Slack / Private Message Drop — page 447

[2021-01-24 07:06:01] [Robert 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. [2021-01-24 07:53:59] [Kristian Andersen] [thread - ID: 2021-01-23 17:49:05] @Andrew Rambaut Great.... [2021-01-24 08:28:42] [Robert Garry] https://www.sciencedirect.com/science/article/pii/S0092867420314562 [2021-01-24 08:29:07] [Robert Garry] Similar picture here. [2021-01-24 08:48:31] [Robert Garry] 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] [2021-01-24 08:49:52] [Robert Garry] Unfortunately no earlier sequence than from day 45, so don't know the baseline sequence. [2021-01-24 08:54:05] [Robert Garry] They also use the Q word [yikes], which perhaps suggests a teaching opportunity re viral population genetics. [2021-01-24 09:00:15] [Robert Garry] https://virological.org/t/emergence-of-y453f-and-69-70hv-mutations-in-a-lymphoma-patient-with-long-term-covid-19/ 580 Of course other immunosuppressed patients like this one here. [2021-01-24 09:10:11] [Robert Garry] https://www.medrxiv.org/content/10.1101/2020.12.05.20241927v3 "N501Y in Spike was transiently detected at day 55 and V157L in RdRp emerged. However, following convalescent plasma we observed large, dynamic virus population shifts, with the emergence of a dominant viral strain bearing D796H in S2 and *
*H69/*
*V70 in the S1 N-terminal domain NTD of the Spike protein." Importantly, no SC2 antibodies until they infused convalescient plasma. [2021-01-24 13:42:44] [Robert Garry] [thread - ID: 2021-01-23 18:02:32] @Eddie Holmes Sorry for the time sink/harassment. Not a good use of your time.