Viral Dose

If starting out with a high viral dose makes a difference, that must play out pretty rapidly, since an infected cell tends to produce somewhere between many and a shitload of new virions.  Influenza A and B produce 500-100 in  chicken egg cells,  HIV produces 1000-3000, SIV produces 40,000-60,000.

Influenza can go from infecting a cell to releasing those 500-1000 new copies in six hours.

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83 Responses to Viral Dose

  1. The Big Red Scary says:

    “If starting out with a high viral dose makes a difference, that must play out pretty rapidly”

    If we very naively imagine that your and my virus populations are both growing logistically at a high rate k with some carrying capacity K, then indeed our virus populations will rapidly have about the same size. Is something like this what is being suggested here?

    (As a epidemiological nai”f, I have no idea how (un)realistic a logistic model is for the spread of an infection within an individual. I’m just trying to understand gcochran’s logic here.)

    Ultimately, the relevance of viral dose is an empirical question, about which a quick search shows that some work has been done, and it seems that it does matter for some strains of influenza more than for others.

  2. szopeno says:

    Could someone with actual knowledge explain if I was wrong? I was thinking it was question of probability game with two outcomes: probability of infection and second, damage before response of organism kicks in.

    I mean by that, first, just by common reason, it can’t be that’s enough for virus to get into your lungs, because we would all be sick in the same time all the time. So viruses must pass many barriers, I guess, before they finally they can start replicating. By this naïve logic, even one extremely lucky virus could start an infection, but on average you would have to get some minimal number of viruses to have a reasonable chance to infect.

    Second, again by completely naïve logic, if you have one place of infection, it will cause less damage that multiple places. I mean, if you would throw sparks at a forest, then more sparks == more potential fires, and more potential fires == more damage before fire control kicks in. So more viral load: more probability it would start infection in many separate places, causing more damage.

    • protokol2020 says:

      Your logic isn’t that naive, at all. Not for my taste, anyway.
      The math which follows this logic and describes everything is quite trickier.
      But this “viral load theory” explains so much. For example. Why don’t mosquitos transmit HIV? The answer, in the light of this, is – but they do! Only not enough of viruses are carried over to the next human. So, there might be a few AIDS patients infected by a mosquito. Might be none yet.

      R0 is always some increasing function of the number of viruses deployed. Everything else being equal. Always.

      • reziac says:

        I’d guess it’s also related to how fast the virus replicates — slower needs more particles to infect, or something like that, since there’s more time for the immune system to get in gear.

        For contrast, canine parvovirus can infect with as few as SIX particles, and in puppies can progress to fatal in 72 hours (with mortality up to 91%).

      • thatchop says:

        Malaria is transmitted to humans through Mosquito saliva, not regurgitated blood. Mosquitoes aren’t in the habit of spitting hard-won meals back into the next victim, backwash is bad for business

  3. brendan r says:

    But what fraction of those copies are functional? Papers like “Most Influenza A Virions Fail To Express at Least One Essential Viral Protein” claim that “up to 90% of IAV-infected cells fail to release infectious progeny”.

    • saintonge235 says:

      I’ve seen the same figure in John M. Barry’s The Great Influenza. He also says that in human respiratory tract cells, the number of virions produced per infected cell runs 1,000-10,000, so the 90% defective doesn’t much matter.

      The only place I can see virus load mattering is in immune system response time. A low initial load may give the body extra time to isolate the infected areas, release interferons, and start destroying the infected cells and released virions.

      • DevOps Dad says:

        And of course, the future coronavirus vaccine will likely combine a mutated virus low initial load and be introduced through the skin, avoiding human respiratory tract cells.

        In the coming months will those desperate to return to work, self inoculate by introducing the coronavirus through a scratch?

  4. James Thompson says:

    Usually there is a dose-response relationship. Vaccination could be conceived as a guaranteed minimal dose exposure, so small that it gives away the enemy’s tricks without letting the castle fall.

  5. jb says:

    One infected cell may produce 1000 viruses, but that doesn’t logically imply that they all successfully infect other cells. Most could end up somewhere in the body where they can’t do any harm, and eventually just fall apart. I think you need to know what R0 is for infected cells; i.e., how many new cells does each infected cell infect. Maybe rather than 1000 it’s only something like 20 or 40. And as with R0 in people, that could vary with circumstances (where the infected cell is in the body) and behavior (whether the body has started to react to the infection). So if cell R0 = 20 and it takes 6 hours for the virus to reproduce, the difference between an initial dose of 1000 and a dose of 160,000,000 (= 1000 * 20^(24/6)) could equal a full day’s progression of the infection.

    The thing is, the progression of the disease isn’t instantaneous. Something must be happening between day 1 when you can start to feel it coming on and day 7 when you call the ambulance, and I would assume that among other things that something includes an increase in viral load (which in any case has to stop increasing exponentially fairly quickly, because math). So it doesn’t strike me as implausible that a small initial dose could make a difference. Even if it gives the body just one day’s jump on the virus, that could be quite significant.

    • jb says:

      I’ll add that I recently saw a very striking photo (can’t find it, sorry) showing a single cell with a horde of viral particles stuck all over it, like ticks on a moose. The surface of a vulnerable cell is like flypaper for viruses, trapping many when one would be sufficient. That would also have the effect of reducing cell R0.

      • jb says:

        Ah, here’s a photo comparable to the one I was talking about. There are literally hundreds of viruses stuck to a single cell! If this is at all typical (and given that nearby cells are the ones most likely to be infected, why wouldn’t it be?), it could easily be the case that an infected cell that produces thousands of viral particles might end up infecting only tens of new cells. That would certainly be consistent with the common experience of an illness taking days to reach its peak.

        (Interestingly, the NYT paywall doesn’t seem to block photos!)

  6. Ultracrepidarian says:

    If I told you a man took one bullet, you’ need more information to guess his fate. If I told you he took 100 bullets, there’s no need for further inquiry.

  7. Smithie says:

    I’ve been thinking about viral dose. Kind of a science fiction idea: What would happen if someone with COVID-19 sneezed in your face, and you immediately took a nebulizer out of your pocket, filled with flu in stasis, and took a huff of flu, at a greater viral dose than COVID-19?

    I’m not so naive as to think that no cells would be infected with COVID-19, but I wonder if you would “get” the flu, and not “get” COVID-19. Or at least get a much milder course.

    But I believe I already got the flu this year, so I’m out. Any volunteers?

    • reziac says:

      There’s no rule that says you can’t have two viral diseases at the same time, especially unrelated viruses. (Frex, in the early days of the parvo epidemic, puppies would get corona, then parvo a week later.)

  8. Really is remarkable that a concept like ‘viral dose’ is not better understood. This seems like an area of biology that should have been studied exhaustively fifty years ago. One can only assume that as infectious diseases have not been a major problem in the west for many decades, that nobody of any significant intellect has deigned to work in this field for a long time. Should be quite interesting to read about the advances in immunology that come about now it’s set to become the hot new field in biology.

  9. Pablo says:

    How about, if you have a few viruses your white cells can kill them, if you have a lot some will escape?

    • j says:

      Hospital and health personnel appear to die at a much higher rate than their general age group. Is that an artifact of the media? Is an effect to exposure to larger virus doses? They have access to privileged care yet their death rate is higher?

  10. Martin says:

    It’s pretty well-established that dose makes a big difference in pneumonic anthrax, a disease that has some parallels to COVID. Granted, those are spores and not viruses…

  11. Peripatetic Commenter says:

    One of our defenses against Influenza is secreting sialic acids in our mucus.

    That allows us to prevent lots of them getting to cells.

    Perhaps we will see (or have seen) the rise of people who also express the ACE2 receptor proteins in their mucus as well.

  12. gothamette says:

    How is it some 80% get sick and need no hospitalization? Viral dose? Better innate immune response? Better adaptive immune response?

    Inquiring minds want to know!

    • reziac says:

      Judging by the symptom sets, I would bet money you could plot nice parallel lines among risk factors, degree of illness, and degree of T3 (thyroid) suppression, or perhaps more accurately elevation of ReverseT3, which would explain the pre-pneumonia shortness of breath.

      • gothamette says:

        “and degree of T3 (thyroid) suppression,”

        I have Hashimoto’s. IRL it makes zero difference in my life. I just take a pill the size of a rice grain or a lentil, and that’s that. But what if I got COVID??

  13. JRM says:

    The immune system has an exponential function, also.

  14. catte says:

    This is a somewhat elementary question about serum therapy: once the foreign antibodies are inside the bloodstream, can the immune system start copying them for itself straightaway? Or does it just decay away with some half life, like any other medication, and it takes the ordinary amount of time for the immune system to be able to independently produce the antibodies?

  15. dearieme says:

    Italy still puzzles me. Now I read:

    “If the monitoring of the … European death toll does not show any excess mortality during the 2019-2020 season, it is nevertheless true that a local increase is present in northern Italy. In the city of Bergamo for example, 652 deaths (all causes of death included) were reported between January 1st and March 21st of this year versus 386 in the same period of 2017, during the last bigger flu wave.

    An interesting fact is that in the same period the city of Milano has recorded 3,283 deaths this year versus 3,792 in 2017. Obviously, further analysis of the demographic data and of local factors will be needed.”

    • The nationwide mortality numbers for week 12 in Italy are public, and they’re through the roof. I don’t know what’s going on in Milan specifically, but Northern Italy as a whole was a hell hole. And I’m pretty sure MUCH more people died in week 14, so that graph will be interesting to see.

      Click to access SISMG_sintesi_2020w12.pdf

    • Just saying says:

      One interesting limitation of the excess deaths statistic:

      In some areas in the US where the stay at home order preceded a large COVID wave, excess deaths fell significantly, since accidents and crime were reduced, due to everyone staying at home. California reported a 50% decline on traffic accidents.

      So it might be necessary to use a more fine tuned statistic, that excluded some kinds of deaths

      • j says:

        The demographic impact of COVID19 is nil. Paradoxically, its psychological and economic impact is tremendous and probably, lasting. We are doing something wrong.

  16. dave chamberlin says:

    Unknown factors we don’t yet understand play large roles in whether a person gets hospitalized or worse because of contracting Covid19. An example, BMI body mass index, if you are truly skinny with very little body fat you have a very small chance of getting a severe case of Covid19. I can see why, but i don’t don’t know if i’m right. A cell gets raided by the virus and it wants to make a huge number of copies, but it can’t, no extra stored energy in the cell. I applaud arguably wrong’s efforts to make a prediction model but I think it is premature, way to many factors are unknown and widely variable at this point. I expect third world dirt poor countries with a low average age and a high percentage of the population malnourished because of poverty will skirt this pandemic with minor effects. But i defer to others who are able to look at greater detail than i can.

    • gothamette says:

      Women seem to have better immune system than men. But that much better? I’m puzzled.

      • dave chamberlin says:

        Everyone is puzzled by this virus. Huge variations in how hard it hits people in multiple factors that don’t yet make sense. Biology is stunningly complex and we humans are flat over confident in how much control and understanding we have of the world around us. We will box this off eventually with a vaccine and forget about all that, until the next time.

        • Steve D says:

          What do you mean “everyone is puzzled by this virus? Tons of people have been saying the hysteria promoted by you people is insane. That it was ridiculous to take those initial parameters out of Wuhan and act like it was a straight line calculation.

          And anyone who tried to point this out was called a goddamn collaborator by people like you. A little humility would be nice.

          • dave chamberlin says:

            Do you honestly think we should have pretended this virus didn’t exist and just keep up with our normal lives as much as we could? just everybody get it all at once and get it over with? Hmmm. Lots and lots of people dying in their homes because the hospitals are full. But life goes on normally, except for the smell. Oh wait a moment, everyone caught this at once, meaning social structure broke down for a while. What no groceries, no fundamental services, that will go over great in our densely populated cities, everyone will just get along and share wont they. Gee Steve, maybe you haven’t thought this out completely…again.

          • Give me some history on what “you people” and “people like you” means with respect to Mr Chamberlain. I don’t keep a notebook of all the commenters here. I can’t tell from the information here if Mr. Chamberlain is deserving of criticism or Steve D is ranting about imagined critics.

      • Steve D says:

        Well as you said in one of your frenzies a while back, some people just can’t learn. Look in the mirror for an example. You crashed the whole goddamn economy over your fever dream.

        • gothamette says:

          I can’t remember saying that, but I’m happy that I have a fan who hangs onto my every word.

          Now go back to your cave and pleasure yourself. Your bat cave.

        • Maciano says:

          I think it’s guys like you, Steve, who need to take some chill pills and some humility lessons.

          People have been warning for this SARS outbreak for a long while, while morons were probably still talking about the goddamned flu. These just-the-flu morons switched their opposition against serious measures to bitching about saving the economy. Had these just-the-flu-guys stopped being wise-asses and a little more alarmist in january, we could have stopped the outbreak with a global travel ban against China. Funny how you never see people talking about that.

          Do you think alarmist wanted lockdowns or depression?

          No: that’s why we were alarmist early and clearly.

          Thing is, sadly, we’re talking about a serious pandemic. There’s a lot we don’t know. It seems like we have SARS on the loose — not a variant, but a successor of the same thing. It’s now more contagious, yet less lethal. Do you get that?

          I’m getting fed up with wise-asses who have been wrong all the way up to the quadrupling of deaths in every city or area where this bug has been allowed to run rampant. There are nursing homes where 30-50% of occupants died of COVID19. I kind of care tbh. Do you just glaze over, cover your eyes and go to your silent place to imagine all those nasty facts away.

          Yes, right now the deaths are mostly concentrated in older and/or weaker people. Do they not count? I guess not. I’m betting if the deaths were concentrated in children, gays or bloodgroup B types, would you also not care? Go back to work and infect away!

          But let’s say the old and weak really don’t count and we all move on, do you want this virus to genuinely become like the flu, visiting us every dark winter and eventually evolve into something that will really kill millions. Apparently so!

          • gothamette says:

            I agree w/you about calling it SARS2.

            And you’re right about this: “These just-the-flu morons switched their opposition against serious measures to bitching about saving the economy. ”

            I hadn’t quite put those together.

            It’s funny how concerned they are about the economy. Normally they say liberal capitalism is the most robust system ever designed by man. But it turns out to be pretty fragile, in their minds.

        • Bert says:

          Before SARS2 became widespread in the U.S. I sent a plan to all the Republican Senators and Legislators whom I believed would be influential. I personally contacted my Republican county commissioner and asked him to pass the plan on up the line. I posted the plan on Sailer’s blog at Unz Review (a total Hail Mary because that website is worthless). The plan called for immediate legally enforced sequestration of persons 58 and older together with logistic and financial support for those sequestered persons. It called for military personnel to live onsite at nursing homes etc. and provide care to residents. It called for mass testing and legally enforced mask wearing in public; I didn’t know at the time that the Federal government could neither test nor supply masks. It envisioned letting younger people continue normal life, including sustaining as much of the economy as could be done without spending by seniors, so that over time some herd immunity would be developed and so that methods of treatment could be worked out in a calm fashion. Well, pieces of the plan were adopted here and there but it was not embraced early on by politicians (when it would have worked) because they preferentially listened to uninformed, silly people like you who said SARS2 was a hoax. And therefore the virus spread and we got a crashed economy. People like you are the ones at fault because politicians know you spoke for many of your age group. I’ve seen how selfish much of the under 40 people are and, having seen that, I don’t really give a damn about your self-inflicted economic pain. As they say sarcastically in Portuguese: “Bem feito.”

          • gothamette says:

            Bert –

            Good plan. Let me add a few details.

            Cut off all flights from any country with an outbreak – that would include Italy, UK, Germany, as of Feb 1, 2020.

            Quarantine NY State.

            Have food shipped into the state (and the city) by the military.

            Confine EVERYONE at home. Test. Allow people to pick up essentials at central supply depots.

            This would have saved lives.

            We would not be seeing the huge racial disparities in CFR. The largest plurality in NYC is Hispanics (as I predicted) because of their job profile.

            Cuomo ordered all “non-essential” people to stay home on March 20. Hispanics and blacks are heavily overrepped in essential services.

            This is something that Mr. Sailer over at Unz doesn’t seem to want to admit with his obsession about skiiers and golfers and partiers, which anyone can see, duh.

            But this could not be, because what passes for a left in this country wouldn’t have allowed it, and what passes for the right would never have considered it.

            • Bert says:

              Your final paragraph nailed it. One might have supposed that the collaboration of a few dozen persons on the internet could have crystallized a plan that would have avoided the current fiasco, and that the Federal government would have seized the initiative to implement a plausible plan. But the only real cooperation that was manifest was among hospital staffs, those admirable people whose current workday is the equivalent of charging a machine gun nest. Now we know how things will go if Yellowstone blows or a Carrington event occurs.

    • dearieme says:

      Again and again I’ve seen data that is claimed to show that the fatter are at more risk but which omit the control of how many people in each age group are fat anyway.

      • dave chamberlin says:

        But that has been isolated. People of the same age with different BMI’s have been compared and the fatsos are way worse worse off.

        • dearieme says:

          I’d be surprised if that weren’t true. My complaint is that the numbers are never presented so that I can see for myself. Why? The incorrigible laziness of journalists? Even amateur journalists online?

    • reziac says:

      Thyroid status. See my remarks above (condensed for television).

    • GAGCAT says:

      Low BMI seems to work but re bidy fat, women have higher body fat for the same BMI and overall population I think but men die at 3x the rate.

    • gothamette says:

      Ventilators may be doing more harm than good:

      Click to access EVMS_Critical_Care_COVID-19_Protocol.pdf

  17. Just saying says:

    When I was looking into the evidence regarding whether or not viral dose matters, there was a study somewhere that said people with a mild case still had a period where they have a lot of the virus in their system.

    So if viral dose does matter, the mechanism might not be as simple as having low amounts of virus in your system the whole time.

    But then there was also quite a bit to suggest that infectious dose might matter. Maybe it’s just getting a head start on learning to fight the virus off, or maybe it’s something more complex.

    There was also some suggestion that cumulative exposure might be hurting health care professionals. But if they already have a lot of virus in their system from their first dose, why would it matter if they got some from another source? I can think of possible answers, but it’s speculative.

    I’d like to look at other viruses that have been studied more, where the literature says there is a clear relationship between viral dose and disease severity.

  18. jay wall says:

    I have a question for all of you who know more about immunology than I do:
    I am about 99+% sure that I had the Covid-19 about 3 weeks ago; and even though I am in a “high-risk” group (75 y.o. male), my case was super-mild. In thinking back and trying to remember when I might have been exposed to the covid-19, I am pretty sure that I was in the middle of a major hay fever attack right around the time when I was exposed.

    So, I am wondering whether the hay fever might have given me partial protection from the covid-19. I can think of two possible mechanisms: (a) My immune system would have already been on red-alert because of the hay fever; and/or (b) The nasal congestion from the hay fever might have kept the covid-19 trapped in my upper respiratory system for a few days, giving me a change to produce antibodies before it got down to the lungs. Does either of those theories make sense?

    FWIW, my only covid-19 symptom that lasted for a long time (almost 2 weeks) was the total loss of sense of smell; all the other symptoms (fever, chest pain, etc.) disappeared in less than 2 days.

    • GAGCAT says:

      Have you had a serum test to confirm the diagnosis?

      I don’t know you but as a guess at greater than 1% probability you lost your sense of taste to zinc tablets or psychsomatically and had a panic attack.

  19. tc says:

    The IHME model has been updated again. Projected deaths for the USA through Aug 4 has been reduced to 60,000.

    • dave chamberlin says:

      Prediction models are interesting but so variable because of rapidly changing and unknown variables that I have little faith in them. 538 has a good article explaining how difficult Covid19 is to predict.

      I will briefly discuss variables that illustrate this. 4 weeks after social distancing rules are put into place and followed by a scared public that obeys these orders death rates drop dramatically. This makes sense, that is how long it takes for an initial infection to progress to death. Now we are seeing the effect of a flattened death rate. Prediction models cannot predict whatsoever what will happen or when it will happen when these strict social distancing methods are relaxed. Secondly these models have minimal understanding of multiple key variables that greatly influence the spread of Covid19. Age, body mass index, weather, population density, autocracy of government, incompetence of government, mutational change, anyone of these factors can greatly change the outcome. My conclusion is no conclusion at this point, basically a huge variation on possible outcomes. Bill Gates whom I respect on these issues, brilliant guy whom has studied possible pandemics for years says we need to shut down the economy for an additional 6 to 10 weeks. I seriously doubt Trump is going to let that happen.

      • Lowe says:

        I checked earlier today, and Google says the total US death count is 12k.

        That is a small number. It looks like the flu, really. Maybe it would have been a lot worse had everything not been shut down, of course.

        But you know what could not be worse right now? The unemployment rate. Six to ten more weeks of this and who knows what will happen.

        • Closer to 15,000 now. The great majority of US deaths have occurred in just the last week. Only a tiny percentage of the population has gotten it so far.

        • dave chamberlin says:

          When you compare it to the flu, all you are succeeding at is convincing everybody you are ignorant. Maybe you want to come back under another name and don’t say that again.

          • gothamette says:


            This article mentions mutations. “Kind of boring.”

          • Lowe says:

            I guess WordPress ate my reply to you, dave. Anyway I am glad you are confident it is not the flu, but that does not impact the death toll or whether it justifies putting millions of poor people out of work, and keeping them there. Which we have done in a couple weeks.

            In my comment I allowed for the possibility that all the measures taken have been necessary. I don’t know. But I experience serious doubts looking at the death figures and projections, the current one being 60k in the US. If six to ten more weeks of this does not cause you pause, that is crazy.

        • gothamette says:

          One to ignore.

        • gothamette says:

          Hey, Lowe: do you carry a DNI and a DNR? Because I really think you should.

      • Peripatetic Commenter says:

        Well, I guess 538 would know how hard things are to predict given their prediction in 2016.

        • dave chamberlin says:

          A different animal. 538 badly predicted the 2016 election, giving Trump only a 25% chance of winning. Which still was pretty high, I mean a 1 in 4 chance isn’t that rare. Cochran called it, I sure didn’t. I have looked more closely at why the pollsters fucked up and it’s interesting. Pollsters can’t call people at home, they have to call them on cell phones. Pollsters say they have accounted for this but guess what, they haven’t. Only people that care a lot about politics answer the pollsters questions. In the 2016 election guess what what happened. People that barely cared about voting and wouldn’t bother to answer a pollsters questions were overwhelmingly for Trump. Hence the 538 screw up. Diversion. scuze me Greg.

          • jb says:

            Every time a pollster calls me (and they always call on my home phone) I give them all the the time they want, because I want to influence the poll results. The people making the calls are always so grateful! They might be on the phone all day and only find five people willing to spend 10 minutes answering questions.

            I don’t think 538 screwed up on the 2016 election at all. The odds they gave Trump were much higher than what he was getting from the rest of the MSM, and the election really was a very close thing that could have gone either way. 25% was actually a pretty good call, and I respect them for it.

            • dave chamberlin says:

              Me too, their prediction models are an accumulation of multiple other polls and Nate Silver and company are some sharp folks.

  20. gkai says:

    Off-topic: there are more and more mentions of plasma-transfusion therapy (plasma from recovered patient is injected into patients suffering from covid-19.
    Is it a one-to-one transfusion, one-to-many or many-to-one? I wonder because this would tell how scalable this would be, and how much potential for preferential treatment there is: many-to-one would make plasma rare and human-harvested, so if it works (it would be among the only real treatment available now – maybe the only one) I can see black market, corruption to get it first, and so on….

  21. j says:

    For some reason Latinos and Blacks in New York are dying of Corona twice the rate of Whies and Asians. Source:

  22. Maciano says:

    This is how the corona naysayers moved the goalposts. I wrote all I could remember, but there are many more ways they downplayed it.

    It’s a local Chinese problem
    It’s not very contagious
    It only hurts Chinese/East Asians
    The deaths in Europe & US are all of East Asian descent
    It’s no worse than the flu (actually the flu is worse)
    Italians also died relatively more of the Spanish flu
    It’s only in European areas with air pollution
    It only spreads in certain temperate zones
    It will go away in the summer
    Only old people die from it
    Only old and weak people die from it
    Only old, weak and fat people die from it.
    People die with COVID, not from COVID
    The HK flu of 1968 was worse.

    We are here:
    – The models said 2 million, we’ll be looking at 100000 deaths tops — OWNED!

    You’re all a panicky girly men who destroyed the economy !

    • dave chamberlin says:

      The new improved complaints

      You pussies wrecked the economy because you are scared of a bad flu bug.
      Let’s get back to work, now!
      You people are to blame for this recession, not Coronavirus
      We were right! It will kill about as many people as the flu!
      Ok, it’s controlled, time to mingle.

      • gothamette says:

        Some of them are using India as an example.


        I mean…. India. How many people die in India that never get recorded?

    • gothamette says:

      “It only hurts Chinese/East Asians
      The deaths in Europe & US are all of East Asian descent”

      I remember the arguments here. What a waste of time these jerks are.

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