Eric Topol Profile picture
Nov 30, 2020 10 tweets 7 min read Read on X
Superhuman #SARSCoV2 immunity
Just published @NatureMedicine
nature.com/articles/s4159…
Our essay on vaccines that give humans immune responses superior to those generated in response to infection, now including #SARSCoV2
@scrippsresearch @ScrippsRTI w/ Dennis Burton Image
To elaborate on the concept of superhuman vaccine immunity:
Each of the 3 examples in our piece are for different reasons.
1. HPV—best, since the human response is weak
2. Tetanus—small amounts of toxin don't elicit strong response)
3. H Flu—the bacterium is sugar coated
2/
This is different from vaccine efficacy.
Take measles. The natural human response to infection provides durable efficacy but the vaccine requires multiple shots and is without lifelong protection. 3/ Image
Superhuman vaccine = superior to typical human response to natural infection
The #SARSCoV2 neutralizing antibody response to mRNA vaccines has exceeded that of many convalescent patients by orders of magnitude
@NEJM bit.ly/33ys84T 4/ ImageImage
The natural human response to #COVID19 infection leaves many patients without a full and/or durable immune response, as nicely depicted (G=IgG, B=B cells, 4=CD4, 8=CD8, A=IgA)
biorxiv.org/content/10.110… Figure 5C @profshanecrotty and colleagues 5/ Image
Several #SARSCoV2 reinfections have been documented in patients without a sufficient IgG antibody response to the primary infection bnonews.com/index.php/2020… 6/
There are still many unknowns about the mRNA (and other platform) #SARSCoV2 vaccines with respect to durability, sterilization immunity (that would prevent transmission) and the role of T cells. 7/
In sum, the results to date suggest #SARSCoV2's spike protein lays the foundation for a potent vaccine-induced immune response that will turn out to be superior to that derived from natural infections. 8/
I recently spoke to @DrPaulOffit about the concept of a superhuman vaccine immune response
medscape.com/viewarticle/93…
He highlighted the #SARSCoV2 inhibition of our interferon response and this point👇 Image
And cited the 3 prototypic examples Image

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More from @EricTopol

Nov 13
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

by @AniaJastreboff and collaboratorsnejm.org/doi/full/10.10…Image
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 Image
Other new anti-obesity drugs in the pipeline, one that also increases energy expenditure
@NatureNV nature.com/articles/d4158…Image
Read 4 tweets
Nov 13
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 diseaseImage
Image
Image
Where we have failed to date: finding an effective therapy. That has to change
science.org/doi/epdf/10.11…Image
Read 4 tweets
Oct 19
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.Image
Image
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
Read 4 tweets
Oct 9
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…Image
"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
Read 4 tweets
Aug 2
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) Image
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) Image
Buckle up; this wave isn't over yet d/t KP.3.1.1's emergence
Read 4 tweets
Jul 21
The new boosters (vs. KP.2) should be available the first week of September. It takes ~90 days make them from the FDA decision on June.

But it didn't have to be that way.......1/5nbcnews.com/health/health-…
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…
Image
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…
Read 5 tweets

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