Ian writes:
I am very much enjoying TWIV, initially due to self-interested information gathering but that moved on to enjoying the personalities and discussions carried out by the people on each show. Thank-you.
I am an interested, to some extent self-interested student of the immune system. I am by no means qualified beyond that.
I have the good fortune to have begun recovery from the immune-system side-effects of lymphoma chemotherapy treatment (I’m about two years out from finishing maintenance treatment). I received infusions of two drugs, Bendamustine, (an alkylating agent in the lineage of many chemo drugs and interestingly, developed in the former East Germany), and Rituximab, a manufactured chimeric (from mice) monoclonal antibody that to a reasonable extent targets the type of B-cells that are cancerous in my case (CD-20 expressing B-cells).
I have had what I understand is a common side-effect of my treatment, neutropenia. Neutropenia is the suppression of the production in the bones of a type of white blood cell called neutrophils. This may be caused by one or both of the infusion medications I received. The neutropenia has led to some serious infection side-effects until recently, when my neutrophil and other immune system levels have been returning to normal, and seem to be holding.
I heard on TWIV that a high (greater than 4) ratio of neutrophils to lymphocytes has been associated with statistically worse outcomes for those who are infected with the SARS-COV-2 virus. My ratio for both neutrophil and lymphocyte measures is currently well in the safe zone based on the literature I have read, but, looking back, in past months the ratio was also low but the absolute values were also much lower than was healthy.
Feng et al. (3) suggest that “A rising neutrophil count and a falling lymphocyte count indicate the intensity of the inflammatory response and damage to the immune system, respectively. ” Beyond the supposition in Feng et al. (3) are there any other hypotheses as to the underlying causes for this imbalance? Being a layperson in these things, I am not expecting to shed any light here on this issue. I am hoping for a small summary of how these two components of the immune system work and change together in response to a viral infection, in this case an infection with the SARS-COV-2 virus. Might other important factors in this be the ability of a person’s body to rapidly manufacture certain types of immune cells in response to infection and the ability of the range of immune system functions to work together in the face of infection? I have heard that the immune system may over-react to the SARS-COV-2 virus so was also wondering what the role of normal balancing and responses among immune cell types might be. In terms of an over-reaction I am thinking of the testing of steroidal treatments, especially early on, to dampen damage from an over-response of the immune system.
Thank-you for your time.
References
- Yang, A. P., Liu, J. P., Tao, W. Q., & Li, H. M. (2020). The diagnostic and predictive role of NLR, d-NLR and PLR in COVID-19 patients. International immunopharmacology, 84, 106504. https://doi.org/10.1016/j.intimp.2020.106504 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152924/
- Ciccullo, A., Borghetti, A., Zileri Dal Verme, L., Tosoni, A., Lombardi, F., Garcovich, M., Biscetti, F., Montalto, M., Cauda, R., Di Giambenedetto, S., & GEMELLI AGAINST COVID Group (2020). Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line. International journal of antimicrobial agents, 106017. Advance online publication. https://doi.org/10.1016/j.ijantimicag.2020.106017 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211594/
- Feng et al., Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis, Frontiers in Medicine – 2020. https://doi.org/10.3389/fmed.2020.00301, https://www.frontiersin.org/articles/10.3389/fmed.2020.00301/full
Michael writes:
Dear TWiVers, would you please ask this of Dr. Griffin during your next podcast with him?
Has anyone looked into using steroids or tocilizumab on “long-haulers”? I have looked for any studies or clinical trials and I can’t seem to find them, but I’m not quite sure how to parse the search terms.
Thank you.
Michael L. Ginsberg, M.D., M.S., FAAP
David writes:
Hi, Twivniks,
It’s 28° C here in Hershey on its way to 37° (or maybe more), not a cloud in the sky.
I don’t remember whether Jon Yewdell mentioned the possibility below in one of his visits. Even so, I thought it would be worth repeating.
There has been recurrent mention that immune responses fade with aging. What about immune regulation? Might it also be disrupted? I know that counteracting immune regulation is an important part of the latest cancer therapies. Are there therapeutics that boost immune regulation rather than reduce it? Such agents might provide a complement to therapeutic immune suppression.
As a non-clinician, I love Daniel Griffin’s reports. If Vincent is America’s virologist, and Fauci is America’s infectious disease expert, then Daniel is America’s clinician.
I’m keeping up with the blizzard of TWiV content. The quality remains unparalleled.
Stay safe and keep on twivvin’,
David
David J. Spector, Ph. D
Professor Emeritus of Microbiology and Immunology
Penn State Hershey
TETRIS: TEst; TRace; ISolate
– K. Spindler
Jamie writes:
Hello Vincent–
Just in case you guys mention Fauci’s wild pitch on the podcast, I wanted to pass along how a caller to a local Boston NPR radio station explained it: “Fauci just doesn’t want anyone to catch anything!” I loved that.
Take care, and I’m loving all the CoV2 coverage,
Jamie
*~*~*~*~*~*~*~*
Jamie Henzy, PhD
Associate Teaching Professor
Biology Department
Northeastern University
Norman writes:
Here, after a Washington Post Freedom of Information lawsuit, is the State Department memo about the Wuhan BSL-4 lab, which started the accusations against the Wuhan Institute of Virology.
This memo is the subject of this Washington Post story:
State Department releases cable that launched claims that coronavirus escaped from Chinese lab
By John Hudson and Nate Jones
Washington Post
July 17, 2020
The State Department has released an internal cable from 2018 detailing the concerns of U.S. Embassy officials in China about a lack of adequately trained personnel at a virology lab in Wuhan, the city that later became the epicenter of the novel coronavirus outbreak.
Leaked contents of the cable sparked unproven speculation from senior U.S. officials beginning in April that the outbreak occurred as a result of an accident at the Wuhan Institute of Virology.
In May, President Trump said he had seen evidence that gave him a “high degree of confidence” that the coronavirus originated in a Chinese lab. When asked why he was confident, Trump said, “I can’t tell you that. I’m not allowed to tell you that.”
(more)
Some more background of the accusations is in this story:
State Department cables warned of safety issues at Wuhan lab studying bat coronaviruses
Opinion by
Josh Rogin
Columnist
Washington Post
April 14, 2020
(more)
It would be interesting if you guys would read the memo and news accounts, and give your opinion about how well they got the science right.
P.S. Here’s the interview with Martha Raddatz in which Mike Pompeo first says that he agrees with the experts who say that the virus was manmade, and then says that he also agrees with the experts who say that it was not manmade.
ABC, This Week
China’s coronavirus response was a ‘classic communist disinformation effort’: Pompeo | ABC News
May 3, 2020
https://abcnews.go.com/Politics/week-transcript-20-mike-pompeo-gov-mike-dewine/story?id=70478442
‘This Week’ Transcript 5-3-20: Mike Pompeo, Gov. Mike DeWine, Ronna McDaniel, Tom Perez
This is a rush transcript of “This Week” airing Sunday, May 3.
By ABC News
May 3, 2020, 9:05 AM
49 min
RADDATZ: And, Mr. Secretary, have you seen anything that gives you high confidence that it originated in that Wuhan lab?
POMPEO: Martha, there’s enormous evidence that that’s where this began. We’ve said from the beginning that this was a virus that originated in Wuhan, China. We took a lot of grief for that from the outset, but I think the whole world can see now.
Remember, China has a history of infecting the world, and they have a history of running substandard laboratories. These are not the first times that we’ve had a world exposed to viruses as a result of failures in a Chinese lab.
And so, while the intelligence community continues to do its work, they should continue to do that and verify so that we are certain. I can tell you that there is a significant amount of evidence that this came from that laboratory in Wuhan.
RADDATZ: Do you believe it was manmade or genetically modified?
POMPEO: Look, the best experts so far seem to think it was manmade. I have no reason to disbelieve that at this point.
RADDATZ: Your — your Office of the DNI says the consensus, the scientific consensus was not manmade or genetically modified.
POMPEO: That’s right. I — I — I agree with that. Yes. I’ve — I’ve seen their analysis. I’ve seen the summary that you saw that was released publicly. I have no reason to doubt that that is accurate at this point.
RADDATZ: OK, so just to be clear, you do not think it was manmade or genetically modified?
POMPEO: I’ve seen what the intelligence community has said. I have no reason to believe that they’ve got it wrong.
—
Norman
New York, NY
Mark writes:
PACE STATION
On the latest TWIV Grumpy was wondering about seeing the ISS overhead. NASA’s got an email alert for that! I’ve been using it for years and it’s great. Sends you an alert in the morning for when you can see it in your locale, how long it’ll be visible, angle in the sky, etc… When it’s just right you can see it trace an arc over the sky over about 6 minutes, even at dusk before it gets dark. It’s great! Definitely check it out all:
https://spotthestation.nasa.gov/
Mark
p.s. a muggy 30’C here, even muggier inside my mask
Ronald writes:
Hello, Twivians! Love your shows. This is Ron, writing you from central Florida, where it is a bit cool (an even 30C today) and windy with sudden outbursts of rain, due to the storm brewing in the gulf.
Finally, a chance to pay you all back, if only a little! When the ISS goes over in the early morning near dawn, or late evening near or just after sunset, the sun reflects off of it and lights it up brighter than any star. It travels across the sky in at most about 6 minutes before winking out.
To see it, go to https://spotthestation.nasa.gov/, enter your location in the box at the top of the map, click on the closest blue pin to your location, and click the “View sighting opportunities” link in the pop up. If there are any opportunities in the next few days, it will list them. For best viewing, look for opportunities with the longest duration and the greatest “Max Height”. Then look across the chart for where it will light up, where it will wink out, and the maximum height of its arc between those two points, and of course, the time this will begin, and then go watch it.
As an example, one of my opportunities is:
Tue Aug 4, 9:30pm, lasting 3 minutes, max height 49 degrees, beginning 15 degrees above NNW, and ending 44 degrees above ENE.
Thus, at 9:30 that night, I’ll want to be looking north by northwest, slightly above the horizon (15 degrees). If I can’t see that horizon, I know it will be heading on an arc towards east by northeast, that passes through 49 degrees (right ascension) halfway between (to the northeast). On a clear night, this will be tough to miss if you are looking anywhere near the directions given. Use a low magnification pair of binoculars with large front lenses and you may even be able to make out the shape just after it winks out. While it is lit up, that would be like staring into a light, but as it winks out, it is still there, it has just gone into the shadow of the Earth and is no longer reflecting.
Rich writes:
Hello Twiv,
As a retired veterinary pathologist who taught viral pathogenesis at Tufts Veterinary School for 30 years, I can’t tell you how much I am enjoying your podcasts. One thing that makes me laugh is your oft used term “herd immunity”. How in the world did a term like that get entrenched in today’s scientific jargon after years of terminology like “epidemic” v. “epizootic”, endemic/enzootic, etc, etc, supposedly making clear distinctions between human and animal disease? Wouldn’t “population immunity” have been more consistent?
Anyway, here’s my question. If people over 50 years of age infected with covid-19 often develop more serious disease, and this is presumably because of a diminished immune response (immunosenescence), why is dexamethasone so effective in preventing many of the deleterious effects of the virus? The comparative effects of dexamethasone on humoral and cell mediated immunity are likely not well known, but I would suspect the drug would dampen immune response in both limbs.
Incidentally, are you familiar with the discovery of synthetic steroids by Russell Marker, an analytical chemist who began his work studying the octane ring. He subsequently developed the octane rating system. In 1938 he proposed a new molecular structure for sarsasapogenin, a plant glycoside, which when degraded by removing most of the atoms in the side chain resulted in a steroid ring subsequently converted to cortisone.
Best Regards,
Rich Jakowski, DVM, PhD, Dip. ACVP
Associate Professor Emeritus
Dept. of Biomedical Sciences
Tufts Cummings School of Veterinary Medicine
Helen writes:
Long time listener! Thank you for supporting teachers!
Helen
Rafael writes:
Sunny & Hot 90 in under siege Portland OR
Olympics: I planned to go with my son this year but oh well
Am I making it next year?
If you were consulting with the Olympics what would you suggest happen to make the highest likelihood that this could go forward?
Consider having a virologist from Japan on your show in the future…
Thank you!
Rafael
Philippe writes:
Hello twiv team,
Congratulations to you ladies and gentlemen you bring great insight into this period.
I believe episode 640 followed by 641 are putting twiv in the spotlight.
Does it show on your statistics?
It should anyway.
Be proud to inform all people, hairdressers, plumbers, carpenters, L&D specialists (myself) up to date and speed with science. You do not take us for fools and you are right.
I took the first 9 lectures on virology course and intend to finish during my holiday.
I am able to discuss sarscov2 with pharmacologists without looking stupid and even challenging them with your insights.
Congratulations, keep up the good work!
Philippe
From vr:
Lib writes:
Hello TWiV!
Thanks so much for the wonderful podcast you’ve been doing during the pandemic. I’m a biostatistician at Northwestern University’s Feinberg School of Medicine in downtown Chicago, so I’ve been keeping very busy with COVID-19 research, and it’s great to be able to listen in on updates instead of having to search for them myself. I am currently working on a serology study of our hospital workers, all of whom were offered a free serology test and over 6000 then agreed to participate in our study, sharing their serology results and answering a brief survey concerning COVID-19 exposures, illness, etc. I would love to send you our paper once it is done.
However, for now I’m mostly writing in about two small things.
First, I also have something to add on to the “guinea pig” comment and the possible mandatory “trial” of a new COVID-19 vaccine in Chinese military. My roommate and good friend was in the US military for four years from 2009-2013. While in training during the fall of 2009, she was given a mandatory vaccine for swine flu, H1N1. All military personnel were required to receive the vaccine – in fact, they are required to receive many vaccines, including some very invasive ones such as smallpox and anthrax. I’m including links to some articles, including a 2007 AMA Ethics article concerning informed consent in the military:
https://www.cidrap.umn.edu/news-perspective/2009/09/h1n1-vaccination-be-required-us-military
While the H1N1 vaccine was FDA approved, and this is of course a HUGE difference to a mandatory trial, I do have one more thing of interest to add – my roommate reports that a superior officer gleefully told her and the other mostly teenage military recruits that that they were “guinea pigs” for this new H1N1 vaccine. An important remember that our military is not a paragon of “informed consent.”
Second, concerning the offhand comment in TWiV 642 about “hot coffee” dropped on one’s lap: This is undoubtedly a reference to a famously misunderstood 1992 case about a 79 year old woman, Stella Liebeck, who spilled McDonald’s coffee on herself.
Links concerning this case:
https://www.caoc.org/?pg=facts
https://www.vox.com/policy-and-politics/2016/12/16/13971482/mcdonalds-coffee-lawsuit-stella-liebeck
Some of the important facts, pulled from Vox article I included above, about Adam Conover’s show Adam Ruins Everything and their episode on the case: by McDonald’s policy, their coffee was at that time heated to up to 190 degrees Fahrenheit, which caused extensive, life-threatening third degree burns to Stella Liebecks’ legs and genitals. All she asked for was McDonald’s to pay her $20,000 medical bills, which they refused, so she took them to court. She ultimately settled from $600,000 dollars. McDonald’s then began changing how it heats up its coffee.
From the Vox article: “’This was an incredibly rare case where a working-class victim actually beat a huge team of corporate lawyers and made the world a better place.”’ So how did the public’s view of this case get so warped? According to Conover, lawyers spent years running a disinformation campaign, which much of the media bought into, holding up the McDonald’s coffee lawsuit as an example of a supposed epidemic of frivolous lawsuits.”
So just a quick reminder that while yes, frivolous lawsuits can happen, many “supposedly frivolous” lawsuits are made out as such by smear campaigns funded by our world’s richest corporations. While vaccine risks are certainly complicated, and the public image of them is particularly bad right now (to our society’s great detriment), I highly doubt vaccine manufacturers are exempt from this media bias against normal people asking for restitution from corporate harm.
Thanks so much again for all you do!
Elizabeth (Lib)
Dave writes:
Greetings from North Central Florida where it is a toasty 36 degrees C.
First I am not trained at all in your field of expertise. I have a few questions that I am sure will remove any doubt of that fact.
After listening to 5 months of TWIV I am confused. Please help me understand. When I hear positivity rates and or mortality rates being tossed around it appears that they are including the total positive test results in the calculations. How can one report any measure which would include qPCR CT values greater that 35 or 36 which represents a measure of non-replication competent RNA? Would this not also potentially have an impact on the number of people being reported as asymptomatic? Dead nucleotides indicates to me a “contamination” measure or post disease artifact measure rather than a measure of how contagious a person would be. Is it not true that pesky RNA contamination in a lab is very difficult to control? Just ask the CDC.
After a review of the literature it also appears that Michael Mina was correct that many in the scientific community turned up their noses at the prospect of using anything than the Gold Standard qPCR for testing
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240272/ .
With what is at stake I cannot fathom why even if the government failed us in the deployment of the low cost antigen testing where were the voices in the corporate world and universities demanding the production of this $1.00 pregnancy type test. My opinion is that the FDA would have to approve the manufacturing and distribution of the test strip because the public and corporate pressure would be so huge they would have to cede to the inescapable logic of the benefit of this type of testing, performed frequently. Michael Mina is spot on!
At this point my head rotates 360 degrees above my shoulders and all that is missing is the pea soup in this horror of a movie.
Thank you for all that your team does to communicate what is and more importantly what is not the current state of the science.
Very respectfully submitted
Dave
John writes:
If fatal cases are highly skewed to the elderly, i.e. nursing homes etc doesn’t that make it difficult to back track to the total number of individuals infected?
Anonymous writes:
Hi TWIV Friends
I have a degree in Geology but I am currently working as just a transportation planner for a commuter railroad on Long Island as we transition through the reopening phases in downstate NY. I’ve been listening to all things TWIV since late March based on a Twitter recommendation by Malcolm Gladwell. BTW he also recently tweeted the Michael Mina TWIV. It says a lot about the service you folks provide when you count the likes of Malcolm Gladwell as a regular.
You can be assured that I will continue to listen after this is “all over”. I have a question about the herd. I keep hearing about studies that place seroprevalence in various locations generally between 5% to 25%. As a matter of fact, I heard on TWIV that Corona Queens is apparently the “Queen of Coronavirus” with 68%.
So my question is what constitutes a Herd? Am I part of the the downstate NYC herd (20%) or NYS herd (10%)? Maybe I’m part of the ‘Merica herd which I figure is between say 1% and 12% seropositive. Given the fact that I work in a major intermodal transit hub should I think bigger? Do the residents in Corona have reason to have a Rosie outlook or should they kiss the prospect of herd immunity goodbye (apologies to Paul Simon)? I’m curious about how to think about this as well as how to respond to people who point to herd immunity prospects based on a study in one location or another
Signed,
Anonymous
Bradon writes:
Dear TWiVers,
I’m writing from Harare (Zimbabwe, a country in Africa), where the weather is a sunny, very dry 20 Celcius. (I’m sorry, I have no idea how much that is in Fahrenheit. Your temperature measurement system confuses me. I was raised with Celcius.) I listen to your show while I clean the house, and would like to thank you for keeping my motivation high to create a hygienic environment in my home!
I only have a bachelor of biology (double majored in plant and human bio, third class pass, no honours thesis), so will defer to your superior wisdom. I’m sorry that this question is distinctly grosser than the four-year-old’s fart question.
My roommates and I all got an infection in January that our respective primary care physicians deny is COVID-19 (without referring us for antibody testing), despite us (and our cat and dog) having all the symptoms of a long-term infection (complete with gastroenteritis) from January to March, or the middle of our summer, which is statistically improbable for a regular flu infection. We’re all experiencing symptoms consistent with the after-effects of COVID (poor pulmonary performance, increased joint pain, etc.) Our respective doctors and our furbabies’ vet argue that “the virus has only existed since March,” so we couldn’t possibly have had it. They refuse to listen to your show, because “Dr. Google doesn’t know better than me.”
Is there a connection between sharing a bathroom with someone and sharing immunity? Specifically, if SARS CoV-2 can stay on smooth plastic surfaces for a few days, and someone with an active COVID infection poops in a toilet that’s in the same room as a toothbrush, flushing the poop without closing the lid, spraying a plume of aerosolized fecal matter onto the toothbrushes in the room, can those toothbrushes then transmit the virus?
Alternatively, is this (fecal plumes landing on toothbrushes) a potential explanation for the results out of Strasbourg regarding outpatients’ cohabiting contacts developing immunity? If the guts of actively infected COVID patients have antibodies, and they sh!t within range of their roommates’ toothbrushes, does putting those toothbrushes in our mouths spread immunity?
I’ve tried to get my roommates to close the lid before they flush. Am I trying to make evidence to support my opinion on lid-down flushing, or is there a case to be made for thoughtlessly spraying sh!t on people’s toothbrushes being a way to spread disease? Our town has annual outbreaks of cholera, dysentery, and typhoid, so “toothbrushes as a transmission medium” is relevant outside of this pandemic.
Physically distant regards,
Bradon
Joshua writes:
Hello and thank you to all I admire at TWiV et al,
Thank you Vincent and thank you to everyone. I do not expect this to get to being read any time soon but I thought it time that I spend some time writing a thank you for what you do (feel free to jump down to the bottom of this email to get to the main point). I am an assistant professor at a Detroit Mercy Dentak in Michigan. I had the distinct fanboy pleasure of meeting Dr. Schmidt at an American Dental Education Association meeting last year, getting to say “It is good to put a face on a voice I have been listening to since grad school”. I am trained in bacterial pathogenesis but have been immersing myself and falling in love with virology as I have been teaching Viral Infectious Diseases to dental students. I want to send a sincere thank you to Vincent for posting his lectures as it has been wonderful to continue learning and adding to my formal graduate training in virology as I continue learning how to teach as well. I have been working from home and trying to connect with students in this time of remote instruction and Dr. Schmidt’s appearance on TWiV was timely and wonderful for my own information and also to give my students another resource to see what getting back into the dental clinic will be like. That episode came at a time when Michigan was getting ready for phased re-entry and our school was in plans to reintroduce students into the COVID-19 era of dentistry. Also, trying to follow your lead of getting out good information, I along with my colleagues have been doing Q&A sessions for our students and faculty for the most recent information on the pandemic.
On a separate note, I have been compelled by the efforts and time commitments from everyone involved in the different TWi’s (I forgot what the term to refer to all on them is TWiX’s?). I have begun venturing back into social media. It is not an easy task to try and put out good scientific evidence based posts and take the time to deal with a lot of the difficulties associated with that. However, your collective dedication to promoting good information has instilled in me the desire and motivation to continue trying. I must say that it has paid off. I have gone through responding to people that just like to bring up conspiracies or talk about headlines without any sound supporting information. Your examples have shown me how to do it constructively and I have a new found respect for the fact that it is just easier to believe something you are told without facts and that we as a scientific community can be a voice of reason and that most out there just do not have the right source. WE can all be that source and do it in a positive and productive manner and it is most definitely worth the time. We can all learn something in that process as well.
I think the most jaw-dropping moment of all this has been the episode with Michael Mina. I was listening as I got ready for another day of working from my home office with the kids running in and out and going crazy (which honestly has been great, much better than working an hour from home everyday and not seeing them). I felt utterly shocked at how much sense all of this made. I have been in discussions in the community about schools reopening and my wife is a teacher. And nothing has felt good enough without the testing. Then, this interview just blew me away. I felt so much better and even more convinced when I heard Rich Brianne and Vincent expressing the exact same feelings. Even as a young investigator who still has a bit of impostor syndrome, I felt that I was validated in hearing you all feel the same way as I was.
I sure do love to ramble, but what scientist doesn’t. Thank you so much for what you all do. I hope you know your efforts are reaching people. I have been posting episodes on social media and I that led to my construction manager/foreman brother posting a huge post about the Michael Mina episode. I told him, if you do not listen to anything else I tell you, listen to me now– go and listen to that episode. He did. He posted.
To quote the beginning of my brother’s post “Long read here, but give it a minute. Give this podcast a listen. The first 45-60 minutes is all you need. Put it on 1.5x and it is done before you are done mowing your lawn. Don’t worry about getting lost in the acronyms, just know these people are among the best in their world. When several of them have their mind blown by one, maybe we should listen.”
Just once more, thank you so much for your dedication. All of you. You are all selfless and the scientific community is indebted to you and should learn from your efforts. I have learned so much and will continue to do so.
Best to you all and thank you again.
Josh
Joshua Thomson, Ph.D.
Assistant Professor
Interim Director of Research Administration
University of Detroit Mercy School of Dentistry
Ginna and Joe write:
Dear TWiV Team,
We are probably outliers among your listeners, as I am an opera singer and my husband is an opera conductor and composer. We live in Santa Fe, New Mexico where it is currently 531.67 degrees Rankine or 72 Farenheit (LOL, we had to look up the Rankine conversion), and we were introduced to TWiV by a friend after the COVID pandemic started. We have become passionate fans. We have lots of time to listen, since our entire industry has ground to a halt for the time being. We always wear masks, distance ourselves from others, and mostly stay home.
We’ve heard every one of your programs since we found out about you, and also listen to TWiP and TWiM. It is so important to us to have access to real science. We have told all of our friends about TWiV, and encourage them to listen so they can get real and cutting-edge information. Program 632 with the comprehensive update on the progression of COVID-19 and the newer discoveries of using steroids (dexamethasone) in the second week and anticoagulants in the third was so useful that I actually transcribed Daniel Griffin’s full update for my mother and for several friends. Program 640 with Dr. Fauci and Program 641 with Michael Mina were also both chock-full of vital information. Michael Mina’s suggestion of an inexpensive saliva test with quick results seems like a no-brainer for widespread adoption to allow us all to have any kind of life outside our homes.
You are the most thorough, reliable source of updates and information on the subject. Thank you for the wonderful service that you are providing, making your expertise available to the general public as well as medical professionals. And you’re a lot of fun!
We wanted to ask you for your commentary on two articles we saw in the news. The first was from Rensellaer Polytehnic Institute, claiming that Heparin may neutralize the virus that causes COVID-19. https://news.rpi.edu/content/2020/07/15/common-fda-approved-drug-may-effectively-neutralize-virus-causes-covid-19 The second was that an Israeli-US team found that Fenofibrate (Tricor) could interfere with the ability of the virus to reproduce. https://www.israel21c.org/downgrading-covid-19s-threat-to-that-of-the-common-cold/
Please keep up what you’re doing. We love the banter, we love the information, and we love being challenged to look up new terminology every time we tune in. Thank you!
Ginna Browning and Joe Illick
Santa Fe, NM
Saskia writes:
Dear TWiV-Team
I am a huge fan of your podcast!
The current pandemic made me (like many others) an enthusiastic TWiV-listener. In February I started listening to Christian Drosten’s podcast (didn’t miss an episode) and wanted to learn much more about viruses. A friend told me about Vincent’s virology lectures and I watched all of them. Of course I also started listening to TWiV, I haven’t missed an episode since the beginning of April (and I am also listening to older episodes as well as some TWiN, IMMUNE, TWiM,…).
After listening to Michael Mina in episode 640, I was as excited as you were by this new way of looking at testing. And I immediately wanted to tell our government experts about it. Since I do not know anyone “up there”, I wrote – with little hope – an email to the Swiss National COVID-19 Science Task Force (https://ncs-tf.ch/en/ – created to advise the Swiss federal government in the current pandemic) . I sent them the links to the MedRXiv preprint and of course to TWiV 640 (see emails – in German – below).
Incredibly, after only 15 minutes, I got the following response:
In English:
” … Thank you very much for the links. This podcast has just been recommended to the team by one of our experts. … “
So the expert team advising the Swiss government are listening to TWiV!
I really hope they will follow Michael Mina’s (and your) advice. In Switzerland we are doing quite OK at the moment, but far too many people behave as if Sars-Cov-2 were gone.
Thank you very much for your fantastic work, I’ll keep listening – as will, hopefully, our government experts in Switzerland.
All the best
Saskia
Zürich
Emails below are older
Hanson writes:
Greeting TWIVers! I’m a Canadian PhD student in Switzerland. The weather here is sunny and pleasant, with a high of about 15 celsius.
Was interested to hear about the idea that there were no false negatives on last TWIV, but there’s a big disconnect between that idea and what is being reported: https://bc.ctvnews.ca/virus-testing-isn-t-as-sensitive-as-originally-expected-can-lead-to-false-negatives-henry-1.4894503#_gus&_gucid=&_gup=Facebook&_gsc=SrjkTJV
And also anecdotes like this one, where the husband (almost certainly) died of Covid but tested negative, while the wife tested positive: https://www.cbc.ca/news/canada/calgary/peru-trip-covid-calgary-1.5519468?fbclid=IwAR0K5z4VtskYXvUfkpDmCbWmZ7j4XSoeTvlyasa8UgO8t2vfP6xTA-LTxFA
Since the qPCR test is based on relative abundance of viral RNA, there are so many places this can fail. It’s been mentioned many times on TWIV that sample collection is a key factor; though I guess the shallow vs. deep nasal swabs had 94% agreement IIRC? But on a mass-testing scale, I have to imagine that simple sample processing issues alone can result in false negatives (RNA degradation, cDNA synthesis reagent degradations, contamination by e.g. alcohols that prevent cDNA synth or qPCR amplification). Even if this only affected 1/100 samples, that’s not nothing.
And then of course there’s possible replication inhibition by primer cross-reaction with say… other coronaviruses or arbitrarily similar viral RNAs that we can’t predict, but may be in high enough abundance to interfere with our assumed 100% efficient SARS-CoV2 amplification. All labs should** look at melt curves for all tests, but do they? An even bigger concern given the strange “CT>35” cutoff, as if a CT of 36 suddenly means virus isn’t present; despite the clear indication that low-abundance viral RNA was amplified. Biology and biologists are pretty good, but we aren’t perfect. The fact that, in the lab, we typically do things in duplicate or triplicate before we validate something as “positive” or “negative” is a testament to these factors.
Does TWIV think the false negative rate really is negligible? Or are we ignoring yet another variable that further fudges the numbers?
Best,
Mark
Global Health Institute, EPFL, Switzerland
Ed writes:
Hello again. Love the show!
I had another thought on vaccines and fomites and life of the coronavirus (or other) on various fomites.
As the virus breaks down on various surfaces outside of a human cell, is there ever a virus state that is harmless to a human being in terms of invading a cell and replicating, but at the same time causing an immune response based on the “de-activated” version of the virus in its breakdown state?
Eddy
Kirkland WA
David writes:
Dear Twiv
You are doing a great job helping keep us busy healthcare workers up to date on the science of Covid-19, thank you so much. I am now walking to work (45 minutes each way) for my daily exercise whilst listening to the podcast… a bit of continuing professional development as well as fitness development!
In terms of the comments about emergency preparedness by hospitals in the UK we all have “Major Incident Plans” which are tried and tested, to deal with sudden disasters resulting in a large single influx of patients such as major car pile ups, stadium disasters etc. We also have plans to allow us to increase surge capacity to deal with winter pressures although these are sometimes less effective than we would hope.
You are quite right that hospitals tend to run right at the limits of capacity much of the time. Over winter in the UK hospitals often report occupancy rates >100% which whilst being scientifically inaccurate is more than we use admission areas and discharge areas to hold patients whilst inpatient bed spaces are turned around to allow the new admission.
The problem with coronavirus is that all of these patients are coming over a very short timescale but also many are not able to be discharged quickly. This is one of the major problems. Imagine one of those sliding puzzles we had as children where every space had a piece of the puzzle so that you can no longer slide the pieces around… that’s what is happening with coronavirus. We have new patients coming in but we’re not able to get patients out to allow for this…
Keep up the great work, love the show and would be lost without you all.
David
Consultant Clinical Microbiologist from the UK