Marc Johnson Profile picture
Sep 18, 2022 19 tweets 7 min read Read on X
SARS-CoV-2 lineages, Cryptic lineages, and a prediction of what the next dominant VOCs will be.
We sequence SARS-CoV-2 from wastewater using a different approach than most. We sequence smallish fragments of the genome so that we can tell if particular mutations are derived from the same virus. This way we are better able to determine if there is anything new circulating. Image
About a year and a half ago we detected something from a St. Louis sewershed that didn't make sense. SARS-CoV-2 lineages whose sequence did not match anything that had been seen from patients. We called these 'cryptic lineage'. Image
Wanting to know if this kind of thing was common, we started collaborating with @DrJDennehy to see if we could find anything similar in other places. NYC also had cryptic lineages. Not the same lineages, but lineages with similar characteristics.
nature.com/articles/s4146…
By the end of 2021, we had identified 9 sewersheds (out of about 180 that were being routinely surveyed) that contained cryptic lineages, including a lineage from California with @RoseKantor.
medrxiv.org/content/10.110…
My obsession with finding and characterizing these cryptic lineages accelerated in 2022. To date we have screened wastewater from around 700 sewersheds. In total we have found 24 putative lineages. I say putative because some of them we have only seen once.
We still didn't know where these lineages were coming from. I was convinced of an animal reservoir. What changed my mind is when we tracked a lineage in Wisconsin with @dho all the way to a single set of bathrooms. There is no animal contribution. It is from a person. Image
What we think is happening is that cryptic lineages are very long-term infections in people (often >1 year). Perhaps GI infections. The hosts are obviously mounting an immune response, but are not able to clear the infection.
Because there are no genetic bottlenecks from spreading from person-to-person, these viruses basically push the evolutionary fast-forward button.
What can these lineages tell us about circulating viruses? These are the sites in the Spike RBD that are most commonly changed in the cryptic lineages. We had seen lineages with these changes long before they were seen in Omicron. Image
When Omicron arrived (shown in red) it had mutations at many of the same sites. The main exceptions were L452 and N460, which were common in cryptic lineages, but were not in Omicron (BA.1). Image
About six months later we started seeing Omicron lineages with mutations at L452. Highlighted in red are the changes in BA.4/5 (which has L452R), but there were also lineages with L452Q, L452M, and others. These lineages took over, but there were still no changes at N460. Image
Finally, a few months ago N460K appeared in an Omicron lineage (BA.2.75). However, it was not combined with any of the L452 mutations. Nonetheless, BA.2.75 and its derivatives have continued to expand and slowly displace other lineages. Image
A few days ago, a new lineage appeared in a MO wastewater sample. Omicron with L452R+N460K (and K444M). This appears to match a new lineage that was just designated as BU.1 a few days ago. Currently there are only 13 sequences in GISAID with this combination of mutations. Image
However, I recently learned from @CorneliusRoemer that I was behind in my lineages. There is another completely independent lineage that arrived at almost exactly the same combination. This lineage is designated BQ.1.1. This group has L452R+K444T (rather than K444M).
In addition, BQ.1.1 has also picked up R346T (also in BA.4.6). We haven't focused as much on this region of spike, but most cryptic lineages that we have checked also have a mutation at this site. It seems to be pretty critical. BQ.1.1 is new, but it seems to be taking off.
There you have it. BQ and BU. I don't know if they will cause a spike in total cases, but barring something completely new appearing, I predict that they will be the dominant VOCs in the coming months.
Addendum. It seems a few other lineages have hit very similar 'jackpot' combinations very recently. In addition to BU and BQ:

BW.1 (BA.5.6 derivative)
BS.1 (BA.2.3 derivative)
BR.2 (BA.2.75 derivative)
other undesignated

They all have N460K, L452R + other changes.
Real pango experts, please correct me if I botch any of these, or have missed any. @CorneliusRoemer @PeacockFlu @siamosolocani @LongDesertTrain

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More from @SolidEvidence

Mar 17
Here is this week's analysis. One mutation popped out as increasing in frequency in the last data set.

S:G842S

Wonder what that is from.

1/ Image
Not a very common mutation. Mostly associated with with XEC.11*
2/
cov-spectrum.org/explore/United…Image
If that's really from XEC.11*, then we should see other mutations from that lineage increasing.

So I looked up the mutations that differentiate XEC.11 from XEC:

Orf1a:V2090F
S:K182N
SV1264L
Orf3a:L85F

3/ Image
Read 8 tweets
Mar 17
I’m very pleased to announce the launch of our LungFish Data Explorer dashboard for tracking SARS-Cov-2 lineages from wastewater.

1/
inkfishmedical.github.io/wastewater-das…
Here’s the problem we hope this dashboard will help solve.  SARS-CoV-2 remains very prevalent in the US.

However, sequence surveillance from patients has plummeted. In addition to fewer samples, the average sequence takes >3 weeks to be reported (and it’s getting slower).

2/ Image
Fortunately, we have wastewater surveillance (primarily through CDC NWSS), which covers a large chunk of the population and has a fairly fast turnaround (<2 weeks).

3/ Image
Read 16 tweets
Mar 1
So what's happening with medical research in the US? This is the cumulative award count from the NIH for the year.

Doesn't look so good.

But it gets worse.
1/ Image
Before grants are awarded, they have to be evaluated in meetings called study sections.

Before a study section can meet, it has to be listed in the federal registry for at least 15 days.

These are the new study section meetings listed in the federal registry this year.
2/ Image
Meetings can't even be scheduled, none of the committed funds are going out.

About 300,000 scientists are wondering if they are going to keep their jobs, and the most vulnerable are the students and postdocs.
3/
Read 4 tweets
Feb 28
There something new on the SARS-CoV-2 landscape, and I’m not sure what it is.
1/ Image
S:S31F and S:K182N are on the rise.

The two aren’t on the same sequencing strand, but I confirmed that they are generally appearing together in the same samples.

2/
The samples are from across the country (CA, WY, LA, CT, PA, WI, etc) and more than one sequencing group, so it’s probably not a sequencing error.

3/
Read 5 tweets
Feb 11
Brief update on the new cryptic lineage we found from Petersburg City, Virginia.

We went back and screened all of the samples from that sewershed since the beginning of 2024 and learned a few things about it.
1/ Image
First, I think I was wrong about the lineage being JN.1 derived. I thought it was JN.1 because it had 22926C (455S), but it looks like it only acquired that recently.

In samples as recent as December the lineage lacked 455S and 456L.
2/ Image
That would mean the lineage is BA.2.86-derived, which suggests it was acquired probably early 2024.

Caveat, as @LongDesertTrain points out, persist infections hate 455S. It’s possible that the lineage was JN.1, but reverted at 455, but then gained 2 nt creating 455A.
3/ Image
Read 8 tweets
Jan 31
Wastewater variant update. This is the composite data from over 1,000 US samples collected over the last 6 weeks.
1/ Image
You have to extrapolate a little bit because several changes are shared by multiple lineages.

It appears that the new lineage I mentioned last week (MC.10.1 + 445P) is around 4% and is the fastest growing of the lot. It now has a PANGO designation - PA.1
2/
LP.8 is still expanding is is probably about 12% now. Since it is a KP.3.1.1 derivative, KP.3.1.1* might become dominant again.

LF.7 seems to be holding on too at about 4%.
3/
Read 7 tweets

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