As I predicted a month ago the number of new COVID cases has decreased in the US. From a high of 70,000 per day to 35,000 per day now. It will likely continue to decrease for some more time.
This is due to many factors, but great national leadership is not one of them.
1/
Why are cases decreasing even though most of us are still susceptible?
2 reasons:
— Increasing proportion of persons at high risk of getting COVID (eg., jobs where u can’t social distance) have already had COVID
— Effect of masks & distancing
2/
But the proportion of people who have been exposed is very low even in hotspots. Less than 10%. Does this mean >90% of us are still susceptible? And if so, why are cases decreasing? jamanetwork.com/journals/jamai…
3/
While we have to assume that we are all susceptible and continue to take preventive measures, seroprevalence studies likely underestimate the proportion of people who have been exposed to COVID. See article by @JoshuaPCohen1@Forbesgoogle.com/amp/s/www.forb…
4/
But even if we do some rough math, and double the seroprevalence we will still have only estimated 10-15% of population as having been exposed to COVID, far lower than what is needed for true herd immunity, but yet cases are decreasing, even in many hot spots. Why?
5/
Which brings us to the big question. Are we all equally susceptible to COVID? Or do some people have cross reactive immunity in which cases the disease is so mild that while you may get a PCR positive result, it doesn’t actually lead to symptoms or permanent seroconversion?
-What happens in Europe happens a month later in the US. In Europe there is a 2nd wave. Our cases can go up dramatically. We have to be careful & continue masks and social distancing because that may reduce viral dose and thereby the severity of COVID 7/
As cases come down leaders will naturally try to take credit. Or my worry is that they may tell people to relax. But to be clear the drop in cases is happening because of reduction in susceptible population and due to behavioral changes, specifically masks. @jeremyphoward
8/
The number of daily cases now is higher than I thought it would have been at this point. But the trend is there.
My feeling is that the drop in cases will be transient and we will have another peak in late fall. But my hope is that the drop in mortality is more enduring.
I also recognize that COVID has a lot of long term consequences. So it’s important we do everything to keep cases down
• • •
Missing some Tweet in this thread? You can try to
force a refresh
In the year 2000, a few of us attended an angiogenesis meeting in Boston. We were there to discuss thalidomide
But a side meeting that evening led to trial that went on to get Velcade FDA approved for myeloma. @NEJM
Story in thread.
Velcade (bortezomib) was first introduced to cancer research by the name PS-341.
It was a novel proteasome inhibitor developed by Julian Adams and colleagues a a potential anti cancer agent. @CR_AACR @AACR aacrjournals.org/cancerres/arti…
The ubiquitin-proteasome garbage disposal pathway in cells is a Nobel prize winning discovery.
Proteins that need to be degraded are tagged with ubiquitin tails. Tagged proteins are degraded by the proteasome complex. (This review has details )
The fascinating story of Thalidomide: how this most notorious drug on the planet, banned in the 1960s, made an incredible comeback and revolutionized the treatment of myeloma.
I will also highlight one person whose role is not recognized: Without Dr. Leif Bergsagel there will be no thalidomide for myeloma.
Read on #MedTwitter
The thalidomide story has many takeaways and lessons.
It shows drug development from bedside to bench and back to bedside.
It shows the power and impact of astute clinicians
It shows the power of investigator courage
The role of serendipity
But let’s start at the very beginning.
Thalidomide was synthesized in 1954, and then developed as a sleeping pill by the German company Chemie Grünenthal in the 1950s.
At the time the only sedatives available were barbiturates which had risks of intentional or accidental overdose.
Because thalidomide was felt to be a drug that cannot cause death due to overdose it was marketed as one of the safest sedatives.
By 1961, it was sold in over 40 countries as a sleeping. It was also tragically used to control morning sickness of early pregnancy.
AQUILA trial for high risk smoldering myeloma published in @NEJM today.
@thanosdimop
Personally for me, it is a huge milestone along 25 years of work that started in 1998. #ASH24 #ASH24VR
This story below may help those interested in a clinical trialist career. 1/
In 1998, as a fellow @MayoClinic I was keen to determine if early intervention delayed progression and improved survival in SMM. #ASH24
In 1999, with the help of Tom Witzig, I led a small phase II trial of thalidomide for SMM. @LeukemiaJnl 2/
I was then so fortunate to examine the natural history of SMM, with the legendary Bob Kyle. Honored to be last author on @NEJM paper that also provided data that most progressions occur in the first 5 years of diagnosis.
The start of the concept of high risk vs low risk SMM. 3/