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.
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'.
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.
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.
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).
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.
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.
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.
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:
Just returning from the CEIRR influenza annual meeting.
Here are my takeaways.
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First the bad news.
2.3.4.4b (which the H5 in cattle is derived from) is a bad ass. In birds it is ridiculously contagious, ridiculously promiscuous, and pretty darn deadly. It spread through typical and atypical US bird populations practically instantly.
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Now the good news.
The lineage has mixed pathogenicity in mammals (don't let your pet ferrets play near wild birds), but generally is very poor at mammalian respiratory spread, even in species where it is highly pathogenic.
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MO COVID wastewater update. Although it's not major, there has been a noticeable uptick on COVID levels the last few weeks.
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In my thinking, there are 3 things that contribute to these fluctuations: the viral lineage, host immunity, and human behavior.
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I don't think the viral lineage has much to do with this uptick. We've been experiencing a gradual takeover of a scattering of JN.1 derivatives, but they have been with us for a while and don't seem to correlate with the increase.
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Update on the Maryland variant, the highly diverse Delta variant from a sewershed South of Baltimore. 1/
This sewershed only started sequencing earlier this year, so I don't know how long it has been around, but it is clearly Delta-derived, which means the infection probably occurred in the second half of 2021, nearly 3 years ago. 2.
The lineage has been showing up pretty consistently in the first sewershed, but on May 21 it also appeared in the sewershed just to the West. Daytrip. 3/
A few points about the H5N1 outbreak that I'd like to share.
1. If we had a pan-influenza wastewater screen in place nationally that differentiates the influenza sources by sequencing (which isn't that hard to do), we probably would have detected this outbreak months ago.
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BTW, we submitted a CDC proposal earlier this year to do exactly this, but the topic was pulled from the BAA so the proposal wasn't even reviewed.
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2. We should not panic about the current outbreak in cattle. You aren't going to get influenza from pasteurized milk, and this virus isn't ready for human-to-human spread (yet).
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