Alex writes:

Hi gang, love the show, thanks as always for bringing us real science with the meat on!

Just wanted to add my understanding on what went wrong with the vaccination rollout that caused people significant injuries in some places, and why there is a difference in opinion on vaccination method in different countries, important for an international audience.

When you have people with plenty of experience administering vaccines, the guidelines in many countries is to simply deliver the vaccine without first drawing back on the syringe, as this extra movement results in increased local bruising and discomfort over the following days, which puts people off coming back.

When you have people with less experience, or different experience, there can be a higher risk of injecting IV instead of IM. Normal policy here would be to mitigate the risk by taking the extra step of pulling back on the syringe to ensure you don’t get blood before injecting. However, during the “as fast as possible” vaccine rollout in 2021, for example, here in the UK, the first policy seemed to have remained in place while enlisting the assistance from less experienced vaccine givers, resulting in severe injuries to the most pro-vaxxers who were first in line.

The experience described is very different to the normal (but rare) documented adverse reactions to the vaccine. For example, getting a metallic taste in the mouth within the first minute is consistent with fast delivery through the bloodstream. Long lasting pain throughout the body was completely disabling, and the politicisation of vaccination made it extra difficult for many to be taken seriously, and apprehensive about becoming too vocal, for fear of having their experience used by the anti-vaxxer camp. These injuries were caused by mistake, and should not be confused in any way with a safety issue with the vaccine itself, when delivered correctly.

Hope this helps,

Alex

Helle writes:

Dear Vincent et al.

Thank you for yet another interesting and entertaining TWiV (episode # 954) – which I only got time to listen to today. With reference to what happens to the environment, if we eliminate some/all mosquitoes, it might be worth taking a look at this book-chapter:  https://pubmed.ncbi.nlm.nih.gov/36260729/ 

Killing mosquitoes: Think before you swat – PubMed

Sincerely, Helle

Helle Bielefeldt-Ohmann, DVM, PhD.  
Australian Infectious Diseases Research Centre, University of Queensland. 
Honorary Associate Professor: School of Chemistry & Molecular Biosciences, University of Queensland. 
Affiliate faculty: Dept. Biomedical Sciences, Colorado State University, Fort Collins, CO. 

Disease usually results from inconclusive negotiations for symbiosis, an overstepping of the line by one side or the other, a biologic misinterpretation of border.  [Lewis Thomas, “The Lives of a Cell”] 

C’est les microbes qui auront le dernier mot.  [Louis Pasteur] 

Prediction is very difficult, especially if it’s about the future.  [Niels Bohr] 

It is said that to await certainty is to await eternity. [Jonas Salk]

Historians even have problems predicting the past. DDD 

Neil writes:

TWiV hosts,

I recently listened to TWiV 956. In response to a question in a letter from Lisa about the relative merits of monoclonal vs. polyclonal antibodies, Rich Condit (at about 1:20:18) made a series of comments on the potential value of convalescent plasma.

Unlike his generally detailed and incisive comments about experiments involving the characterization of viruses and viral infections, Rich’s remarks about therapy with convalescent plasma were less detailed, did not directly reference specific studies, and did not address what sorts of characteristics such studies should possess in order to be reliable guides to case management. The latter point is important because the results of studies on the therapeutic utility of convalescent plasma from individuals who have survived COVID-19 are complicated to interpret.

Your former guest, Arturo Casadevall (who Vincent mentions and is cc’d on this message) is one the chief proponents of the therapeutic potential of convalescent plasma for COVID-19.  Arturo has extensively studied, in one sense or another, antibody therapy for COVID-19 and other infectious diseases. He has repeatedly emphasized that this treatment modality is most likely to be effective for patients with SARS-CoV-2 when used early in the course of infection and when the antibody titer (a measure of the antibody concentration) is above an empirically established threshold for neutralizing activity (which does not imply that non-neutralizing antibodies cannot contribute to immunity). Unfortunately, many studies, including some randomized clinical trials, did not adhere closely to these sensible but not always easily followed guidelines.

Below, I provide a link to a 2022 article that provides “Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma”:

https://www.acpjournals.org/doi/10.7326/M22-1079

The next link, below, is for an article entitled: “COVID-19 Convalescent Plasma and Clinical Trials: Understanding Conflicting Outcomes.”

https://journals.asm.org/doi/full/10.1128/cmr.00200-21?rfr_dat=cr_pub++0pubmed&url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org .

Two considerations worthy of note: 1) immunocompromised patients may be more likely to benefit from treatment with convalescent plasma than immunocompetent patients [e.g.: Lang-Meli et al., J Clin Immunol. 2022 Feb;42(2):253-265], and 2) there is experimental evidence to suggest that antibodies in many convalescent plasmas can neutralize Omicron variants [e.g.: Sullivan et al., Nat Commun. 2022 Oct 29;13(1):6478]. 

Another significant point is that if convalescent plasma for COVID-19, used early and with appropriately high neutralizing titers for SARS-CoV-2, is not therapeutically effective, it would be important to understand why that is the case. There is no obvious mechanism to account for polyclonal neutralizing antibodies for the virus not being “intrinsically” effective for protecting against disease to some meaningful degree if used when most appropriate and at adequate titer. Of course, otherwise effective antibodies could fail due to other components of plasma that might somehow counteract the benefits of the antibody.

Given the documented risk of viral escape from monoclonal antibodies in COVID-19 and data from many studies of antibody-mediated neutralization of SARS-CoV-2 and other viruses, there is reason to expect polyclonal antibody populations to offer a lower risk of such escape based on mutation-driven antigenic variation. On this point, Lisa’s expectations are consistent with standard immunological thinking.

Best regards,

Neil Greenspan

———-

Neil S. Greenspan, M.D., Ph.D.

Professor of Pathology

Senior Editor, Pathogens and Immunity

Case Western Reserve University

Arturo writes:

Vincent, Rich and Kathy,

I listened to the episode and agree with Neil Greenspan that some aspects of the discussion about convalescent plasma are not ‘right’ – a lot of work has shown it to be effective if used early on and it is currently recommended by the IDSA, AAP and ICEL for use in immunosuppressed patients.  As we have lost ALL the mAbs CP is now the only antibody-based therapy available.  At Hopkins we stopped using mAbs two weeks ago and are now relying on CP.  I think it would be good if this topic was covered again in more detail.  I would be happy to join you guys again and chat about what happened since I last visited in early 2021.   Here is the Hopkins study conclusively establishing the efficacy of CP in outpatients

https://pubmed.ncbi.nlm.nih.gov/35353960/

Here is a preprint from our group (hopefully to be published soon in Nature Communications) showing that if you give CP in the first five days of infection it is as good as the mABs…for a fraction of the cost.

Outpatient regimens to reduce COVID-19 hospitalizations: a systematic review and meta-analysis of randomized controlled trials | medRxiv

Arturo

November 30, 2022

Neil writes:

Vincent, Rich and Kathy,

Yesterday, about three hours after I sent my email message to you about antibodies and COVID-19, the Physician-in-Chief of the medical center where I work sent out a communication that included the following:

—-

COVID-19 Monoclonal Treatment Bebtelovimab No Longer Recommended 

A Message for UH Providers, House Staff, Nurses and Pharmacists from …

The COVID-19 monoclonal antibody, bebtelovimab, is no longer recommended for treatment of COVID-19 due to an increase in the circulation of SARS-CoV-2 Omicron subvariants BQ.1 and BQ.1.1 in our region. There are currently no available monoclonal antibodies that remain active against these new subvariants. (bold red text added)

—-

Best regards,

Neil Greenspan

Brenda writes:

Came across this on Twitter

This bit bothers me:

Without a mechanism to direct the mRNA to particular tissues, we must assume the mRNA will be taken up haphazardly. Expected result: auto-immune damage to vital organs.

I have been listening to IMMUNE for a while. It is where all my understanding of how the immune system works and how mRNA vaccines are handled by the immune system. The above statement seems quite at odds with the understanding I have acquired. 

Can you clarify?

By the way I did a bit of checking on the Twitter author’s credentials on Wiki

https://en.wikipedia.org/wiki/Bret_Weinstein

former professor of evolutionary biology

Maybe Nels might care to comment too?

Brenda Steele. 

Black Isle Scotland

April writes:

Hi TWIV team,

You were musing about why some of you haven’t gotten COVID. I have an idea, you guys are working with so many infectious agents over the years that your immune system is turned up. I’m on COVID island too

April

Craig writes:

Ok, I finally overcame inertia and set up on Patreon so I could become a member, after the episode last weekend.

I was confused but thrilled to hear your episode with Chiara Mingarelli.  I’ve studied astronomy since before pulsars were discovered, but viruses started studying me decades before I started studying them through your podcast.

I was surprised though that no-one brought up Jocelyn Bell, now Dame Jocelyn Bell Burnell, who discovered pulsars.  But it was her advisor who was given the Nobel Prize.  She continued her work and has won many honors since then, but she’s high on the list of women whose scientific work was not correctly recognized at the time.

Craig

Andy writes:

I would LOVE a This Week in Gravity and would be a subscriber the instant I could.

Also please keep doing what ya’ll are doing because it’s great

Andy

Atlanta

Daniel writes:

The holiday season is just so infectious isn’t it? 😉Have a great season and a happy new year!

Suellen writes:

Dear Vincent and TWIV team —

After about six straight days of rain, today is clear and cold, around 49 degrees F. Tomorrow, more rain.

I really enjoyed TWIV 962 with the Mingarelli sisters and all that great astrophysics talk! Usually your digressions are more along the lines of gardening, feeding apples to deer, or something else I can easily understand, but this episode was so special! I did not follow all of it, but then, I often don’t follow all of the virology talk — however, it was great to see a smart woman scientist talk about astrophysics. If she starts a podcast, I will definitely be listening!

And, especially for Rich, I’m sending this link to the “Backyard Squirrelympics” done by Mark Rober — who, as it happens, is an engineer at NASA and also a squirrel lover and nerd. One hobby of his is building these elaborate, very well-constructed squirrel challenge stations. I think Rich will enjoy this, and I hope you all do, too.

Backyard Squirrelympics 3.0- The Summer Games

Best to all —

Suellen in Roswell, GA

PS — Just caught the 30-minute special episode with Dr. Paul Offit and it was OUTSTANDING! So much better than the little sound bites you get from most news shows, and of course the questions from you and Rich were intelligent, and not dumb like the ones usually asked by news hosts. I sent the episode on to my family physician, because I really think the info is pertinent and would be useful to physicians who are actually making decisions for patients. 

Katy writes:

Hello TWIVers,

I have been listening to your podcast since the beginning of the pandemic and have truly appreciated your science based conversations and clinical updates with Dr. Griffin. The witty banter between you all is entertaining as well.  

I’ve enjoyed so many episodes over the past two years;  most recently; I really dug episode 960:  Getting funky with Dan Wilson!  I now subscribe to his youtube channel and ordered up a spike t-shirt from vaccinated.us.  And, yes, I remembered to use the microbetv code!  

Episode 962: Chiara Mingarelli takes the pulse of the universe was awesome even though I understood about 70% of the conversation.  No worries, though, I shared a link to the episode with an aerospace engineer friend who absolutely loved it!.  I write in today, because at the end of that episode; Rich’s ‘pick’ was a squirrel proof bird feeder.  This reminded me of my son’s favorite YouTuber, Mark Rober, and his ‘journey’ to find a squirrel-proof bird feeder.  Mark Rober is a scientist who makes learning about science super fun for my 13 year old son and we always enjoy the videos he produces.  His squirrel videos are our personal favorites and I thought Rich would get a kick out of them too.  His glitter bomb videos are pretty entertaining as well. 

Keep up the great work, I really appreciate and love what y’all do!  

In gratitude,

Kathy 

https://www.youtube.com/watch?v=hFZFjoX2cGg