New data mRNA vaccine 4th dose timesofisrael.com/israeli-trial-…
—HCW, 154 Pfizer, 120 Moderna, + control group
—Increase in antibodies > 3rd dose
—Little effect on Omicron cases
—No data yet for ? severe disease, memory B/T cells, higher or more durable protection
—Uncertain benefit/need
Last week @UKHSA published their new data on Omicron and 2 dose vs 3 dose vaccine effectiveness (VE) vs infections assets.publishing.service.gov.uk/government/upl…
In people w/o prior Covid, the booster approximately doubled VE, the 62% isn't bad (point estimate)
But
It falls off pretty fast, this vs Omicron (and Delta) symptomatic infections. So an important unresolved question is whether the 4th dose helps prevents this attrition of VE over time vs symptomatic infection and severe disease
Israel has given a 4th dose to well over 500,000 people (of 9 M population) abcnews.go.com/International/…
Testing is aggressive (>8X US/capita) but this graph of their Omicron wave isn't encouraging vs infections with 3rd booster rate 54% (US 24%), 2-shot vaxx 64% (US 62%)
Last point, which I cannot emphasize enough:
3rd shot protection vs Omicron hospitalizations, severe disease, death is remarkably high, about as well preserved as 2 shots vs ancestral strain, and a very different look compared with VE vs infections assets.publishing.service.gov.uk/government/upl…
Further highlighting this dichotomy in Israel
Impact of cases vs impact on severe disease/hospital or ICU admits/death ourworldindata.org/covid-metrics-…
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New @NEJM
A whopping (~90%) reduction of progression to Type 2 diabetes with tirzepatide (GLP-1 drug, dual receptor) vs placebo in a randomized trial of >2,500 participants with obesity, absolute reduction of 10/100 treated
In other GLP-1 new publications today
—Country-wide Sweden reduced hospitalizations for alcohol or substance abuse with these drugs jamanetwork.com/journals/jamap… @JAMAPsych
—Concerns about discontinuation jamanetwork.com/journals/jama/… @JAMA_current
Other new anti-obesity drugs in the pipeline, one that also increases energy expenditure
@NatureNV nature.com/articles/d4158…
A dedicated issue of @ScienceTM on #LongCovid
—Sex-specific differences, with perspective by @VirusesImmunity and @SilvaJ_C
—Insights for therapies @AndreaCoxMDPhD
—Deconvoluting "Osler's Web" @MichaelPelusoMD @DeeksSteven @DrMaureenHanson @SaydahSharon
—+RECOVER Trial, Lyme disease
An elegant @Nature study by @AkassoglouLab has illuminated our understanding of the role of fibrin (component of blood clots), #SARSCoV2, and brain inflammation in Covid and #LongCovid.
This discovery and more in the new Ground Truths podcast, with transcript, key figures (such as as the one below) and citations. Open-access. Link in my profile.
A clip from our conversation. Unknowingly, @AkassoglouLab was gearing up for understanding this complex pathophysiology for many years before Covid hit
For treatment, it's not just as simple as preventing fibrin clots. It's isolating the pro-inflammatory action of fibrin, targeted by the antibody
Covid and increased risk of major adverse cardiovascular events (MACE) 3-years out
2-fold increased for any severity of Covid
~4-fold increase for Covid requiring hospitalization
"a coronary artery disease equivalent"
interaction with non-O blood types
@uk_biobankahajournals.org/doi/10.1161/AT…
"A major finding from our analyses was that the risk
of MACE among the subset of hospitalized COVID-
19 cases without known CVD (ie, primary prevention
patients) was comparable to (or even slightly higher than) the risk in patients with CVD, PAD, or diabetes but without COVID-19."
"one of the first examples of a gene-pathogen exposure interaction for thrombotic events"
I think it's the first one documented, likely others to be unraveled
New US Covid genomic surveillance
The KP.3.1.1 variant is on the move to become dominant, more of a challenge to our immune response than KP.3 and prior variants (especially without new KP.2 booster when we need it for high-risk individuals)
It's the deletion 31/31 that makes the KP.3.1.1 spike different, but otherwise 2 mutations away from KP.2 (R346T and Q493E)
Buckle up; this wave isn't over yet d/t KP.3.1.1's emergence
We've known about KP.3's marked growth advantage since April and could have made the call then to make the new booster. That would have been aligned well with the current wave (available in July) 2/5 erictopol.substack.com/p/are-we-flirt…
But the FDA has tried to force fit Covid into an annual shot like flu, even though all data tells us it doesn't follow an annual pattern. Even the CDC acknowledges this now
3/5cdc.gov/ncird/whats-ne…