Jeff writes:

I was watching TWIV 989 last night.  When you and your group are discussing some of the papers I don’t understand much of the  discussion.  If you want a more general audience , then I  think it would be best to speak to that audience and define  for us non virologists what you are talking about.   I know this takes more time, but I think it will keep your audience larger and better informed.  I find your topics fascinating, but there are many times I am completely lost in the jargon. 

Thanks again


Jeffrey N Cowen MD FACC, FACP, FCCP


Columbus, OH

Paul writes:

Dr. Racaniello,

I was infected with Covid before vaccines became available, as were many others. We didn’t have a choice to be vaccinated.

To my surprise, the public health apparatus immediately cast doubt on immunity from infection, which was fine initially, but within a year, there was substantial research looking at the immune response from infection.  All research pointed to a robust response.

Upon vaccines being introduced, the same type of research was conducted and found a similar, robust response.

To this day, public health has refused to admit the high quality of immunity received from natural infection, and I would argue, better immunity, in numerous ways.

Indeed, no one should risk infection without vaccination.  Vaccination should be considered a bridge to more safely be infected. That said, for public health to deny infection derived immunity, whether actively or passively, is scientifically proven, creates mistrust.

People want the truth.  They despise when people in authority withhold information in order to achieve a desired outcome (I know better than you).   Public health should fully admit the supporting immunological data on infection, and also recommend strongly, to be vaccinated for safety.

The work of scientists like Shane Crotty, Michel Nussenzweig, Florian Krammer, Jackson Turner and many others has shown that in almost every capacity, infection bests vaccines in establishing underlying immunity, other than a lower, more heterogeneous, initial, antibody response.

-Greater memory B cell magnitude and diversity

-Greater memory T cell magnitude and diversity

– Lower antibody decay rate

-Substantially greater dimeric IgA response in the upper mucosa

-Substantially greater tissue resident memory in the upper mucosa.

Why can’t public health share these facts? Are ordinary people incapable of making their own decisions?

I would also argue that public health’s charade on infection has caused harm – recommending vaccines at 3 months post infection is maddening.

Somatic hypermutation after infection can last for up to a year.  As you know, this phenomenal process can greatly broaden one’s memory B cell repertoire.  Vaccinating at 3 months stalls, if not disrupts all together, this process.  Why on earth would public health rob someone of this benefit after having gone through an infection, especially knowing that infection typically prevents reinfection for 6 months or more.

As, always, I love the show,


Paul writes:

As a follow up to my previous email, I’ve attached this paper by Shane Crotty, which you may have already read.  It is one of the most complete papers I’ve seen covering the totality of Covid immunology and is supportive of the email I sent before.

One aspect that is missing is the immune response post second infection without vaccine.  Although there may be more heterogeneity than with hybrid immunity, I suspect that the quality of the response is much like hybrid.  It seems the preponderance of quality that comes from hybrid immunity is a product of the engagement, via antigen challenge of the quiescent, immune memory created by infection.

As for a vaccination recommendation by CDC at 3 months, I waited ten months for one dose of Pfizer (not 2).  I based my decision on understanding somatic hypermutation/affinity maturation and 15 research papers that determined the second dose of a prime series did not offer any additional benefit.  Florian Krammer, who’ve you’ve had on TWIV, was an author on one of those papers.

I was taught how to do research, how to do it without bias, to always present all of the facts, make recommendations and let the recipient make their own choices.



Gabriela writes:

Hi TWiVers,

Love the show. I began listening when I started learning English when I was in college in Mexico in 2009 or 2010. As a veterinarian that later became a Virologist, I must say you have had a huge influence on my career path. Thank you for all the science communication you have given to the world!

On TWiV 987, Arturo mentions convalescent plasma, while in your legend it is called “convalescent serum”. Serum and plasma both come from the liquid portion of the blood that remains once the cells are removed (as Arturo described), but that’s where the similarities end. Serum is the liquid that remains after the blood has clotted. Plasma is the liquid that remains when clotting is prevented with the addition of an anticoagulant, for example EDTA. Therefore, the plasma contains other things like fibrinogen. I heard twivers interchangeably use these two words, but they are not. Hope this helps to differentiate them!

Love y’all!

Gabby Toomer DVM, MSc, Ph.D.

Research Virologist

Microbiology and Molecular Biology Division

IIT Research Institute

Desiree writes:

I have heard you mention on your show that the MRNA COVID vaccines are essentially a three dose vaccine. Is this true for everyone? I have healthy 9 and 12 year old boys that received two doses of the Pfizer vaccine in December of 2021.  I am a healthy 42 year old woman with no underlying conditions and I received my two doses of Pfizer in July of 2021. Is it essential that myself and two children receive a third dose?  We have not had COVID. Up until Jan of this year we had been continuing to be extremely safe (masking, kids attending virtual school) due to my mother having a bone marrow transplant, living with us and needing to stay as healthy as possible.  Now the kids are back in school, we are getting back out into the world and I am wondering if we are still protected at all?  I cannot seem to find any studies regarding the longevity of T cells after mRNA vaccines. I am not interested in vaccinating to increase antibodies and prevent infection for a few months, but I do want to be sure we are still protected from the worst case scenarios.

Thank you so much for your help!


Kansas City

Grace writes:

My name is Grace and I am a second year student at Caltech studying biology. I have a few questions in regards to Paxlovid. I am very curious as to what makes the drug specific to targeting enzymes that help COVID viruses replicate. How does Paxlovid not interfere with enzymes in healthy cells? Also, is it possible that Paxlovid, or drugs similar to it, can be used to lessen the impacts of other viruses besides COVID?

Thanks so much!


Beth writes:

Hello All — In light of the discussion of the DOE report on the origin of the SARS-CoV-2, I think you will appreciate  a couple of pieces I read recently. In Intelligence Analysis is Not Scientific Investigation, Cheryl Rofer explains why intelligence analysis is not a good way to investigate the origins of the pandemic. 

The other piece, by Jonathan Katz, is in the March 1 edition of his Substack newsletter, The Racket. It’s called “There is no lab leak theory,” with the subhead, “It’s still just vibes in search of a hypothesis.” His thesis is right there. People claiming the pandemic is the result of a leak of the virus from a lab don’t even have a theory to explain it. They just have a bunch of assertions.

Both articles focus on the fact that the lab leak proponents have no data to back up their supposition.



Alexandria, VA

Ken writes:


I am a pleased Patreon supporter of TWIV and found an unexpected bonus amongst all the enlightening discussions in a recent TWIV podcast. Your recommendation of the application Grammarly has convinced me to add that extremely useful computer application to my computer. I am so impressed with the free version that I will follow your lead and purchase the Premium version to show my support. In preparing to invest in the upgrade I came across the following information on their web page that will enable me to make a very meaningful donation to the people of Ukraine. <>  .

Might I suggest that a mention of the relationship between the people at Grammarly and Ukraine on TWIV would undoubtedly help in their “stand-with-ukraine” effort?

Best wishes and thank you and the other TWIVers for providing a pond of rationality and knowledge in a vast ocean of inane and ignorant humans,


David writes:

Hi TWIVers,

Gak! Old habits die hard. On TWIV 989, the group lapsed back into repeatedly referring to percent homology, rather than percent identity. If these large proteins are 65% identical, they are certainly homologous, i.e. descended from a common ancestor.

By the way, although they couldn’t experimentally solve both structures because one protein was not expressed, but with AlphaFold and similar algorithms, they could build reliable models of two proteins that are 65% identical. This would allow them to ask if the structure of key residues in the binding epitope was conserved.


P.S. Why we are not seeing new monoclonals being developed? It has more to do with expected time on the market than the ability to develop therapeutic mAbs for the various omicron variants. The UK does better sequence based surveillance than we do and documented five waves driven by five different SARS-CoV-2 variants in 2022 alone. Newly emerging variants are presumed to have some level of immune escape. Even if you could screen for a new mAb, express it in commercial quantities, and get it through regulatory approval in months, which would be a remarkable feat, its commercial life could be only a few months before a new variant which escapes this mAb would likely emerge. To stay in business, a biotech company needs to develop commercially viable products so failure in months is a problem.

P.P.S. Thanks for the shout out on TWIV 989

David J States, MD PhD FACMI

Chief Medical and Science Officer

Angstrom Bio, Inc.

Carol writes:

The Exceptions: Nancy Hopkins, MIT, and the fight for Women in Science

This excellent book, written by Kate Zernike (NY Times and previously at Boston Globe) describes the discrimination against, disrespect for, micro-/macro-aggressions from the Old Boys Club, marginalization of outstanding, brilliant women in science.  The story focuses on the path and career of Nancy Hopkins, but includes other luminaries she interacted with during her professional career. It ends with the acceptance of the equity committee report by President Vest that documented wage, space, teaching, institutional support and other measures which systematically disadvantaged the women on the faculty.  Today the situation has improved dramatically at MIT, with more women at every level and in many leadership positions.


Carol Shoshkes Reiss, PhD

Editor-in-Chief, DNA and Cell Biology 

Professor Emerita, Biology Department

New York University