Marc Johnson Profile picture
Nov 1, 2022 7 tweets 2 min read Read on X
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. Image
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. Image
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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More from @SolidEvidence

Oct 28
Cryptic lineage quarterly update, last update for now.

I save the weirdest for last. Read to the end.
1/ Image
A lineage popped up in our cryptic screen because most of the seqs did not have the s2m deletion (meaning it was from 2022 or earlier).

The sample was from 9/30 in Texas. Population is 780, so it isn’t even on the NWSS map.

I don’t know where the sample was from.
2/ Image
So next I checked the RBD, and it was virtually blank. Decent coverage, but no mutations to speak of.
Very weird.
3/ Image
Read 8 tweets
Oct 26
Cryptic lineage quarterly update, part 3
Cleveland variant.
If you missed part 1 and 2, they are here.
x.com/SolidEvidence/…
x.com/SolidEvidence/…
1/
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.

More about s2m here, if you are interested.


3/
Read 11 tweets
Oct 23
Cryptic lineage quarterly update, part 2
BA.1 and Delta
If you missed part 1, it is here.

1/
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/ Image
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.
3/
Read 12 tweets
Oct 22
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/ Image
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.

2/
Or read our paper on the lineage we almost tracked down.

3/
sciencedirect.com/science/articl…
Read 14 tweets
Oct 2
Update on the Bavarian cryptic lineage that @LongDesertTrain spotted.

This lineage first popped up in August but has been consistently present since.


1/ cov-spectrum.org
Image
The lineage is derived from BA.5.1.10, but taken at face value, it has over 90 additional mutations and deletions.

2/ Image
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.

3/ Image
Read 4 tweets
Aug 17
I'm giving the variant update at the SAVE meeting on Monday so I thought I'd put out a preview for comment.

We are now at our 4th 'high water' mark since the Omicron wave based on wastewater surveillance.

1/ Image
I thought I would give an abbreviated summary of the last year in variants.

A little over a year ago BA.2.86 started circulating, a lineage that was almost certainly derived from a persistent infection.
2/ Image
BA.2.86 was pretty fit, but it was still sensitive to a lot of Class 1 antibodies.

However, it quickly picked up S:L455S (making it JN.1), which evaded these antibodies, and it was off to the races.
3/ Image
Read 15 tweets

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