Going to wrap up 2021 with an optimistic thread.

If we can avoid creating worse variants with molnupiravir, COVID19 can finally become like the flu in 2022.

1/n
The SA experience, mirrored in Western countries so far, suggests Omicron IFR is an order of magnitude lower than previous variants. This is due to preexisting immunity and lower virulence of Omicron.

2/n
nytimes.com/2021/12/30/wor…
Specifically, deaths per counted case in SA are 16% of the Delta wave so far, but cases are almost certainly undercounted several-fold.

3/n
Many cases were found in SA hospitals by routine screening of asymptomatic people, and the same is true in the US, and we're see ~4x higher viral RNA in wastewater than the Delta peak, compared to 1.3x by official testing.

4/n
`
This suggests actual infection fatality rate (IFR) of Omicron is probably 5-10% as a conservative guesstimate of Delta. If Delta has a IFR of 1.5% in the US, then we're at a IFR of 0.075-0.15.

An average seasonal flu has an IFR of 0.05-0.1 in the US.

5/n
Flu has an IFR of <0.1% because it doesn't usually cause viral pneumonia in health younger adults, and most have partial immunity. Flu deaths are in older and immunocompromised, like COVID19.

See slide 8 in the "coronadeck" (rest of deck outdated)

6/n
Yes SA is younger than Western countries, but the preexisting immunity levels were similar, and the ~10x IFR reduction was seen across ages in SA, as far as we can see, so the same 10x should apply to any population regardless of age distribution.

7/n
The evidence for lower virulence of Omicron continues to build, with recent studies finding less lung pathology in multiple animal models. People aren't small animals, but these particular models were chosen for being very susceptible to disease.
nytimes.com/2021/12/31/hea…

8/n
So what are the conditions necessary to get us to a flu-like state with COVID19? We need >90% with immunity to protect them from death from seasonal SARSCoV2 waves. We will have that, if not 100%, by early 2022.

9/n
A high level of immunity also keeps infection rates low so that the chance of getting COVID19 in each year may drop to<50% even without masks, like the flu.

10/n
We then need annual boosters, both so that we can maintain this state of low endemicity, and so that when we do catch SARSCoV2 eventually, our immune system will be ready to clear SARSCoV2 rather than give it a chance to cause pneumonia.

11/n
Finally, we need the virus not to make big jumps in evolution. Naturally coronaviruses mutate in people at a rate of 2 nucleotides per transmission event, and those events happen 4 days apart on average, and then people clear the virus.

12/n
This is a low enough rate that we are unlikely to get major jumps in immunoevasiveness each year (would be more akin to flu antigenic drift than the large antigenic shifts we fear). This allows existing immunity to remain effective and any breakthroughs to be mild.

13/n
Omicron was an exception in having enough mutations in the spike receptor binding domain (16) to evade most prior immunity. Why it happened is a mystery; could have been a long infection in an immunocompromised person.

14/n
We got lucky Omicron happened to be less virulent too. To prevent future Omicron-like antigenic shifts that are also more virulent and can outpace a humoral reactivation and T cell organ protection, we need to do two things in the future.

15/n
Obviously, we need to vaccinate the world to reduce the ability of the virus to pick up a large number of mutations in immunocompromised hosts, or even just a smaller number of mutations in healthy hosts which will still be bothersome.

16/n
This will make antigenic "shifts" rare enough, and the spread of any shifted virus slow enough, to hopefully buy us time to adapt our vaccines. Companies can then have a schedule of forecasting and adapting their vaccines ahead of time for each fall, exactly as with flu

17/n
The 2nd thing we need to do is severely limit molnupiravir (MOV) use. MOV accelerates viral mutagenesis by 5x (Merck's data) and doesn't reduce viral levels for the first 2 days. So in that time patients on MOV are breeding grounds for potential antigenic shifts

18/n
If the potential for molnupiravir to create worse variants is a surprise, it's because the risk has been overlooked in the rush to have something against Omicron. Ironically MOV is not very effective at all, and Omicron is milder. More info here

19/n
So does it mean that Omicron is a good thing to get and nothing to worry about? No. Just as you wouldn't go out and catch the flu, I can't imagine anyone wanting to go out and get Omicron. It will still set you back a week, and then do the same for your close contacts.

20/n
And just as you wouldn't go visit grandma with a bad flu, you should avoid seeing people with weaker immune systems if you have Omicron or may have it after being exposed. You should thus avoid those New Year parties unless you like getting sick or getting others sick.

21/n
Now the next variant to create a wave may not have the inherently milder severity of Omicron. It could be Omicron regains some lung infection ability, or the next variant is not derived from Omicron. But as long as it's not both antigenically shifted and infectious...

22/n
... then in high-immunity countries our preexisting immunity will limit severe outcomes. Hence it could be like a regular seasonal flu most years, and how we think about the risk of antigenic shift and a particularly bad epidemic could be similar to the risk of shifted flu.

23/n
So that's it. I'm hoping next year we can start making COVID19 like flu: get an annual booster, tell your friends and family to do the same, stay home if you're sick.

But we need to vaccinate the world, and we need to avoid molnupiravir.

Wishing everyone a healthier 2022.

n/n

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More from @michaelzlin

1 Jan
For a new year tried out a new mask, the 3M Aura N95 mask. Wow what a night and day difference. Didn't realize a mask could be this comfortable. Most amazing thing: speech comes through clearly.

My colleague @AbraarKaran is correct: CDC should be pushing better masks like these
These are $3 each and worth it. You can buy a 3pack (or 10pack) and rotate between them. On the 3 days off you let the mask air out to evaporate odors and let any viruses in them die off. More info on this thread.
Not only did HHS and CDC failed to push for mass manufacturing of these masks earlier (a problem since the previous administration when @RickABright was overruled on the matter) but CDC continued to push wrong or obsolete ideas about N95s
Read 13 tweets
31 Dec 21
More evidence a booster helps prevent you from catching Omicron. We knew that already from Pfizer but this study looks at risks within households, which is useful info as it provides an absolute rather than relative risk in a common situation
The chart ET posted is confusing, as it normalizes to the "fully vaxxed" state. Leaving aside the heterogeneity of this population (vaxxed at different times, and includes some unknown % with the less effective 1-shot J&J), normalizing to unvaxxed would be better. So I redid it.
As you can see the relative protection from intra-household infection for a boosted person is 48% for Omicron and 84% for Delta vs unvaxxed. 48% is lower than the 70% Pfizer measured, but that's expected for the higher-exposure household setting compared to community transmission
Read 8 tweets
30 Dec 21
Thanks Dr. Hildreth for speaking out on the dangers of molnupiravir to "the health of the world". We need more people with foresight and integrity like you and @RickABright speaking up
Drs. Hildreth and Bright were inspirations for my essay on the risk of molnupiravir creating immunoevasive strains.
Peter Weina @peterweina, director of the Defense Health Agency, also voted against molnupiravir at the 11/30 AMDAC meeting out of concern for generating new variants. The meeting has been poorly covered in most articles, but here's a good one below

amp.dailycaller.com/2021/12/23/mer…
Read 5 tweets
29 Dec 21
Reordered the COVID19 meta-thread by date.

2020.03: Introducing the #coronadeck, explaining what we knew about SARSCoV2 based on its 80% identity to SARSCoV1. Discussed evidence for masks. This was back when CDC and WHO were saying they were ineffective.
2020.04: On why SARSCoV2 disease should have been called simply SARS2 or vSARS or even simply SARS, rather than the meaningless COVID-19.
2020.04: Wherein I appeared on CBC to advocate for mask wearing, because studies show it works to prevent viral infections. On the other side was a doctor following public health talking points, that masks were ineffective.
Read 29 tweets
27 Dec 21
ICYMI, on 12/23, the last news day before a long holiday break, FDA approved the viral mutagen molnupiravir as an at-home COVID19 drug. It sounds worrisome because it is. I wrote in the @washingtonpost that immunoevasive variants could arise from its use.
washingtonpost.com/outlook/2021/1…
If molnupiravir gives rise to enhanced mutants of SARSCoV2, it will prolong the pandemic and cause countless deaths and needless suffering. Yet it's only 30% effective in preventing hospitalization, similar to generic antidepressant and far worse than the 89% of other antivirals.
FDA knew of the concerns about mutant viruses escaping from patients taking MOV. This was discussed at the AMDAC FDA advisors meeting 1 month ago and contributed to the 10 no votes. It was revealed Merck didn't know what mutations occur in patients and when viruses are cleared.
Read 32 tweets
23 Dec 21
Would you prefer (1) we get back to normal activities sometime, or (2) we make new vaccine-evading coronaviruses continuously, suffer widespread breakthrough waves, and wear masks forever?

If you chose #1, then know this: Merck's molnupiravir should not be approved.
Molnupiravir is, to put it in clear terms, a potentially dangerous and virus-enhancing drug. It is not an effective antiviral medication outside of the confined conditions of cell culture and hamster cages. I'll explain below.
Well known independent voices have brought this up, such as @CT_Bergstrom (renowned skeptic of bad research) @WmHaseltine (HIV pioneer) and @JamesEKHildreth (FDA advisor). Others such as @chasewnelson have done more in-depth analysis. I'm here to try to explain the issue simply.
Read 135 tweets

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