As Omicron has washed over the US, infecting perhaps 25% of the population already & likely to reach 40% by mid-February—see thread by @trvrb below—it has driven down almost all other respiratory pathogens, with one curious exception I’ll get to later. 1/9
This is not entirely unexpected. Viral infections trigger both innate and adaptive immune responses that can prevent infection by other viruses. Behavior changes likely contribute to this pattern as well. 2/9
There have been some claims that rhinovirus infection protects against SARS-CoV-2 infection. As you can see in the graph below, SARS-CoV-2 and RV prevalence seem almost perfectly inversely related in recent months. 3/9 news.yale.edu/2021/06/15/com…
Rhinoviruses typically peak in spring & fall & are lower during winter, when influenza, coronaviruses, HMPV, RSV, & other viruses thrive, suggesting these viruses & RVs compete & inhibit one another in some way. Great article on RVs by @MackayIM below. 4/9 virologydownunder.com/rhinovirus-ram…
One would expect more closely related viruses to compete most vigorously. The rapid displacement of one SARS-CoV-2 variant by another in this pandemic seems to confirm this. 5/9
The history of influenza also suggests closely related viruses undergo intense competition. It’s thought H3N8 dominated in late 19th c. but was replaced by H1N1 in the 1918 pandemic. H1N1 in turn was displaced by H2N2 in 1957, which vanished when H3N2 appeared in 1968. 6/9
Curiously, H3N2 has persisted through the emergence of H1N1 in 1977 (possible lab leak) & pH1N1 in 2009. The paper linked to below suggests this is because the 2 major proteins on their surfaces are quite different & antigenically distinct. 7/9 journals.asm.org/doi/10.1128/mB… 6/
This makes the one exception to the downward trend in all non-Omicron respiratory pathogens all the more remarkable. As Omicron has risen, everything else has fallen—except the seasonal coronaviruses, which have risen in step with Omicron. 8/9
OC43, NL63, and 229E have all contributed to the recent rise in seasonal coronavirus cases. (HKU1 has been absent for nearly 2 years now.) I don’t have any idea why this would happen. I’d love to hear what others’ hypotheses are though. 9/9
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There's been some speculation about why, despite persistent immune activation, germinal center activity, & overall elevated Ab levels, LC patients here had very low anti-spike Ab titers. I want to highlight one interesting speculative hypothesis & offer another possibility. 1/10
The ever-fertile mind of @Nucleocapsoid proffers the possibility that exosomes could be responsible for viral spread in some tissue reservoirs. I don't know much about this topic and so don't have much to say at the moment, but I'm trying to l learn. 2/
I'll offer one other possibility: the deep lung environment (or some other tissue reservoir) favors either an extreme RBD-up or extreme RBD-down conformation.
Background: The receptor-binding domain (RBD) of the spike trimer can be up or down. It has to be up to bind ACE2... 3/
A fascinating new preprint w/one very unexpected finding suggests, I believe, that a large proportion of Long Covid may be due to chronic infection in a particular bodily niche, which could be crucial for finding effective LC treatments. It requires some explaining. 🧵 1/33
First, a brief summary of the relevant parts of the preprint. They examined 30 people (from NIH RECOVER cohort) for 6 months after they had Covid, taking detailed blood immunological markers at 3 time points. 20 had Long Covid (PASC), 10 did not (CONV). 2/ biorxiv.org/content/10.110…
The PASC group showed signs of persistent, pro-inflammatory immune activation over the 6-month time period that suggested ongoing mucosal immune responses, including elevated levels of mucosa-associated invariant T cells (MAIT). 3/
Wow, BA.3.2 hits its 4th continent with a new sequence from Western Australia.
Reminder: BA.3.2 is a saltation variant resulting from a ~3-year chronic infection. It is very different from and more immune-evasive than all other current variants. 1/4
It was collected July 15, & is most closely related to the recent S African seqs from May & June.
It has an NSP5 mutation known to be beneficial (ORF1a:K3353R) & 2 new NSP12 mutations, which is unusual. Its 9 synonymous mutations indicate it has been circulating somewhere. 2/4
Seems clear now that BA.3.2 is not going away anytime soon. Its overall impact so far has been negligible, but at first BA.2.86's was as well. Once it got S:L455S (becoming JN.1) the dam burst & it set off a new wave in the global North. The question now is.... 3/4
BA.3.2 update: another sequence from the Netherlands, June 18 collection.
It belongs on the same branch as the GBW travel seq (tree gets confused by ORF7-8 deletion). Also, there are 3 artifactual muts in the GBW sequence (as usual), so the branch is shorter than it looks.
Bottom line, in my view: BA.3.2 has spread internationally & is likely growing, but very slowly. If nothing changes, its advantage vs circulating lineages, which seem stuck in an evolutionary rut, will likely gradually grow as immunity to dominant variants solidifies... 2/9
So far, this seems like a slow-motion version of what we saw with BA.2.86, which spread internationally & grew very slowly for months. But then it got S:L455S & exploded, wiping out all competitors. Will something similar happen with BA.3.2? I think there's a good chance... 3/9
Quick BA.3.2 update. Another BA.3.2.2 (S:K356T+S:A575S branch) from South Africa via pneumonia surveillance.
This means that 40% of SARS-CoV-2 sequences from SA collected since April 1 (2/5) and 50% collected after May 1 (1/2) are BA.3.2. Its foothold seems strong there. 1/3
2 interesting aspects of the new BA.3.2: 1. ORF1b:R1315C (NSP13_R392C)—This mut is in all Omicron *except* BA.3. So this may well be adaptive.
2. S:Q183H—First known antigenic spike mut seen in BA.3.2, not a major one, but one we've seen before—eg, LB.1/JN.1.9.2.1 2/3
I think the unusually long branches in the BA.3.2 tree indicate 2 things: 1. Slow growth globally—fast growth results in many identical sequences, if surveillance is sufficient
2. Undersampling—BA.3.2 most common in poorer world regions with little sequencing of late. 3/3