On the one hand, we may have a tiny bit of cheery Covid news, in that Omicron indeed may produce a lower level of hospitalizations. The notion that it doesn’t typically settle in the lower lungs and produce viral pneumonia appears to be borne out. GM provided a technical explanation for those who like that sort of thing:
I don’t think I explained that before but it looks like Omicron has very poor S1/S2 cleavage, even though the FCS [furin cleavage site], if you just look at the mutations, was expected to be actually enhanced. But it seems that the conformation overall shifted and the loop that was exposed to the proteases before is now closed most of the time. So it does not get cleaved. What that means is that it now no longer relies on the TMPRSS2 protease, but just on ACE2. Nobody expected such a shift to happen — it always looked like the ACE2+TMPRSS2 pathway is much more efficient, but here we are.
That will require a bit of explaining too, but this cartoon illustrates it well:
SARS-CoV-2 can enter cells via two routes, both routes require spike activation by proteases.
Route 1: Cell surface fusion, triggered by TMPRRS2. Route 2: endosomal fusion, triggered by cathepsins.
So far SARS-CoV-2 has favoured Route 1. pic.twitter.com/x2qsNpIKpO
— Joe Grove (@GroveLab) December 30, 2021
Basically there are two pathways — the endosomal, which requires endocytosis of the whole virus particle, and does not rely on S1/S2 cleavage, but just on ACE2, and the direct fusion, which relies on ACE2+TMPRSS2.
But here is the interesting thing — the alveoli actually have little ACE2, only the AT2 pneumocytes express it, and even there it’s not all that high. What drives infection there is the fact that there is a little bit of ACE2 plus quite a lot of TMPRSS2. So it goes the fusion way. It then drives syncytia formation, which is very destructive.
But without the S1/S2 cleavage, it has to only rely on ACE2.
Which, again, is not superabundant in the alveoli, but there is a lot of it in the bronchi.
Thus the tropism shift and likely the milder respiratory symptoms — less infection in the lower lung, less cell-to-cell fusion. An important caveat is that we have no idea what happens elsewhere in the body, how much LongCOVID, etc….
But then there is the question about SARS-1. Because SARS-1 is also poor at S1/S2 cleavage, yet it is much more pathogenic than SARS-2. So what is the mechanism there? The likely explanation is that SARS-1 is much more powerful at shutting down IFN signalling, thus can replicate to higher levels inside the body before innate immunity kicks in. And that allows it to turn lungs into goo even though it does not have an FCS….
Something to watch.
GM also said in a separate take that this improved understanding of Omicron (early on he gave a wonky explanation of how no one sequences the viruses in full, and the ways in which the shortcuts have shortcomings) meant that the idea that Omicron and Delta couldn’t benefit from a cross mutation even if that were to happen now is not the case, there could be adaptive gain if that were to happen.
However, as GM pointed out in passing above, we still don’t know about Omicron and long Covid. Omicron is also hitting kids hard, and children under five are among the demonized unvaxxed, since Pfizer admitted its shots didn’t elicit an adequate antibody response among two to five year olds:
⚠️Totally “mild”—US pediatric #COVID19 hospitalizations nearly 2x last year’s all-time high. Kids shouldn’t be hospitalized—kids shouldn’t be getting #LongCovid. Kids have their whole lives ahead of them. Let’s protect the kids. 🙏
— Eric Feigl-Ding (@DrEricDing) January 2, 2022
— Eric Feigl-Ding (@DrEricDing) January 2, 2022
And on the other hand, even if Omicron might be less deadly, getting it does not confer lasting immunity. And the baseline for how many people died from Covid, particularly younger cohorts thought to be not generally vulnerable, has been revised upward. From the Center Square (hat tip Paul R):
The head of Indianapolis-based insurance company OneAmerica [with $100 billion in assets] said the death rate is up a stunning 40% from pre-pandemic levels among working-age people.
“We are seeing, right now, the highest death rates we have seen in the history of this business – not just at OneAmerica,” the company’s CEO Scott Davison said during an online news conference this week. “The data is consistent across every player in that business.”…
Davison said the increase in deaths represents “huge, huge numbers,” and that’s it’s not elderly people who are dying, but “primarily working-age people 18 to 64” who are the employees of companies that have group life insurance plans through OneAmerica.
“And what we saw just in third quarter, we’re seeing it continue into fourth quarter, is that death rates are up 40% over what they were pre-pandemic,” he said.
“Just to give you an idea of how bad that is, a three-sigma or a one-in-200-year catastrophe would be 10% increase over pre-pandemic,” he said. “So 40% is just unheard of.”….
Most of the claims for deaths being filed are not classified as COVID-19 deaths, Davison said.
“What the data is showing to us is that the deaths that are being reported as COVID deaths greatly understate the actual death losses among working-age people from the pandemic. It may not all be COVID on their death certificate, but deaths are up just huge, huge numbers.”
He said at the same time, the company is seeing an “uptick” in disability claims, saying at first it was short-term disability claims, and now the increase is in long-term disability claims.
Now you might say, but isn’t this out of line with excess death estimates? Yes, but an insurer is in much better position to have granular information about deaths, and Davison says his company’s experience is shared across the industry. Second, it’s often forgotten that some of the changes during Covid would have reduced deaths. For instance, in the first Covid wave, in early 2020, Alabama locked down in anticipation of an infection spike that turned out to be mild compared to the likes of New York and California. Alabama had negative excess deaths due to the reduction in driving and therefore road accidents.
And before you try to find a silver lining, this news is not likely to be positive for Social Security solvency. Even though the US is a sovereign currency issuer and we could pay for Social Security if we wanted to, the convention is that it operates as a trust. More people dying young means fewer people paying into the system. More people getting disabled young also means fewer paying into the system and some (most?) collecting Social Security disability. And an even sicker aged population means higher Medicare costs.