7 ms·

I've seem people theorize about this before saying maybe it's good news because that means it's less fatal than we thought and therefore maybe we're closer to h

I've seem people theorize about this before saying maybe it's good news because that means it's less fatal than we thought and therefore maybe we're closer to herd immunity. But I saw an epidemiologist talk about how an R0 of 2 meant you needed 50% of people to be immune for herd immunity, and an R0 of 3 meant you needed 66%. This would mean it'd need to be even higher - the article says 82%. We're nowhere close to that now - even northern Italy, they're estimating that maybe 10% have caught it.

hprotagonist 7y ago
yes, this is why measles vaccination rates must be nearly total. measles has an R_0 somewhere beteween 14 and 18 (!!!)
- greglindahl 7y ago
  A second is that the measles vaccine fails more often than many others. The combination drives the necessary vaccination rate quite high, and the risk isn't just the unvaccinated kids, it's a % of the ones who thought they were fully vaccinated.
roel_v 7y ago
Also, it seems that people with low severity symptoms don't build up a lot of antibodies, so they're not sufficiently immune. So out of that 10%, only some count towards the herd.
- ztjio 7y ago
  Citation?
  - sroussey 7y ago
    From the last sentence in the conclusion: "Stronger antibody response was associated with delayed viral clearance and disease severity." https://www.medrxiv.org/content/10.1101/2020.03.24.20042382v1.full.pdf https://www.medrxiv.org/content/10.1101/2020.03.24.20042382v...
    - mirimir 7y ago
      That's very interesting. > First, we observed three types of antibody responses in COVID-19 patients, strong, weak and non-response. Second, we found that the earlier response, higher antibody titer and higher proportion of strong responders for IgM and IgG were significantly associated with disease severity. Third, the weak responders for IgG antibodies had a significantly higher viral clearance rate than that of strong responders. These data indicates strong antibody response is associated with disease severity, and weak antibody response is associated with viral clearance, which resembles SARS and MERS. I have a wild-ass guess. I vaguely recall that antibody response and cellular immune response generally tend to be inversely proportional. And that IgM antibody response is an aspect of allergy. So maybe strong antibody responders tend to have weaker cellular responses, and more wet lung problems.
  - roel_v 7y ago
    Preliminary results from a Dutch study I was reading about a few hours ago, in Dutch, that I came across through news.google.nl - although because I'm in a different timezone now, google news has been refreshed, and I can't find this specific one any more. So take that as you will...
- goalieca 7y ago
  That's not what i've seen. They're looking at it for blood transfers and finding asymptomatic people have sufficient loads. edit: i think this is logical (for my rudimentary knowledge) given the cause of death is not directly related to the virus. The symptoms of dry cough and fever are all the bodies response. Even the shortness of breath and pneumonia might be attributed to inflammation. Perhaps the asymptotic people just don't have such a strong response for whatever reason.
  - hilbertseries 7y ago
    Do you have a source for this? Haven’t read that yet.
    - flor1s 7y ago
      I've seen it mostly in the Dutch news until now. The source is the Dutch CDC (RIVM) via Marion Koopmans (Professor of virology and head of the virology department at the Erasmus Medical Center). Article in Dutch (translated title: Mild corona virus symptoms seem to lead to lower creation of antibodies) https://nos.nl/artikel/2329846-milde-coronaklachten-lijken-minder-antistoffen-op-te-leveren-wat-betekent-dat.html https://nos.nl/artikel/2329846-milde-coronaklachten-lijken-m...
      - hilbertseries 7y ago
        This article says that people with mild symptoms have fewer antibodies and says it’s unclear if they can be reinfected. Further it doesn’t mention asymptomatic cases.
- akvadrako 7y ago
  You don't even need to be infected to develop the right antibodies: https://www.randombio.com/coronavirus2.html https://www.randombio.com/coronavirus2.html You may not have a lot of them, but you have already evolved targeted killers.
fpgaminer 7y ago
> because that means it's less fatal than we thought Don't we already have solid numbers on the fatality rate because of the Diamond Princess? A change in estimated R0 wouldn't affect that.
- sooheon 7y ago
  Diamond princess is a non-stochastic sample, with all its attendant biases.
  - throwaway_pdp09 7y ago
    What does that mean?
    - kaybe 7y ago
      People on cruise ships are usually not a good sample of the general population, for example, the mean age is quite high.
      - btilly 7y ago
        But it is also a sample with few in the sickest bracket, who are a disproportionate fraction of deaths. And the number of deaths is sufficiently small that it is consistent with a wide range of death rates.
    - projektfu 7y ago
      Another way to put it is that the study is enumerative and not analytic. Unfortunately, just about every study being done on COVID is enumerative. https://en.m.wikipedia.org/wiki/Analytic_and_enumerative_statistical_studies https://en.m.wikipedia.org/wiki/Analytic_and_enumerative_sta...
  - rsync 7y ago
    "Diamond princess is a non-stochastic sample, with all its attendant biases." But isn't it a non-stochastic sample in the right direction ? Which is to say, the demographics of budget cruise line passengers are almost a worst-case. They represent the most susceptible cohort. What we can infer from Diamond Princess is that the general population will, all else being equal, fare better statistically.
ignoramous 7y ago
> ...R0 of 3 meant you needed 66%. This would mean it'd need to be even higher - the article says 82% For anyone curious, R0 = 3 means iff 2 in 3 people (66.66%) [0] are immune would R0 drop to 1 [1]. So, when R0 = 5.7 (the value proposed by tfa for SARS-CoV-2), 4.7 in 5.7 (82.45%) would need to be immune for it to drop to 1 [1]. Why should R0 drop to 1 [1]? It means each case leads to only 1 successful transmission of the infection. This implies constant incidence over time. If a greater proportion are immune, then incidence will decline. Why "herd immunity" isn't enough? ...problems arise because herd immunity is not the same as biologic (immunologic) immunity; individuals protected only by indirect herd effects remain fully susceptible to infection, should they ever be exposed. This has advantages, in protecting individuals with contraindications to vaccination or those who for other reasons miss vaccination, but it also has its disadvantages. Measles and mumps outbreaks among university students, and pertussis in adults, are among examples of the consequences of accumulation of susceptible individuals who have not been protected by vaccination, and escaped infection because of a herd immunity effect earlier in their lives... This means that there is a need for immunization programs to maintain high vaccine coverage, together with surveillance and outbreak response capabilities, as numbers of susceptible individuals accumulate in older age groups. From: https://academic.oup.com/cid/article/52/7/911/299077 https://academic.oup.com/cid/article/52/7/911/299077 [0] This assumes a 100% effective vaccine (E = 1) in ((R0 − 1)/R0)/E. If, for a given vaccine, E < (R0 - 1)/R0, it'd be impossible to eliminate the infection through that vaccine. (R0 − 1)/R0 is known as the "herd immunity threshold." [1] What I really mean is R0 x S = 1. See: https://en.wikipedia.org/wiki/Endemic_(epidemiology) https://en.wikipedia.org/wiki/Endemic_(epidemiology)
- zodiac 7y ago
  Nitpick: changes in the number of immune people change R, not R0
  - ignoramous 7y ago
    Yes, thanks. R or R-eff is more like it, but for the sake of simplicity I chose to instead leave a footnote about inaccurate usage of R0.
- 7y ago
ekianjo 7y ago
> even northern Italy, they're estimating that maybe 10% have caught it. How do we know unless we do randomized antibody testing in the population?
- ineedasername 7y ago
  It's just a lower accuracy level of estimate, not an invalid method. For example you can know that an infected person that had no known contact with another infected person means that there is in fact at least one other infected person out there. Yes, not as accurate as random population testing, but it's a difference of degree, not kind.
- T-hawk 7y ago
  One way to extrapolate: excess deaths. Look at the overall death rate for an area and compare it to the normal value when there isn't an epidemic going on. If there is a difference that is larger than your number of known Covid deaths (which is true for Italy by a factor of somewhere between 2x and 5x), you can assume you're undercounting your Covid deaths by that factor, and your overall Covid infections by at least that factor.
  - sooheon 7y ago
    This still involves guesswork wrt the ratio of deaths to infections (IFR). Proper statistical sampling is the only way to get an actual answer.
  - cjhopman 7y ago
    The usefulness of that approach decreases as people's behavior otherwise changes. For example, accidents account for ~10% of deaths. It's quite feasible (and I think we already have data to support this) that that has dropped a lot due to people's behavior changing in response to covid-19.
    - eanzenberg 7y ago
      Forget accidents, there’s a dropoff in heart attack, stroke, and cancer deaths as every death now is attributed to Coronavirus.
gpderetta 7y ago
Which also means that a larger percentage of the population will end up being infected.
xyzzyz 7y ago
With R_0 of 2, you need to have 50% immune to have herd immunity, but in practice, you’ll have more people than that that will end up infected before the epidemics dies out. Think about it: when over 50% of people get and survive the disease, rendering them immune, the epidemics doesn’t just immediately stop. What happens instead is that since average sick person transmits it to 2 people, but one of them is immune, less than one person gets the disease, and the epidemics starts the exponential die-out. However, as it dies, people still get infected, albeit slower and slower until it stops altogether. The epidemics final size equation is F = 1 - exp(R_0 F). For R_0 = 2, F is around 80%, despite the herd immunity kicking in already at 50%.
- nullc 7y ago
  This is one reason that "herd immunity through everyone getting exposed and lots dying" is not the same thing as "herd immunity through vaccination". If you vaccinate a big chunk of the population when only 1% are currently infected, you hit R(effective) = 1 much sooner. While becoming immune through infection essentially guaranties there are a tremendous number of infectious persons at the point R(eff) drops to 1.
randomsearch 7y ago
Is it not the case though that R0 is dependent on all sorts of factors, including social distancing? So if we keep some social distancing, presumably we can reach the equivalent “herd immunity” with far far fewer people infected, such that society can operate in a reduced capacity until a vaccine arrives.
guscost 7y ago
Wait for the serosurveys before assuming how far it has already spread - would it be surprising if yet another estimate about this thing turned out to be way off base?

hprotagonist 7y ago

yes, this is why measles vaccination rates must be nearly total. measles has an R_0 somewhere beteween 14 and 18 (!!!)

greglindahl 7y ago
A second is that the measles vaccine fails more often than many others. The combination drives the necessary vaccination rate quite high, and the risk isn't just the unvaccinated kids, it's a % of the ones who thought they were fully vaccinated.

roel_v 7y ago

Also, it seems that people with low severity symptoms don't build up a lot of antibodies, so they're not sufficiently immune. So out of that 10%, only some count towards the herd.

ztjio 7y ago
Citation?
- sroussey 7y ago
  From the last sentence in the conclusion: "Stronger antibody response was associated with delayed viral clearance and disease severity." https://www.medrxiv.org/content/10.1101/2020.03.24.20042382v1.full.pdf https://www.medrxiv.org/content/10.1101/2020.03.24.20042382v...
  - mirimir 7y ago
    That's very interesting. > First, we observed three types of antibody responses in COVID-19 patients, strong, weak and non-response. Second, we found that the earlier response, higher antibody titer and higher proportion of strong responders for IgM and IgG were significantly associated with disease severity. Third, the weak responders for IgG antibodies had a significantly higher viral clearance rate than that of strong responders. These data indicates strong antibody response is associated with disease severity, and weak antibody response is associated with viral clearance, which resembles SARS and MERS. I have a wild-ass guess. I vaguely recall that antibody response and cellular immune response generally tend to be inversely proportional. And that IgM antibody response is an aspect of allergy. So maybe strong antibody responders tend to have weaker cellular responses, and more wet lung problems.
- roel_v 7y ago
  Preliminary results from a Dutch study I was reading about a few hours ago, in Dutch, that I came across through news.google.nl - although because I'm in a different timezone now, google news has been refreshed, and I can't find this specific one any more. So take that as you will...
goalieca 7y ago
That's not what i've seen. They're looking at it for blood transfers and finding asymptomatic people have sufficient loads. edit: i think this is logical (for my rudimentary knowledge) given the cause of death is not directly related to the virus. The symptoms of dry cough and fever are all the bodies response. Even the shortness of breath and pneumonia might be attributed to inflammation. Perhaps the asymptotic people just don't have such a strong response for whatever reason.
- hilbertseries 7y ago
  Do you have a source for this? Haven’t read that yet.
  - flor1s 7y ago
    I've seen it mostly in the Dutch news until now. The source is the Dutch CDC (RIVM) via Marion Koopmans (Professor of virology and head of the virology department at the Erasmus Medical Center). Article in Dutch (translated title: Mild corona virus symptoms seem to lead to lower creation of antibodies) https://nos.nl/artikel/2329846-milde-coronaklachten-lijken-minder-antistoffen-op-te-leveren-wat-betekent-dat.html https://nos.nl/artikel/2329846-milde-coronaklachten-lijken-m...
    - hilbertseries 7y ago
      This article says that people with mild symptoms have fewer antibodies and says it’s unclear if they can be reinfected. Further it doesn’t mention asymptomatic cases.
akvadrako 7y ago
You don't even need to be infected to develop the right antibodies: https://www.randombio.com/coronavirus2.html https://www.randombio.com/coronavirus2.html You may not have a lot of them, but you have already evolved targeted killers.

fpgaminer 7y ago

> because that means it's less fatal than we thought Don't we already have solid numbers on the fatality rate because of the Diamond Princess? A change in estimated R0 wouldn't affect that.

sooheon 7y ago
Diamond princess is a non-stochastic sample, with all its attendant biases.
- throwaway_pdp09 7y ago
  What does that mean?
  - kaybe 7y ago
    People on cruise ships are usually not a good sample of the general population, for example, the mean age is quite high.
    - btilly 7y ago
      But it is also a sample with few in the sickest bracket, who are a disproportionate fraction of deaths. And the number of deaths is sufficiently small that it is consistent with a wide range of death rates.
  - projektfu 7y ago
    Another way to put it is that the study is enumerative and not analytic. Unfortunately, just about every study being done on COVID is enumerative. https://en.m.wikipedia.org/wiki/Analytic_and_enumerative_statistical_studies https://en.m.wikipedia.org/wiki/Analytic_and_enumerative_sta...
- rsync 7y ago
  "Diamond princess is a non-stochastic sample, with all its attendant biases." But isn't it a non-stochastic sample in the right direction ? Which is to say, the demographics of budget cruise line passengers are almost a worst-case. They represent the most susceptible cohort. What we can infer from Diamond Princess is that the general population will, all else being equal, fare better statistically.

ignoramous 7y ago

> ...R0 of 3 meant you needed 66%. This would mean it'd need to be even higher - the article says 82% For anyone curious, R0 = 3 means iff 2 in 3 people (66.66%) [0] are immune would R0 drop to 1 [1]. So, when R0 = 5.7 (the value proposed by tfa for SARS-CoV-2), 4.7 in 5.7 (82.45%) would need to be immune for it to drop to 1 [1]. Why should R0 drop to 1 [1]? It means each case leads to only 1 successful transmission of the infection. This implies constant incidence over time. If a greater proportion are immune, then incidence will decline. Why "herd immunity" isn't enough? ...problems arise because herd immunity is not the same as biologic (immunologic) immunity; individuals protected only by indirect herd effects remain fully susceptible to infection, should they ever be exposed. This has advantages, in protecting individuals with contraindications to vaccination or those who for other reasons miss vaccination, but it also has its disadvantages. Measles and mumps outbreaks among university students, and pertussis in adults, are among examples of the consequences of accumulation of susceptible individuals who have not been protected by vaccination, and escaped infection because of a herd immunity effect earlier in their lives... This means that there is a need for immunization programs to maintain high vaccine coverage, together with surveillance and outbreak response capabilities, as numbers of susceptible individuals accumulate in older age groups. From: https://academic.oup.com/cid/article/52/7/911/299077 https://academic.oup.com/cid/article/52/7/911/299077 [0] This assumes a 100% effective vaccine (E = 1) in ((R0 − 1)/R0)/E. If, for a given vaccine, E < (R0 - 1)/R0, it'd be impossible to eliminate the infection through that vaccine. (R0 − 1)/R0 is known as the "herd immunity threshold." [1] What I really mean is R0 x S = 1. See: https://en.wikipedia.org/wiki/Endemic_(epidemiology) https://en.wikipedia.org/wiki/Endemic_(epidemiology)

zodiac 7y ago
Nitpick: changes in the number of immune people change R, not R0
- ignoramous 7y ago
  Yes, thanks. R or R-eff is more like it, but for the sake of simplicity I chose to instead leave a footnote about inaccurate usage of R0.
7y ago

ekianjo 7y ago

> even northern Italy, they're estimating that maybe 10% have caught it. How do we know unless we do randomized antibody testing in the population?

ineedasername 7y ago
It's just a lower accuracy level of estimate, not an invalid method. For example you can know that an infected person that had no known contact with another infected person means that there is in fact at least one other infected person out there. Yes, not as accurate as random population testing, but it's a difference of degree, not kind.
T-hawk 7y ago
One way to extrapolate: excess deaths. Look at the overall death rate for an area and compare it to the normal value when there isn't an epidemic going on. If there is a difference that is larger than your number of known Covid deaths (which is true for Italy by a factor of somewhere between 2x and 5x), you can assume you're undercounting your Covid deaths by that factor, and your overall Covid infections by at least that factor.
- sooheon 7y ago
  This still involves guesswork wrt the ratio of deaths to infections (IFR). Proper statistical sampling is the only way to get an actual answer.
- cjhopman 7y ago
  The usefulness of that approach decreases as people's behavior otherwise changes. For example, accidents account for ~10% of deaths. It's quite feasible (and I think we already have data to support this) that that has dropped a lot due to people's behavior changing in response to covid-19.
  - eanzenberg 7y ago
    Forget accidents, there’s a dropoff in heart attack, stroke, and cancer deaths as every death now is attributed to Coronavirus.

gpderetta 7y ago

Which also means that a larger percentage of the population will end up being infected.

xyzzyz 7y ago

With R_0 of 2, you need to have 50% immune to have herd immunity, but in practice, you’ll have more people than that that will end up infected before the epidemics dies out. Think about it: when over 50% of people get and survive the disease, rendering them immune, the epidemics doesn’t just immediately stop. What happens instead is that since average sick person transmits it to 2 people, but one of them is immune, less than one person gets the disease, and the epidemics starts the exponential die-out. However, as it dies, people still get infected, albeit slower and slower until it stops altogether. The epidemics final size equation is F = 1 - exp(R_0 F). For R_0 = 2, F is around 80%, despite the herd immunity kicking in already at 50%.

nullc 7y ago
This is one reason that "herd immunity through everyone getting exposed and lots dying" is not the same thing as "herd immunity through vaccination". If you vaccinate a big chunk of the population when only 1% are currently infected, you hit R(effective) = 1 much sooner. While becoming immune through infection essentially guaranties there are a tremendous number of infectious persons at the point R(eff) drops to 1.

randomsearch 7y ago

Is it not the case though that R0 is dependent on all sorts of factors, including social distancing? So if we keep some social distancing, presumably we can reach the equivalent “herd immunity” with far far fewer people infected, such that society can operate in a reduced capacity until a vaccine arrives.

guscost 7y ago

Wait for the serosurveys before assuming how far it has already spread - would it be surprising if yet another estimate about this thing turned out to be way off base?