1/ You’ve probably heard the #Omicron “stealth” sub-variant, BA.2, is spreading rapidly in places like Denmark. We’re tracking the signal and, while there’s a lot of uncertainty, a picture is emerging. A thread on what we’re learning. @RickABright @jessicamalaty @amymaxmen @Tuliodna

2/ Like most VoCs, #Omicron can be divided into multiple sub-variants. The most common one–often just referred to as #Omicron–is BA.1. Unlike BA.1, BA.2 can’t be easily distinguished from Delta using PCR. So, for this analysis we relied on genome sequences shared in @GISAID.

Two panel figure showing the (left) the evolutionary relationship of BA.1 and BA.2 to each other and to the rest of the SARS-CoV-2 lineages and (right) a global map showing the 50(ish) countries where Omicron BA.2 has already been identified by genome sequencing. These data come from the GISAID initiative and were generated by NextStrain.

3/ In Denmark, BA.2 is spreading rapidly, despite BA.1 leveling off. This worrying trend is why scientists, including analysts at PPI like @ZacharySusswein & @KaitEJohnson9, are investigating.

Figure shows the epidemic curves for BA.1 (green), BA.2 (orange), & all other (purple) SARS-CoV-2 variants in Denmark from Dec 15th 21 - Jan 15th 22. The y-axis is rate per 100 thousand individuals and the plot shows that BA.1 was the dominant strain until around Jan 10th, when BA.2 surpassed it in prevalence. However, BA.2 was present at low levels as far back Dec. 15th (when the plot starts). The other non-BA.1 or BA.2 variants have been steadily decreasing. Data from GISAID analysis by PPI.

4/ But, there are A LOT of ways that data biases can “trick” us into thinking a variant is spreading faster. We’ll rule them out as we walk you through our findings.

5/ First, labs could rush genomes they think are stealth #Omicron (BA.2). We saw this with BA.1 in the US. In Denmark, the data show no evidence for this bias, with time between collection and posting to @GISAID being nearly identical for BA.1 and 2.

Figure shows the lab time of genomes from sample collection to submission to the public repository on GISAID for BA.1 (green) and BA.2 (orange) by week in Denmark between Dec 6th and Jan. 20th. There is no statistically significant difference between the two lineages in terms of time to submission. Data from GISAID, analysis by PPI

6/ Second, the surge in BA.2 might only be happening in a single city or region of Denmark. Think early days of #COVID19 in the US being largely confined to NYC/Boston. Again, this is not what’s happening in Denmark. How can we tell?

7/ Across Denmark, ​​BA.1 #Omicron waves preceded BA.2 in every region, and despite these BA.1 waves, we find that BA.2 is increasing exponentially. This analysis relies on a rough estimate of variant prevalence, but Denmark has very good surveillance.

Figure shows the epidemic curves for BA.1 (green), BA.2 (orange), & all other (purple) SARS-CoV-2 variants at the region-level in Denmark from Dec 15th 21 — Jan 15th 22. The five regions all show the same pattern. BA.1 was the dominant strain until around Jan 10th, when BA.2 surpassed it in prevalence. However, BA.2 was present at low levels as far back Dec. 15th (when the plot starts). The other non-BA.1 or BA.2 variants have been steadily decreasing. Data from GISAID analysis by PPI.

8/ We estimate that BA.2 is quickly replacing BA.1 in Denmark (in more technical terms it has a doubling time of 4–5 days relative to BA.1). Said differently, the epi data show that BA.2 is outcompeting BA.1. This is a worrying trend and one that we are watching closely.

Figure shows the estimate prevalence of the BA.2 variant across the five regions of Denmark. Across all five regions, the growth rate in the prevalence is very similar. Data span from Dec 15th 2021 through Jan 15th 2022 and the y axis goes from 0% to 70%. Data from GISAID, analysis by PPI

9/ We are not the only ones reporting a growth advantage of BA.2 in Denmark. Multiple groups finding similar patterns is the kind of evidence we look for with newly emerging variants. Consensus is one way to build confidence in results.

Tweet shows the growth of BA.2 Omicron in Denmark.

10/ Concerningly, we find similar growth rates of BA.2 in India vs. other variants (doubling every 4 days). This is a sign we look for when a variant has a competitive advantage, spread in multiple countries despite the high prevalence of other variants. Important caveat follows.

Figure shows the proportion of viral genomes from India submitted to the GISAID initiative that are BA.2. Data span from Dec. 14th 2021 through Jan 16th 2022. The prevalence of BA.2 was quite low (~0%) in mid-Dec, rising rapidly to ~75% by mid Jan. Data from GISAID, analysis by PPI

11/ The data from India are noisier (it’s a *much* bigger country than Denmark & has lower prevalence). The dynamics of Delta vs BA.1 vs BA.2 don’t look exactly the same either. We wouldn’t hang our hat on these results, but they are consistent with the emerging BA.2 pattern.

12/ In Germany researchers have again found similar patterns.

Tweet shows that BA.2 cases are growing exponentially in Germany, especially in Berlin.

13/ And also in the UK.

Tweet shows that BA.2 is increasing rapidly in the UK

14/ Genome sequences from individuals arriving in Japan that test positive for SARS-CoV-2 show evidence for widespread BA.2 across South East Asia. These findings are consistent with genomes from in-country-based surveillance outside of Japan.

Tweet shows the distribution of BA.2 genomes identified in travels arriving in Japan and in individuals who test positive across countries in Asia.

15/ Finally, it might also be that there are mutations present in Denmark BA.2 that make these viruses unique from other BA.2s (a sub-sub-variant). Based on recent data, this again does *not* seem to be the case.

Figure shows the evolutionary tree of recent BA.2 genomes from a number of countries. Importantly, there is no evidence that sequences from Denmark cluster together in a way that would suggest a unique set of mutations defines these sequences. Data from GISAID, analysis by PPI.

16/ Our partners in the US are scanning for BA.2 in wastewater & clinical samples. Right now, BA.2 is rare.

Tweet shows that the BA.2 variant is still quite rare in the US.

17/ BUT wastewater testing from Marc Johnson’s lab at @mumedicine shows that BA.2 is in the US, and spreading fast. This aligns with what we would expect given trends in other countries. As our environmental surveillance manager, @megan_b_diamond says, “Waste before case.”

Figure shows the percent of sewer sheds in Missouri with Delta (green), BA.1 (blue), and BA.2 (orange) between late Nov. 2021 and mid Jan. 2022. BA.1 quickly rose from ~0% of sewer sheds in early Dec. 2021 to 100% of sewer sheds by early Jan. 2021. BA.2 has been present at low levels, but has started increasing.
Inset from the previous figure where the y-axis ranges from 0–10% and the x-axis covers the period from Nov 30th 2021 through Jan 11th 2022. The BA.1 variant (blue) spreads rapidly in early Dec., but now BA.2 is increasing rapidly (starting in late Dec 2021).

18/ There’s no data yet on BA.2 severity nor on its risk for vaccine breakthroughs. However, we need to watch the science here very closely over the next few days.

Tweet discusses how we still don’t know enough about severity and/or vaccine breakthroughs for BA.2

19/ What’s next? As with the currently dominant #Omicron (BA.1) the advantage for BA.2 could be because it’s better at spreading (higher R0) and/or it’s able to re-infect individuals w/ immunity to BA.1 (immune escape). We’re investigating this now w/ epi data & will report out soon.

20/ Huge thanks to the @GISAID initiative and their incredible community that makes these kinds of analyses possible.

21/ Our analysis, along with others on Twitter, are only possible because data and insights are being shared publicly. Join the network we’re building @ppi_insights, share your information with the world, and help us create a #PandemicFreeFuture.



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