Eric Topol Profile picture
physician-scientist, author, editor https://t.co/AWqrOxpoZP
eDo Profile picture Robert Varipapa Profile picture porteredly - we know who T is, Vote him out. Profile picture Todd Lyons Profile picture Duxinaro Profile picture 111 added to My Authors
24 Sep
"These complications, which at times are the only features of #COVID19 clinical presentation, have occurred even in cases with mild symptoms and in people who did not experience any symptoms" science.sciencemag.org/content/early/…
a 🧵to explain 1/
For those who don't know me, I'm a cardiologist, have been for 35 years, and still practicing. And seeing patients is still my favorite part of what I get to do.
I tried to read all that's been written in English to date on this topic and to contextualize it in this essay 2/
The virus can get into the heart and specifically heart muscle cells because it is drawn by ACE2 on the surface of these cells, along with cooperation of cofactors, such as heparin sulfate. That entry has been confirmed by autopsy series 3/
Read 16 tweets
23 Sep
You know things are really screwed up when @RandPaul is asserting there's cross-reactivity and herd immunity to Tony Fauci
ICYMI, a video highlight for the day. 💪Tony
Don't mess with Tony.
Tribute by @jimmykimmel
time.com/collection/100… #TIME100 Image
Read 4 tweets
22 Sep
"These are some of the most important clinical trials in history, affecting a vast majority of the planet’s population. It’s hard to imagine how much higher the stakes can be to get this right. Cutting corners should not be an option." 1/
nytimes.com/2020/09/22/opi…
@nytopinion
The primary endpoint in these trials— infections—will likely be mostly mild. For example, in the @pfizer trial, a sore throat and a + PCR test counts as an event. Are these the infections that we want to suppress with a vaccine? Is that a good proxy of effectiveness? 2/
There are interim analyses, some w/ stopping rules during the trials
—4 looks for Pfizer, 1st is at 32 events
—2 looks for Moderna, 1 look in Astra Zeneca (US) trial
—A trial could be stopped on the basis of very limited number and severity of such events, declaring efficacy 3/
Read 9 tweets
19 Sep
We have the protocols. Now we know how there will very likely be an Emergency Use Approval (EUA) for a vaccine prior to November 3. The company and political motivations are fully aligned.
1. The criteria for an EUA is that it "may be effective"
fda.gov/regulatory-inf… Image
2. Nearly every day we hear from @pfizer's CEO @AlbertBourla that they will know if their vaccine is working by the end of October.
Only the Data and Safety Monitoring Board is reviewing the data at specific intervals, the interim analyses
So how will they (Pfizer) know that?
3. The 1st interim analysis for that trial is at 32 events, infections, which can and likely will be mild. The stopping rules as reviewed by @biosbenk @EmoryRollins are "aggressive" and "unusual" for the number of interim analyses (4) and Bayesian approach
github.com/benkeser/pfize… Image
Read 18 tweets
16 Sep
A rapid #SARSCoV2 test suitable for home use using #CRISPR with validation data
nejm.org/doi/full/10.10… @NEJM by @zhangf and colleagues ImageImage
From the supplementary material.
Looks promising ImageImageImageImage
I've spoken with the @Sherlock_Bio team who are adapting this for a home test and I hope they can accelerate the process. We still need @US_FDA to accept home testing— to date they've been quite resistant.
Read 4 tweets
16 Sep
First read out from a neutralizing antibody clinical trial. A step in the right direction for this class of drugs that could be used in many ways vs #COVID19.
Why is this important?
1. This is the 1st clinical trial of a drug specifically designed for #SARSCoV2. All previous trials were repurposed drugs (HCQ, dexamethasone, Remdesivir, etc). Safety data are encouraging
2. The class of drugs has the potential to be used as a prevention in high-risk individuals, and intervention in mild to moderate covid (as in the current trial) or severe, subcritical. The data from non-human primates supports this multi-pronged use.
Read 6 tweets
15 Sep
Our informative and refreshing podcast w/ @nataliexdean, a guiding light in the pandemic
medscape.com/viewarticle/93… @Medscape w/ @cuttingforstone
A🧵summary
1. "We're struggling right now in the United States....there's a lot of uncertainty"
2. We need a coordinated response of "all these public health things that people don't always appreciate, they add up." Some places in the US are doing it well.
Explains forward and backward contact tracing.
3. On herd immunity confusion, a term that is usually in the context of vaccines. See below.
We need to focus on "proactive strategies to protect people"
Read 14 tweets
13 Sep
Why is stopping a #SARSCoV2 vaccine trial early such a bad idea?
A proper clinical trial is statistically powered to make a call at its completion
There's wobble, random chance, in events during a trial
The true beneficial effect has turned out less in some trials stopped early Image
The trials are reportedly powered to detect 50% efficacy w/ a lower 95% CI of 30%. That's not nearly as high as ideal
Stopping early:
— could even exaggerate that
— could impact other placebo-controlled trials
— could also miss relatively rare but important adverse safety events
The @pfizer CEO again today asserted they will know by the end of October whether their vaccine w/ @BioNTech_Group works @FaceTheNation
cbsnews.com/news/covid-vac…
That can only be determined by stopping the trial early.
And they're not releasing their stopping rules.
It's all wrong
Read 4 tweets
12 Sep
Does #SARSCoV2 directly infect @brain cells?
A brief review of the evidence
1. An exhaustive @TheLancetNeuro clinical review suggested this but w/ little supportive data thelancet.com/journals/laneu…
2. The mechanism for loss of smell has invoked both direct viral invasion of the olfactory bulb and indirect effects
Direct jamanetwork.com/journals/jamao… @JAMAOto
Indirect
advances.sciencemag.org @ScienceAdvances
3. A very recent, in-depth review of the pathogenesis of #SARSCoV2 and the nervous system concluded the evidence is inconsistent
cell.com/cell/retrieve/… @CellCellPress
Read 7 tweets
9 Sep
My podcast w/ Paul Offit, one of the world's leading lights on vaccines, regarding #SARSCoV2 vaccine development
medscape.com/viewarticle/93… @Medscape
It's rich and I'll summarize key points here 🧵
1. "It's an unprecedented moment...as long as the Phase 3 trials don't get truncated"
2. Things we're learning about the virus
--not affected by seasons
--can cause a vasculitis
--unusual multi-system inflammatory syndrome in children
--strong predilection for nursing homes
3. What about #LongCovid?
Read 14 tweets
9 Sep
Today's a very big day fo #AI medical research
There are major publications of consensus statements and guidelines published @NatureMedicine @LancetDigitalH @bmj_latest on protocols, trial design, and reporting
Here's my commentary @NatureMedicine nature.com/articles/s4159…
Here are the Consensus Statements which reflect extraordinary, international, collaborative effort
Led by @DrXiaoLiu @Denniston_Ophth and colleagues
nature.com/articles/s4159…
nature.com/articles/s4159…
@NatureMedicine 👏👏👏🙏🙏
Read 5 tweets
8 Sep
This will likely (hopefully) not turn out to be any signal of trouble at all. But it reinforces the principal concern for safety for such programs that will ultimately be implemented in tens of millions of healthy people.
Apparently the individual w/ the adverse event has a transverse myelitis, a neurologic condition which can result from infections or an immune system disorder. The adenovirus component of the vaccine may have been a trigger nytimes.com/2020/09/08/wor… Image
Here's everything we know (not too much) at this point about the safety concern
by @KatherineJWu @katie_thomas with @llborio Image
Read 4 tweets
7 Sep
Senegal crushed it and deserves recognition for their exemplary response to the pandemic
usatoday.com/story/news/wor… @USATODAY @dshesgreen Image
So much for the Global Health Security Index
(slightly off base) Image
Read 4 tweets
6 Sep
Just published @CellCellPress is the most extensive study of the immune response in covid-19's multisystem inflammatory syndrome in children (MIS-C) cell.com/cell/fulltext/… by @karolinskainst
—Key differences v. Kawasaki and acute covid-19
—Candidate autoantibodies identified ImageImageImageImage
Other recent publications on MIS-C and the immune response
Read 4 tweets
4 Sep
These vaccine announcements tell us how it's virtually impossible to have Phase 3 complete by November 3rd
23,000 of 30,000 currently enrolled @Pfizer/@BioNTech_Group program

1/
That means another 24,000 participants need to get their 2nd dose still, which occurs a month after the 1st.
Then 2-3 weeks to get the full immune response.
Then exposure to infections
Then moderate or severe infections as events
2/
Pfizer CEO: "We expect by end of October, we should have enough...to say whether the product works or not."
The 1st interim analysis is at 32 events
statnews.com/2020/09/02/exp… @matthewherper @statnews
Even 32 events for placebo, 0 vaccine (likelihood ~0) wouldn't cut it to stop 3/
Read 6 tweets
4 Sep
Why are kids less susceptible to serious #COVID19 illness?
A new, ★ review of the 5 clues @PNASNews
pnas.org/content/early/…
7 @KidsAtColumbia @ColumbiaMed
@KaminskiMed @YaleMed @StanfordMed and colleagues Image
The fixed link pnas.org/content/early/…
This is really an exceptional review of everything we know about kids and @COVID19
It's rich, my highlighted version ImageImageImageImage
Read 4 tweets
3 Sep
Today we learned ~1/3 Big Ten athletes who were #COVID19 + had abnormal heart MRIs, consistent w/ myocarditis, even those without symptoms. If anyone still is questioning whether this virus attacks the heart, it's denialism.
There have been multiple reports of heart involvement with #COVID19, including young athletes, and replication of @GladstoneInst iPSC-> heart cell findings. Very little is known about heart inflammation among asymptomatics (unlike lung Δs)
Documented #SARSCoV2 particles in heart cells in a tragic case of an 11-year-old girl
Read 6 tweets
3 Sep
A little primer on independent Data and Safety Monitoring Boards (DSMB), who will be reviewing the #SARSCoV2 vaccine trials to adjudicate safety and efficacy, making recommendations to the clinical trialists 1/
Consists of a multidisciplinary group of several members: clinical trialists, biostatistician, bioethicist, and experts in topic (virologist, immunologist, epidemiologists, vaccinologists)
The timing/schedule of data review usually based on enrollment 2/
The data are teed up by the biostatisticians. The DSMB is blinded to vaccine or placebo groups. There is ordinarily a time lag/gap from the "cleaned" dataset reviewed by DSMB that is behind ongoing events 3/
Read 8 tweets
2 Sep
On the #SARSCoV2 immune response and vaccine I just did a podcast with Dennis Burton, a leading immunologist and vaccinologist and co-faculty @scrippsresearch. We covered so much a long🧵summary was needed
soundcloud.com/prescrippsions… 1/x
Optimism. "The pandemic is not going to be with us forever"
(This comes from a leader of the HIV vaccine program) 2/x
1st line of defense, interferons: will they likely be helpful given as an early intervention?
Yes, but we have to be very careful 3/x
Read 16 tweets
1 Sep
Very good news on durable IgG antibodies to #SARSCoV2 from the Iceland experience
Just published @NEJM
nejm.org/doi/full/10.10… >4 months out
Iceland was one of the best performing countries vs #COVID19, starting PCR screening in January, before there was even a patient diagnosed. As a result, along with tracing/isolation, they have a seroprevalence of only 0.9% (US is now >14%, estimated) and IFR 0.3%.
The editorial is rich with context
nejm.org/doi/full/10.10…
1. "Unprecedented snapshot of seroconversion rates" with various antibody isotopes, different antigens
2. 56% cases confirmed by virus (PCR) testing so 44% infections would've been missed w/o antibody
3. 2 Waves graphic
Read 4 tweets
1 Sep
Circumstantial evidence for fecal-aerosol #SARSCoV2 transmission "chimney effect" of toilet flushing in a high-rise building with escape of bioaerosols in the drainage system
acpjournals.org/doi/pdf/10.732…
Just out @AnnalsofIM ImageImageImageImage
I couldn't resist: when💩hits the fan.
Here's the editorial
acpjournals.org/doi/10.7326/M2… ImageImageImage
A very good @PostOpinions essay by @j_g_allen @HarvardChanSPH with the practical, precautionary steps you can take
washingtonpost.com/opinions/2020/… ImageImage
Read 4 tweets