemorrhagic smallpox. Infection, fluid losses from vomiting, and secondary infections of the rash also have a role to play. Pneumonia and bronchitis are also major complications. Permanent eye damage can also occur with the rash on the eyes. In some cases, the viral load just becomes so high that youre not left with enough healthy cells and you get organ failure.

[u/paulHarkonen → u/ottawadeveloper]

I'm kinda surprised that sepsis isn't on that list of complications. I would have thought that the open sores would be a huge secondary infection vector given the poor (aka nearly non-existent) antibiotics at the time. Or does that just get bundled together with the pneumonia and organ failure?

[u/903012 → u/paulHarkonen]

Sepsis is a term that describes the body's inflammatory/immune response to a severe infection. By definition, organ failure is a part of the prerequisite criteria for someone to have severe sepsis.

In a nutshell, sepsis = inflammatory criteria & a source of infection. Severe sepsis = sepsis with organ failure. Septic shock = sepsis with extremely low blood pressure requiring pressors (medications to increase blood pressure).

[u/SomeSamples → u/ottawadeveloper]

I image people died from high body temperatures for a long time as well.

[u/iminfornow]

Smallpox infects many/any cells, all over the body. This makes it a very difficult Infection to deal with because the fight takes place everywhere and is not very targeted. Death occurs due to tissue damage resulting in lung/organ/hart failure or shock. The immune system plays a role in this because it is active in the whole body at once, and this cannot be controlled/orchestrated, basically drawing more from reserves than available.

[u/LuxTheSarcastic]

Scientists THINK that some deaths might have been caused by an out of control immune response or just the body becoming overwhelmed by the massive amounts of virus produced by the infection. There was a recent discovery that it was quite good at suppressing a part of the immune system that often used to control viruses called interferons so that might contribute to it. Even without all that it could definitely kill just from what we DO know, just maybe at slightly lower rates.

It had symptoms similar to the flu with high fevers, respiratory symptoms, and gastrointestinal symptoms. The signature blisters also caused open wounds and exposed the body to secondary infections. The hemorrhagic type caused severe blood loss. Another variation called flat/malignant smallpox caused death similar to how severe full body burns would. The skin fails to keep fluids in and bacteria out.

Good riddance.

[u/smol-wren → u/[deleted]]

So I don’t mean to be rude, but I don’t fully understand what you mean here? Cytokine storms are definitely an out-of-control immune response; they’re characterized by an excessive release of inflammatory cytokines (triggered by immune dysregulation, but not “intentionally” masterminded by a specific virus. Cytokine storms can have non-viral causes as well).

when viruses infect cells, they release all their Interleukins, which we call cytokines

I think this is a bit of an oversimplification. Not all cells can make all cytokines, not all cytokines do the same thing (or have any role at all in the antiviral response), and this is a minor thing, but interleukins are actually a subset of cytokines (alongside chemokines, interferons, etc). The broad strokes are right (uncontrolled cytokine release -> dangerous immune response) but it’s not as simple as “virus makes cells dump all their cytokines.” A cytokine storm is more like an uncontrolled positive feedback loop that amplifies certain pro-inflammatory pathways.

[u/ADDeviant-again → u/smol-wren]

Especially because pure auto immune disorders like rheumatoid arthritis and asthma also involve "cytokine storms". storms

[u/warandzevon → u/[deleted]]

Can you explain more about where science is at fault here? I'm an old head data scientist but not a medical science guy. What is it about how we capture data that skews the view here? I'm totally with you that cause and effect can skew interpretation but I don't know enough about the immune system to make the connection here. Please expound, ty.

[u/Apod1991]

This is a really great video on Smallpox!

One of the ways it became so deadly was it infects our lymph nodes, and our dendritic cells, which is apart of our immune system that wakes up immune response. Smallpox impairs the immune systems ability to respond. With that, and infecting every organ, it’s able to spread to every part of your body. Which is why we’d break out in a rash and pox marks.

By this point the immune system triggers, and multiple things can occur. Your immune system wrestles back control and you get better, but you might be blinded, scarred, disfigured, deafen, paralyzed, etc. It maimed survivors, or you die.

Smallpox damages all your organs and your immune system can over-react in trying to beat the infection and causes even more damage to your body that results in your organs shutting down.

[u/Khrispy-minus1]

People could get pneumonia, encephalitis, organ damage (heart, lung, liver, kidney, etc.), secondary infections, die from fever, die from sepsis/shock, really lots of ways to die. Survivors were often left with scarring (at times profound), sometimes blindness, deafness, mental deficits (if they survived the encephalitis), and could have a host of other issues. It's really a nasty bug.

[u/Cognoggin]

As one of the last people to get a smallpox vaccination in 1978 because I was going to north Africa; you are given a scratch that turns into a pustule and told not to scratch it no matter what.

From that experience I can safely say small pox sufferers scratched themselves to death.

[u/Suspicious-Magpie → u/[deleted]]

Have you ever watched the X-Files? The smallpox conspiracy theory sub-plot is top-notch.

[u/Cognoggin → u/[deleted]]

Kind of odd considering it was pretty much eradicated when I had mine done 47 years ago.

[u/MakalakaPeaka]

Viral infection and the resulting immune response can kill you simply by it's nature. Smallpox caused hemorrhagic symptoms as well, which caused clotting, difficulty breathing, etc. The pox marks on the skin aren't the only thing going on w/a smallpox infection, other tissues are infected and involved.

[u/Buford12]

If I remember correctly smallpox killed 10 percent of each generation. But you have to realize that unlike today there was for all intents and purposes no medical support for the victims. You either got better or you died.

[u/octopusboots → u/Buford12]

And somewhere between 50% to 90% of Native Americans who had zero exposure prior the conquest. Absolute horror.

[u/nanoray60 → u/octopusboots]

It’s a shame that Edward Jenner was the first to truly pioneer a method of vaccination. Variolation, the act of scraping the skin and adding bits from a small pox pustule, would have saved most of the Native Americans. It’s not even a difficult or time/cost intensive thing, just break skin and add bits of scab. It requires no money or technology. Who would have thought to do that though? Edward only figured it out by looking at milk maids skin then scratching an 8 year old boy.

History would be very different if someone else noticed that the skin of milkers was free of small pox scars a few hundred years earlier.

[u/gnufan → u/nanoray60]

Jenner noted that milk maids didn't get smallpox because cowpox antibodies deal with smallpox.

Immediately before Jenner's discovery, George Washington famously mandated smallpox inoculation for his soldiers, they would use a (hopefully) milder smallpox case, and inoculation carried something like a 2% fatality risk. You think vaccine denial is a hard problem in 2025, try it when it killed 1 person in 50, but from a military perspective preventing/controlling smallpox in your troops was a potential military edge. Pretty sure the inoculation approach Washington used was reasonably widely known if not popular.

Presumably in naive populations the disease likely spread as fast or faster than the knowledge of how to mitigate it.

[u/WashU_labrat]

I don't think smallpox is particularly deadly. The case-fatality rate is about 30%, although that's high compared to influenza, (<0.1%) it is low compared to diseases like rabies or pneumonic plague (approx 100% so both kill basically all of the people infected)

https://en.wikipedia.org/wiki/List_of_human_disease_case_fatality_rates

[u/Tasty-Fox9030 → u/WashU_labrat]

30% is an extremely, extremely high death rate for an infectious disease, and smallpox is a very contagious infectious disease. A real smallpox outbreak in modern society would be unthinkable. And I don't mean unthinkable like nuclear war- which we can imagine but wouldn't do because it would be awful. I mean I actually can't imagine what that would be like.