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1. 2021-02-20 09:18 Andrew Rambaut open
   @Kristian Andersen I generally agree - I am 100% convinced that B.1.1.7 is different from everything in its origin story but has converged on the same peak.
2. 2021-02-20 09:23 Andrew Rambaut open
   I guess the first question to demonstrate is that has there been a shift in the adaptive landscape (rather than just alot more unusual stuff happening because there are shed loads of cases - although that too). Possible reasons for awide-spread shift in the population level landscapes are 1) NPI, 2) deployment of anti-viral treatments, 3) increasing seroprevalence 4) ? anything else? Then there is the possibility of a shift in within host landscapes - more chronic infections, possibly inimmuno-compromised, possibly treated. Here it is a numbers game - more infections mean more of these and more chance some of them hit this population-fit fitness peak and then transmit onwards.
3. 2021-02-20 09:38 Kristian G. Andersen open
   Yeah, these are good - I think very likely #1 (broadly defined) and #3 - not sure about #2.
4. 2021-02-20 09:43 Robert F. Garry open
   ? anything else? Perhaps something about the demographics shifted too - no data just an impression that a lot more young adults started to get infected in the second wave. That may be because US sucked at testing early on and young adults were getting infected just not counted. Young adults also more likely not to adhere to NPI. In terms ofthe "numbers game" the fact that SubSaharan Africa remains largely devoid of massive outbreaks til you get downto South Africa tells me they are different (which makes the Uganda variant all the more important) - my bias basedon some serology that we are ~sitting on~ trying to get out tells me differences in exposure to seasonal coronaviruses (known and perhaps unknown) could be driving the difference btwn Africa nd the rest of the world.
5. 2021-02-20 09:47 Kristian G. Andersen
   Worth adding to the same speculations - what might we expect the future to look like? I have little doubt that the virus will escape our vaccines relatively quickly, meaning we will still continue to see cases - there's no herd immunity here. That scenario may seem like doom, however, it's possible that via vaccination and (re)infections there will beenough immunity to protect against severe disease. I think most virologists believe this is the likely outcome - i.e.,SC2 becomes the common cold. However, I am very concerned this is wishful thinking. SC2 does not appear to be another ccCoV to me. It can infecta huge range of animals and a huge range of tissues. It can infect not just the upper airways (like ccCoVs), but alsolungs, hearts, and other major organs (in fact, pretty much all of them). Some of the reinfections have been severe and have organ involvement (I believe?). To my knowledge, that has never been described with ccCoVs, unless patients have been immunocompromised. So while I'm sure _some_ immunity will _almost_ always be better than none, I am not convinced that this will simply fade into the background like ccCoVs, as I think many scientists believe. It's a very attractive scenario creating a huge confirmation bias. But do we honestly and seriously believe that once most people have gotten that one shot - or been infected - this will become just another ccCoV?I certainly hope so, but I have a hard time convincing myself the data support such a scenario being the most likely outcome.
6. 2021-02-20 09:49 Kristian G. Andersen open
   > trying to get out tells me differences in exposure to seasonal coronaviruses (known and perhaps unknown) could be driving the difference btwn Africa nd the rest of the world India too. That place is the most mysterious of all to me. _Some_ level of cross-protection would support the notion that SC2 could become just another ccCoV, albeit slightly more severe - but less so than e.g., flu. Dunno.
7. 2021-02-20 10:19 Robert F. Garry open
   Couple of things that are hopeful in terms of whether some sort of "herd" immunity is going to get us out of this mess. 1. Galit's data on OC43 that she showed at last wks conference - prior exposure/existing immunity to OC43basically precluded severe disease. 2. new data showing that a vaccination [one dose] on top of a prior infectioninduces a "massive" and "broad" immune response. 3. exposure to B.1.351 does induce good neuts to .1.351 and 4.the African experience [good point about India], which I think reflects a near universal blanket immunity to"seasonal" CoVs including probably a beta or two we don't yet know about. BUT, I'm the optimistic one.
8. 2021-02-20 10:25 Robert F. Garry open
   I think a scenario of a yearly vaccination with constant updating [stabilized spike of course] is the most likely outcome - and yes it's not the flu so there will a a death toll, so not pretty. Monoclonals (in combo) - again being updated could blunt this. ASnd, some hope for a small molecule drug. Universal CoV vaccine - not so hopeful.
9. 2021-02-20 10:27 Andrew Rambaut open
   @Kristian Andersen Yeah - these are not all likely hypotheses I just want to get everything on table.

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