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1. 2021-01-24 06:28 Robert F. Garry open
   So, these are the papers {plus another somewhat similar one focusing more on the deletions that I was reviewing for one of the glams] that triggered my unfortunate use of the "Q word," an old lazy bad habit from HIV days.https://www.nejm.org/doi/full/10.1056/NEJMc2031364 https://www.nejm.org/doi/full/10.1056/NEJMc2031670 Asmentioned, we have a similar chronic patient - 8 months with positive SC2 pcrs. [shared file(s): image.png]
2. 2021-01-24 06:36 Robert F. Garry open
   The patient above is different than the second series of patients beow. First, the mutants don't show up til day 75-they show up in a group incuding Eeek, and a bigger deletion at Y145. Other variants with diff constellation ofmutations then come to dominate at different times, including a "transient" larger deletion that includes L18. Would have really been nice if the authors had given a little more info about depth of coverage etc. [shared file(s): image.png]
3. 2021-01-24 06:44 Robert F. Garry open
   The difference in the second series is that in every case most of the variants are present in the first sample. Other mutations get added later but these are outside of spike. With one exception you don't see a mutation appear and then "disappear." The Tulane patient has a spike deletion in the first sample [A243/L244] and adds a few substitionsin spike on the second sample taken three months after the first. More KGA seq to come on later samples.
4. 2021-01-24 07:06 Robert F. Garry
   If you are still with me - the main point I want to make is that our Tulane immunosuppressed patient had zero antibodies to SC2 spike and nucleoprotein to date. Zilch. Rituximab plus Bendamustine - very low WBC. Unfortunately we don't have antibody data on the NEJM patients, but we do know that the first NEJM patient above was blasted with Rituximab and high dose steroids. We're going to try and measure T cell responses in the Tulane patient, but not expecting much. Bottom lines: 1. some immunosuppressed patients may have just by chance been infected with variants arising in their communities OR the variants came up *really* fast. 2. immunosuppressed patients can select for variants over time -months , but the population dynamics are complex. 3. immune escape perhaps less important than fitness as a selective pressure in immunosuppressed patients - some of the fitter variants just happen to be in epitopes.4. By whatever mechanism a LOT of the same mutations appear via independent events in these immunosuppressed patients.
5. 2021-01-24 07:53 Kristian G. Andersen open
   @Andrew Rambaut Great....
6. 2021-01-24 08:28 Robert F. Garry open
   https://www.sciencedirect.com/science/article/pii/S0092867420314562
7. 2021-01-24 08:29 Robert F. Garry open
   Similar picture here.
8. 2021-01-24 08:48 Robert F. Garry open
   This patient in the Cell case study[!] is a bit more like the first NEJM patient. Some Mutations persist, others wink in,wink out. [shared file(s): image.png]

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