Thread by @SolidEvidence

I found (or rediscovered) another cryptic lineage this weekend, and this is the weirdest one yet.

Sometimes it almost feels like someone is playing an extremely elaborate prank on me.

I'm not sure even I believe this one.

1/

The lineage is from a sewershed in Switzerland. The group submitted hundreds of sequences recently and the lineage appeared twice in samples from late last year, both times from the same sewershed.

2/

The lineage is derived from B.1.416*, a lineage that circulated in late 2020 and was most prevalent in Switzerland.

I’m still working on reconstructing the genome, but there were several revealing bits in the parts I’ve analyzed.

3/

I'm actually pretty sure I saw this same lineage from samples in 2021. Same sewershed and many of the same changes, but the lineages is MUCH more divergent than before.
4/

Here was the first clue. The samples had lots of sequences that still had the s2m element, which meant it was not BA.2 or XBB-derived, but those sequences lacked G29742T, so it wasn’t Delta or XBD-derived.

It also had T29758G, which told me this was probably a cryptic.

5/

The samples had sequence that lacked R203K/G204R, which meant it was pre-B.1.1, but it had C28833T, which was the first clue that it was B.1.416-derived.

6/

The wild part is the RBD. It had multiple deletions and the overall sequence is significantly changed. I would have thought this were a sequencing mistake, but the same nearly identical mutations and deletions appeared in both samples.

7/

Almost every AA that contacts ACE2 is mutated or deleted in this Spike; could it even still bind ACE2?

It’s possible the sequence is not real, but there were thousands of reads, and it wasn't a reconstruction. It was raw reads.

Could the RBD change this much?

Thoughts?
7/7