A single line often inverts meaning once you see what it
answers, so neighbouring messages are always shown.
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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.
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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.
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@Andrew Rambaut Great....
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https://www.sciencedirect.com/science/article/pii/S0092867420314562
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2021-01-24 08:29
Robert F. Garry
Similar picture here.
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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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Unfortunately no earlier sequence than from day 45, so don't know the baseline sequence.
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They also use the Q word [yikes], which perhaps suggests a teaching opportunity re viral population genetics.
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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.