Thread by @Ayjchan

On the SARS2 mink outbreak in Denmark: "genome sequences of human and animal strains will continue to facilitate detailed analyses by partners... WHO... are working with Danish scientists to better understand the available results" who.int/csr/don/06-nov…

However, no Danish mink SARS2 sequences are publicly available yet. (Please let me know if it becomes available!) So it's tough to tell exactly which SARS2 mutation combos to be looking at.

Regardless, ending mink farming is a good preemptive move to reduce covid outbreak risk.

One reason why the Danish PM decided on mink culling was that "this particular mink-associated variant identified in both minks and the 12 human cases has moderately decreased sensitivity to neutralizing antibodies."
Raising concerns about vaccine efficacy against the mink SARS2.

I'm going to use the @CovidCg online resource to understand what SARS2 mutations have been detected in North Jutland, Denmark where these mink outbreaks occurred, when the mutations emerged in humans, and whether they can be seen elsewhere in the world.

The first thing I noticed, looking at the SARS2 genomes from North Jutland, is that these are being sampled in an insanely regular manner; once a week. Nice job!

One of the mutations said to be found in the mink version is this dark blue double residue deletion in the spike NTD.

covidcg.org it was first detected in early August, becoming more prevalent over the last 2 months. And the 2 most commonly co-occurring mutations (ie mutations that show up alongside the double deletion in the same virus isolates) are the very common D614G and Y453F.

Looking at each of these spike mutations individually, the double deletion in the NTD has appeared several times and in at least 5 different continents, as early as Europe in March. Visual made from the covidcg.org Compare Locations feature.

Inside of Europe, this double deletion first appeared in Italy in March 2020, and has recently become more prevalent in the Faroe Islands and Denmark.

Inside of Denmark, this double deletion was detected only in August, with quite a broad distribution across different Danish regions sampled for SARS2 sequences.

How about the Y453F Spike RBD mutation?

In Denmark, it was first detected in June and in North Jutland.

Across Europe, Y453F was first detected in Denmark (North Jutland) but later also seen in Switzerland, Russia, and the Faroe Islands. (You can do all this analysis of 100,000s of SARS2 genomes in seconds using covidcg.org)

I'm using the @CovidCg covidcg.org site live right now and typing tweets live to show you the analysis.

So, how about worldwide? Y453F has also appeared in Africa and North America.

This mutation has been covered extensively by other scientists

https://twitter.com/jbloom_lab/status/1324139464818479105

https://twitter.com/jbloom_lab/status/1324409358944407554

Just want to allay fears here about this mink mutation escaping vaccines or antibodies - there is only data that it escapes 1 of Regeneron's antibodies. This is why Regeneron and other therapeutic antibody developers have to test their antibodies against emerging mutants and...

Apply therapeutic antibodies in combination (these are called antibody cocktails; more than one antibody in the treatment) so that even if the SARS2 variant in the patient can escape one antibody, the other antibody may likely still work against the mutation...

In this illuminating @Regeneron @ScienceMagazine paper, they test their antibodies individually and in combinations against different existing SARS2 variants that have been detected. science.sciencemag.org/content/369/65…

Ultimately, @Regeneron was able to show that none of the existing SARS2 variants (at that time, August 2020) could escape or evolve to escape /their cocktails of noncompeting antibodies.

So, although the spike double deletion and Y453F mutation are not very new, are there other spike mutations we should pay attention to in North Jutland, Denmark?

Again using the @CovidCg covidcg.org resource developed by @DevermanLab (especially @atchen_)...

It looks like the A222V variant (green) is growing in prevalence; Y453F (purple) and double deletion (blue) for comparison.

Another one mentioned by other scientists: I692V (orange) which appeared in September but is not in the more recently sampled+sequenced SARS2 isolates in North Jutland.

Also G769V (maroon) seemed more prevalent in September but less so in October.

These I692V, G769V variants that fall outside of the RBD in the spike have not been tested in the @Regeneron study as far as I can tell from their figures, albeit they tested a G769E variant:

Just continuing my exploration of each mutation. The A222V variant - it's been around since early days (March, 2020).

G769V also been around since March but clearly growing in case counts in Europe. I switch between using cumulative counts vs % sequences on the vertical axis depending on what looks easier to interpret. You can try it yourself on covidcg.org

I692V looks more interesting; has only been detected in North Jutland, no other region/country in the world - at least based on the data available on @GISAID Appeared in August, 2020.