Eric Topol Profile picture
Dec 13, 2020 8 tweets 10 min read Read on X
Why 2 proline (P) substitutions will go down in history.
Introducing 2P's at the beginning of the central helix (CH) stabilized the spike protein's confirmation upon entering cells.
From the Jan 10 #SARSCoV2 sequence, this 2P Δ was incorporated into the mRNA vaccine designs /1 Image
This was a result of elegant #3D structural biology work @NIH (Barney Graham), @scrippsresearch (Andrew Ward) and collaborators from a @PNASNews paper that was rejected 5 times! pnas.org/content/114/35… /2 ImageImage
Without the 2P design, the mRNA vaccines would have failed.
The remarkable story is told well by @Carolynyjohnson
washingtonpost.com/health/2020/12… /3 ImageImage
The @PBS video explanation is outstanding, by @DrJoeHanson with @McLellan_Lab @UTAustin key driver in this structural biology breakthrough /4 ImageImage
More on the spike protein's confirmation dynamics in this perspective on a new paper @cellhostmicrobe cell.com/cell-host-micr…
Original report cell.com/cell-host-micr… ImageImage
Knowing how the spike protein changed confirmation upon cell membrane fusion was key (and how to Δ it), and the details were furthered by this recent work.
Extraordinary video of the spike protein in motion
w/great cover @oooitsplasma @ScienceMagazine /6 ImageImage
There are 4 #SARSCoV2 vaccines that incorporate the 2P design. Besides @moderna_tx @BioNTech_Group/Pfizer, @Novavax and @JNJNews. And thanks @goodwish916 @WardLab1 @KizzyPhD who I did not acknowledge earlier or didn't have their twitter handle
For an enthralling account of the 2P substitution and its big impact, you can listen or read the transcript thisamericanlife.org Starts at 40 min, with @goodwish916 @McLellan_Lab @KizzyPhD and Barney Graham @ThisAmerLife w/ @dkestenbaum

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More from @EricTopol

May 16
The connection between #SARSCoV2 and neurodegeneration
@TheLancetNeuro
Quotes below:
1. SARS-CoV-2 infection should be considered as a risk factor for Alzheimer’s disease, even though the distinction between causation versus disease acceleration is not clear.thelancet.com/journals/laneu…Image
2. Inflammation in patients with COVID-19, and controlled experiments show prolonged neuro-inflammation after mild SARS-CoV-2 infection
in macaques.
3. A direct correlation has been reported
between prior SARS-CoV-2 infection and increased risk
of Alzheimer’s disease (figure).

4. So far, the estimated lifetime cumulative risk of dementia due to hospitalisation for any viral infection is 1·48 (95% CI 1·15–1·91).
Read 4 tweets
Apr 26
The FLiRT variant KP.2 begins its takeover for Covid cases in the US, now accounting for 1 in 4 cases
covid.cdc.gov/covid-data-tra…
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I've reviewed the FLiRT variants and their implications in a Ground Truths (link in profile) Image
The 2 mutations in the spike that account for KP.2's rise to dominance, compared with the JN.1 variant which has prevailed for months Image
Read 5 tweets
Jan 22
Breaking down the risks and benefit for lecanemab, the amyloid beta-directed antibody vs Alzheimer's drug approved @US_FDA last year. It doesn't look good.

@AnnalsofIM acpjournals.org/doi/10.7326/M2…
Image
A new systematic review of these antibodies looks even worse @AnnFamMed doi.org/10.1370/afm.30…



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Fixed link for this important paper
annfammed.org/content/22/1/5…
Read 4 tweets
Jan 4
My oped on the JN.1 variant and the 2nd biggest US wave of infections (after Omicron) since the pandemic began
@latimes @latimesopinion #LongCovid latimes.com/opinion/story/…
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Recent @CDCgov #SARSCoV2 wastewater data for current wave (vs Omicron Jan 2022 and subsequent waves), graph by @luckytran Image
Sorry, @washingtonpost, but this is not "another Covid-19 uptick" as you put it in your Health Alert. You ignore the best metric for infections that we have at present—wastewater—focusing only on hospitalizations
washingtonpost.com/health/2024/01…
Image
Read 4 tweets
Nov 23, 2023
3 New #LongCovid reports
1. Vaccination protection—1 dose 21%, 2 doses 59%, 3 doses 73% among ~590,000 people in Sweden (strong association)
bmj.com/content/383/bm…
Image
2. 3-year prospective follow up of a cohort of ~1350 participants, hospitalized in China
—Lung function restored back to baseline in most
—Higher risk of reinfection that people w/o Long Covid
—Half w/ persistent symptoms
thelancet.com/journals/lanre…
3. At @RSNA annual meeting, brain MRI with microstructure imaging (DMI), participants with #LongCovid vs controls had microstructure changes associated with impaired cognition, sense of smell and fatigue
eurekalert.org/news-releases/…
Image
Read 6 tweets
Aug 25, 2023
Big news #ESC2023 and @NEJM
In a placebo-controlled randomized trial of people with obesity + heart failure (with preserved ejection fraction). semaglutide (Wegovy) markedly improved symptoms, exercise time, reduced inflammatory markers (and weight loss)
nejm.org/doi/full/10.10…

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This also tells us something about the underlying mechanism of heart failure with preserved EF—metabolic dysfunction and attendant systemic inflammation—not previously acknowledged or confirmed
The accompanying editorial lays this finding out well. Prior studies of weight loss didn't help HFpEF
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Read 4 tweets

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