This is somewhat tangential, but I have a broader version of the usual "But what about Long COVID?" question, partially inspired by the likelihood of many more breakthroughs likely to stem from Omicron.

I'm curious if you have a sense of why the topic is often not addressed when talking about headline COVID risks - both in the popular media and often among experts. There's obviously plenty of mentions and articles about it, but I would say the (vast) majority don't mention it or mention it as an afterthought.

I personally don't have a great answer, but my intuitive sense is that it likely means that the more serious cases aren't as common as some estimates have suggested. I.e. if longterm strong versions of Long COVID (e.g. severe chronic fatigue & brainfog) were quite common (say in 10% or even 30% of cases) then we would be hearing about it MUCH more from many corners and with increased urgency.

An alternative explanation could be that the lack of good data makes it hard to write a good story about it but I'm not fully convinced by that one.

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Disposable N95 respirators aren't that great; they generally provide a poor fit and that makes them prone to leaks. If everyone wore the things, this leakiness wouldn't be a problem, since they'd still prevent aerosols from accumulating indoors despite leaks. Unfortunately, most people aren't going to wear them (thanks to the CDC/WHO/most public health officials).

Fortunately, way better PPE exists in the form of elastomeric respirators. Elastomerics offer better fit, filtering (N100 filters), and comfort than N95s. They last forever too. Their only disadvantage is that they muffle speech somewhat.





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If South Africa is only 25% vaccinated and the hospitals aren't overwhelmed yet, wouldn't that support a "more mild" hypothesis?

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It is still way too early to make any kind of assessment on Omicron. Remember that pretty much every optimistic scenario for Covid has been wrong. Vaccines were amazingly efficacious on wild strain covid, but those times are long past.

Not to say it will be a disaster, but anybody with any degree of caution should bunker down, get boosted, double mask, avoid as many social interactions as possible, be prepared for another winter of shelter in place.

I don't have any confidence that our health care bureaucracies or government agencies have learned anything from this debacle, so take any recommendations with a grain of salt.

Oh, and have a Merry Christmas

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Thanks for this, the available media can be confusing, and as always I'm grateful for your help in finding solid resources.

Something I am still confused about, though, and maybe you can point to a good summary, is the effect of variability in the spike protein. The cartoon model of the infection process doesn't really have variability here, it posits a kind of lock-and-key metaphor, where, on the one hand, the spike protein allows the virus to enter the body's cells and do its damage, and/but also antibodies matched to the spike protein allow the immune system to detect and neutralize the virus.

But, as many resources and your text above point out, the emergence of variants complicates this picture. Changes to the spike protein open a gap between what the virus is and what the vaccines alert the immune system to look for, but also maybe open a similar gap between what the virus brings to the fight and what the receptors in your body will accept, and with what degree of enthusiasm.

I guess my question is, are these entirely empirical questions where we have to wait for the data, or is there some history or modeling or something that can provide some clue about how much variability we need to see before it changes the game entirely?

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Since boosters are critical to not getting Omicron, I studied one of the upward-ramping bar charts that shows the higher and higher numbers of people who have gotten two shots, or the one of J&J. Then I made a vertical mark at 6 months ago and a horizontal mark across to today. I looked at how many of the additions were within the past 6 months. It looked like about 20%.

Given that we now know that the protectiveness of the Pfizer and Moderna vaccines declines after 6 months anyway, it seems to me that the number to focus on now is vaccinated and, if more than 6 months ago, boosted.

Do any of you know of charts that show either the number boosted, or the number of more recent than 6 (or 2 for J&J) vaccination plus booster?

It seems to me that this is the number we should be focusing on. Ideally we would incorporate those with the initial full vaccination plus a case of covid, but, since we do not have that latter number, I'm looking for the best data we have on what our society's immunity level is now.

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So a study out of South Africa now says 2 dose Pfizer is 70% effective vs hospitalization for Omicron, compared to 93% for Delta:


I have a couple of questions about this study that the article doesn't answer:

1. Does it measure drop in conditional P(hospitalized| infected) or in raw P(hospitalized)?

2. Does it correct effectively for the likely increased proportion of "incidental" infections among the hospitalized, i.e. people who are positive for Covid and maybe symptomatic but aren't hospitalized *because* of the severity of their COVID symptoms?

These questions seem more consequential this time around than before and I wish the articles would make them clearer.

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In the best-case scenario in which Sars-CoV-2 remains widespread, lets assume it turns into a mild cold, even for initial infections and that the new strains never cause long Covid. We'll still be able to track it, and will have a vast machinery to do so. After lockdowns and losing relatives, lots of people have phobias. I'm wondering if it could remain a severe problem for many years both for individuals who are scared of COVID and with regard to sticky government regulations, with both likely tied to politics in some complicated way? Thus was not the case after the 1918 flu because it was only decades after that the different strains of flu could be distinguished and tracked.

As a disclaimer, this is a thought experiment with some assumptions that might not be realistic. I was thinking how to turn it into a pure psychology/political/sociological question.

Future severity reduction could well depend entirely on pre-existing immunity and might require widespread vaccination of children. We'll need answers on Long COVID after vaccination breakthrough cases (whether long-term symptoms arise with enough frequency to pose a threat), and for that studies are needed over relatively long timeframes. Also, we'll need to see not much worse threats after breakthrough cases in the vaccinated aged than what nursing homes were dealing with pre-COVID with the various viruses already going around. All these things may or may not veer in the good direction.

Probably, for balance, I should sketch out a worst-reasonable-case scenario, but it's too hard to feel out what the boundaries for this virus are, other than postuating having to frequently update vaccines, lots of nasty breakthrough cases with Long COVID, continuing severe problems in nursing homes, and having to be vigilant with children. I think a Stephen King scenario would require a new virus. The rapid Omicron spread does raise the possibilty though we may need to become really fleet-footed with vaccines as it seems to be able to spread faster than our current ability to update.

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Here's a question from a recent patient I didn't have an answer to:

"I'm a 50 year old, fully vaccinated (no booster) male. My 70 year old mother-in-law with a heart condition is also (with the booster). What is the likelihood I will contract COVID (of any variant) and spread it to her over the holidays?

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The usual concept with immune escape is that the virus has optimal binding to start with to a target on the cell it wants to infect. The binding site on the viral protein is a very good antibody target because the antibody will form a physical barrier, making it impossible for the virus protein to bind its target on the cell. So, this part of the virus protein has to be changed to escape antibody targeting, and that's difficult to do without losing some degree of binding, so there could be tradeoffs, with a bias towards becoming milder.

However, what we've seen with Sars-CoV-2 is that each of the subsequent strains through Delta has massively better binding to Ace2 than the original virus. That's still untested, to my knowledge, for Omicron, but it shares mutations with Alpha, Beta, Gamma and Delta that enhance binding to Ace2 in these viruses. So the virus has been able to repeatedly have its cake and eat it too. This suggests to me that Spike might have been poorly optimized for human Ace2 to start with, and while that was the case it was able to improve binding and lose some antibody binding at the same time. That road should be only so long, and after that we'll certainly still see variants appear, but maybe there's hope the tempo will be slower. But this is just guessing on my part.

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Disappointing that there were no policy recommendations is only contingent: if the data show X do x' if the date show Y do Y'. For example should companies be working on getting Omicron variant-optimized vaccines approved? If not now under what conditions?

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I feel that much of what is concerning (or confusing) about omicron is clarified by these illustrations of potential relationships between severity, transmissibility/immune evasion, and cases or deaths.




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