This was a highly collaborative project.
Many thanks to @wcassias, @KatiaKoelle, @dho, @trvrb, and @tcfriedrich. Incredible leadership and mentorship from start to finish on this project from @LouiseHMoncla. And, of course, my partner in crime/science, @GageKMoreno. 2/12
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The emergence of
#SARSCoV2 VOCs is concerning and raises
s about vaccine updates. Growing evidence says VOCs might arise during long-term infxs, but the vast majority of infxs are acute. So, we asked: can novel variants arise + transmit efficiently in acutely infected ppl? 3/12Show this thread -
To answer this
, we deep seq’d viruses from 133 #SARSCoV2 genomes and 28 putative household transmission pairs, and take advantage of our large consensus-level surveillance dataset (n=5,517) from the community where these individuals reside. 4/12Show this thread -
Genetic diversity within hosts was very limited. Most of the infxs we looked at had ≤5 iSNVs, the majority of which were low frequency. Most iSNVs can only be found once and the variation that was shared was homopolymers and Wuhan-1 reversions. 5/12pic.twitter.com/JSXWmTt4rn
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Half of all putative household transmission pairs (14/28) share no iSNVs at all. A quarter of these pairs (7/28, purple) share more iSNVs than expected by chance (chance = random pairs, grey). Not enough shared variation to infer transmission w/o epi data. 6/11pic.twitter.com/LXSKygUnLs
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We found a *single* instance of a within-host iSNV arising later at consensus levels. Even w/ a relatively dense dataset, we find NO evidence of iSNVs commonly giving rise to consensus SNPs along phylogenetically linked infxs. iSNVs in *acute* infxs ≠ consensus diversity. 7/12
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Transmission bottlenecks in household pairs are *narrow* and sensitive to the variant calling threshold. Narrow bottlenecks → diversity is lost at the time of transmission → limited shared diversity in households and in phylogenetically linked infxs! 8/12pic.twitter.com/5nzeWykE1J
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Results of
#SARSCoV2 within-host studies have varied a bit. We think it’s in part bc#SARSCoV2 is particularly vulnerable to method error. Our study emphasizes the importance of duplicate sequencing for any studies relying on low-freq iSNVs to infer biological processes. 9/12pic.twitter.com/pAxIL8jKZS
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Overall, our data suggest acute infxs are unlikely to be common sources of novel variants. Future work is needed in long-term infxs / immunocompromised hosts where there is more time for mutations to arise, selection to act, and transmission to occur. 10/12
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Check out these other great
#SARSCoV2 within-host studies from@katrina_lythgoe and@alvalesano: 11/12 https://science.sciencemag.org/content/372/6539/eabg0821 …https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009499 …Show this thread -
Check out these
#SARSCoV2 studies looking at evolution in chronic infxs: 12/12 https://www.nejm.org/doi/full/10.1056/NEJMc2031364 … https://academic.oup.com/jid/article/223/1/23/5934826 …https://www.nature.com/articles/s41586-021-03291-y …Show this thread -
BONUS. One of our favorite parts of working on a new manuscript is getting to choose a new color scheme. This paper’s color scheme was inspired by the amazing women of the 2021 inauguration.
https://github.com/ciannabp/inauguration …Show this thread
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We deep seq’d
carefully at long-term infxs.
1/12 