It’s a bit disconcerting to find we are a day further into a fast moving crisis yet I don’t have the sense anything both new and meaningful has emerged. But it still seems useful to try to clarify some of the claims floating about as well as a few new Omicron factoids that that have emerged but seem a lot less dispositive than the press enthusiasm would have you believe.
As usual we are very grateful for the help of our Covid Brain Trust and I am quoting more liberally from them than I did our also very valuable Brexit Brain Trust. The reason for hewing to our sources’ words more closely is I don’t want my interpretation to distort meaning.
And What Pray Tell Do You Mean By Severe?
Alarms appear to have gone off at WHO and the CDC after a spell of “initial signs are that Omicron isn’t that bad:
The World Health Organization is concerned that the omicron variant is being dismissed as mild, even as it spreads at a faster rate than any previous strain https://t.co/Xsr5nVgQRP
— Bloomberg (@business) December 14, 2021
European CDC says a "rapid increase in Omicron cases is imminent," warns that exponential growth will "rapidly outweigh any benefits" of a potentially reduced severity
— BNO Newsroom (@BNODesk) December 15, 2021
Oddly we have to go to Daily Mail rather than Twitter for a pointed recap of our CDC’s more downbeat outlook:
And remember, even if Omicron is actually is less nasty on average, it’s so highly transmissive that hospitals will be overwhelmed:
New @IndependentSage statement:
Omicron is doubling so fast that sheer numbers will v likely outweigh any advantage of reduced severity (if it exists). To prevent NHS being overwhelmed in a few weeks & for a safer Xmas we need to act now. Not next week, not after Xmas, now. 1/2
— Prof. Christina Pagel (@chrischirp) December 15, 2021
And there is an offset that Thomas Peacock, the scientist first to post on B.1.1.529 before it was called even that, noticed immediately: that it probably evades monoclonal antibodies. Our GM was quite certain that would be the case, and our IM Doc now has pretty some pretty sick patients who are not responding at all to Regeneron, which has an EUA for use as a Covid treatment and is generally seen as effective. German researchers confirmed yesterday that Regeneron’s and Eli Lilly’s Covid treatments are not effective against Omicron. GlaxoSmithKline’s cocktail Xevudy still appears to work in vitro, but that may not translate as well in vivo.
The loss of some, perhaps all, monoclonal antibodies as Omicron remedies means that some patients that could otherwise have been treated outside a hospital will wind up being admitted. This is an offset to any average reduction in severity.
So it should not come as any surprise that, so far, deaths in Gauteng are tracking previous Covid waves:
Finally, here's an updated graph (log scale) of reported #COVID19 DEATHS during each wave in Gauteng ??
— Ridhwaan Suliman (@rid1tweets) December 16, 2021
Yet as our GM was correct to warn, the “mild” meme, as the hot take meant to preserve Christmas festivities and shopping, has become anchored. The press is pumping out even more articles to try to normalize Covid, such as the Atlantic’s Don’t Be Surprised When You Get Omicron. Gee, how about instead running a public service piece like “What You Need to Do to Not Get Omicron.”
GM reacted, quoting the article and then commenting:
One by one, the symptoms I knew so well on paper made their real-life debut: cough, fever, fatigue, and a loss of smell so severe, I couldn’t detect my dog’s habitually fishy breath.
Mild brain damage.
Once you know you’re infected, hang tight, limit your encounters with other people, and just take care of yourself.
As discussed earlier today, all the effective treatments need to be started early on. So what exactly is the advice to “just take care of yourself” on your own going to achieve?
And what are they going to do with the monoclonals and Omicron? There is only sotrovimab [GlaxoSmithKline] that actually still works and that is presumably in very short supply. But do they still refuse to give to the vaccinated (which are no longer actually vaccinated)?
IM Doc was even more disturbed:
This article is a sterling example of the vaccine only mantra.
“Stay home and take care of yourself.”
This is the terminal lunacy of VAX VAX VAX.
The problem is that many of these people are being told to stay home while they are turning blue and coughing up their lungs. And this week in my area 85% of the COVID outpatients are fully vaccinated with 30% of those boostered. It is as if the entire medical industrial complex has learned not a fucking thing in 2 years.
I cannot tell you how ashamed I am of where my profession is today.
The fact that our media is still putting out this kind of tripe to mislead the masses is yet another sign of the mass delusion.
IM Doc pointed out how the “mild” meme was doublespeak:
I think Americans think of “mild” as a head cold. I think the medical establishment thinks of “mild” as not being admitted. The non-admitted, however, can be violently ill, trust me.
GM wanted to understand exactly what “violently ill” meant. IM Doc again:
That is a medical intern phrase – it means very very sick – but not quite hospital level. And it is also very age dependent – younger people can handle this much better than older people.
I have 7 patients with COVID right now that my office and I are calling twice daily. They would all fall into this category.
By definition, they all have someone to watch them at home.
Some of the symptoms we are dealing with today – temps up to 103, severe shaking racking chills, sweating enough to soak the sheets 1-2 times daily, severe coughing, vomiting their guts up, severe myalgias.
These people are sicker than just a flu. However, not quite admission. Mind you, the criteria for admission has been higher lately, we have just not had the bed space – and people really do not want to be in the hospital.
This is most definitely not the average course of influenza….
We do not really have people deteriorating where they cannot get them to the hospital on time. WE KEEP A VERY TIGHT LEASH ON THEM. Unfortunately I do not think many Americans have a primary care practice that does this.
They also have very strict parameters to call us instantly.
And I call them twice a day. Most of the time there are 5-7 people. Some days upwards of 15. The highest has been 22 – but that is absolutely not the norm. It really gets quite crazy.
This is the large reason why I and my staff are so exhausted. To keep them out of the hospital and safe at home is just enormous amounts of work.
Unfortunately, I think myself and my practice are the extreme exception. I do not get the idea this level of care is being done by most practices. I just feel obligated to keep them at home as best we can.
IM Doc also underscored yesterday that even though he might have some Omicron cases (due to failure to respond to Regeneron) it was still too early in the course of a normal Covid case for any to be admitted.
Delta-Omicron Recombination Unlikely
Some readers were concerned by news reports of Moderna’s chief medical officer telling MPs that Delta and Omicron might recombine. GM was perplexed. His reaction was even if that happened, it would not appear to give the new variant any real advantage. But Delta and Omicron circulating at the same time (as opposed to Omicron pretty quickly becoming dominant) could still be very nasty. GM:
There isn’t much that Omicron can obviously gain from Delta and vice versa. Omicron has the immune escape, it has FCS enhancement, it has the N protein packaging improvement, it has the Nsp6 deletion, so what exactly is there in Delta that will make it fitter by recombination? And vice versa — Delta has those transmission enhancing features too. Some of the AYs have accumulated further ORF and Nsp mutations, so there might be some room for improvement there, but it will be marginal.
The bigger problem will be that you will have sick people in the same rooms in hospitals and they might become cross-infected, which should worsen the outcomes.
The Lack of Interest in Treatments
Biomedical professor KLG had said from the get-go that he expected the approach to Covid to come to depend heavily on treatments, as it has with HIV. The fact that we have instead gone all in with limited efficacy, comparatively short-lived vaccines is a big departure.
PlutoniumKun of our Brexit brain trust had found some hints in the Japanese press that Japanese doctors were prescribing Ivermectin and added:
From what I understand of the Japanese medical system, it wouldn’t surprise me at all if they are giving it to patients without telling them….Those who have lived in Japan will confirm I think that getting a straight answer from a Japanese doctor on any medical topic is nearly impossible.
Epidemiologist Ignacio noted:
One of the problems with Ivermectin, IMO, is the hospital-centric view that dominates medicine. It is well known that some approaches with medicines might work in early stages of infection (very early so as to be considered nearly preemptive) and only or mostly work if administered timely. This is, or can be the case of Ivermectin. When you go an do clinical trials the result is “It has no effect” and that might be the case if the design of the trial results in too late delivery to notice an effect. But in real life practice it might be the case that words have circulated among Japanese doctors in the sense that it indeed does something.
IM Doc described how the CDC has hung doctors out to dry:
When you have been doing this as long as I have, you have a memory of what happened before and with that comes certain expectations about what should be happening now. I think that is what separates the older than 55 crowd from the under 40 crowd.
We do not even have to go back to AIDS. I am thinking of the last 2 events in my career where there was exceptional involvement from the CDC. In 2018, we had the vaping crisis. In 2012 or thereabouts, we had the West Nile issue. Although that virus had been with us since 2001 here in the USA, it really exploded in the summer of 2012 in the Deep South in the USA. I will not include the 2014 Ebola problem. The CDC was very involved there but that never really had to be taken nationally, these other 2 examples did.
In both cases, there was frequent, at times weekly updating from the CDC about treatment options and guidelines. There was intense discussion of what seemed to be working and what did not. In both cases, these treatment options were obviously non-approved for these purposes by the FDA. There was a crisis, and this is what we have available, and this is how you should be using them. This is what works. This is what does not work. And this is our evidence why we feel the way we do. This was constant from the CDC in both cases.
That has simply not happened at all in COVID. Here we are 2 years into this. There is not a single shred of treatment advice from the CDC outside of the inpatient setting. Let’s face it – most antiviral efforts have to be done immediately. That would mean where I work in an outpatient setting is the golden hour. If we wait till the patients are in the hospital they are going to have much worse outcomes. The agencies are saying nothing about outpatient therapy and have put forth nothing. We have worldwide studies on fluvoxamine, ivermectin, HCQ, steroids, VIT D, VIT C, Zinc, and I am sure there are many others. We now have monoclonal AB. A question – have you ever heard Dr. Fauci discuss monoclonal AB in a positive way? If you have please show it to me.
There has been no guidance at all about any of these therapy options. There has been lots of censoring, hectoring, belittling, and confusion. It is unusual to find a physician willing to engage any of these therapies, despite some of them having overwhelming positive signals in early outpatient therapy.
There is not ONE single bullet. By now, 2 years into this we should be throwing all kinds of things at these patients – anti-virals, anti-clotting agents, anti-inflammatory agents. But we are doing nothing.
Again, our CDC has done nothing to help with this at all. NOTHING. Not only the CDC. In previous events, there was treatment advice flowing from medical schools around the country. CRICKETS.
We have gone all in on the vaccine approach and have done so from the beginning.
Now, the bill is due. My office is literally flooding with vaxxed and boosted patients that are very ill. We are in a precarious situation with the hospitals of America. They are in much worse shape employee-wise than many Americans would dare dream.
I feel all alone. I feel it is my sworn job to keep as many of these people safe and out of the hospital as possible. But there is literally no help from the CDC at all VAX VAX VAX. Here is the problem – about 85% of these patients in my practice that are now positive and getting sicker by the day are already VAXED Many of them boostered. We are in the middle of a crisis with the hospitals – and we simply cannot fill them up the way we have.
Hyping of Way Too Preliminary Report of Omicron Bronchial Replication
This finding is being hyped in the mainstream media, such as Reuters, as if Omicron won’t take hold in the lungs and will nicely and courteously stay up in your bronchial passages:
Very interesting analyses about the virology of #Omicron, which may explain the faster spread of this variant.
According to a new lab study, Omicron infects & multiplies ~70x faster than the Delta variant and the wild type SARS-CoV-2 in the human bronchus, but not in the lung.
— Muge Cevik (@mugecevik) December 15, 2021
Help me. It typically takes five to seven days from symptom onset for Covid to produce viral pneumonia, in cases where it advances that far. The NHS indicates that the most rapid onset of garden variety pneumonia is 24 to 48 hours, with several days more common, strongly implying that 24 hours is bleeding edge.
Thus concluding anything about possible disease evolution at 24 hours for pathogen that normally takes well over a week after exposure to get really ugly (recall symptom onset averages 5 days after exposure) is quite a stretch.
GM was also skeptical and pointed out that Delta was hard to make behave in vitro and that may be true of Omicron, further complicating reaching early conclusions:
They found greatly increased replication in bronchus cells but reduced replication in lower lung tissue.
And now the narrative is that it is becoming an URT [upper respiratory tract] infection.
But this makes no sense — in the same plot they have Delta showing the same pattern, and Delta was more severe than WT [wild type], not less, and this is what every study finds, so it’s not even controversial.
And they tested this only up to 48 hours, but that is not how this works in actual human bodies — it starts as an URT infection then moves further down. So if you have 70 times more virus in the middle lung, you should be seeding a lot more of it in the lower lung, even if it replicates a bit less there, and the net effect is negative…
Everyone is in a mad rush to put out results as quickly as possible and as a result they are not even thinking how damaging putting out incomplete data with premature conclusions can be…
But there is more to this story.
Another factoid, from Vineet Menachery:
“A bit inside virology, but #omicron grows very poorly and causes very little CPE. This makes interpretation of replication data difficult since most measures are dependent on CPE based measures. Doesn’t mean that data is wrong, but magnitudes maybe a bit fuzzy.”
Menachery is someone who studied coronaviruses before the pandemic, i.e. one of the few OG coronavirus scientists and someone who knows this stuff inside out
But apparently Delta is not that easy to grow either. Yet both are hypertransmissible. So there is some major poorly understood difference between in vivo and in vitro…
Then this preprint came out too:
Which is mostly yet another neutralization study, but the supplement is interesting:
Here, they grew it up to 96 hours in VeroE6 cells.
And you see a curious thing — Delta shoots up real fast, but even WT [wild type] grows much better than Omicron, which initially goes down at from 0 to 48 and only then ramps up.
Yet it is hypertransmissible like nothing seen before…
I have no explanation nor can I square any of this (or any putative reduced virulence) with the mutations in the virus.
It’s a wait and see for the fog to disperse…