What do we know about Omicron? I fear most ppl are unfortunately too optimistic. They're missing the Key Omicron Question.

Here's a summary of what we know about Omicron, and the key question that remains unanswered:
2 numbers matter in epidemiology: the transmission rate and the fatality rate.

The transmission rate tells you how many people are likely going to catch a virus, and how hard it will be to fight it.

Once you catch it, the fatality rate tells you how bad it will be.
Then there's 2 complications: these numbers interact in weird ways.

1. Ppl believe that viruses that become less lethal spread better.

2. Yet a less lethal virus might end up killing more.

How do we make sense of it all? Let's dive deep
1. Tranmission rate
This thing is growing FAST
(source: )
The transmission rate (here Rt, how many ppl infected by a source infection) is 3-4x higher than for Delta! OMG! Is Omicron 3-4x more transmissible?
Hold on a sec.
With an R0 of 6, Delta is already among the most contagious viruses we know. If Omicron was 3-4x more contagious, it would be the most contagious virus we've ever seen. Way more than smallpox. Unlikely. So what might be going on?

Immune escape
Maybe Omicron is not spreading faster than Delta because it's more contagious. Maybe it's just better adapted to its environment: one where everybody is immune, either through vaccine or previous infection

Most ppl in South Africa and EU are indeed immune
This graph shows the possible scenarios. Omicron is on the black line. If it had the same R0 as Delta, it could be 3x more contagious if it escaped immunity 40% of the time.

It could be half as contagious with an 80% escape.

So how much does it escape immunity?
A lot. A bunch of lab tests have all seen the same thing: substantially fewer antibodies (up to 40x)

Now antibodies are not the only immune defense, and 40x fewer antibodies doesn't mean 40x less antibody defense. Is there any data from the wild? Yes
After 6 months, 2 doses of Pfizer give you a 60% lower chance of infection (not hospitalization, that's much higher), but for Omicron it's probably ~40%. So it would be 1/3 less efficient.
FWIW the wisdom of the crowd predicts that Omicron's R0 will turn out to be about the same as Delta's, at ~6

(source: metaculus.com/questions/8755…)
OK so Omicron is probably ~as contagious as Delta (+/-) but escapes immunity. Makes sense since the virus has mutated SO MUCH. Look at all the mutations compared to Delta

(source: )
This virus comes from a completely different branch! It appears to have evolved in parallel, from an early variant, and is very different from from the original, Alpha, and Delta.

Is this a sign? Maybe we've finally found this elusive virus that evolves to be less virulent?
It wouldn't be without precedent. Look at what happened in the 1918 flu: the 3rd wave killed much less, and then it disappeared.

Is this happening now? Is this virus bypassing immunity, infecting everybody, but not killing them, and strengthening their immunity along the way?
2. Fatality Rate
We're *just* at the time when we should be seeing deaths going up. Nothing so far, but it's to be expected. The next week will be defining.
What are predictors of deaths? Hospitalizations. These are indeed growing in SA.
The jump happened on Nov 27th. 2 weeks to death is usual. So we should expect deaths to go up. The question is how much.
ICU and ventilator patients are much lower than Delta at the equivalent moment. We can assume this will continue, which means there will be fewer deaths. YAY!
The community agrees: it thinks there's only a 15% chance Omicron is more lethal than Delta
Are there other predictors? What about what are doctors seeing? Across the board, milder symptoms. Another good news!
Listen to this doctor: she's just not seeing the same level of aggressiveness. Yes!
But hold on a sec: is this because the virus is less lethal? Or because we're more immune?

As I've explained in the past, we should *not expect COVID to become less lethal over time*.

True for Alpha, true for Delta, likely true for Omicron.
This is due to passage: the same reason that makes a virus more transmissible tends to make it more lethal, *unless it needs to evade death to be more transmissible*. This is not the case in COVID
By the time somebody dies, he's been usually isolated for weeks. Ample time for the virus to become more aggressive and pull up the time of death without suffering in terms of contagiousness.

But if this is true, why would the virus appear less lethal? Immunity.
Immunity levels in SA and EU are very high, either through natural immunity or vaccines. Up to 80-90%.

So the virus had to evolve for immune escape, and that's what it did.
But it didn't need to evolve for lower lethality. Why would it?
Key takeaway: this virus
- Is likely about as transmissible as Delta
- Has more immune escape
- My guess: is probably ~as lethal for naive immune ppl, but *a bit more* lethal than Delta against immunized people

Which leads us to the Key Omicron Question:
What's the fatality rate of Omicron vs. Delta for
-Vaccinated or previously infected?

Evidence➡️the most likely outcome is that Omicron is worse across both, but since vaccinated and previously infected have grown since Delta, it doesn’t appear to be the case.
This weird effect has a name: it’s Simpson’s Paradox
I go into much more detail about all of this in this week’s article, The Omicron Question
Subscribe to receive follow-ups on Omicron, and more of Uncharted Territories articles.

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More from @tomaspueyo

15 Dec
I only see 2 ways out of COVID:
1. An endemic disease that kills a few hundreds of thousands/million of ppl every year
2. A disease eradicated through global vaccination campaigns

I fear there's no 3. A virus that becomes less lethal over time and blends in like a cold
Note that 1 and 3 are pretty similar. In both cases, the disease is endemic and kills a few people every year. The cold doesn't, but the flu does, at ~0.13% of the sick every year.

But what if it wasn't 0.13%? What if it was 0.4%? Would we accept that? It's the ≠ btw 1 and 3
The reason why think we can get to 3 is because that's what probably happened to the 1918 flu: it's H1N1, and after killing so many ppl, it ended up evolving to kill less so it could spread more.
Read 10 tweets
14 Dec
Everybody is very optimistic about Omicron.
I HOPE they're right.
I FEAR they're prey to a statistical error, Simpson's Paradox:
Simpson's Paradox says that you can see a trend because you're mixing two populations, but when you separate the populations, the trend is the opposite.
For Omicron, we might be mixing two populations: immune (through vaccinations or natural immunity) vs. naive (ie they have neither).
Read 6 tweets
7 Dec
4 paradoxes of feedback, one core insight, and 18 tools to get the best feedback:
Paradox 1: the more painful feedback is, the more important it is to get it.
Read 31 tweets
7 Dec
Why Europeans colonized America before Africa, in two maps and one story:

Map 1:
Northern Africa, bordering the Mediterranean, has been part of the Eurasian cultures for thousands of years.

South of that, it didn't get conquered until the 19th century, while America got conquered 3 centuries earlier despite being farther. Why?
For centuries, there was the Sahara barrier. The distance to cross was just too big. Impossible by foot, and only possible by sea through the Red Sea in the East, on the path to India, because of inhabitable stops on both sides
Read 14 tweets
9 Nov
Why is Africa the way it is?
Why are its countries where they are?
The relationships between them
The people? The deserts?

Here are X to easily understand Africa better (politics, geography, history, demographics, climate & more)
One of the key ways to look at Africa is through this map: its river basins.

Let's start with the big one in the northeast. It's the Nile's watershed.
Here's northeast Africa at night. See that flower in the middle? That's the Nile through Egypt.
100 million Egyptians live within ~15 miles of its banks. That's ~99% of them.
More details here.

Read 29 tweets
14 Oct
Parag and I talked for over an hour about migration and the impact it will have in the 21st century. We covered:

- How current nationalism & the image of immigration is short-sighted historically
- The + borders you have, the - borders you have
- The existence of empires today
- African pop growth is overestimated
- The winners of the 21st century will be the most successful states at attracting immigrants
- Which countries would benefit from receiving hundreds of millions of migrants, and why. 
- What does the majority think about migration?
- The problem of Gen Z vs. Gen ɑ
- What do Germany and Japan have in common
- The optimal size for a country
- Terraforming Siberia
- How elderly Germans are changing their minds about immigration&seek it instead of fearing it
- How Bulgaria’s immigration approach has is doomed
Read 6 tweets

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