Mike writes:

Hi Everyone

I have been helping people with questions they have regarding SARS-Cov-2 and COVID-19 since the pandemic began. October 13 2021 a paper was published in journal  “Viruses”.

SARS–CoV–2 Spike Impairs DNA Damage Repair and Inhibits V(D)J Recombination In Vitro

Hui Jiang  and Ya-Fang Mei 

Viruses 2021, 13, 2056. https://doi.org/10.3390/v13102056

This paper has quickly been seized on by anti vaccine and mandates groups as the newest reason not to use mRNA based vaccines. All they see is “DNA damage” in the title and it spreads like wildfire.

Is there a way for you to cover this paper in your discussion?  Interest in using this paper to discredit mRNA vaccines has quickly risen over the past two weeks. I am particularly interested in what they mean by “overexpression” of the spike protein; how over expressed?

Any help you can give me would be greatly appreciated.

Keep up the good work, I could not do what I do without TWIV.

Thanks

Mike

John writes:

Vincent, + et al.

Your comment that your wife pays your advice no heed brought this to mind.  It’s from George Beadle’s autobiography, An Uncommon Farmer. 

So this is ca. 1932, at Cal Tech.  Beadle, his wife, and Barbara McClintock are in his wife’s Model A Ford roadster.  So two future Nobel laureates, and she was driving.  There’s seating for just two in one of those, so Beadle was riding the runningboard, which was illegal on account of blocking the driver’s view.  They were pulled over.  McClintock says, “Oh, it’s OK, officer.  You see, he’s her husband and she can see right thru him.”   IIRC, he said the cop let them go.

Otherwise, dry and chilly of late in Greater Braddock.  The last 3 or so nights have been below 0C.  Sunny today and warming ahead.

Regards,

John

Mauro writes:

I started dipping into the archives and felt like watching those movie prequels where you find out how the characters came to be. Episodes like Concerto in B, the ones with Michael Mina, Shane Crotty and Tony Fauci… They were not only fascinating but they also happen to be the start of some current TWiV expressions and traditions, like re-starting picks of the week, Racanielling, “just” a *whatever field*, and more… There’s a living TWiV culture!

It’s also funny to hear your thoughts back then and contrasting them to what ultimately happened, like when Vincent had doubts about the Pfizer vaccine working, because it coded only for the RBD.

Thanks for keeping me sane (although we don’t have the control of me not listening to TWiV this past year, so we’ll never know if it was really you). Let’s say you kept me up to date and provided an excellent example of authentic “science talk”. I can assure you though, that you’ve made me healthier during my commutes, dishwashing, floor-mopping, lab-working, and, dare I say, some incidental toilet sitting. 

In Argentina a famous singer saluted his crowd with a, now classic and beloved, saying: 

GRACIAS TOTALES !

Mauro,

“Just” a plant molecular biologist.

PS: I laughed every time you said epitopes. I wish you ended episodes with it every now and then 🙂

Fernando writes:
Hello from Germany, Twiv. See, not only viruses can spread far and wide. 

I have been a short term listener and my podcast app does not allow for any type of interaction, but the last episode with Gregory Zuckerman made me come to email to say that it was really good and thank you for it.

Best regards,

Fernando

Bonn, Germany (but I am a Brazilian)

Suzanne writes:

My dearest, lovely virologists,

You have been a cooling salve for my burned and battered blue soul living in my deep red state. (WV where it is cloudy, damp, and hovering around the freezing mark)

I have been fascinated with microbes since I was in 2nd grade and read about Joseph Lister, John Snow, and Louis Pasteur, among others.  Alas, I am the daughter of high-school drop outs.  They believed education is for rich sissies and a woman’s place is in the kitchen.  So now while I am working in a menial job, I have you with me.  I have downloaded every episode.  I have listened to all of them many times.  I have learned so much. 

They say to do one step better than the generation that precedes you.  My daughter has a master’s in Public Health and my son is studying engineering.

I try to remember the words I do not know.  I look them up when I get home.  I wish you had a TWIV for Dummies.  I love when Brianne or Rich give the definitions as the podcast unfolds. 

Keep up the wonderful work. Much love and socially distanced hugs.  

Your devoted listener

Joe writes:

Hi, all,

I’m one of those who found you during the pandemic and have enjoyed learning from you and sharing what I learn with others. I went back to the early days and am working my way back to the present, but also listening to the new ones as they come out. (Bird-flu episodes made me understand the lack of crows here in Cleveland Heights. I’m happy to report seeing them again, though still far fewer than 20 years ago.)

I don’t recall hearing specifically about this study on the show. I was having a discussion with a friend who is more concerned than I am. My position was that my current full-Pfizer vax status is all I need and when I’m with known-vaxed folks I’m pretty darned safe. 

They are still worried about any infection and got boosted but are still very cautious/concerned and maybe think I am being foolhardy. 

They stated that it is clear that vax effectiveness is waning. I asked what evidence gave them this idea. 

They shared this Times article:

https://www.nytimes.com/interactive/2021/11/11/science/vaccine-waning-immunity.html?referringSource=articleShare

 which links to this study:

https://pubmed.ncbi.nlm.nih.gov/34619098/

What do you think about its claims? It does seem to say that we are still good against severe illness and hospitalization, but how are we against lower level infection? How are we for risk of catching COVID-19 and passing it to others?

Thanks,

Joe

Vr note from conclusions: “Our results provide support for high effectiveness of BNT162b2 against hospital admissions up until around 6 months after being fully vaccinated, even in the face of widespread dissemination of the delta variant. Reduction in vaccine effectiveness against SARS-CoV-2 infections over time is probably primarily due to waning immunity with time rather than the delta variant escaping vaccine protection.”

Mark writes:

Hi guys. Love the show; very high quality, and interesting topics and reviews. 

I have a quick question/concern about Merck´s new antiviral, molnupiravir. I understand it is a viral mutagen, working by causing “wobble” in copying viral template RNA, and with enough errors present the resulting nucleic acid becomes nonfunctional.

I also understand that the dosing recommended for this effect will be multiple times (4) daily for multiple days.

As a (retired) pediatrician, I am only too aware of the difficulties of getting families to take their medications as prescribed. Very often, three times daily meds turn into twice daily, and twice daily can be once a day or skipped now and then. Patients are only human, and outpatient dosing on a demanding schedule can often be difficult to adhere to.

I am wondering if anyone has studied the viral effects of administering low dose molnupiravir. I assume the published qid regimen was selected for good anti-viral effects, but I am concerned that the “real-life” (i.e., lower dose) administration will possibly be mutagenic, and of low enough dosing to allow survival of possibly more robust viral variants. If the drug is used widely, even a relatively rare variant effect would then become more likely.

Again, great podcast. I appreciate the time and effort you guys bring to the table.

Bianca writes:

Hello twiv team,

I am writing from Townsville, Australia where at 7pm it is 27.1C, 72% humidity. I am a lash technician currently studying my Bachelor of Social Work. My job allows me to wear my headphones most of the day and I have thoroughly enjoyed listening…. to the point that I considered changing my degree! I then realised I probably do not have the brains for it. Anyway, I found your amazing podcast last year around March when I needed the extra information, having ADHD, I need to know every little bit of information possible about these things and I can honestly say that your team has kept me well informed. I may get lost every now and then, I also may have to pause the podcast to google a word, but in general you are all fantastic at explaining terms for us non-scientific listeners.

I have truly struggled through this pandemic in attempting to teach people how to research and make an informed and educated decision … and that’s not research on Facebook and tiktok! I always refer them to your podcast, but what I am finding is that they do not want facts, they want something to fit into their idea of government control, medical freedom and pro-choice (new version of anti-vax). We have been really lucky in Australia, we have had just over 190,000 cases and 1882 deaths.  My sunny state of Queensland has been the most fortunate and so far, we have only had 3 confirmed cases in Townsville, with a population of around 185,000. And this is where the problem lies, our vaccination rates are pathetic! I feel the fact we haven’t had to face a pandemic, bar a 6-week Australia wide lockdown, a few weeks wearing masks, our lives have not really changed. But they will be on December the 17th when rules come in for the vaccinated and unvaccinated.

So, my questions to the team are:

We have a South Australian Professor who has developed a protein-based vaccine, Covax-19, and has been somewhat “bagging out” mRNA vaccines. Are you able to explain the difference between the two? I feel he is doing it as he has developed a vaccine that isn’t mRNA, but he has also mentioned that the technology is too new to know the long-term effects.

I, along with my husband, sons: 20, 17, 15 and 13 are all fully vaccinated with Pfizer and blessed to not have had any side effects bar sore arms…. And in saying that most the people I know have not had any serious side effects. So, my next question is, are the serious side effects, including death from the vaccine really under reported? Are they exaggerated? From what I have found they seem to be within an acceptable percentage alongside other vaccines.

I have pretty much lost faith in humanity, and I am embarrassed to be a part of such a self-entitled society, with little to no respect for others. The unvaccinated minority seems to be the loudest and I am constantly having to defend and justify myself for making a well informed, educated choice in vaccinating myself and my family.

Sorry for the longish email and thank you for keeping me sane, informed and inducing a love for virology!

Kindest Regards,

Bianca

John writes:

Vincent, Brianne,

Thoroughly inhospitable here in Greater Braddock – a clammy and overcast <4C all day incl light precip, some of which was in solid form.  All I managed was trimming a few trees.

But 829 made up for that!  Most of my questions from yesterday answered re. Paxlovid!  Very cool!  And “molecular warheads” – I like that!  I will be passing this along to my usual suspects and other friends incl one in the Chem Dept who has seen a decline in the performance of his students since the epidemic, to his despair.  (Are you seeing this @ Columbia?).

It makes perfect sense that the protease would be highly conserved within the coronaviruses.  It has 11 sites that it needs to cleave with great fidelity.  Any mutation in the protease is likely to be detrimental to cleavage at at least one of those sites, which would wreck the whole process.  Instead, if one site is getting cleaved sub-optimally, evolution is going to favor adjustment of that site to better suit the protease. 

You also touched on UDP-glucuronosyl transferase.  It makes sense to me that that would be found in olfactory mucosa – UDP-glucuronosylation is a common mechanism for getting rid of poorly soluble compounds, and a lot of odorants I think fall into that category.    The substrate for that enzyme, UDP-glucuronic acid, is produced from UDP-glucose by an unusual, 4-electron-transferring, NAD-linked dehydrogenase, UDP-glucose dehydrogenase.  My old colleague David Feingold worked on that enzyme for many years, and nearly 30yrs ago my lab determined its amino acid sequence.  Dr. Feingold was multi-lingual and so this is just a preface to a great story about that – one that deserves a separate email to keep from diluting this one.

Finally, the oak stake in the heart of that Toxicol Reports opinion thing is the great study that Daniel covered in 823, that followed 11M people, ~6.5M vaccinated/4.5M not, and showed that the UNvaccinated are 3x MORE likely to die of COVID UNrelated causes vs. vaccinated.

https://www.cdc.gov/mmwr/volumes/70/wr/mm7043e2.htm

Cheers,

John

Justin writes:

GOP is a death cult. It blows my mind there are still people who would rather get sick and die or get their family and friends ill than do something that’s free https://www.cnn.com/2021/11/14/politics/flu-partisan-divide-analysis/index.html 

Justin

“There is a cult of ignorance in the United States, and there has always been. The strain of anti-intellectualism has been a constant thread winding its way through our political and cultural life, nurtured by the false notion that democracy means that ‘my ignorance is just as good as your knowledge.” -Isaac Asimov, “A Cult of Ignorance” by Isaac Asimov, Newsweek, January 21, 1980, p. 19.

Lisa writes:

Dear TWIV Team,

I enjoy and benefit from all you do. Thank you.  

I think your listeners might enjoy the podcast Criminal and specifically Episode 176, The Red Flag.  It is about an investigation into a series of hepatitis C infections, and it shines a light on how insufficient human resource policies and inaction can rip huge chunks out of even our most trusted and admired institutions. 

Sincerely,

Lisa 

Sperryville, VA