Katerina writes:

Dear Vincent and TWiV crew,

Thank you for discussing our recently published paper “A novel lineage-tracing mouse model for studying early MmuPV1 infections” in episode 907. I am a long-time listener and patron of TWiV, so it was a fantastic surprise to hear your insights and feedback!  Since our paper was constrained by a word limit, we did not have the chance to expand the discussion as much as we would have liked so I did want to address one small point:

Lineage tracing models, in contrast to virus reporter models which are more commonly used in virology, are better suited to follow the progeny of cells which initially received the viral genome. After the initial activation of the heritable reporter, cells could be traced even after they have lost the viral genome. Thus, while our model clearly enables studies of cellular dynamics during the first few days of viral gene transcription, it also lays the groundwork for following cells after viral gene transcription has stopped. Hopefully in the future this strategy will enable us to address questions such as mechanisms of persistence and potentially “hit-and-run” effects of the virus.

Thank you again for taking the time to discuss our work,

Best regards,

Katerina Strati
Associate Professor
Dept. of Biological Sci.
University of Cyprus

Mathias writes:

Dear TWiV team,

Hope you all are doing well!

I am a big fan of TWiV, and while was listening to the episode 907, I realized that during a discussion on SARS-CoV-2 in cats and dogs, you guys were wondering about clinical signs in deer infected with SARS-CoV-2.

I am a postdoc at Cornell University – Ithaca NY, and in collaboration with National Animal Disease Center/USDA/ARS – Ames IA, we conducted two cohorts inoculating SARS-CoV-2 in WTD in a lab set condition (high containment facility/ABSL-3).

In the first study (https://journals.asm.org/doi/10.1128/JVI.00083-21) (open access 😉 ), we assessed the susceptibility of WTD fawns and the ability to transmit the virus to their contacts. We have shown that fawns SARS-CoV-2 inoculated shed high viral titer (~10ˆ6 PFU/ml) and are able transmit the virus to other fawns in the same room, even with no direct contact, most likely by aerosol. These results raised a red flag and made us consider investigating SARS-CoV-2 in free-ranging WTD.

Then we decided to conduct a second study (https://doi.org/10.1371/journal.ppat.1010197) (open access 😉 ), we investigated the transmission dynamics of SARS-CoV-2 fawns by adding contact animals on days 3, 6, or 9 pi and defined the major sites of virus replication during the acute phase of infection. Additionally, we assessed the evolution of the virus as it replicated and transmitted between animals.

Going back to the question about clinical signs in deer infected with SARS-CoV-2, no clinical signs were observed in any of the animals from both studies. Except for a slight and transient increase in body temperature on day 1 or 2 pi. Obviously, we should consider that these were observations based on a small number of experimentally infected deer. However, if the same happens in natural infections, it could benefit viral transmission among free-ranging WTD.

Thanks for all you do sharing high quality information!

Kind regards,



Mathias Martins, DVM, MS, PhD
Postdoctoral Associate – Diel Lab
Department of Population Medicine and Diagnostic Sciences
College of Veterinary Medicine
Cornell University

Windy writes:

Hi TWiVers,

I am a student in Bi115 (Viruses and applications to biological systems) at Caltech. Thank you guys for your amazing contents on virology, immunity and the COVID clinical updates. 

I have a question when I was viewing episode 898. When you guys talked about microneedle patches vs intramuscular administration of vaccine, I was thinking, would the patch method offer more protection to viruses that transmit using skin contact (like HPV) versus influenza because the patch immunization method is more similar to the natural transmission route of the virus? Just a speculation. 

Best regards,


Amy writes:

First, I would like to thank you for doing these podcasts. I am a regular listener and appreciate your peer review of latest evidence and helping me better understand immunology and virology.

My question is how do vaccines, at the cellular level, protect against severe covid in a person who has autoantibodies against interferon alpha and omega? Do they not protect? I wonder if some patients, whom the vaccine supposedly ‘failed’, were those who had large amounts of these targeted autoantibodies prior to infection?

I’m a nurse, vaccinated and boosted, who’s exhausted from dealing with the fallout of misinformation and the antivax movement.

Thank you,


Anonymous writes:

I have esophageal strictures and can’t swallow most pills.  I am also at a fairly high risk for severe covid.  Even though I am vaccinated and boosted, I really like the idea of having a backup like Paxlovid available.   

However, I have just read on drugs.com about Paxlovid:   

“The tablets should be swallowed whole and not chewed, broken, or crushed.”  

So is Paxlovid not an option for people like me?  

This guideline makes sense to me with time-release medications, or with drugs that can damage the stomach, but I’m unclear about what is behind this requirement in the case of Paxlovid.  The phrasing is “should be” rather than “must be”.   

Is it just that pills were swallowed whole during the trials and have not been tested if they are broken or crushed?  or is there a chemical, pharmacological or physiological reason that it is necessary for an intact pill to arrive in the stomach before it is broken down by the digestive system? 

Under Dosage Forms and Strengths, the drugs.com entry also says that “Nirmatrelvir is supplied as an oval, pink immediate-release “, so it’s not a matter of delayed release (at least with this component).

Thanks in advance.   I really appreciate your Friday clinical updates as well as Vincent and his other guests.   It’s like a breath of fresh air to hear scientific and professional discourse without drama and hysteria.  It’s like an island of sanity in the roiling sea of Youtube 😉

Mike writes:

It’s 27°C (81°F) and a clear in NYC.

When I got my first booster (so far), I made the mistake of thinking that I should try to “spread the material” as if it were fertilizer, and got the shot in my right arm, having gotten the first two in my left arm.

Now, after reading the article referenced below (and listening — again — to the “B Cell Boot Camp” episode), I see that I was using a completely mistaken metaphor. It’s more like: Put a book in an otherwise empty room, and a “student” appears. Put more books (on the same general subject) in the same room, and the student reads them and builds on the knowledge gained from the previous books.

But, if you now decide to go to a *different* empty room, you have to put a copy of the *first* book there, and the “new student” who appears reads only that one book, and adds (almost) nothing to the more comprehensively educated person in the first room.

(It’s a start…. It’s a bit too “magical”, but someone who is better with metaphors should be able to bring it into commonsense, “real-world” imagery.)

Ok: here’s the haiku:

=   =   =   =   =   =   =   =   =   =   =   =   =

  Haiku for “Recall of B cell memory on vaccination location (Science Immunology)”

   — (mentioned in “TWiV 899: COVID-19 clinical update #114 with Dr. Daniel Griffin”)

Flowers in full bloom
I feel ill on occasion.
Same arm! …right, I know.

  – Mike in NYC

Ben writes:

Dear Twivsters,

Like many other people, I have been suffering from pollen allergy (grasses, birch) since I was a kid. 

I learnt during Vincent’s Virology Live classes last year that measles can erase a lot of the immune memory.

I was wondering today about the impact of this effect on allergies. Could this also reset the body’s “overly ambitious” response to pollen? Or is this mediated by a different part of the immune system?

Not that I would want a measles infection to get rid of allergies, but maybe we could learn something about the underlying mechanisms, to help develop treatment, maybe using a model?

Thanks for all you do and stay safe

Ben (Biolution), the guy with the “Back to the Future” T-shirt at the Richard Ernst lecture in Zürich

Jerry writes:

Dear Rich and other TWIVerati;

Congratulations on having bumped our local Sunday NPR line-up. Although a latecomer to your podcast, having only become TWIVaware since the beginning of the pandemic, I’m now a true devotee. You’ve even managed to hook my wife, who is the head of Medical Genetics at our university and so much better positioned to understand the nuances of your discussions, compared to me, a mere neuroradiologist and health services researcher. Not only are you my go-to source for all questions virological, but your wit, wisdom, healthy skepticism, and rational approach to science and life has been sustaining and entertaining during this past pandemic period. So thank you.

I was partaking in my usual Sunday morning ritual of listening to TWIV and on your episode 907 Rich mentioned a lack of familiarity with receiver operating characteristic (ROC) curves- a topic that for once was in the wheelhouse of radiologists, since ROC curves are frequently used to report the accuracy of diagnostic tests.

As you know and have discussed on TWIV, sensitivity and specificity are two common metrics for assessing diagnostic accuracy of dichotomous (positive or not) tests. For many if not most diagnostic tests, one can choose the threshold for test positivity which will in turn alter the sensitivity and specificity. Take Ct values for RT-PCR; a given lab may report values of 24 and below as “positive” compared to some sort of reference standard, this would then result in one set of values for sensitivity and specificity. However, the same lab could have used a different Ct threshold for positivity, resulting in different sensitivity and specificity values. Thus, a limitation of simply reporting sensitivity and specificity is that it only examines how well a test performs for a given positivity threshold. ROC curves examine test performance across the entire spectrum of positivity thresholds by plotting sensitivity vs. 1-specificity. You might recognize: 


as the likelihood ratio (LR), or in English, the likelihood that a patient has a positive test result if they have the disease (sensitivity) over the likelihood that they have a positive test result but don’t have the disease (1-specificity). This ratio is another useful metric for assessing test performance, and often the following rule of thumb is used: LRs >10 essentially rule-in a disease and LRs <0.1 rule-out a disease.

Examining the entire range of test performance allows the comparison of tests by calculating the area under the ROC curves (or AUC). The maximum possible AUC=1 (perfect sensitivity and specificity) and a test with no useful diagnostic information has an AUC=0.5.

ROC curves also allow one to look explicitly at the trade-offs at each threshold for sensitivity/specificity. Usually, opting for a higher sensitivity results in a lower specificity and vice versa.

There are many resources on the web explaining LRs and ROC curves, for example, the Centre for Evidence-Based Medicine (https://www.cebm.ox.ac.uk/resources/ebm-tools/likelihood-ratios). One nice article summarizing ROC curves is by Fan et al Can J Emrg Med. 8(1): 19-20. 2006: https://doi.org/10.1017/S1481803500013336

Sorry for this lengthy missive, but consider it a tribute to TWIV that I was inspired to write this email on a Sunday afternoon. I hope that I helped to clarify rather than confuse.


Jeffrey (Jerry) G. Jarvik, MD, MPH
Professor, Radiology and Neurological Surgery
University of Washington School of Medicine

Alan writes: 

Likely animal reservoir for Pasturella pestis strain of Black Death found in Marmots of Kyrgyzstan reported in Nature on 6.15.2022:


Note: It only took 684 years to find the likely animal reservoir for the Black Death. Thankfully, no one was blaming it on Chinese alchemy. Now, we must encourage field researchers to find a likely animal reservoir for SARS CoV2 in order to lead the WHO to revise their recent report:

Alan Caroe, M.D.
Las Cruces, NM