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.
1/
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.
2/
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).
3/
3. What we should be concerned about is that fact that the viruses is getting way too many chances. It keeps expanding its tropism. The more animals it replicates in, the more chances it gets to sample new configurations.
4/
4. When the virus makes it way it to pigs, that is when we need to start getting really nervous. Pigs are a mixing vessel where flu is more likely to adapt to respiratory spread in humans.
5/
5. In my opinion we should be focusing our attention on wastewater testing downstream of meat processing plants (for all types of animals). It wouldn't matter what tissue the virus is in, it would end up in the water and give us an early warning.
6/
We've detected and sequenced pig influenza from such sewersheds before (not H5N1), so I know it can work.
7/
6. Most important, we shouldn't shy away from surveillance because we want to avoid a panic. There is still time to stay ahead of this, but if we aren't careful I think it's just a matter of time before H5N1 makes it to humans.
8/8
4.
• • •
Missing some Tweet in this thread? You can try to
force a refresh
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/
Classic new cryptic lineage from Maryland (South of Baltimore). It's a Delta-derivative (2-3 year old infection). 1/
This one is practically a caricature of a cryptic. It has 6 of the classic Sarbeco reversions. 2/
I'm too lazy to make a figure, but the core RBD is:
417T, 420N, 431G, 440K, 444R, 446N, 450E, 452Q, 460K, 477N/D, 483Y/F, 484I, 486P, 490Y, 493K, 498Y, 499T, 500N, 501T.
3/
This is weird. I was going through public wastewater sequences and found another BA.1.1 lineage that didn't get the memo that it is supposed to be extinct.
This time is was from Sioux City, Iowa (which is on the Nebraska border) in February. 1/
However, then I checked and realized that there were actually 3 BA.1.1 sequences deposited from Nebraska in the last month. They are very divergent, but closely related to each other, and they are from at least 2 different patients. 2/
I'm pretty sure the lineage from wastewater is the same sub-clade.
BA.1.1 has S:371L, but both the wastewater BA.1.1 and the patient sequences have S:371F.
Cryptic lineages desperately want to restore this glycosylation site (I've seen it restored 4 different ways), but the reversion is EXTREMELY rare in circulating lineages.
26/
Then there is the RBD. The cryptic lineages really want Q498H (the sequence in bats) or 498Y. As I mentioned, these changes are extremely rare in circulating lineages.
Seems this change probably has more to do with the tissue than with the species.
27/
Finally, the change in SC2 that messes up the s2m (29758T).
The s2m stem loop is a highly conserved RNA structure among some Corona, Astro, and Picorna viruses (which generally all infect the GI tract).