For those of you that have asked me why I am convinced that cryptic lineages are coming from people, I can finally point to a pre-print with @dho and many fantastic collaborators in the UWisc and Wisc Public Health. medrxiv.org/cgi/content/sh…
It's pretty straightforward. We started with a sewershed that produces enough wastewater to fill about 30 olympic swimming pools a day. We sampled about a quarter cup.
But something didn't smell right.
It had a cryptic lineage, a SARS-CoV-2 RNA that was completely unknown.
For the next several months my collaborators continued to take sub-samples from throughout the sewershed and sent them to me to figure out which one 'didn't smell right'.
With each round of sampling we further narrowed the source of the cryptic lineage.
We finally narrowed the source to a single manhole, and then to a single set of bathrooms.
The sample from that bathroom contained by far the most SARS-CoV-2 RNA I had ever seen from a wastewater sample. We could have diluted it a million-fold and still detected the lineage.
This bathroom was not used by any rats or white tailed deer. The signal was coming from a person.
We also learned from this 'homogeneous sample' about the complete viral sequence. It was from a lineage that circulated over a year ago.
The person has been infected a long time.
We still don't know which person is the source (most were tested by nasal swabs and were negative), and more importantly, we don't know why the lineage is not spreading.
We suspect that the source is a long-term COVID infection of someone's GI tract.
There are still a lot of questions that need to be answered, but we have at least started to figure out what the right questions are.
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My favorite way of finding cryptic lineages by screening for what I call the ‘s2m fix’.
s2m is an RNA element at the end of the SC2 genome that has been deleted from all lineages in circulation for over 2 years.
If you see the s2m sequence, you know it is an old lineage.
2/
A distinctive thing about cryptic lineages is about a third of the time they pick up a very specific mutation in their s2m sequence. T29758G. It’s actually a reversion to the sequence found in bats.
BA.1 cryptics. BA.1 infections all occurred in late 2021-early 2022. If there is good coverage, BA.1 lineages are easy to spot because they have a unique Spike insertion that no other lineages have had. 2/
There were hints of a few BA.1 lineages across the country, but there were only 2 that were really clear, one in San Diego and one in Western Colorado.
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Cryptic lineage quarterly update, part 1
Recent BA.2-XBB cryptics
Cryptic lineages are unique, evolutionarily advanced SARS-CoV-2 lineages detected from wastewater from an unknown source.
1/
We are almost certain that these lineages are derived from individuals that have been infected with SARS-CoV-2 for several years that are shedding a ton of viral material.
If you want to know why we think these are from humans, read this thread.
The lineage is derived from BA.5.1.10, but taken at face value, it has over 90 additional mutations and deletions.
2/
BA.5.1.10 stopped circulating back in January, 2023 in Germany, so this person was presumably infected for at least 18 months before they 'popped' and started showing up in wastewater samples.