Derek Lowe: Omicron Update (Dec 17) | Hacker News Reader

Derek Lowe: Omicron Update (Dec 17)

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79 pointsherodotus59 comments

> South Africa is the furthest along in the Omicron world, from what we can see, and although their cases have rocketed up, their rates for hospitalization and death have only been a fraction of what was seen in the earlier waves.

That is pretty good though, all things considered. Spreads fast, but is mild enough. If the next variant is going to be even better in this regard, we should be happy. It may, given enough people catch this variant with mild symptoms and develop immunity. Maybe we should re-think the strategies involving restrictions and vaccination.

If the mutations continue, at some point the mortality rate will likely meet the mortality rate of the seasonal flu. Hopefully we can then compare COVID to the season flu on any large media outlet / platform without being canceled, so that we can accept it as such and not rework our lives a dozen times a year around restrictions.

> Hopefully we can then compare COVID to the season flu on any large media outlet

It will never happen, humans take more and more to recover from traumatic events and people who claim that it's time to put the traumatic event behind our back and go on with our lives are singled out as irresponsible .

See the 2008 financial crisis, we are still doing QE, Fed balance sheet would never go back to normal , we have scam companies worth hundreds of billions and perhaps the most scammy one just went above a trillion in financial value with no real tangible product presence in a market in which commands a 1% presence.

I guess it depends on the person, but this doesn't square with what I see, and I live in what's considered a very liberal area with relatively strict mandates. People are going to bars & clubs, eating out, holiday shopping, etc. Even people who are being more cautious right now are itching to get out and do stuff. I think we'll recover just fine.

> likely meet the mortality rate of the seasonal flu

We should consider the possiblity that we are already there with omicron.

I thought the pushback on the comparison to flu was the conclusion that's intended to draw. The 2018 flu outbreak hospitalized approximately 710,000 Americans[0]. Public health professionals generally thing flu should have more public attention, so saying we should be unconcerned because now we have another disease as impactful as flu, I can see them objecting.

0. https://www.cdc.gov/flu/about/burden/index.html

According to the CDC, the flu caused 12,000-52,000 deaths a year in the US between 2010-2020 [0]. While covid caused more than 800,000 deaths in the US over the past two years, and more than 36,000 US deaths over the past month alone [1]. At this point, covid is still orders of magnitude deadlier than the flu.

[0] https://www.cdc.gov/flu/about/burden/index.html [1] https://covid.cdc.gov/covid-data-tracker/#trends_totaldeaths

...it’s 12k-50k per year. So just (“just”) one order of magnitude or so.

Since June 2020, flu deaths have been in the single digits or teens most months, while covid deaths have been in the thousands or tens of thousands each month [0]. So covid is around 3 orders of magnitude more deadly than the flu.

[0] https://www.cdc.gov/nchs/nvss/vsrr/covid19/index.htm

Can't compare apples and oranges. For flu seasons, regular classification applies. For pandemics, all persons that die with Covid are Covid deaths.

Apples and oranges.

is this also a thing in the states? in germany even people who died from accidents but have tested positive for covid (either pre or post mortem) are counted as died from corona - not kidding.

- https://www.zdf.de/nachrichten/panorama/corona-tote-rki-stat...

- https://www.heise.de/tp/features/Wer-zaehlt-als-Corona-Toter...

It’s a thing in the States, too, and it makes it difficult to see the facts clearly. I have no idea why we’re handling the data on COVID so differently from previous diseases and pandemics, though I’d be interested to hear a plausible, non-conspiracy-theory explanation.

Cause of death is on the death certificate, but there is no law of nature that there must be exactly one cause. The assignment of cause of death is thought to be biased in many cases, perhaps even subject to political pressure. Maintaining consistency of public health statistics about COVID19 from one time to another (or from one locale to another) is very desirable to sustain the practical usefulness of the statistics in assessing consequences of public health measures. It may be reasonable to expect that classification of COVID19/non-COVID19 deaths by public health officials based on arbitrary but more objective measures (such as time period from COVID19 diagnosis to date of death, used in the UK) may improve the value of the statistic.

> previous diseases and pandemics

This is not a new problem. Life insurance companies believe that many suicides are misreported on death certificates as accidents because the person completing the certificate does not want to prevent recovery of insurance proceeds by the deceased beneficiaries; prevention of social stigma is also thought to reduce reporting of AIDS, STD's, suicide, liver disease, recreational drugs, etc as a cause of death.

There may be arguments for decades to come about who did well in controlling COVID-19 and who told the truth about it.

> I have no idea why

We are why. We are the subjects of both politics and medicine, a disconsonant duo locked in an awkward embrace, and they want to embrace us, gently guide us, and disturb us a little as possible, because we determine both the course of the pandemic and the will of the governed in the nations we inhabit, jostling about and wondering why.

During the pandemic, the CDC has been also been counting deaths with the flu [0]. So we do have an apples to apples comparison. And covid has been around 3 orders of magnitude more deadly than the flu.

[0] https://www.cdc.gov/nchs/nvss/vsrr/covid19/index.htm

There is no guarantee of that at all. Many diseases get worse over time

https://www.politifact.com/factchecks/2021/dec/08/facebook-p...

If only we had endless medical capacity for those who will not have it "mild"

Well, it is better than the mild ones not having it mild either, but worse.

As far as I know, mild cases are only confirmed for vaxxed people.

I wonder about, say, how non-vaccinated 16-25 years old people are affected by Omicron vs. Delta.

Did you find any statistics saying that?

SA was only around 20% vaxxed when the omicron wave started and everyone with boots on the ground there seems to be saying it’s milder.

Could be.

I also heard SA has a much younger population than most western countries, so "mild" should be used with caution.

> given enough people catch this variant

Please see the point Derek Lowe makes in the first article, of Dec 2 (point which I have abridged in this page): cases of mild immune response which let the virus dwell for a long time in the organism can be the proper places for a virus to develop mutations.

Also, the paragraph closing this article of Dec 17: that the main future mutations will be of high contagiousness and low impact is a non granted possibility.

Yeah, fair enough. I mean, after all, mutations are random, it can get worse.

> cases of mild immune response which let the virus dwell for a long time in the organism can be the proper places for a virus to develop mutations.

that's practically irrelevant or you'd have to demand lockdowns for any virus and its uncle because they all mutate all the time. is that what you want?

It's not mutations that are the threat, it's mutated COVID-19.

> is that what you want?

Those remarks were not about policies.

Those remarks seem to remain quite valid to stress the maxim, "do not jump to conclusions" ("Careful with that reasoning, Eugene"): apparent mild symptoms, hence the idea of getting infected possibly being almost a good thing: actually, there are a number of issues one can suspect or know.

Incidentally, there are articles today (The Atlantic (Katherine J. Wu), CNA - I think - and more) about those "mild symptoms" being a definitely partial side of the story. And, importantly, "symptoms" and "_damages_" are two different things. One of the recent pieces of news mentions lowered sperm count and quality after infection with the latest variant: that is damage which is not a symptom - it is not apparent.

Policies remain a matter to be built over the base of the analysis from discipline specialists, mediated by politicians that are supposed to apply said tentative knowledge and emerging hypothetical policies in the "big picture" of the complexive networks of interests, and apply good "common" sense to restrict the "man with a hammer" syndrome typical of specialists (so that ideas in the class of "no cars, no accidents" are censored).

My policy - since you kindly show interest in my opinion -, is "Be careful as opposed to sloppy", in general, because that is the world I would want to live in. The consequences of such careful attitude policy remain to be analyzed by specialists to tentatively assess potential outcomes, nothing is granted before full consideration. (Although, I remain convinced that if that had been the applied maxim, the virus would have lasted only a few weeks before extinction, save for complications relevant to animals as vectors.)

I'd really like to see an analysis comparing covid to the flu. There's the vaccine and omicron making it less deadly than before, but I have no idea by how much.

I think it's really important to stress that while it is obviously great to see fewer people in hospital, that alone doesn't tell us very much about the severity of the variant, or the expected outcome in other countries.

We would already expect the number of hospitalisations second wave to be way lower, because of the effect of higher levels of immunity through vaccines and previous infection versus the first wave. The Discovery Health research from South Africa [1] suggests that Omicron might result in about 30% fewer hospitalisations versus an equivalent Delta infection, but it's still early days and it's hard to get clear data given the number of confounding factors. The early research from Imperial in the UK [2] says:

"The study finds no evidence of Omicron having lower severity than Delta, judged by either the proportion of people testing positive who report symptoms, or by the proportion of cases seeking hospital care after infection." with the notable qualification that "hospitalisation data remains very limited at this time."

Even if it's substantially less severe, it does seem certain from the way it's ripping through the UK at the moment that it spreads extremely quickly – and even with a lower chance of hospitalisation, we could quickly see a very large spike in the number of people requiring care, with the corresponding stress on already overstretched healthcare.

I'm definitely a bit concerned about the amount of "it's basically just a cold now!" chat we've been seeing – something we'd all like to be the case because pandemics are shite. But anecdotally I have witnessed first-hand quite a few people I know here in the UK being pretty blasé in the run up to Christmas and getting quite sick as a result.

[1] https://www.discovery.co.za/corporate/news-room#/pressreleas...

[2] https://www.imperial.ac.uk/news/232698/modelling-suggests-ra...

> And notably, the virus that causes COVID-19 is most transmissible before symptoms set in, so its harmfulness to its host may not be as strong an influence on how it evolves as the trade-off model suggests.

> "The virus, speaking anthropomorphically, just wants to spread and have its genes replicated," said Dr. Amesh Adalja, an infectious disease specialist at Johns Hopkins University, in an interview. "If the best way for it is to spread by causing severe symptoms, it will continue to do that."

https://www.politifact.com/factchecks/2021/dec/08/facebook-p...

not sure I understand the reasoning here because the behavioral response to covid at a collective level will always depend on the harmfulness of the disease regardless of when symptoms set in.

We are going to take stronger measures against harmful diseases, and that reduces their fitness inevitably. The claim that a disease always evolves towards being more harmless is obviously not true due to mere chance, but in the long run there is a clear advantage to it. Rather than cherry-picking examples to prove the point I think it's more accurate to say the article cherry-picks counterexamples like multiple Malaria strands competing against each other in the same host or a rabbit disease that became more deadly to overcome an immune response. None of which is long-term adaptive.

We are talking about the relative evolutionary fitness of different variants, so until we have the ability to decide whether to avoid someone based on what variant they have (and may not be showing symptoms of), I don't see how behavioral response enters the picture.

Do you think Politifact is a good source for that information? I'm sure there are other less-biased alternatives that discuss that subject.

A minor point in here corrected a misconception I didn't realize I held:

> T-cell mechanisms are also crucial, and T-cell data are much harder to come by. Since you don't see the number of papers in that area as you do for antibody profiling, it easy to think that they don't matter as much, but that's not true.

I'd be really interested to hear someone in microbiology opine on the difficulties in measuring T-cell and other non-antibody data? What makes it so much harder?

You're probably looking for an immunologist.

Not the expert you're looking for, but I recall a past Derek Lowe article mentioned in passing that it was much more labor-intensive (presumably by a trained lab tech) to get T-cell data. Again, this is just my memory of a past Derek Lowe article, which I might be misremembering.

There are mechanisms for t-cell testing in reasonably wide use now. from what I understand its not done that much comparatively is because its bloody expensive.

I think one of the mechanisms is here: https://en.wikipedia.org/wiki/ELISpothttps://en.wikipedia.or...

However I would take all of this with a pinch of salt. I asked my doctor friend about it, they said "We use t-cell tests for a bunch of things, but its really expensive. I can't remember what thing we were looking for, probably TB, everyone had TB in that ward, so it might be that."

One thing I’m curious about and on which I haven’t been able to find any good data/information is whether the drop in vaccine efficacy is a function of time since last dose (i.e. due to waning over time) or whether the third dose drives up total antibody or T-cell activity and/or broadens the immune response which leads to it being more effective against Omicron.

My spouse and I have both had boosters but my child has only had two doses because they only recently authorized use for children ages 5-11. I think my spouse and I are fairly well protected but it’s uncertain if my child is well protected or not given the timing of everything.

I am not updated on this, but is COVID-19 much of a concern when it comes to your child, especially after having received two vaccines already?

Fair question. My general understanding is that the risk is very low for children, especially when it comes to severe disease and/or death (though there are still some questions about long-term effects), and even more so now that they have been fully vaccinated with two doses.

I’m mostly just curious if we’ll see booster recommendations for children as we have for adults and if the efficacy impact of Omicron is due to time or something inherent to the two-dose vs three-dose mechanisms at play.

And generally as a parent I’d prefer to see my child not get sick at all, though I know that’s basically unavoidable. That being said, I like to understand what the risks involved are if possible.

I'm in a similar position: I've had three mRNA doses, vaccines here may start to be available to my children next week

I wouldn't want them to be the weak link, but having them partially immunized during a delta/omicron peak may be sub-optimal...

Any data/analysis on the subject would be welcome

3 boys at home, all with a COVID-19 infection last December. The one already after the puberty got long COVID, the one "in the start of puberty" had only mild long COVID and the youngest one (7) was asymptomatic.

Some friends noticed also this puberty "cut". But statistically, I cannot tell if this is significant or not, because you never have the information "12 good in puberty" or "11 no signs of puberty yet".

No scientific data unfortunately, but this BBC article explains that even though it's the same substance each time, the effect develops further over multiple doses, and goes on to describe what that means using metaphors.

BBC News - Omicron: Why do boosters work if two doses struggle? https://www.bbc.co.uk/news/health-59639973

Excerpt:

"Fortunately for us - while the contents of the syringe may be identical, a booster is not just more of the same for the immune system.

The protection you're left with after the third dose is bigger, broader and more memorable than you had before."

We have a 1 year old. We try to avoid intentional exposure, but the knowledge I have indicates COVID is no more of a threat for children than many other viruses. Flu, RSV, etc all have similar risk profiles in young kids. As such, we approach COVID the same way we approach many other things.

Wash hands, avoid known sick people, monitor conditions, avoid known bad situations.

We are avoid daycare facilities for now since that would introduce a many-to-many situation where an outbreak is inevitable.

Where were all the people saying "I told you so" about viruses getting milder over time when Delta came around?

Everyone is dead already

> A team in Hong Kong has announced that in their cell assays the Omicron variant seems to reproduce up to 70 times faster in the upper respiratory tract, while at the same time being much slower to reproduce in lung tissue

> What About Immune Evasion? How Much Protection Do Vaccines Provide? This part of the story isn't completely worked out yet... Most of that [information] is antibody-based data, and ... while this is important, it is not the last word on real-world immune protection[: ]T-cell mechanisms are also crucial, and T-cell data are much harder to come by

> the Pfizer protease inhibitor ... does appear to be just as effective against Omicron, but its supply will not be enough to make any real difference at all in the coming weeks

From the "introduction" of Dec 2:

> Where Did It Come From? Omicron ... is not a direct descendant of the Delta strains ... An immediate hypothesis was that Omicron may have developed in a single immunocompromised human patient over a period of weeks or months[: ... y]ou don't just immediately kill everything off - you give the virus or bacterium a chance to overcome a lesser challenge before turning up the pressure a bit more, letting mutations accumulate and try their worth over and over as the challenge slowly increases. That's just what's going on inside a coronavirus patient if they can't mount a full immune response. The virus and the immune system engage in a prolonged battle where neither one can land a decisive blow, and things just keep on evolving. This is why they tell you to take your full course of antibiotics when you have a bacterial infection, and why effective vaccines actually suppress variant formation: if you kill off the pathogens as quickly as possible, they don't have time to explore their mutational landscape

> the Pfizer protease inhibitor ... supply will not be enough to make any real difference at all in the coming weeks

Tautalogically so in the US, anyway, where the FDA has inexplicably still has not approved (or emergency authorized) it for use.

On one level I agree, but realistically I think they may not feel much of a hurry to do so since there isn't a significant supply ready to distribute. My understanding is that they already have authorization to use whatever they have, essentially as additional testing.

As of Nov 29,

> Pfizer now expects to make 80 million courses of COVID drug Paxlovid by the end of 2022

That's a ton of supply!

I'm not sure what you're quoting from, but ... that's more than a year from now.

End of 2022. That doesn't help us in 2021.

to me its sounds like its too slow. how many variant have we had this year already?

I hope the pill from pfizer can withstand the evolution cycle of this blasted virus.

For those following - these treatments are 40 pill treatments. For the 50M odd cases we've had we'd need 40*50M pills (2 billion pills).

Assume a daily global rate of around 600K cases per day we'd need 24M pills per day.

USA alone is perhaps 100K cases, so 4M pills per day. Do they really have this volume ready to go?

I'm not aware of a single study showing that for vaccinated folks the pills do anything. Not saying they don't, but it would be helpful to have ONE study.

As to why the FDA has not approved, they are reasonably clear. One issue is that COVID, and particularly omicron variant which dominates, is just not that lethal.

EDIT: This part is incorrect below

These pills work in interesting ways, ie, generating MORE mutations.

β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells https://pubmed.ncbi.nlm.nih.gov/33961695/

So before you jam 2 billion doses into folks there is going to be a bit of an evaluation.

If Omicron turns out to have high fatality rates then I suspect things like these therapies will be fast tracked a bit more.

you describing here merck treatment, not pfizers

> For those following - these treatments are 40 pill treatments.

> These pills work in interesting ways, ie, generating MORE mutations.

> β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells https://pubmed.ncbi.nlm.nih.gov/33961695/

You're way off-base. You're talking about Merck's Molnupiravir (Lagevrio), which is both less effective (~30% vs ~88%) and already approved.

Pfizer's Paxlovid (Nirmatrelvir) is not mutagenic.

It is a 15 pill course (5 days x 3 per day), not 40.

Also, Pfizer thinks as of Nov 29 that they can make 80M courses by EOY. The US has purchased at least 10M of them.

Has Pfizer submitted the clinical trial data to the FDA? The last I heard (a week ago?) was that they were going to do it "in a few days".

This presser from the 14th claims final data was submitted[1]. I don’t know the exact details of both processes, but somehow the EU has authorized it already, on presumably the same data.

[1]: https://www.pfizer.com/news/press-release/press-release-deta...

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