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15 Dec, 5 tweets, 3 min read
1/5 Another lab study showing extreme Omicron evasion of NAbs—33-44x reduction for mRNA & AZ. Zero detectable neutralization for J&J, Sputnik, Sinopharm, and—crucially—a majority of convalescents. Infection + mRNA vaccination, on the other hand, holds up well. h/t @dgurdasani1
2/5 Seven out of the eight monoclonal antibody (MAb) treatments currently in use are rendered useless by Omicron. The other (sotrovimab) has 3-fold reduced neutralization vs Omicron. Note: this study used VSV pseudovirus expressing Omicron S protein, not live virus.
3/5 ACE2 affinity increased compared to ancestral SARS-CoV-2, though still lower than that seen in Alpha. No info on Delta, though in silico analysis estimates Omicron binds more tightly than Delta. biorxiv.org/content/10.110…
4/5 Intriguingly, this study found Omicron RBD binds mouse ACE2 effectively while Alpha & Beta RBDs do not. This is confusing to me because previous studies showed Alpha & Beta *could* bind murine ACE2. I don't know what to make of it.
5/5 The paper title refers to 6 of 44 MAbs the authors analyzed that neutralized Omicron well and which they believe can be usefully targeted by future vaccines & other treatments.

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Ryan Hisner Profile picture
16 Dec
1/8 Maybe the most well-designed antibody study on Omicron yet. The 🧵 is very well written & the figures are the clearest & best I've seen. Awesome work. Takeaways:

3-dose mRNA > Infection + mRNA >>>> Recent 2-dose mRNA

Moderna > Pfizer >>>> natural infection or J&J
2/8 We already knew J&J primary vaccination was much inferior to either mRNA shot, but this study indicates J&J inferiority remains even after boosting with mRNA, which is troubling. Image
3/8 Excellent, comprehensive, and enlightening thread on this subject below by @michaelzlin. He makes the case that J&J recipients need 2 mRNA shots, & I don't see how anyone could disagree. Lots of other great insights here as well. Highly recommended.
Read 8 tweets
Ryan Hisner Profile picture
14 Dec
1/4 We're about to get a preview of what's going to happen with climate change in coming decades. You cannot wait until hospitals are overwhelmed to take action. It's too late.

Similarly, if you wait until climate catastrophe is upon us, the game is up. You waited far too long. Image
2/4 I think few people understand that even if we were to begin dramatically cutting CO2 emissions today & go zero carbon by, say, 2040, the world would continue to warm for some time, & the already severe climate change effects would continue to worsen.

npr.org/2021/04/14/981… Image
3/4 The parallels with Covid don't end there. One likely reason we see such pathetically insufficient action on climate change is that the worst costs will be borne by the poor. And inhabitants of poor countries don't get to vote in rich-country elections. Image
Read 4 tweets
Ryan Hisner Profile picture
14 Dec
1/6 Imagine that: Omicron is undergoing phenomenally fast exponential growth in the US, just like in the UK, Denmark, and South Africa. Crossing the Atlantic didn't impair its transmissibility. Who could've guessed?

Dec 6—3%
Dec 7—7%
Dec 8—13% Image
2/6 Take it from the master himself, Trevor B: "There is an inevitable very large wave of Omicron. It's going to happen." nytimes.com/live/2021/12/1… Image
3/6 There's such an air of fatalism around all this, as if we are utterly incapable of doing anything that could dampen or avert a devastating Omicron wave. Hospitals are already at max capacity in many states. An Omicron tsunami approaches, & we collectively shrug our shoulders.
Read 6 tweets
Ryan Hisner Profile picture
27 Nov
1/8 Extremely important 🧵. There is a reason many VOCs have emerged from South Africa. These variants often evolve in chronic infections in immunocompromised hosts, accumulating adaptive mutations as they evade the host's immune response. Around 20% of S. Africans have HIV.
2/8 When HIV+ people are treated properly with antiretrovirals, their immune response is sufficient to respond to vaccines and clear infections. But shockingly, only 71% of HIV+ South Africans have access to antiretrovirals (ARVs). This is a moral outrage.
3/8 It's an outrage first & foremost because these are fellow human beings unnecessarily suffering from a chronic, devastating, and treatable disease. I don't understand all the reasons so many of those HIV+ still lack access to antiretrovirals...
Read 8 tweets
Ryan Hisner Profile picture
26 Nov
1/ In other words, not as good as fluvoxamine, which in per-protocol analysis of a randomized controlled trial (ie among patients who actually took ≥80% of the treatment) reduced hospitalizations 66% (CI: 46-79% reduction) & deaths 91% (CI: 53-99%) w/an excellent safety profile.
2/ At ~$4 per course, one would think fluvoxamine would be getting at least as much attention as a promising Covid treatment as the $700 Merck drug molnupiravir (which has raised concerns that it might facilitate variants if a full course is not taken).
3/ Unfortunately, I fear that without a major pharmaceutical company to lobby politicians and regulators to recommend its use, it appears doubtful that fluvoxamine will be prescribed off-label for Covid except to a very small number of people.
Read 5 tweets
Ryan Hisner Profile picture
25 Nov
1/9 Something seemed familiar about the Q498R mutation. Then I remembered: @_b_meyer, examining in-vitro evolution of RBD mutations, predicted this mutation could emerge & lead to a variant with higher infectivity & immune evasion than any existing ones. nature.com/articles/s4156…
2/9 Q498R was not just one of many mutations they predicted: it was far & away their top candidate to become a major RBD mutation. It's the only novel mutation they mention in the abstract, noting that it requires the N501Y mutation to confer increased ACE2 binding affinity.
3/9 They used yeast to display human ACE2 receptors, then let various versions of SARS-CoV-2 S RBD compete against one another, with the highest binding-affinity RBDs advancing to the next round.
Read 9 tweets

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