Specifically, this is not a question asking how easily a virus spread in a population (airborne, asymptomatic spread, etc), but regarding the mechanism or the "havoc" it wreaks once inside a person's body.

Edit: The question is based on the assumption that, once a human body can readily recognize the virus signature and starts flooding the blood with anti bodies, the virus won't be a problem.

  • Today, We have no prior immunity to COVID; 400 years ago, Americans had no prior immunity to smallpox either.
  • Both virus can be effectively combatted once the body has immunity (recognization and anitbody production).
  • Yet, smallpox is so much more lethal and its damage horrifying.
  • 2
    $\begingroup$ I would suggest not asking multiple questions at once as it runs a risk of getting flagged as too broad. In each point you have made some assertions - please add references for the same. e.g. for point 2 add references for the paper/book/article which details which cell types are affected by covid/measles etc. For the third point you have your own hunch - have you done any research for the same? If yes, add references; if no, mention that. Finally please complete the tour from your profile to understand what qualifies as a good question/answer. $\endgroup$
    – Roni Saiba
    Dec 7, 2020 at 16:22

1 Answer 1


I think this is an interesting question, and I've been struggling to put together a good answer to it for a while. Unfortunately, everything I came up with just boils down to "some viruses are more deadly because they kill more cells faster" which is pretty circular. A detailed understanding at the subcellular level of what happens during virus infections doesn't exist.

It's instructive here to look at the evolutionary pressures on human-infecting viruses. SARS-1 was about 10x as deadly as SARS-2, but it was contained quickly, while SARS-2 is on track to infect a substantial portion of all humans on the planet. SARS-2 is more successful because of, not in spite of, its lower lethality. Because many infections are asymptomatic, the infection can't easily be contained. If we look at things this way, the asymptomatic infections are the ones that go "according to plan" for the virus, and the severe cases and deaths are unwanted collateral damage. Severe cases of COVID are associated with the presence of viral RNA in the blood. But SARS-2 primarily enters new hosts through droplets expelled from infected hosts' respiratory systems. Any viral activity outside of the respiratory system cannot produce these droplets, and is therefore "wasted effort". This is similar to polio, which causes no symptoms when it transmits successfully by replicating in intestinal cells, but causes paralysis when it gets stuck in the dead end of its host's nervous system.

So, if viruses are most successful when they cause no disease, shouldn't they all quickly evolve into harmless versions? They don't because the "sweet spot" of asymptomatic transmission is the unstable result of an immune response that is just effective enough. If a virus fights the immune system either too hard or not hard enough, the infection will end too fast to spread effectively; due to the death of the host or the virus, respectively. Similarly, if a virus is too "aggressive" in entering cells it will damage tissues that don't lead to transmission or new infections, but if it is not aggressive enough it will not be enter those tissues it needs to make, e.g. respiratory droplets carrying new virus in the case of SARS. Since a lethal disease still results in some transmission but complete suppression by the immune system doesn't, it's more evolutionarily favorable for viruses to err on the size of causing worse disease.

Edits for changes in the question:

I think the differences between covid-19 and smallpox are a bit misleading. The big differences between the two diseases is that, while the human populations most affected by smallpox were naive to the virus, the virus was not naive to them. Smallpox is believed to have been infecting humans since at least the 3rd century BCE. It had a lot of time to evolve tricks to defeat the human immune system. And as a dsDNA virus with a 186,000 base pair genome, it had plenty of space to store those tricks. For comparison, SARS-CoV-2 has a 30 kb RNA genome, and poliovirus has a 7.5 kb RNA genome. However, Herpesviruses have been infecting humans since before humans were human, have large genomes, but only cause disease when the immune system is suppressed or nonfunctional. In those cases, however, it is quite effective at spreading throughout the host and can kill. So we see that herpesviruses also rely on the immune system of the host to stay in their sweet spot, they just have a different strategy than smallpox. Since smallpox has been exterminated and herpesvirus is in nearly every human on earth, we can say the mild strategy is the unequivocal winner, at least for now.

  • $\begingroup$ This is true. There were mysterious burst of horrible disease burst into the scene and just killed droves in short period of time from the well-known Athens, Justinian to less well known ones as late as the (1800s?). These disease don't last long. And modern version of the disease we are dealing with today like Cholera are less lethal as well. There is this tendency to converge to the sweet spot. This "meta" is indeed very interesting, thank you for mentioning it. However, my question is really about the details inside one individual, not the meta. $\endgroup$
    – eliu
    Dec 10, 2020 at 15:16
  • $\begingroup$ Yes, unfortunately, how viruses interact with cells and the immune system is mostly only known in broad strokes. $\endgroup$
    – timeskull
    Dec 10, 2020 at 15:22
  • $\begingroup$ actually, if you want to focus on a comparison between covid and smallpox, there are a few things we can say. I'll edit them in. $\endgroup$
    – timeskull
    Dec 10, 2020 at 17:22
  • $\begingroup$ I have some somewhat-informed hunches. My original question before edit focused on "attacking of the adaptive immune system", and the depth the attack goes, do you just infect front line workers and presenters? or do you attack the antibody factory?. Also I don't believe in "killing body cells" is the cause of death, more like "causing disorder". Septic shock for example, it pretty much immune system overreacting and killing the host instead of what baterias are doing. $\endgroup$
    – eliu
    Dec 10, 2020 at 17:55
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    $\begingroup$ It might have something to do with what particular cells a virus can attack. E.g. just abou everyone gets cold viruses, yet they seem to only attack the respiratory system, and mostly cause a week or so of mild discomfort. HIV attacks the immune system, and can proliferate there for years before causing accute symptoms. A lot seems to depend on the specific method a virus uses to enter cells. The COVID virus latches on to specific receptor molecules, the much more deadly Ebola virus uses a "non-specific engulfing process called macropinocytosis". (Not enough room for links :-() $\endgroup$
    – jamesqf
    Dec 10, 2020 at 19:00

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