Louisa writes:

Hi, 

I am a pediatrician working for the Indian Health Service, and am helping reservation schools with protocols, etc for this fall.  Your podcast from July 4th discussed that there are many schools that are testing students and staff weekly.  Are the schools you reference doing NP swabs?  Mid turbinate?  Our State Health Department has only validated NP swabs, and we do have ample testing supplies and are testing our IHS staff every 2 weeks – but I can say now from personal experience that testing young kids weekly if using NP swab is going to be a challenge in and of itself given the invasiveness and discomfort of that test.  Would love more information on this, I am trying to push our clinic to just do anterior nares sampling but we have too many NP brushes and our leadership is concerned that the wrong brush will increase false negatives.  

Thanks!

Louisa

Peter writes:

Hello team TWiV!

I’m writing from Truro, MA, where it’s 29 C and gorgeous. I’m overlooking the spot where the pilgrims landed 400 years ago (months before crossing Cape Cod bay to Plymouth).

Love you folks and very much appreciate your honest talk and occasional Vincent rant (what I call Racan-yelling!) I’m a doctor and a scientist, just the wrong kind, a Political Science PhD. 

In TWiV 638, while talking with Viviana Simon you ask about a faster COVID-19 test, and she agreed one might be coming. Are you aware of that Quidel has an FDA-approved Sofia 2 SARS Antigen FIA test that gives results in 15 min. (See https://www.quidel.com/immunoassays/rapid-sars-tests/sofia-sars-antigen-fia ) Local CareWell Urgent Care locations are offering the test. What are your thoughts?

One other quick question. I’m a data analyst and a few bits of data have been bothering me. There’s a good news – bad news story I recently heard on NPR. They reported that Nir Menachemi, the Chair of Health Policy and Management at Indiana University’s Fairbanks College of Public Health, was reporting a survey study showing that roughly 3% of Indiana’s population had been infected, about half without symptoms, and that the lethality rate of infection was 0.6%. Other studies in NYC have suggested lethality of as little as 0.5%. This is better than the original estimates of 1% or more. Here’s the bad news.  As of today, the US has 133,000 deaths and there was much concern about the number of  cases crossing 3 million. But if lethality is between 0.5 and 0.6% and we have 133,000 dead, that suggests between 21 and 26 million people had been infected. And that’s as of several weeks ago, because it takes time to die. Why aren’t more doctors and scientists helping the media understand that the infection is much more widespread than 3 million cases would suggest (as if 3 million isn’t bad enough)?

Thanks for all you do,

Peter

Fred writes:

Dear TWiV crew,

Thanks for your hard work communicating the State of the Science of viruses (the kind that make you sick!) to the world in general. I greatly appreciate the podcast, and listen (at 1.5X speedup) on my nightly walks.

One question I have about testing… the PCR test has high sensitivity and thus a high PPV (maybe I’ve learned something!), but not high specificity so there is a meh NPV. PCR  thus are not well suited for saying who is not infected because of the false negatives. I found a Johns Hopkins paper which seems to say there are more than 50% false negs in the first 4 days of infection, and in the 20-30% range at symptom onset. Even with a negative PCR test, Bayes would argue for additional evidence before declaring someone “not infected.”

I think antibody tests may miss a significant fraction of people who were infected too, so we can’t use an antibody screen and then do a PCR on antibody positives, even if antibodies appear early enough in the course of an infection to be useful.

T cell reactivity seems to be not a good choice either, even if we could do it rapidly, because the Singapore paper had T cell reactivity in people with no known exposure to SARS-CoV-1 or SARS-CoV-2.

Given all the above, with the high false negative of the PCR, how does a testing program test often enough to find infectious cases early? Does weekly testing leave a window for a super spreader to kick off a new round of whack a mole? What is the optimal testing protocol for TeTrIs?

The JH reference: https://www.acpjournals.org/doi/10.7326/M20-1495

Regards, Fred

Ryan writes:

Hello from Gettysburg PA! It is 302.15 degrees Kelvin and partly sunny here on July 11, 2020.

I am a long time TWIV, TWIM, TWIP listener but this is my first time writing. These shows offer amazing insights and have been the background accompaniment for many projects around our small farm.

I wonder if you could discuss the merits of pooled RT-PCR tests for COVID. I’ve run many RT-PCR assays for genes and microbes, but never on pooled samples. Should it be considered part of the school and college re-opening strategy?

All the best,

Ryan

Jon Cohen writes:

I much enjoy TWiV. A couple of things in your last episode could use some clarification.

The CanSino approval for the military basically allows the company to use military regulations, rather than the regulatory approval process. I have been told by a Chinese health official that no one in the military has been vaccinated as part of that allowance, but they wanted this provision in case of ship or base outbreaks.

The U.S. military has a long history of pushing for exemptions to U.S. FDA regs. Our system differs from China, but to my non-lawyer mind, it seems to be a matter of degree, not kind. 

https://www.tandfonline.com/doi/abs/10.1080/08989620212967

https://usaphc.amedd.army.mil/PHC%20Resource%20Library/Mil_%20Laser_Exemption_FS%2025-025-0212.pdf

As for Warp Speed and transparency, the 5 candidates that David Tuller mentioned were not disclosed by Warp Speed. This was reported by the NYTimes according to senior administration officials. There is no information about how Warp Speed has chosen candidates.

I have covered this at some length:

https://www.sciencemag.org/news/2020/07/operation-warp-speed-s-opaque-choices-covid-19-vaccines-draw-senate-scrutiny

Best,

Jon

PS Since I sent this note, Warp Speed held a press teleconference and named four vaccines that are explicitly part of the project. (Interestingly, Warp Speed likes to crow about its transparency, but one of the two “senior administration officials” on the call insisted that comments could only be attributed to a senior administration official. The other one, Janet Woodcock, was on the record.

The 4 candidates they’ve selected are no surprise: Moderna, J&J, Oxford/AstraZeneca, and Novavax.

Matt Frieman writes:

 I wanted to show you the paper that you were asking about when you were discussing the Novavax vaccine.  They sure did get $1.6 Billion last week on top of ~$350M from CEPI and ~$60M from DOD.

I was the one that did all the neutralizing antibody experiments and mouse experiments.  Also below are the 2 other MERS vaccine papers I published with them using the same technology several years ago.  

The vaccine uses a double mutant of Spike where there is a furin site mutation and a mutation in the stalk which locks the protein into the pre-fusion state.  This likely keeps it in a realistic structure to the outside of a virus.  They also used their insect cell system where they express full length Spike in insect cells, extract the protein and then form these little florets of 4-6 Spikes stuck together at their C terminal transmembrane domain. They call these nanoparticles.  There are EMs of them on their website and in the MERS papers below.  There is nothing extra added to make them “nanoparticles” unlike what Rich was suspecting.  They stick together at their transmembrane domain and that’s what forms the particles. Mixed with their adjuvant, they make very nice multimeric antigens for vaccines.  

The new SARS2 paper is really nice, showing particle size and thermostability, nice mouse protection, neuts in mice and baboons, great B and T cell responses etc.  Phase 1 trial almost ending soon with that data coming out as soon as it’s all done.

Hoping this is a good vaccine, that is safe and effective.  Phase 2 and 3 trial sites are around the world.  Fingers crossed. Data look good so far.

thanks

Matt

Matthew Frieman, PhD

Associate Professor

Department of Microbiology and Immunology

University of Maryland School of Medicine

Michael writes:

Vincent, et al., 

First, thank you all for taking the time to produce TWIV. I find it a hugely valuable source of information that I can trust because you are all clearly so knowledgeable but also so honest about the areas of scientific uncertainty that exist with respect to SARS-COV2. 

I am curious whether the general support among the panelists for the re-opening of school (expressed in Episode 635) would extend to preschools. I ask because I am aware that some of the measures typically recommended to prevent transmission of the virus in a school setting may be difficult to implement in a preschool environment. For example, physical social distancing for preschool children is developmentally problematic given that children in this age group require touch and other physical interaction for proper emotional development. Moreover, with children of this age, any mask-wearing requirement is likely to be honored primarily in the breach. Many preschools will also lack the separate rooms by which to divide the student body into smaller groups. Toys, which often end up in the mouth, are commonly shared across the entire group of students. Playground equipment is also shared and difficult to sanitize. And, then, of course, there is the general matter of hygiene being an area where the students are commonly equal measures unpracticed and unconcerned.

If your view is that preschool should re-open despite these challenges, what is the basis for that recommendation, and what would be the measures you might advise in order to keep the students and staff safe? Would you, for example, require that teachers wear N95 masks? Would you limit the total number of hours per day that a teacher should be present in the classroom to reduce viral loading? Would you require frequent testing of students and staff? If so, where would you expect/recommend the funding for that testing to arise if, as is the case with most preschools, there is no endowment upon which to draw? Would you forbid the sharing of toys and activities? How would you recommend that schools manage meal times? Would you require certain types of air filtration/purification? Would you require eye coverings given that children of this age are not particularly good at covering their cough?

Of course, I realize that you might recommend all of the measures I’ve described above. But which are the measures without which you would not recommend a re-opening?

Thanks, in advance, for your thoughts on this. And, again, thank you, thank you, thank you for all your TWIVing. 

Michael

Anon writes:

Hello from Rockford Illinois where it’s 90 Fahrenheit and 82% humidity. My wife is a school teacher and I attached the official guidelines for return to school this fall. I thought you might find this informative

He sent: https://drive.google.com/file/d/1Ql4_augsrV6H7AQek5xS_dpCqzTS1LBo/v iew?usp=sharing 

Anonymous writes:

Dear TWiV,

Every day I look forward to listening to your latest podcast. I live in southern CA, and for the past 20 years I’ve worked as a hairstylist in a salon frequented by the rich and famous. I’ve always had an interest in science and factual information, although I have no real higher education. I come into contact with hundreds of people, and have developed close client relationships. I listen to as much science news and podcasts as I can, read books,  and pass on interesting tidbits in conversations. You’d be surprised how many seemingly normal, monetarily successful, and supposedly highly educated people plan their lives according to whether or not mercury is in retrograde! Some even plan haircuts according to the waxing or waning of the moon! A lot of them are antivaccers. 

I haven’t worked in the salon since March 14th, and mostly stay indoors. I miss my clients, but luckily I’m an artist, and spend my time drawing and sewing, and listening to your podcast. I’ve had to look up so many things, and I’m learning so much! I have done the occasional house call, and even that limited interaction with the “public” has brought into sharp focus the lack of understanding of science. No one knows what a journal is or what a preprint paper is, or what it means to be published. No one knows how science works, or how to get information from a reliable source. I find that most people get their information from headlines and other people, and as science progresses, people think “they’re changing their minds” and that “everyone says something different” and the most frustrating and common one: “we all have our opinion, and it’s up to people to decide which side to believe”. I think this gets to the root of the problem in our country. Average people don’t know how to find sources and don’t know how science works. Average people are confused and have given up. Average people have decided to just “live their lives”. I have a unique perspective, having contact with thousands of people, with an hour’s worth of conversation with 8-10 different people a day. Very few of my clients know how science and research is done. Most of them are superstitious, and a lot of them repeat conspiracy theories as plausible fact. Most of them went to reputable universities. (Obviously they didn’t major in science). And now, because it seems people have given up, I feel that going back to work in a salon is a high risk of infection. For example, an assistant tested positive for SARS cov2 and came back after a week, and when a coworker complained, she was sent home for another week. The salon never closed. No one was told they were in the salon on the days she worked. No one was told to get tested. She wasn’t  required to get a negative test. I’m sure it wasn’t laziness or negligence, but rather a lack of understanding. 

It’s unbelievable to me that most people have little or no understanding of basic science, when I am able to understand, and I’m a hairstylist. People don’t know who to listen to or where to get their information. Unfortunately, the politicians are loud, and the scientists are busy. 

Thank you for your podcast. I’ve forwarded it to many people, but no one has the patience to try to understand what the heck you’re talking about. 

PS can you discuss more about the link between blood type and covid19?

Imants writes:

Good morning-

I’ve only recently begun listening to your podcast, and I thank you for what you do. Some of the frustrations that you expressed in episode 637, along with your brief reference to Winston Churchill brought to mind a quote that has been at least apocryphally attributed to Winston Churchill. I wanted to share this quote with you here, because I feel like it’s as relevant as ever: “You can always count on Americans to do the right thing – after they’ve tried everything else.”

Ok, keep up the good work!

Cheers