Independent action hypothesis (IAH), dose response, and ID50 thread 🧵
IAH = idea that each single virion has chance to infect
Dose response curves. Related to the ID50, or infectious dose to make 50% of organisms sick. Measuring how much of a pathogen is needed to cause %age of infection.
A thread about stuff the talking heads don't want you to know.*
(*In fairness they probably don't understand it.)
Keywords: #DoseResponseCurve #ID50 #ID10 #QMRA #QuantitativeMicrobiobialRiskAnalysis
Dose response curve for SARS-CoV-1
In order to develop a dose‐response model for SARS coronavirus (SARS‐CoV), the pooled data sets for infection of transgenic mice susceptible to SARS‐CoV and infection of mice with murine hepatitis virus strain 1, which may be a ...
A single droplet about 50uM large has a 37% chance of containing a single virus.
https://www.pnas.org/doi/10.1073/pnas.2006874117
So, you'd need say 500 droplets to hit mucus membranes and deliver 200 viruses (to cause infection 50% of time).
Kiss of death for droplet.
We are done here.
(Napkin math obviously.)
Of course, numbers rough, ID50 not settled, viral load (that calculates how many in each droplet emitted) may vary, sizes of droplets may vary, but theory here seems solid.
More information about virus particles in droplets, if anyone comes across, would be greatly appreciated.
The assumption has always been one large droplet would contain all the virus particles needed to infect - but I've never seen this elaborated, calculated, discussed anywhere except by the aerosol people who calculate how many in the tiny aerosols
Fine particles may have MORE than coarse. This in fact may make sense. Anyway, some numbers in this paper. No time to review right now.
2020 Fennelly
https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30323-4/fulltext
--- SARS-CoV-2:
Haas. "Action Levels for SARS‐CoV‐2 in Air: Preliminary Approach"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251121/
Estimated dose response approach to SARS-CoV-2. From April 2021 so it's well out of date. Also, not experimental, just laying out a framework.*
*(I give you the best commentary - do the talking heads do this? Of course not.)
Quantitative microbial risk assessment has been used to develop criteria for exposure to many microorganisms. In this article, the dose–response curve for Coronavirus 229E is used to develop preliminary risk‐based exposure criteria for ...
--- SARS-CoV-2:
Here is another article that is estimating dose response for SARS-CoV-2:
Parhizkar, Wymelenberg, Haas, Corsi. 2021-10. "A Quantitative Risk Estimation Platform for Indoor Aerosol Transmission of COVID‐19"
Aerosol transmission has played a significant role in the transmission of COVID‐19 disease worldwide. We developed a COVID‐19 aerosol transmission risk estimation model to better understand how key parameters associated with indoor spaces ...
--- Tuberculosis:
Dose response for TB on a plane?
"Enough is enough! I have had it with this mf TB on this mf plane"
[ed. stop fooling]
- Low rates but superspreaders
- Use of mask (by source and/or susceptibles) can reduce infection incidence by 10x
Jones et al. ‘Characterizing the Risk of Infection from Mycobacterium Tuberculosis in Commercial Passenger Aircraft Using Quantitative Microbial Risk Assessment’. Risk Analysis 29, no. 3 (2009): 355–65. https://doi.org/10.1111/j.1539-6924.2008.01161.x.
--- TB dose estimated to be 1.6 Colony Forming Unit (CFU)
That might be about 1 to 2 bacteria, dear peoples of the world.
"Infection by a single bacterium was hypothesized by Dannenberg and the results of our study support his hypothesis (5)."
Saini et al ‘Ultra-Low Dose of Mycobacterium Tuberculosis Aerosol Creates Partial Infection in Mice’. Tuberculosis (Edinburgh, Scotland) 92, no. 2 (March 2012): 160–65. https://doi.org/10.1016/j.tube.2011.11.007.
--- SARS-CoV-2:
"on the order of 10 aerosolized virions"
Bazant, Martin Z., and John W. M. Bush. ‘A Guideline to Limit Indoor Airborne Transmission of COVID-19’. Proceedings of the National Academy of Sciences 118, no. 17 (27 April 2021).
--- Article with minimum infective dose for a bunch of different viruses:
TINY AMOUNTS MAKE YOU SICK
Doses of <1 TCID50 of flu, rhinovirus, and adenovirus ... infected 50% of people ...
"Similarly, low doses of the enteric viruses, norovirus, rotavirus, echovirus, poliovirus, and hepatitis A virus, caused infection in at least some of the volunteers tested."
Yezli et al ‘Minimum Infective Dose of the Major Human Respiratory and Enteric Viruses ...’.
https://doi.org/10.1007/s12560-011-9056-7.
I don't have time to post more but it probably just takes one virus to productively infect you. You inhale x virions and the one gets through.
Infection is likely pretty stochastic.
For more, read about the "independent action hypothesis" (that one pathogen can cause infection)
Also interesting are articles studying how many virus genomes they find in the infected; it is very few.
@ProfCharlesHaas talks about it all here. Highly recommended.
https://chaasblog.wordpress.com/2020/05/18/its-the-dose-response-stupid/
--- Influenza:
Ten particles for flu infects half the time (one ID50). From 1954.
Was looking for something else completely
This is why of course all the fomite studies they have to absolutely cover surfaces with virus to get anything infected.
Oh wait that _disproves_ fomites, silly me.
Carry on, ridiculous hand wash. /S
https://www.microbiologyresearch.org/content/journal/micro/10.1099/00221287-10-3-457
SUMMARY: Particle counts of influenza virus preparations were made by two independent techniques; there was good agreement in the counts found by the two methods. Counts made on four strains of influenza virus and one strain of ‘incomplete’ virus showed that at the agglutination end-point there was about one virus particle per red cell. Parallel infectivity measurements of these strains made under optimal conditions showed that about ten virus particles corresponded to one ID 50.
The fomite thing still has me stumped re: Covid. Are they a danger or not?
Thanks. So hands to mouth or eyes is okay without danger of infection?
I do not like the phrase "without danger of infection" as that implies it can never transmit that way.
However, I would say that the efforts ought to be put into protecting against other modes.
So basically, a very low probability? Of course, I'm with you on all other mitigations- a must!
So low that if you go looking for proof of it, the articles trying to support it generally use wording expressing doubt it is a real mode.
It can't mathematically support outbreaks. You need to coat finger with virus to get some to transmit. No explanation for how gets to mouth other than "we touch face a lot". Etc. It's nonsense.
Big picture: things tend to die when outside our bodies for any length of time.
Did you know we secrete RNAse on skin that eats viruses? 😄
Thank you! That's really helpful!
Sorry for Twitter link but
1.
https://twitter.com/jmcrookston/status/1334851435444531200
https://nitter.net/jmcrookston/status/1334851435444531200
2.
https://twitter.com/jmcrookston/status/1415746706533195785
https://nitter.net/jmcrookston/status/1415746706533195785
I will eventually get all this moved over here and deleted there.
I definitely will check it out. Thanks!
Oh, and thank you for the info and all your hard work. Much appreciated.
I always tell people if it makes someone feel good to wash, or whatever, then do it, but in a modern sanitary society, I doubt we are catching any substantial number of infections from door handles (etc) versus over millions of years the viruses adapting to our (animals') weak spot: lungs.
By the way the washroom should be a bloodbath of infection no? Because basically nobody washes their hands and _the fomites_ 😮 😉 .
But it's not. Although I bet the air ain't good in there.
Thanks, Lightning. That's the first time I've found the phrasing acceptable. Nice choice of words! I finally get it!
Yeah, I figure it's better to be safe than sorry. I'm all for overkill on mitigations.
Jonathan
PlantingTrees😷🇨🇦🌻👠
Lightning Bjornsson* 