There have been a number of overview threads on the emerging variant designated as @PangoNetwork lineage B.1.1.529, @nextstrain clade 21K and @WHO Variant of Concern Omicron. I'm not going to attempt to be comprehensive here, but will highlight a few aspects of the data. 1/16
Global systems for identifying novel variants and rapidly sharing data are working well with 91 genomes from Omicron viruses shared to @GISAID from specimens collected between Nov 11 and Nov 23 from Botswana, South Africa and Hong Kong. 2/16
These viruses are visible on @nextstrain as "21K (Omicron)" shown here in red (nextstrain.org/ncov/gisaid/af…). They do not descend from previously identified "variant" viruses and instead their closest evolutionary connection is to mid-2020 viruses. 3/16
This extremely long branch (>1 year) indicates an extended period of circulation in a geography with poor genomic surveillance (certainly not South Africa) or continual evolution in a chronically infected individual before spilling back into the population. 4/16
This long branch does not appear to be an artifact of subsampling. A CoVariants "focal build" that pulls in related genomes also shows this long branch (nextstrain.org/groups/neherla…) as does a search with UShER (genome.ucsc.edu/cgi-bin/hgPhyl…) for placement on the full SARS-CoV-2 tree. 5/16
As noted by @Tuliodna these viruses bear a remarkable constellation of mutations in the spike protein that are concerning in terms of predicted immune escape coupled with increased transmissibility. 6/16
You can see the striking accumulation of mutations in the S1 domain of the spike protein just by plotting S1 mutations against time and coloring by clade (nextstrain.org/ncov/gisaid/af…). Omicron viruses bear many more S1 mutations than previously circulating variants. 7/16
Besides this mutational profile, the other critical data point is apparent rapid spread in South Africa. Here, I wouldn't trust frequencies of genome data at the moment as there has been urgent sequencing and deposition of S dropout samples collected from Gauteng. 8/16
This causes a straight forward genome frequencies analysis to overestimate rate of spread of Omicron. Instead I'd focus on rapid increase in proportion of S dropout tests in Gauteng as well as other provinces in South Africa (screen grab from ). 9/16
This rapid increase across provinces is concerning and suggests that Omicron is outcompeting Delta in the current context in South Africa. I'd hope for modeling work using this S dropout data to better quantify relative fitness of Omicron vs Delta in the following days. 10/16
However, rather than looking at raw frequency of genomic lineage or clade assignments, we can take a phylodynamic approach to estimate clade growth. This approach uses a molecular clock along with branching patterns in the phylogeny to infer viral population dynamics. 11/16
We did this previously for early data in Washington State to infer the introduction time and rate of exponential growth when community transmission was first identified in Feb/Mar 2020 (Figure 2B of bedford.io/papers/bedford…). 12/16
Here, I took the exact same approach using 77 available Omicron genomes from South Africa and Botswana. This yields a median estimate of a common ancestor at Oct 7 (95% CI between Sep 19 and Oct 21). This seems consistent with first detection in a sample from 11 Nov. 13/16
This also yields a median estimate of exponential doubling time of 4.8 days (95% CI between 2.6 and 8.7 days). This median estimate can be compared to a 3.4 doubling time for early spread in Washington State. 14/16
Growth rate (in absolute terms and relative to Delta) will be become clearer in the following days, but at the moment, I believe we're looking at a variant that potentially has significant immune evasion and that appears to be spreading rapidly. 15/16
The world should be immensely grateful to @Tuliodna, @ceri_news, @nicd_sa, the Network for Genomics Surveillance in South Africa and the Botswana Harvard HIV Reference Laboratory for discovering this variant and immediately alerting to its existence. 16/16

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More from @trvrb

22 Nov
Did vaccination drive the evolution of variant (Alpha, Beta, etc...) SARS-CoV-2 viruses? This is a legitimate scientific question, but after looking into it I don't believe this to be the case. 1/19
Grenfell et al. 2004 (science.org/doi/10.1126/sc…) lays out the conceptual foundations for thinking about this problem. This figure is a bit hard to parse, but basically vaccination will increase population immunity and move rightward on the x-axis. 2/19
This will increase the strength of selection for immune escape (blue line), but will decrease viral abundance (red line). The rate of viral adaptation (black line) depends on both selection and abundance and so is maximized at an intermediate level of population immunity. 3/19
Read 19 tweets
17 Nov
I support making boosters broadly available for those 18 and older. Even if breakthrough cases are generally mild in younger age groups, there is significant societal benefit to reducing circulation. 1/6
nytimes.com/2021/11/16/us/…
Currently Washington State is seeing almost 30% of cases as breakthrough cases (doh.wa.gov/Portals/1/Docu…). 2/6
Here, I think of @alexismadrigal's piece on the implications of a positive COVID test (theatlantic.com/health/archive…). It's crazy to me that we're saying to healthy younger individuals they must isolate for 10 days after a positive test, but that they're not eligible for a booster. 3/6
Read 6 tweets
15 Nov
The evolution of SARS-CoV-2 in the past year has been remarkable with Delta increasing transmissibility by perhaps 2.2X over "non-variant" viruses. 1/14
We should expect this evolution to slow as SARS-CoV-2 continues to adapt to the human host, but when should we expect this? Here, I propose that we've already seen slowing between 2020 and today. 2/14
One very important concept here that I keep coming back to in thinking about evolution is @GreatDismal's quote that "the future is already here. It's just not evenly distributed yet". 3/14
Read 14 tweets
13 Oct
I've meaning to write a "COVID endgame" thread for a while and I apologize this is somewhat delayed compared to media interviews like science.org/content/articl… and statnews.com/2021/09/20/win… and to recent seminars like . 1/17
Here, I've been trying to think about what COVID will look like in its endemic state, ie once the (more or less entire) population has immunity to the virus, blunting transmission and disease relative to the pandemic state. 2/17
I expect endemicity to be achieved at different times throughout the world due to inequities in vaccine distribution and I expect this to be a soft transition rather than a sudden flip of a switch. 3/17
Read 17 tweets
11 Oct
I realize this is rather late to the party, but I wanted to provide a look at the prospects of Mu variant virus. I believe we can conclude that Mu appears more transmissible than all circulating variants except for Delta, but Delta is substantially fitter than Mu. 1/9
If we look within Colombia, we see Mu becoming predominant around May 2021, outcompeting other endogenous South American variants Gamma and Lambda. However, recent sequencing suggests that Delta is successfully invading on this Mu background (nextstrain.org/ncov/gisaid/so…). 2/9 Image
In neighboring Ecuador, we see a heterogeneous mix of Alpha, Gamma, Iota, Lambda and Mu by June 2021. Delta has been successfully displacing most of this diversity since July 2021, while Mu has remained relatively stable (nextstrain.org/ncov/gisaid/so…). 3/9 Image
Read 9 tweets
28 Sep
I'm honored and completely overwhelmed by the recognition from @macfound and @HHMINEWS. Flexible funding with a multi-year commitment is the professional scientist's dream and I'm incredibly grateful for this opportunity. 1/4
For me, like others in the field, responding to the pandemic has been a ceaseless and exhausting endeavor. But I'm immensely proud of what the teams at @nextstrain, @fredhutch and the @seattleflustudy, as well as the larger scientific community, have accomplished. 2/4
That said, it's difficult for me to sort out my feelings about these awards, as they are so intertwined with the pandemic. It feels perhaps uncomfortable to be professionally rewarded for doing something that felt like a moral imperative. 3/4
Read 4 tweets

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