A thread on S gene drop out patterns in SARS-CoV-2 tests done at @my_helix .

Summary:
- we observe S gene drop out since mid October in US. Up to 0.5% last week.
- more sequencing of the virus is needed in the US.

blog.helix.com/sars-cov2_uk-v…
2/
A new variant of SARS-CoV-2 named B.1.1.7 has been reported in the UK beginning of December, and is likely more transmissible.

Follow these experts: @firefoxx66 @jcbarret @richardneher to know the latest about the variant.

Also @CDCgov summary: cdc.gov/coronavirus/20…
3/
One key point is that the B.1.1.7 variant has not been identified in the US so far.

But the US is doing very little sequencing of the virus compared to the UK for example. So really, we need more information.
4/
Helix does a lot of COVID testing, 2 million samples so far. To test by RT-PCR, we look at 3 targets:
- S gene
- N gene
- Orf1b gene

1 variant in SARS-CoV-2 B.1.1.7, the H69del/V70del overlaps probes to amplify the S gene and leads to S-gene drop out in results
5/
Importantly, the H69del/V70del is a recurrent mutation that is present in many different SARS-CoV-2 lineages. NOT just B1.1.7.

See: nextstrain.org/groups/neherla…

So seeing S gene dropout is not seeing the B.1.1.7 mutant. B.1.1.7 lineage has a Y at amino acid 501 of the S gene. You
6/
Last intro tweet: S gene drop outs do not impact the results of the PCR tests because there are 3 targets.
Goal of looking at 3 viral targets is to be able to deliver results when infected by CoV2 with a mutation overlapping probes in 1 target.
7/
- We saw close to 0 counts of S gene dropouts until October.
- Since October, counts of S gene dropouts are increasing in the US.
8/
This is out of a large number of tests. Looking at fraction of positive results with S gene drop outs shows:
- about 0.5% of the tests last week that have a S gene drop out.

This means 0.5% of tests have the H69delV70del variant.
9/
Helix tests in all 50 states. So we looked where we observed S gene dropouts.
- In mid-October it is mostly limited to Massachusetts.
- Now observed in 19 states. Still highest in MA. Then OH and FL.
10/
Again, this does not mean we see B.1.1.7. But we see H69del/V70del in the US.

More than what we see from sequencing coming from the US where only 25 H69del events have been reported in the US, 22 of them before October. nextstrain.org/groups/neherla…
11/ There is small chance that S gene drop outs are due to another variant (not H69delV70del) overlapping the probes to amplify S. But the prior and recurrence of H69delV70del are such that it is likely the most common explanation for these drop outs.
12/
We hope that looking at S gene dropouts may help to monitor for potential emergence of B.1.1.7.

This study also highlights the need of more viral sequencing in the US.
13/
This was a great team effort led by @genesareclever @jameslu20, with analysis and input from many @my_helix colleagues incl. @kellyschiabor @ETCirulli @EyaSpectre @simonjwhite71
Would love to hear feedback & comments from experts:
@K_G_Andersen @ewanbirney @firefoxx66 @trvrb @mugecevik @richardneher @Cambridge_COGUK

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