Vincent Rajkumar Profile picture
Oct 12, 2021 12 tweets 3 min read Read on X
What about natural immunity? A thread.

I'm not a virologist or vaccinologist. I'm addressing this issue as someone whose career has been focused on plasma cells, the cells that make antibodies, for over 20 years. 👇
1) When first exposed to an antigen, virus or vaccine, the immune system produces a primary immune response. On exposure to same antigen again, it produces a better, bigger, and more durable secondary response. Basic immunology. microbiologynotes.com/differences-be…
Sometimes the first infection gives a long enough exposure to the antigen to stimulate the secondary response. Sometimes it's not. Depends on the virus and duration of infection.
So even if someone had COVID, it's better to get the vaccine also to ensure a better, durable secondary immune response. More IgG producing cells, more long lived memory cells.
Given the rate of reinfections we are seeing, it is worrying that COVID doesn't seem to produce an enduring immune response in everyone.

It's possible that 2 vaccine doses given too close to each other may also not produce a durable secondary response. (Why some need boosters).
2) If someone has not yet had Covid, then between getting immunity from the vaccine versus virus, even if the virus induced response is for argument sake better, it is much more risky to acquire immunity that way. It is far safer to get it through a vaccine.
3) Testing for antibodies and then deciding who to vaccinate and who not to is not realistic when we have 70 million eligible left to vaccinate in the US.

4) The virus is also mutating. The more infections we have, the more risk of mutants. Hence the push for vaccinations.
5) There are side effects with the vaccines as there are with any medicine. But truly serious ones are very rare compared to risk of COVID related complications or death. 215 million people have been vaccinated in the US. 3.75 billion people in the world: Almost half the world.
6) There will always be people who doubt the efficacy of vaccines because they hear someone got severe Covid despite vaccines and therefore why bother. Actually vaccines reduce your risk of severe Covid by 90%. They work: Randomized trials and Real world data.
More here on clarifying doubts about vaccine efficacy.
So yeah whether you had COVID or not better to get vaccinated. This is the advise I have given my own family.
Update: We know now from the omicron wave 2 important things.

1) Boosters help. More exposures to same antigen increases protection. Get the booster.

2) Prior Covid "natural immunity" doesn't protect fully. Better to get vaccinated. Including booster. bbc.com/news/health-60…

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More from @VincentRK

Jun 27
What’s up with Beta 2 microglobulin (B2M) and myeloma?

Why is it the sole non-cytogenetic marker used in the new IMWG high risk definition?

Why does it matter whether the creatinine is high or not?

Thread
1/
Beta 2 microglobulin goes up in myeloma with either increasing tumor burden OR decreasing renal function.

Thus a high beta 2 microglobulin in myeloma is a reflection of high tumor burden or renal failure or both.

We need to distinguish why the B2M is high!
2/
When B2M is high, it confers adverse prognosis, but why it is high determines what you can do about it.

If the B2M is high because of tumor burden our strategy will be different than if it’s high due to renal failure.

3/
Read 7 tweets
May 24
The remarkable story of Velcade.

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. Image
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…Image
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 )

PS-341 was a proteasome inhibitorascopubs.org/doi/10.1200/JC…Image
Read 13 tweets
May 18
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 serendipityImage
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.Image
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. Image
Read 20 tweets
Dec 9, 2024
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/ Image
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/ Image
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/ Image
Read 12 tweets
Dec 9, 2024
Just out: Paradigm changing AQUILA randomized trial in high risk smoldering myeloma #ASH24
@thanosdimop @NEJM

Daratumumab significantly prolongs time to active myeloma and overall survival. Proud to be a lead investigator of this trial

Slides in thread nejm.org/doi/full/10.10…Image
Main Findings

Daratumumab prolongs:
-Time to active myeloma
-Time to CRAB
-PFS2
-Overall Survival

Plus: Low toxicity, no detriment to QOL, & limited duration therapy. #ASH24 #ASH24VR Image
390 patients with high risk SMM randomized. Largest trial in SMM ever conducted.
Limited duration therapy.

Significant improvement in time to progression to active myeloma or death with Dara.

Benefit seen in almost all subgroups. #ASH24 Image
Read 13 tweets
Aug 24, 2024
Why are prescription drug prices are far higher in the US that other developed countries.

I’ll break it down. A full 360.

1/ We don’t negotiate prices at launch of a new drug. Others do. Image
As a result, we spend billions on common drugs that other countries spend a fraction of the price on.

Some drugs we pay 10 or 100 times more!! Image
2) Generic and biosimilar entry, adoption, and utilization is slower in the US, and there are many barriers.

Timely and adequate free market competition is critically important for lowering price. Image
Read 21 tweets

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