i think a lot of people are misunderstanding the mechanism behind "shift to endemicity" in a CoV.
it's not at all due to the *virus*. yes, endemic HCoVs have certain mutations (such as a preference for closed RBDs on Spike where the CTD is the RBD) but those are from...
it's not at all due to the *virus*. yes, endemic HCoVs have certain mutations (such as a preference for closed RBDs on Spike where the CTD is the RBD) but those are from...
...selection pressure *once in the endemic state*.
what causes the shift is the virus going from antigenically novel to us having prior immunity. @dylanhmorris wrote a great article on this that is *highly* worth a read: theinsight.org/p/novelty-mean…
what causes the shift is the virus going from antigenically novel to us having prior immunity. @dylanhmorris wrote a great article on this that is *highly* worth a read: theinsight.org/p/novelty-mean…
but to expand a bit: once we have immunity to a virus, generally* the virus stops being able to cause *disease*. in some cases, immunity is more-or-less sterilizing, i.e. you *generally* don't get symptomatic disease.
*yes i know about Dengue. ADE has not been observed here.
*yes i know about Dengue. ADE has not been observed here.
in other cases, the virus is still able to escape some layer of our immune system & cause some amount of symptoms, be it via flu-like replication kinetics or antigenic drift.
in the case of HCoVs, it's primarily the latter:
in the case of HCoVs, it's primarily the latter:
https://twitter.com/jbloom_lab/status/1339939720558563328
but here's the thing! you're still immune b/c your immune system has several arms that in this case are partially redundant. T cells get to clearing virus-infected cells while memory B cells undergo SHM to work around the antigenic drift.
*this* is why we think of HCoV-OC43 as a "common cold".
say what you want about #COVID19 & kids <12 but as a *general rule*, it's mild. not necessarily harmless, but mild. similar case for the endemic HCoVs.
say what you want about #COVID19 & kids <12 but as a *general rule*, it's mild. not necessarily harmless, but mild. similar case for the endemic HCoVs.
by the time you're 12 you're almost guaranteed to have caught mild HCoV-OC43, HCoV-HKU1, HCoV-229E & HCoV-NL63.
by the time you're re-exposed to them, a reinfection is like a vax breakthru: you have immune memory.
by the time you're re-exposed to them, a reinfection is like a vax breakthru: you have immune memory.
this means the immune system is able to keep things in check before things get out of control, it goes haywire & you get the constellation of symptoms we now are familiar with as "severe #COVID19".
crucially, there's nothing about the *coronavirus* that's all that relevant here. HCoV-OC43 has an accessory 2'-5' phosphodiesterase, which means unlike #SARSCoV2 it can shut down the OAS3-RNase L pathway. HCoV-NL63, like #SARSCoV2, uses hACE2 as an entry receptor.
& perhaps most importantly, the genomes, esp. the core replicase (orf1ab) are highly similar amongst all CoVs.
endemic HCoVs in a naive population would not be the slouches that people think they are. 1889-1890 was likely HCoV-OC43.
endemic HCoVs in a naive population would not be the slouches that people think they are. 1889-1890 was likely HCoV-OC43.
it's just that b/c none of them are novel at an age where they are *likely* to cause disease do we consider them mostly harmless.
*this* is the projected final state of #SARSCoV2.
importantly, it'll only happen once we *all* (12+, at least) have immune memory to it. not sooner.
*this* is the projected final state of #SARSCoV2.
importantly, it'll only happen once we *all* (12+, at least) have immune memory to it. not sooner.
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