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Michael Lin, MD PhD 🧬 Profile picture
Michael Lin, MD PhD 🧬
@michaelzlin
Assoc. Professor of Neurobiology & Bioengineering @Stanford ☘️🧪🦠🧠🌈🔬📖🇺🇲🌏Neurons, viruses, proteins, medicines. Bad manners blocked. Also @MichaelLinLab
Postcards of the Hanging(s) Profile picture The Holocron Profile picture Jörg 🌻 @j_honegger@swiss.social Profile picture Paul Leo Profile picture S. Diamond-Myrsten Profile picture 15 subscribed
Jul 18 • 11 tweets • 3 min read
Basically Pelosi figured out Donilon was the one feeding Biden hopium-spiked poll results, and leaked it out.

Once it was proven that there really was bad info in the inner circle, that gave everyone else confidence in their own eyes. The emperor really was naked. “Put Donilon on the phone,” Ms. Pelosi told the president, referring to Mike Donilon, the president’s longtime aide, according to people familiar with the exchange, which was reported earlier by CNN. “Show me what polls.”

Go Nancy!

nytimes.com/2024/07/18/us/…
Jul 17 • 12 tweets • 3 min read
Biden has COVID-19 again. He had first symptoms today, positive test today, and first Paxlovid dose today.

As the early Paxlovid will limit immunostimulation by virus, I predict he will suffer rebound again, unless he gets 10-day course, or he is given a strain-matched vaccine. Image Biden's DO does not seem to follow the science. The rate of rebound is 26% if started within the first 2 days of symptoms or positive test.

Sure, FDA and CDC and Pfizer still claim it's less than 3% and no different than no-Paxlovid, but it fools nobody
Jul 17 • 4 tweets • 1 min read
The question is when Biden's inner circle (all 4 of them) will tell him the truths:

That he's dropping in most polls.

That 2/3 of Democrats prefer a different nominee.

That he looks low-energy and confused in recent appearances, and the contrast with Trump keeps getting wider. Citations. Dropping in most polls: "New Democratic-funded polling shows Biden losing ground to Trump in key states"
cnn.com/politics/live-…
Jul 9 • 15 tweets • 4 min read
I intuited that early start of Paxlovid blunts immunity, allowing viral rebound once drug ended. I thus predicted both Joe and Jill Biden's rebounds (before they occurred), as they started Pax on day of symptoms.

A math model now supports the intuition:
nature.com/articles/s4146… "The model identifies that earlier initiation and shorter treatment duration are key predictors of post-treatment rebound."

The model shows that early therapy reduces the number of infected cells secreting innate immune signals (IFNs) that then activate antibody production.
Jun 30 • 10 tweets • 3 min read
"Short- and long-term neuropsychiatric outcomes in long COVID in South Korea and Japan"

Higher recorded rates of cognitive deficit (2.7x), insomnia (2.4x), anxiety (2.2x), mood disorder (1.9x), and stroke (2.0x) in the year after COVID-19 infection.

nature.com/articles/s4156…
Image Big caveat: Retrospective association study, so major possibility of reporting bias. People who recently got COVID may be more likely to seek care and diagnosis for any new health problem. The study tries to control for this but there's no way really to eliminate it entirely.
Jun 3 • 17 tweets • 5 min read
Documents for the June 5 FDA VRBPAC meeting are out.

Advisors will be asked to answer the question "For the 2024-2025 Formula of COVID-19 vaccines in the U.S., does the committee recommend a monovalent JN.1-lineage vaccine composition?"

fda.gov/advisory-commi… Documents now include company presentations. Meeting has started and love video link is below

youtube.com/live/weaKQiFk_…
May 26 • 10 tweets • 3 min read
The summer wave is starting in the Bay Area. Several people I know have gotten sick and SARSCoV2 wastewater is back to high levels, higher than the winter 2020-2021 wave and almost halfway up to 2021-2022 Omicron. Image Looks like we'll have Dec-Jan (tightly synchronized by holiday gatherings and cold weather) and a looser June-August (spread by vacation gatherings, travel, and maybe some Southern to Northern hemisphere transfer) each year
Mar 13 • 38 tweets • 10 min read
Pleased to report, at long last, the publication of ML2006a4, our SARS-CoV-2 protease inhibitor for COVID-19, in @ScienceTM.

Compared to nirmatrelvir, the inhibitor in Paxlovid, ML2006a4 binds more tightly and has greater antiviral activity in vivo.

science.org/doi/10.1126/sc… @ScienceTM This paper tells the origin story of nirmatrelvir and ML2006a4 (they are brothers) and reveals why these two drugs work so well.

It also explains the chemical basis for ML2006a4's superior activity, which goes back to a deliberate decision we made back in 2000.
Jan 23 • 7 tweets • 3 min read
So much for viruses evolving to less pathogenicity.

As I've said before, we might expect viruses to become more transmissible, e.g. by replicating faster or suppressing immunity. That's not less pathogenic.

A new report shows recent variants suppress innate immunity more. There are a lot of plots, but the general gist is that BA.4/5 infection in cells generates less IFN and other innate immunity cytokines than earlier BA.1/2, and BA.4/5 shows less gain from innate immunity suppression by a drug (ruxolinitib) (because it suppressed it already)
Jan 21 • 17 tweets • 5 min read
Actually a person who could have sparked COVID19, accidentally or not, has been ID'ed in the open for a long time.

The name is Zhou Yusen. Evidence?
1. He filed a patent for SARS2 vax in 2/2020, when others only knew of SARS2 from 1/2020
2. He died from a rooftop fall in 5/2020 Those facts are not disputed, but somehow not widely discussed.

The theory isn't mine. It is described in detail by former Assistant Secretary for Preparedness and Response at the US Department of Health, Dr Robert Kadlec, above and more recently below

skynews.com.au/australia-news…
Jan 19 • 10 tweets • 3 min read
Just published: Another useful difference between Novavax over RNA vaccines has just been discovered.

3x RNA vaccines induce IgG4 antibodies, which clear antigens poorly and is associated with immunotolerance.

By contrast, 3x Novavax does not induce IgG4. IgG3 antibodies bind Fc receptors on phagocytic cells like macrophages so that viral particles bound to them will be ingested and destroyed. This antibody-dependent phagocytosis (ADP) is a crucial part of the immune response to viruses...
Jan 18 • 26 tweets • 7 min read
The full DEFUSE proposal on gain-of-function experiments on bat coronaviruses is available, and I'd say it's quite shocking. It does not lay out a plan to create SARSCoV2, but does propose to identify and culture natural sarbecoviruses with the ability to infect human cells. A 🧵 There are threads interpreting the DEFUSE proposal as intending on making SARSCoV2. A careful read shows that is not the case. However the intention was to identify natural viruses with features that would help them infect cells. So it may be not much of a difference functionally
Jan 4 • 7 tweets • 3 min read
In 2023 about 70,000 Americans died of SARSCoV2, although >95% have some immunity. That's about 2x the usual annual deaths attributed to flu.

In people with immunity, SARSCoV2 has an infection fatality rate similar to flu, but it's much more contagious and widespread. Image We spent years of effort trying to eke out small decreases in flu fatality. COVID19 has undone that and more, with >1M deaths in 3 years and now a higher hospitalization and fatality burden than flu. Image
Nov 22, 2023 • 8 tweets • 2 min read
Moderna's RNA vaccine was a copy of BioNTech's, per the EU

That means Novavax was the *only* US company to create a COVID-19 vaccine with their own research

No, Pfizer didn't create a COVID-19 vaccine. They licensed from BioNTech, a German company

fiercepharma.com/pharma/covid-1… Even more impressively, Novavax did it as a company on the edge of bankruptcy. That means FDA staffers aren't going to treat its applications with kids gloves (they didn't), because they aren't sure there's a high-paying job at Novavax awaiting them

Nov 22, 2023 • 7 tweets • 2 min read
"The FDA and Moderna’s cosy relationship: how lax rules enable a revolving door culture"

Two FDA staffers, Fink and Goswami, who evaluated Moderna SARSCoV2 vaccine now have jobs there, with translational and clinical director roles in infectious disease.

bmj.com/content/383/bm… This is corruption, plain and simple. FDA staffers have a huge incentive to approve drugs from the more established companies that can offer them stable highly paid jobs. The big unspoken carrot adds to the probability that bad drugs getting approved. Molnupiravir, anyone?
Oct 25, 2023 • 8 tweets • 2 min read
"Anti-COVID drug accelerates viral evolution”

nature.com/articles/d4158…
Image Pretty much as I wrote here, the week molnupiravir was approved, in December 2021: "A new drug to treat covid could create a breeding ground for mutant viruses"

By understanding mechanism, you can predict these things, 2 year before data can prove it.

washingtonpost.com/outlook/2021/1…
Oct 21, 2023 • 30 tweets • 7 min read
24h after my Novavax COVID shot (and flu shot), and very happy. Much milder side effects than my 5 earlier COVID vaccines.

It's just my experience of course, but I'm hopeful we may finally have a sustainable and acceptable format for annual vaccinations.

A short 🧵 Image Earlier COVID19 vax were 4 Pfizer original and 1 Moderna bivalent, plus a BA.5 infection in 2022 summer 3 weeks after #4.

All RNA vax shots produced noticeable side effects of fatigue and/or headache within 24h.

This time no fatigue or headache after Novavax and flu.
Sep 27, 2023 • 6 tweets • 2 min read
Missed this excellent commentary calling for FDA to share all data on Paxlovid. FDA gave it full approval based on the one trial in nonimmune patients (now irrelevant) while another trial in immune patients (relevant) trended to but did not meet endpoints. medpagetoday.com/opinion/second… Meanwhile Pfizer had run more trials but didn't reveal the data.
Sep 27, 2023 • 9 tweets • 3 min read
New article on Paxlovid rebound in @nytimes shows that people are finally accepting what I always proposed: Early Paxlovid suppresses virus levels before the immune system can mount an effective response, until the drug ends and the virus pops up again.
nytimes.com/2023/09/26/wel… "The theory behind Paxlovid rebound is that the treatment is so effective at suppressing the virus that the immune system does not ramp up its cellular and antibody defense" Image
Sep 10, 2023 • 14 tweets • 5 min read
There are now several studies looking at how neutralizing sera from XBB breakthrough infection is on EG.5 (an XBB derivative now dominant) and BA.2.86 (the new kid on the block).

First here's a nice map of immunogenic distance based on mouse work

Ref: biorxiv.org/content/10.110…
Image As you can see, BA.2-5 were as immunoevasive from D614G (ancestral SARSCoV2) as SARS1, hence the new boosters last year (although they shouldn't have been bivalent)

EG.5.1 covers the same distance, requiring another booster, which this time will be pure XBB as it should be
Jul 28, 2023 • 15 tweets • 3 min read
In case you weren't sure what to think of peer review:

Reviewers and editors demanded the Proximal Origin paper make their preferred conclusion

Every scientist complains about papers being held hostage by reviewers. The PO case shows the problem has implications beyond science. Remember how some authorities would dismiss preprint results they disliked (e.g. breakthrough infections, lower VE of J&J, higher VE of Moderna) by saying they weren't reviewed?

Reviews are meant as a QC step, but when reviewers impose their views, they can make articles worse