6 ms·

The idea that it takes significant viral load to initiate infection makes it quite interesting to try and form a mental model of how transmission takes place. F

by zmmmmm 6y ago

The idea that it takes significant viral load to initiate infection makes it quite interesting to try and form a mental model of how transmission takes place. For example, you have a globule of viral particles that float through the air and lodge in the respiratory system. According to the "viral load" theory, this is unlikely to initiate infect by itself. We need repeated doses, possibly over a period of time. You could theorise that the inflation of risk is no more than that from the linear sum of the doses, ie: any given "dose" has the same probability of inducing infection. However the "viral load" idea suggests that multiple exposure is worse than just the sum of independent random events. It suggests there's some sort of interaction whereby multiple doses within a short period of time are especially potent, as if the viral products from independently replicating infections in the respiratory system are able in some way to reinforce each other and make it more likely than two independent chances that an overall infection will take hold. Curious if there is any work in this regard that would elucidate the underpinning process of infection.

IAmEveryone 6y ago
I don't quite understand your logic, but the more common view is rather the opposite: repeated small exposures are the best way to get exposed, if you cannot avoid it completely. The mechanism is essentially variolation: giving your immune system some exposure so the adaptive immune system can start the process of building immunity, but so little that the innate immune system still has a good chance of winning this first round. Then, of course, there's basic mathematics: viruses multiply exponentially. Assuming a single virus particle can theoretically infect you and, at the other side of the spectrum, that getting full-on sneezed on can deliver a billion virus particles, the time difference is enormous: that one virus particle would take 30 viral life cycles to grow to a billion, even if unchecked. At a few hours per generation, this could provide your immune system with a few days to a week of head start.
- JamesBarney 6y ago
  The confusion between you an OP is what you mean by short. He means over minutes, I assume you mean over days.
fierarul 6y ago
I've been trying to wrap my head around the 'viral load' theory too. This goes against the mainstream notion of what getting a virus means. I've never heard before of people getting a worse case of flu because somebody else sneezed harder on them! It makes sense that with an initial small load the immune system might get a chance to wipe out the infection immediately. But I assumed that once infection does happen and cells start mass-producing the virus then it gets pumped into the whole body really fast. Turns out this might not be true and that the immune system ramps up response at the same pace regardless of the infection severity, which seems entirely unexpected?!
- hcknwscommenter 6y ago
  In a cell culture dish, if you hit a bunch of cells with a load of about 1 virus per cell, you get a really low number of infected cells. If you hit a bunch of cells with 10 virus per cell, you get really high infection rates. It is possible a similar thing happens in the body. And yes, the immune system can only ramp up so fast. There is a lot that has to happen between original recognition of the invader to neutralizing antibody production at scale. It's a weeks long process.
  - Gibbon1 6y ago
    Thing to consider the innate immune systems is always at work. Likely if it doesn't get overwhelmed or somehow evaded there is a chance it'll squash an infection by itself.
    - aaronchall 6y ago
      This thread makes the most sense to me. If you watch the videos of the particles people emit when sneezing or talking loudly, you'd be astonished (I was). Apparently these particles can hang in the air for very long periods of time and circulate throughout an enclosed space. It seems to me that the more of these particles you inhale, the more spots in your lungs they could land. If this thread is correct, the infection sites would be somewhat localized, especially to start. A person could potentially have one or two internal infection sites and their immune system respond in plenty time for them to avoid noticing the effects of the virus infections, whereas the same person could get many, many infection sites throughout their lungs, and then eventually be completely unable to breathe as each location slowly spreads to cover a large surface area of the lung. The implications are that anything you can do to reduce your chances of inhaling these particles increases your chances of not getting a noticeable infection. This means avoiding enclosed spaces with others and wearing masks. I wonder if masks will become the new style.
roenxi 6y ago
Maybe; but that theory is a little suspect since presumably this entire pandemic started from a single viron and viruses grow so quickly that a single infected cell can produce ~1,000 new virus particles (dunno how may a coronavirus produces, that figure is something I Googled for HIV). Starting dose does matter but surely people risk infection from even a tiny dose.
- lmm 6y ago
  I thought the theory was that the first infected human acquired it from an infected animal? So it's quite possible that infecting humans requires significant exposure.
- hcknwscommenter 6y ago
  "presumably this entire pandemic started from a single viron" I have no idea where you get this from. It is likely that someone got bit or scratched or sneezed on by a bat or cat of some type at the Wuhan "wet" market. Or they caught it somewhere else from a bat or cat but went to the "wet" market and spread it in the asymptomatic period.
- tonyedgecombe 6y ago
  Perhaps all you need is somebody with a compromised immune system.
lmm 6y ago
> According to the "viral load" theory, this is unlikely to initiate infect by itself. We need repeated doses, possibly over a period of time. I don't think that follows at all. The viral load theory says infection happens when a large quantity of the virus enters your body (implicitly over a short period of time), whether from several sources or from a single concentrated/powerful source. That suggests that e.g. close contact with one infected person for several hours is probably more dangerous than casual contact with several infected people.
- zmmmmm 6y ago
  I guess what makes me feel that doesn't fit perfectly is the "continuous contact for 15 minutes" rule. If straight up load was the main driver then I'd have thought time would be a less important factor. But I can see if you simply assume load is proportionate to time in contact then you can model it as purely a function of total viral load.
01100011 6y ago
My model is: - A virion has to infect a cell before it becomes inactivated. It could encounter something in the intercellular space or extracellular matrix which renders it inactive, or it may be exposed to something in the environment for long enough to become inactive, like a random O3 molecule or hydroxy radical perhaps. - The virion can successfully enter a cell but something can happen to interfere with replication, like a mutation event or some localized cell state, like the cell is preparing for mitosis, apoptosis, etc. - The virion successfully enters a cell but the cell is destroyed by the immune system before significant quantities of virus are produced. I'm just guessing, because I don't have much more than a basic understanding of microbiology. I think it is definitely possible to become infected via a single virion though.
- chadcmulligan 6y ago
  Thats been my assumption - its a race between the virus finding the right spot that allows access to the cell and something else destroying it. Either the corona virus needs a very specific spot to allow access, or there's a number of steps that have to occur before a successful infection. Either case requires a lot of virus particle to infect for the probabilities to be in its favour.
- clairity 6y ago
  you were doing pretty well until that last sentence. you enumerated some of the many difficulties a virion has of infecting you, and then came to a puzzling conclusion that doesn't follow at all from the previous statements. the chance of one virion in the environment infecting you is essentially zero, for the reasons you state as well as many others. you need to accumulate billions of chances for 'essentially zero' to reach a 'miniscule chance', and many orders of magnitude more to reach 'maybe', 'probably', and 'definitely'. infection is unlikely if you don't love sitting directly in the respiratory exhaust of strangers all day.
  - 01100011 6y ago
    My point is that it is theoretically possible but practically impossible. Rare events sometimes happen. With no background in biology, I can't say what the actual probability is. Is the chance of a single virion infecting a cell 1 in a sextillion, or only 1 in a million? In either case, it is still possible, as far as I understand the definition of the word 'possible'.
Izkata 6y ago
Something I learned a month or two ago as others puzzled over this: The human body has two immune systems. The adaptive immune system is the one where you create antibodies to fight against specific pathogens. It takes more energy for your body to do, so it doesn't activate immediately. The innate immune system works generically against a large variety of body invaders. If it succeeds in fighting off a virus, you don't develop antibodies for it. The viral load theory is, by my understanding: * Too small a load, and the innate immune system fights off the virus quickly. You don't get sick. * Cross the threshold where the innate immune system can't handle it - the virus replicates too quickly - and you do get sick, and have to generate antibodies to fight it off effectively. * Past that threshold, the larger the load worse your sickness is going to be and/or the longer your recovery is going to be (all other things equal), because the body still has to ramp up while the virus can start replicating immediately.
- nkurz 6y ago
  Interesting. Does this mean that in the "too small a load" case that you do not develop any immunity to future infection? Do you have any links with more information about this?
  - Izkata 6y ago
    My description above is a bit of a simplification since I'm still picking this knowledge up myself - I have no specific links, it's pretty much what you'd find on Wikipedia or others' comments on here. In particular, one example of something I think I phrased badly above is antibody generation not happening immediately. I remember people saying that getting tested for antibodies right after they recover few to none are found, but a week or two later they start reliably testing positive. This tells me that yes antibodies do start getting created pretty quickly, but takes a while to reach critical mass and become effective (but it doesn't matter because the innate immune system worked effectively enough).

by zmmmmm 6y ago

IAmEveryone 6y ago

I don't quite understand your logic, but the more common view is rather the opposite: repeated small exposures are the best way to get exposed, if you cannot avoid it completely. The mechanism is essentially variolation: giving your immune system some exposure so the adaptive immune system can start the process of building immunity, but so little that the innate immune system still has a good chance of winning this first round. Then, of course, there's basic mathematics: viruses multiply exponentially. Assuming a single virus particle can theoretically infect you and, at the other side of the spectrum, that getting full-on sneezed on can deliver a billion virus particles, the time difference is enormous: that one virus particle would take 30 viral life cycles to grow to a billion, even if unchecked. At a few hours per generation, this could provide your immune system with a few days to a week of head start.

JamesBarney 6y ago
The confusion between you an OP is what you mean by short. He means over minutes, I assume you mean over days.

fierarul 6y ago

I've been trying to wrap my head around the 'viral load' theory too. This goes against the mainstream notion of what getting a virus means. I've never heard before of people getting a worse case of flu because somebody else sneezed harder on them! It makes sense that with an initial small load the immune system might get a chance to wipe out the infection immediately. But I assumed that once infection does happen and cells start mass-producing the virus then it gets pumped into the whole body really fast. Turns out this might not be true and that the immune system ramps up response at the same pace regardless of the infection severity, which seems entirely unexpected?!

hcknwscommenter 6y ago
In a cell culture dish, if you hit a bunch of cells with a load of about 1 virus per cell, you get a really low number of infected cells. If you hit a bunch of cells with 10 virus per cell, you get really high infection rates. It is possible a similar thing happens in the body. And yes, the immune system can only ramp up so fast. There is a lot that has to happen between original recognition of the invader to neutralizing antibody production at scale. It's a weeks long process.
- Gibbon1 6y ago
  Thing to consider the innate immune systems is always at work. Likely if it doesn't get overwhelmed or somehow evaded there is a chance it'll squash an infection by itself.
  - aaronchall 6y ago
    This thread makes the most sense to me. If you watch the videos of the particles people emit when sneezing or talking loudly, you'd be astonished (I was). Apparently these particles can hang in the air for very long periods of time and circulate throughout an enclosed space. It seems to me that the more of these particles you inhale, the more spots in your lungs they could land. If this thread is correct, the infection sites would be somewhat localized, especially to start. A person could potentially have one or two internal infection sites and their immune system respond in plenty time for them to avoid noticing the effects of the virus infections, whereas the same person could get many, many infection sites throughout their lungs, and then eventually be completely unable to breathe as each location slowly spreads to cover a large surface area of the lung. The implications are that anything you can do to reduce your chances of inhaling these particles increases your chances of not getting a noticeable infection. This means avoiding enclosed spaces with others and wearing masks. I wonder if masks will become the new style.

roenxi 6y ago

Maybe; but that theory is a little suspect since presumably this entire pandemic started from a single viron and viruses grow so quickly that a single infected cell can produce ~1,000 new virus particles (dunno how may a coronavirus produces, that figure is something I Googled for HIV). Starting dose does matter but surely people risk infection from even a tiny dose.

lmm 6y ago
I thought the theory was that the first infected human acquired it from an infected animal? So it's quite possible that infecting humans requires significant exposure.
hcknwscommenter 6y ago
"presumably this entire pandemic started from a single viron" I have no idea where you get this from. It is likely that someone got bit or scratched or sneezed on by a bat or cat of some type at the Wuhan "wet" market. Or they caught it somewhere else from a bat or cat but went to the "wet" market and spread it in the asymptomatic period.
tonyedgecombe 6y ago
Perhaps all you need is somebody with a compromised immune system.

lmm 6y ago

> According to the "viral load" theory, this is unlikely to initiate infect by itself. We need repeated doses, possibly over a period of time. I don't think that follows at all. The viral load theory says infection happens when a large quantity of the virus enters your body (implicitly over a short period of time), whether from several sources or from a single concentrated/powerful source. That suggests that e.g. close contact with one infected person for several hours is probably more dangerous than casual contact with several infected people.

zmmmmm 6y ago
I guess what makes me feel that doesn't fit perfectly is the "continuous contact for 15 minutes" rule. If straight up load was the main driver then I'd have thought time would be a less important factor. But I can see if you simply assume load is proportionate to time in contact then you can model it as purely a function of total viral load.

01100011 6y ago

My model is: - A virion has to infect a cell before it becomes inactivated. It could encounter something in the intercellular space or extracellular matrix which renders it inactive, or it may be exposed to something in the environment for long enough to become inactive, like a random O3 molecule or hydroxy radical perhaps. - The virion can successfully enter a cell but something can happen to interfere with replication, like a mutation event or some localized cell state, like the cell is preparing for mitosis, apoptosis, etc. - The virion successfully enters a cell but the cell is destroyed by the immune system before significant quantities of virus are produced. I'm just guessing, because I don't have much more than a basic understanding of microbiology. I think it is definitely possible to become infected via a single virion though.

chadcmulligan 6y ago
Thats been my assumption - its a race between the virus finding the right spot that allows access to the cell and something else destroying it. Either the corona virus needs a very specific spot to allow access, or there's a number of steps that have to occur before a successful infection. Either case requires a lot of virus particle to infect for the probabilities to be in its favour.
clairity 6y ago
you were doing pretty well until that last sentence. you enumerated some of the many difficulties a virion has of infecting you, and then came to a puzzling conclusion that doesn't follow at all from the previous statements. the chance of one virion in the environment infecting you is essentially zero, for the reasons you state as well as many others. you need to accumulate billions of chances for 'essentially zero' to reach a 'miniscule chance', and many orders of magnitude more to reach 'maybe', 'probably', and 'definitely'. infection is unlikely if you don't love sitting directly in the respiratory exhaust of strangers all day.
- 01100011 6y ago
  My point is that it is theoretically possible but practically impossible. Rare events sometimes happen. With no background in biology, I can't say what the actual probability is. Is the chance of a single virion infecting a cell 1 in a sextillion, or only 1 in a million? In either case, it is still possible, as far as I understand the definition of the word 'possible'.

Izkata 6y ago

Something I learned a month or two ago as others puzzled over this: The human body has two immune systems. The adaptive immune system is the one where you create antibodies to fight against specific pathogens. It takes more energy for your body to do, so it doesn't activate immediately. The innate immune system works generically against a large variety of body invaders. If it succeeds in fighting off a virus, you don't develop antibodies for it. The viral load theory is, by my understanding: * Too small a load, and the innate immune system fights off the virus quickly. You don't get sick. * Cross the threshold where the innate immune system can't handle it - the virus replicates too quickly - and you do get sick, and have to generate antibodies to fight it off effectively. * Past that threshold, the larger the load worse your sickness is going to be and/or the longer your recovery is going to be (all other things equal), because the body still has to ramp up while the virus can start replicating immediately.

nkurz 6y ago
Interesting. Does this mean that in the "too small a load" case that you do not develop any immunity to future infection? Do you have any links with more information about this?
- Izkata 6y ago
  My description above is a bit of a simplification since I'm still picking this knowledge up myself - I have no specific links, it's pretty much what you'd find on Wikipedia or others' comments on here. In particular, one example of something I think I phrased badly above is antibody generation not happening immediately. I remember people saying that getting tested for antibodies right after they recover few to none are found, but a week or two later they start reliably testing positive. This tells me that yes antibodies do start getting created pretty quickly, but takes a while to reach critical mass and become effective (but it doesn't matter because the innate immune system worked effectively enough).