TWiV 1372: Clinical Update with Dr. Daniel Griffin

0:00This Week in Virology, the podcast about viruses, the kind that make you sick.

0:10From Microbe TV, this is TWIV, This Week in Virology, episode 1372, recorded on November 5th, 2026. I'm Vincent Racaniello, and you're listening to the podcast, all about viruses. Joining me today from New York, Daniel Griffin. Hello, everyone. What's on your tie, Daniel? Blue? So actually, for those that can see closely, it's these little yellow gram-negative rods. It's playing. Hercinia pestis. I see. Which has been in the news lately. You know, not only has it been in the news lately, but yeah, I was thinking that, you with what happened this week, maybe, you know, the end of the plague or something.

0:58So, okay. So I got political there a little bit. I see. But all right, let's start with a quotation because we have a lot to talk about. And, you know, I actually, I don't know if you know this, Vincent, I spent a lot of time on these quotations, sort of trying to pick something. I heard, yes. And when I got this one and the more I went into, you know, Wilma Rudolph's story, I was like, Oh, this one's perfect. So never underestimate the power of dreams and the influence of the human spirit. We are all the same in this notion. The potential for greatness lives within each of us. And I don't know if you knew this story and maybe your listeners, but this is by Wilma Rudolph.

1:40And she was an American sprinter who overcame polio as a child. That's right. Went on to become a world record-holding Olympic champion, international sports icon, and track and field. She won a bronze medal in the 4x100 meter relay at the 1956 Summer Olympics in Melbourne. Melbourne? How do we pronounce that? Melbourne. Yep. Melbourne, Australia. She also won three gold medals in the 100 and 200-meter individual events and the 4x100-meter relay at the 1960s Summer Olympics in Rome. She was acclaimed as the fastest woman in the world in the 1960s. Cool. And she had polio as a kid. I was out running today, and I don't run very fast.

2:29But I was thinking, like, how fast could she have been if she had not had polio, right? Wow. Yeah, but she was born before the polio vaccine. That's it, right? 1940. Yeah. So yes, maybe she would have been faster. I mean, it has to take something away, right? It's pretty amazing, right? Yeah. So, you know, polio. I was thinking we should make a list of polio survivors that have gone on to accomplish things in this world. So is that quite a number? Oh, we got a lot of people. It's Zach Perelman, Neil Young, right? Many others. All right. Well, let's start off with some good news. Feel free to jump in with some other good news.

3:09So among the winners who helped flip the House and Senate during the midterm elections were six doctors and public health professionals who were supported by – I don't know if people know about this – 3.14 Action Fund. It's a political action committee dedicated to bolstering Democratic candidates with STEM, science, technology, engineering, and math backgrounds. I didn't know about it, but I guess that's pi, that number, right? Yeah, that's 3.14. At least they stop at the four. Well, you know, Bernie Sanders wants to get rid of PACs, so this may have to go. You have to get rid of this, right?

3:48Yeah, I don't think they're a good idea because it lets anybody give as much as they want, right? It's a problem. It's that whole, what, Citizens United stuff where it's not Citizens United. It lets very wealthy people like Elon Musk try and change things, although he failed this time. Yeah, spent hundreds of millions of dollars to try to push an election in there. People had an idea that they did not want this anymore. It was quite clear. Yeah. And there's a – we would like to say that they saw the tragedy of public health, but we know it has a lot more to do with the war in Iran, with affordability, with a lot of people being upset with sort of this police state that ICE has created for many of us.

4:34But let's go through because it is exciting that we're going to have health professionals, right? That's great. In Washington. Of course, the guy in Louisiana is departing, right? Cassidy. Cassidy's going, which is good because he's the one responsible for RFK Jr. He didn't hold the – dude, you weren't reelected. You're done anyway. You could have at least prevented – well, we're going to talk about what you could have prevented. So in the Senate, we had Dr. Annie Andrews, a pediatrician, South Carolina, flip the open seat previously held by the late Lindsey Graham. Now, she is the first Democratic doctor elected to the Senate in nearly 60 years alongside El-Sayed, first ever pediatrician senator.

5:24That's cool. Yeah. Now, Dr. Abdul El-Sayed, also physician trained. He's an MD, PhD, and he was a former Detroit Wayne County health director. He spent some time at Columbia at Mailman, and he won the open seat. He completed medical school but pursued public health rather than residency or practice. And then in the House – actually, there's a quote. I should read this quote. The last time a Democratic doctor sat in the Senate, Congress passed Medicare and Medicaid. So we're expecting big things. Okay, in the house, we've got Dr. Richard Pan, another pediatrician. Look at that. I'm a little worried we're losing our pediatricians when we need them most, but maybe they can do California's 6th District and highlighted for prior work on vaccine policy in California.

6:26Mitchell Berman, registered nurse, emergency room nurse, Wisconsin's 1st District. Christina Knickerbocker, an oncology nurse practitioner and Air Force veteran, Ohio's 10th District. And Dr. Adam Hamawi, surgeon, former U.S. Army combat surgeon, New Jersey's 12th District. All right. Great. That's all great. It's good to have physicians in Congress for sure. So I'm excited that we're going to have some healthcare. I think you need to run sometime, Daniel. You know, I did think about it. There was a, yeah, so it's a backstory. We'll talk about that some other time. You have the savvy to do it.

7:14You speak well. You could do it. People would like you, yeah. Yeah, I mispronounce things though. I have to have you there to be like, Vincent, have we say that? All right, anyway. Okay. All right. But right up front, and I'm going to talk about this twice because, you know, we hemmed and hawed a little about what Cassidy could have prevented. And there's two quotations that I think are – I don't know. I'm sure we didn't coin these. But, you know, the first is when, you know, when you mix politics and science, what do you get? Politics. And the other is if you mix politics and medicine, you get dead children.

7:50And yes, you know, it's only been, it hasn't even been two years, and we have children dying in the U.S. of a vaccine-preventable illness that we haven't seen these deaths in quite a while. So let's take the first one. Child dies from measles in New York State's first fatal case in 30 years. You know, Vincent, I talk with my kids and my wife about, well, we see what's going on, but at least here in New York, it'll be okay. You know, we live in 50, you know, somewhat united, somewhat not United States, but at least here in New York, we have these good vaccine laws that protect them. You know, Daisy, maybe at some point she's going to, you know, be with child.

8:35She's my oldest. But here, a child in New York's North County died after contracting measles, the first death in the state from the viral disease in 30 years. This was announced Monday by Governor Kathy Huckle, said the death was a signal that public health protections were eroding as a growing number of families forego vaccinations. Child died in Lewis County, northeast of Syracuse. Pennsylvania, another measles-related death, an unvaccinated resident of Jefferson County. There's some confusion whether it's the sixth or seventh death. And a baby, this is hot off the press, unfortunately, today, a baby in Wisconsin has died from measles.

9:19So third death just this week, an infant in Wisconsin. This is the first death in the state from measles in 36 years. This is really unacceptable, right? There should be no measles deaths in the U.S.? There really shouldn't. And we didn't have them. No? And this is all attributable to RFK Jr.? It really is. I mean, you know, proof of the pudding. Like, we had eliminated measles. We did not have children in the U.S. dying of measles. RFK Jr. comes in, destroys our public health infrastructure, and we have children dying. I mean, I just don't understand why this isn't the top of everyone's list.

10:03Like everyone's talking about, we've got to impeach Egg Seth. I'm like, I think the first person we have to get rid of is the one responsible for little children dying of vaccine-preventable illnesses, for lying to people, for misinforming them. Because these parents are making decisions that they think is in the best interest of their child because someone in a position of power is lying to them for personal gain. He will probably resign before January so they can't go after him. All right. We're going to talk about these again. Mpox in California, four cases of clade 1 Mpox, recently reported out in Stanislaus County.

10:45Chagas in Texas. A couple of things here. So the article, Autoxidus Acute Chagas Disease with Fulminant Myocarditis in a Texas Infant Exposed to a Peridomestic Environment with trypanosoma cruzi-infected vectors in animal. This is published in CID. So here they describe the case of an autochthonist. Like this is a little child, didn't leave the country, living in Texas, doing what little kids do, put things in their mouth. And this peridomestic investigation revealed trypanosoma cruzi-infected vectors in animals. 10-month-old Corpus Christi presents to the hospital fever up to 38.9C, rash, fatigue, diarrhea, bilateral periorbidema, vomiting, and the blood smear shows these tripomastigotes, these motile infective forms.

11:39So it's lost the flagellant, so the tripomastigotes become the amastigotes, develops fulminant myocarditis, toxic megacolon, just horrible hospital course that they describe here. Is there anything you could do to prevent this? I mean, obviously the trypanosomes are there, right? That's interesting. Like, what do you do? Like, is this really a failure of public health? Was he probably bitten by a vector? Or he may have actually put a bug in the mouth or something, right? Because they found it in the local environment. Yeah, this is a problem because this is what happens in other countries, right?

12:16Yeah. But I just don't know what you would do to prevent it other than keep the child indoors. But there could be the bugs indoors as well. Yeah. And it'll be interesting. We might get a guest to join us, a couple of guests to join us at ASTM and H2 who are doing a documentary on Chagas. We can ask a lot of these questions like, how do we control Chagas? So sort of a teaser for our listeners that we'll have an upcoming deeper dive into Chagas. Is it controlled in other countries at all? Not really, actually. Yeah. Okay. So aside from Texas, where else is our trypanosomes in the U.S.? Do you know?

12:56Actually, they're all the way up. Like there was the issue, I think, in Tennessee. So there are the – it's a different type of reduvid bug. But yeah. And one of the differences that we thought would protect us, which is not going to protect you if the kid puts it in the mouth and eats it, is some of the South and Central American reduvid bugs, when they're feeding, they'll defecate sort of right away. And so they'll bite and there'll be an open wound, but then they'll leave infected feces, infectious feces, and that gets rubbed in the wound. The ones in the US eat and then defecate later. So is the idea that that reduces it.

13:40But we see Chagas in dogs, right? Because they'll eat the bugs. And here, the concern was that maybe this child actually ingested a bug. Wow. All right. Mysterious anthrax outbreaks kills hippos in Africa, raising concerns for human spread. This is in nature. So an anthrax outbreak has killed at least 30 hippos. In the DRC, they've got enough problems going on. There are no cases in people so far. They're monitoring it. The dead animals were first found in September in the Virunga National Park in eastern DRC. Lab tests confirmed they died from anthrax. This is an infection caused by the bacteria Bacillus anthraxis.

14:21The outbreak comes at the same time as they're dealing with the Ebola and cholera and ongoing humanitarian challenges. So hopefully we'll have some updates on what exactly has happened there. It's pronounced anthracis. Anthracis. Yeah. I want to go back to the Chagas. Could you treat this kid? Oh, yeah. Yeah. And they did. And actually, what was sort of a, if you read the article, there's benzinibazol and nifertamox. And they're not exactly that easy to get immediately. So there were some challenges they described at accessing the medicines as quickly as they would have liked. But would you even know to diagnose this?

15:04That's the thing, right? The interesting thing is you look at a blood smear. You could see the trip of mastic oats on the smear. So if you had a child with fulminant myocarditis, would you do a blood smear? I mean, I think in this situation, you're in Corpus Christi, Texas. You've got megacolon. You've got myocarditis. I think it starts making you add that to your differential. You look at a blood smear and you say, there it is. Well, this would be a good twip case, wouldn't it? It would, actually. Yeah. Especially if it happened in New York City. Or they'd called me. Yes. Yeah, no, it's a tough case.

15:43So this anthrax in hippos, I mean, they have other problems with humans, infectious diseases, but I don't like seeing the hippos dying either. No, no. Yeah, I mean, it's not great to see the hippos die. And of course, they're also being really careful in how they're handling and disposing of the carcasses. All right. And just while we have basically become a neglected tropical disease country, dengue. 60 new cases in just the past week. Florida's dengue total jumps to 485. And this is from Florida. That's a lot of dengue. Yeah, lots of dengue. We're up to 485. And that was 60 cases of locally acquired dengue just this last week.

16:28Well, you know, Florida wants to protect the mosquitoes, so that's what you get. Is there some effort to protect the mosquitoes in Florida? I guess so. Well, they keep electing the right, you know, the right government officials if that's their goal. All right. Bird flu over last weekend. Health officials in Yakima. Is that how you pronounce that? Yakima County, Washington. Yakima. Yakima. Yeah, chemo. So basically, there were two more folks sickened with H5N1 avian flu, including one person who died after hospitalization for severe illness. Is this the bovine one or the D1? You know, I'm assuming it's a D1 just because the person died, but let's take a look here.

17:16Let's see if we can... Because they have an outbreak in cows in Washington. Yeah, it didn't, when I tried to link to the page. Let's, I don't know if this, does the CIDRAP tell us? So it doesn't say which. Oh, wait. So this one, one have, so the cows have B3.13. B for bovine and benign and D for ducks and deadly. So they don't say what the human cases are, But I guess if the person died, it must be D, right? They are in this like right above the H5N1 detected in cowl milk tank. They talk about genetic sequencing from the virus, at least in the cattle in the nearby farms, has the B3.13. Yep. Okay.

18:05All right. And this one I was showing to my daughter, Daisy. Look at screw worm. Look what's going on with screw worm. It's really moving, isn't it? I mean, look at it. It's in Texas and New Mexico, Arizona, and it's going to move north as well. It's already starting. It's halfway up New Mexico. And if you look at it, so we had four cases, August, three cases, September, 36 in October. We've already had 24 and it's like the 5th of November. Remember, remember the 5th of November. So we're up to 113 animal cases. There was a case in a cat in New Mexico. And if you follow this link, I put in a link, you can actually go through and see all the different animals that have been infected so far.

18:51The gunpowder plot, right? That was November 5th. That's what, you know, Guy Fawkes Day. Today's Guy Fawkes Day. I can't wait to celebrate. Remember the guy. Do you know that poem, Vincent? I saw the movie. Remember, remember the gunpowder treason? Yeah, right. Okay. All right. Ebola. We are in over 10 ,000 cases, 10 ,563 confirmed, 5 ,130 confirmed deaths. And you can look at the line. It's just – it's going. There's no plateau. It hasn't started to decrease in slope at all. It is a straight line. Yeah. It's really remarkable that it's so much bigger than the West African outbreak was in the same number of days because that was the biggest ever.

19:40Yeah. So this may surpass that. It's on track. Most people are predicting that it will. But maybe, you know, maybe in a couple months, the U.S. can kind of get itself back together and we can help, which historically is something that we would do. All right, back to measles. And just to repeat, right? So we had a death in a child in New York, first fatal case in 30 years. We had another death in Pennsylvania. And then we had a baby in Wisconsin die from measles. That's the first death there, 36 years. And we are up to over 5 ,000, 5 ,051 cases of measles so far this year. Looks like the U.S. has a rash on this map.

20:33321 cases just this last week. Wow. And, you know, some of them are in Pennsylvania. 77 in Pennsylvania or up to 1 ,467 in Pennsylvania. So big, big chunk there. 210 in New York State, though. So, yeah. and this is, I mean, I think everyone listening, right? Like, you know, you're listening, talk to someone else, you know, talk to anyone who will care. Like, this should not be happening. This is not okay. We're supposed to live in a country where children are supposed to be safe, right? They have to wear bike helmets. They have to sit in a child seat. You have to wear a seat belt when you're in a car.

21:14There's a lot of things we do. You can't shoot off your firearm in a suburban setting. And our schools should be safe. We shouldn't have children dying there. Okay. New York State launched its own respiratory disease tracking dashboard. We talked about this last week. It's really interesting. You can look at hospitalizations and cases, right? And it's good to look at both. I'll leave in a link. Because you can see that the COVID hospitalizations were actually kind of high and still are higher than the flu hospitalizations. They're coming down, the flu hospitalizations are shooting up, and the cases for flu are shooting up while the COVID cases are heading down.

21:57I mean, still in the thousands, by the way, just in New York State. But I wanted to give a little bit, I'm going to give a little primer, primer. Primer, I think is our, Kathy says, call it primer, right? I think that's correct. Primer. Primer. On, you know, so what happens? So here you are, right? You're a TWIV listener. You're in the know, runny nose. You're not feeling well. Maybe you got a fever, maybe a little cough, trouble breathing, right? So you've got at least initially an upper respiratory infection. It might progress to a lower respiratory tract infection. So, you know, what are the ones that we worry and test mostly for.

22:35We test for COVID. We test for flu. We test for RSV. Why do we do that? It's actually a flu A and B. That's why we call it the quads. You got flu A, flu B, RSV, COVID. The main reason we're testing is these are ones that either we can do something about or we want to try to keep you from spreading it to others, right? So COVID, right? We'll talk about early antiviral and folks around you can actually get something to keep them from getting it, right? You can get post-exposure prophylaxis. Same with flu, early antiviral, post-exposure. RSV, you really want to avoid giving that to the little kids, giving it to the older folks.

23:12But let's say you do that flu or that COVID or maybe even do the quad test and they're all negative. You still have something, right? I ran into this this week. Person's like, oh, I did the test. It was all negative. I'm like, but you have a fever, you're coughing, you feel crummy, you don't want to get out of bed. No, but I did the test. I don't have anything. I'm like, yes, you do. And they're like, well, I canceled some stuff, but I'm still going to go to this eye appointment. I'm like, why are you going to go to the eye appointment? You give the eye doctor? You think they want to feel the way you feel?

23:43Just kind of keep that in mind, folks. Let's try not to, you know, I mean, we all went to kindergarten. We learned to share, but they were not talking about illness. All right.

23:54Flu, starting to see activity, starting to see the green turn to yellow. and orange. I got Louisiana down there. This stuff is a little behind, I can say behind the eight ball, right? So this is week ending October 24th. We're two weeks ahead of this. So really, we're really seeing the flu activity start to pick up across the country. So you could see COVID's going down, maybe. Flu's on the way up. Not a lot of RSV activity when you look at the epidemic trend from the CDC. But flu activity is already here and we already had our first pediatric flu death of the year. And actually a bit in the news because I think, I don't know if this was the same death, but it's the mom of a little child that died of flu basically being like, hey, I didn't know.

24:47I mean, these are vaccine preventable deaths and people are not getting their kids flu shots. All right. And we ended up with, you know, 193 deaths last year. We ended up over 200 deaths the year before in little children. All right. So get those flu shots. And then if you do get flu, there's treatment. Not only is there treatment, but there's post-exposure prophylaxis. All right. RSV, we're starting to see some activity, but this is interesting. Let's look at this map. We've got RSV, wastewater viral activity level. And normally, if our listeners, well, have been following for years, normally, right, starts down in Florida, then Alabama, Georgia, it kind of moves up.

25:31But we have this odd, right? You got this moderate activity in Texas, high activity in South Dakota, and low in Alabama, Florida, low in New Hampshire, very low everywhere else. Yeah, it's weird. Yeah. But do you see any RSV these days? So we haven't seen it yet. And I talked to my daughter, pediatric ICU nurse, and she's like, they haven't seen any cases yet. I haven't seen any cases yet. I was trying to look into, does this have any impact vaccination, right? We now have RSV vaccines. We now have the RSV monoclonals for the little kids. Are we going to see a whole different pattern now that we have these effective interventions?

26:15Maybe. Yeah. Vaccines are good. Yeah. Vaccines are good. All right. You can repeat that as much as you want. All right. COVID update. Even with the blue washing, we still have, you know, quite a bit of COVID activity going on here. Yeah. I don't know. This is like a persisting plateau there, right? Yeah. Which is what we've seen in, you know, times past, which sort of bounces around. Maybe it's going to go down now. I'm a little worried that we're going to have enough background that when everyone gets together for that Turkey Day here in the United States that, you know, you've got to show up.

26:54It doesn't matter how sick you are. Well, you know, the last year's peak ended by the beginning of November, right? It was down already, but we're not there. So this is going to go further. That's the concern, that this is enough activity that when we get into the holidays, it's just going to go right into our winter. Well, you know, folks, you should be prepared, get vaccinated. Yeah, get vaccinated. People have stopped getting vaccinated. Just remember, you get vaccinated, you're going to reduce your risk of ending up with COVID, the disease, symptomatic, by about half, and also all the other things.

27:31I mean, COVID's not good, as we keep talking about. Well, let's talk about it. The article, Susceptibility of Human Neural Stem Cells to SARS-CoV-2 Entry Mechanisms and Glycohalix Influence, published in PLOS One. So these investigators hypothesized that neural stem cells derived from human ectoderm might be susceptible to SARS-CoV-2. So they used pseudotyped viral particles, both wild-type and Omicron spike variants. They confirmed efficient transduction in neural stem cells, NSCs, with Omicron variants preferentially utilizing endocytosis-mediated entry. I don't know why they have to use transduction.

28:14Why can't they say infection? That would work. That would work. I mean, transduction has a specific meaning. It means moving a piece of DNA from cell to cell, right? Phage-mediated transduction. Yeah. Yeah. So this is not right. Come on, folks. Actually, you're right, because they are talking about infecting them with an endocytosis-mediated mechanism. Keep it simple. It's infection. Yeah, so they're infecting neural stem cells, successfully infecting neural stem cells. Yeah. And they're concerned, right? Because if you can successfully infect these stem cells, well, who cares about stem cells?

28:50You know who cares about stem cells? Little babies developing fetuses, right? So they're worried about a teratogenic issue, right? That's a fancy word for birth defects or the mom loses the pregnancy. So, all right, I'll leave in a link because they're beautiful pictures. I don't know what it means, though. I mean, this is cells in culture, right? The real question is, does this ever happen in people? So we don't know, right? But they say here, maybe you say at the end, you should be on the lookout for, yes, These suggest future clinical studies and long-term surveillance of infants and children exposed in utero are necessary to explore neurodevelopmental deficits.

29:34I think that's a good idea anyway. Yeah. Yeah. Some of us should be doing that first, but, you know, this is interesting lab work, right? Yeah, but, you know, as I say, who knows what it means? These are just cells in culture. Yeah, yeah. And you don't know, maybe in the animal, they're not susceptible to infection. It can happen. And does the virus get to where it needs to get to even, you know, get endocytosed to the stem cells? Yeah. If you take a human kidney, a human who has polio, the kidney is never infected. But if you put kidney cells in culture, you can infect them with polio virus. So if you did that and you infected them, you say, oh, the kidney is a site of polio infection.

30:15But it's not. So that's why I'm complaining a little. Well, let's do the other study. Let's compare the risk of maternal complications and adverse infant outcomes among pregnancies with or without COVID-19 in the sentinel system. So let's look. Let's see. Is this a problem? And so here we look in PDS, and we have a retrospective study that looked at basically COVID-19 infection during pregnancy. They looked at the timing. They looked at the severity. and they looked at adverse outcomes for mom, adverse outcomes for the baby, and they're going to look from 2020 to 2023. They're going to look at 70 ,000 pregnancies with COVID-19, and there was a modestly increased risk of ending up with a C-section, preterm birth, and this was seen with severe COVID-19 compared to pregnancies without.

31:12And actually, there's a nice, you can really see the preterm delivery. You've got good severe COVID, non-overlapping intervals. C-section, you know, just to show the data there, you can actually see that there's a little bit of an overlap. But it does look like, particularly with severe COVID-19, there might be a trend towards, you know, particularly at the very bottom, severe COVID-19. There you get away from the overlap. But here's the study where they could have looked at neurodevelopmental defects. So they could follow these kids for a while and do that. That would be, I mean, they got, yeah, they got this data.

31:46So that would be to go on and follow. But then somehow you got to separate out is the issue because it's preterm birth. You got to match the preterm birth somehow. Yeah. Some challenges. All right. So remember COVID, we've got some vaccines. You've got a lot of choices there. So, you know, now's the time to get your COVID vaccine as well. All right. And we're going to wrap up with a few. So we've got three articles here in the post-acute sequelae late phase. So first one, the article, Post-Vaccination, Chemosensory Dysfunction, Changes Following SARS-CoV-2 Vaccination in a Global Study. This was published in Investigative Otolaryngology.

32:32So here they looked at individuals with COVID-19 hemosensory impairment, basically folks with smell and taste issues after they got COVID-19. And they're looking at, what if we give you a vaccination dose? Is that going to help you? You mean after they lose their taste or smell, they get vaccinated? Exactly. Yeah. They either lose or it's disturbed. And so they go ahead and now we're going to... And we've done this. Let's give you a vaccine and see if somehow that affects what's going on. So more than 90 % of participants reported no change in smell or taste following vaccination. But among the folks, so 10 % of folks actually thought there was some kind of improvement.

33:17And of the folks that thought there was some type of improvement, there's this parosmia. So some thought that was better. There's this phantasmia. I don't know if you know, it was people like, I smell something burning. And it's like, no, nothing's burning. So sometimes that got better. 10 to 20%, they had like the distorted taste where things maybe tasted metallic or things like that, that got a little better. 3 % of people said it actually was worse after the vaccine. So not a lot of evidence supporting vaccination to improve these chemosensory distortions. But, you know, if somebody's desperate, this is something that, you know, maybe, right, we had 10 % of people getting better.

34:00But remember, 3 % of people said actually got worse. We don't have any controls here who are not vaccinated, right? I think that's the problem, right? Like, where those people are just going to get better anyway. Yeah. Because that's really what you need. Yeah. Yeah. Because a certain number of people are going to probably get better anyway. And did these people get better or worse? Yeah. You need to compare it to a non-vaccinated cohort. Absolutely. Exactly. Yeah. Yeah. All right. Now, this is a preprint. We don't do preprints a lot, but this seemed like something that gets used enough that I wanted to, you know, go through, spend some time and share this.

34:35And this is the preprint, Low-Dose Naltrexone for Post-COVID Fatigue Syndrome, a randomized control trial posted on MedArchive. And I have to say, like, the whole thing about trying Naltrexone, it's a little challenging, right, as a provider, because you got to work with a compounding pharmacy, and you start with like 0.5 milligrams, and then you gradually increase it by half a milligram, finally get up to 4.5 milligrams if you can. And so here they look at, does naltrexone help with post-COVID fatigue? This is a decentralized, randomized, parallel group, double-blind, placebo-controlled clinical trial.

35:13Folks are randomized one-to-one to either get the low-dose naltrexone, and they're going to start at one milligram. They're going to go up to 4.5 milligrams if they're tolerated, or they're going to do placebo. You can do this for 16 weeks. and the primary outcome was fatigue severity. Basically, no difference. Did not help. Same as placebo. What is naltrexone usually used for? It's really pain, but at higher doses, not this sort of low dose. So that's why you have to like compound it because you're using it in this sort of, you know, odd off-label way. All right, this is our last one. And this, you know, I spent a lot of time thinking about this.

35:58I just put it in today. The article, Metformin at the Time of COVID-19 Infection and Risk of Long COVID, a Target Trial Emulation Study Published in the Journal of Medical Virology. So here they conducted a new user analysis of metformin prescribed within six days of documented infection with SARS-CoV-2 versus experimental control. So basically, folks were going to get metformin or fluvoxamine or fluticasone or ivermectin or montelukast, and the primary outcome was long COVID or death. Now, in the primary analysis, 4 % in the metformin group developed long COVID versus 8.5 % in the control group.

36:49So about a 50 % reduction. And then if you actually look, and I sort of broke down so we can look at the different ways they looked at it, it really looked like you were seeing the biggest difference the sooner you got started, right? So if you waited and you didn't start it for like 14 days, not a lot of separation. But if you started it right away, zero to one day, or even if you started it zero to six days, you saw this separation in the number of folks that ended up getting long COVID. I mean, a couple of thoughts. What is 8 % seems really high, right? That 8.5 % of folks are going to get long COVID.

37:32because this is Omicron mostly that we're seeing here. So 8%, 1 in 12 folks. I was thinking about this when I was out running today, right after I thought about how slow I was compared to that Olympic athlete that survived polio. And just thinking, we don't think 1 in 12 people that get COVID end up with long COVID. That seemed very high. And that's always been sort of an issue with some of these studies, is that somehow it ends up pretty high placebo numbers. And I'm not sure exactly what was the dosing, right? Because in the COVID out, it was really this sort of complicated up titration. So I don't know.

38:07Any thoughts there, Vincent? Yeah. I mean, there's an effect. It's just small, right? Yeah. Yeah. And these other drugs, they were used as controls, right? Yeah. But 4%. So that's like a number needed to treat of 25. That's not terrible. No, but it's not what we need, right? Yeah. I just don't know what makes you respond to this as a long COVID patient, right? Yeah. I don't know if we have a good mechanism or good understanding of what's going on here. So you don't want to give it to everyone, right? So that's a challenge. Who are you going to give it to? I mean, some of the features here. So the COVID out trial, you know, you had to be basically obese.

38:49This was a lot broader, you know, look at people. So not everyone was obese. And so, yeah. And also, I don't know if people are excited. Like, hey, you know, you've got a, you know, usually about, you know, I think one or two percent chance of long COVID. Maybe we go from two percent to one percent. This might be a hard sell. Yeah. So particularly if you're using like this complicated, like start with this and then gradually increase it. And then, you know, what are you going to stay on it for months? People are kind of like, I'm sort of done with the COVID. I don't know if I want to be on this for, you know, six months.

39:26All right. No one is safe until everyone is safe. I'm hoping that we can embrace that and we can start making at least our country a safer place for children and pregnant women and people whose immune systems are not fully there. Really just for, you know, no one is safe until everyone is safe. So your favorite time of the year, Vincent. We've switched to the Microbe TV fundraiser. So actually, I should say now for November. And actually, folks, this is November till December. So this is like NPR. We're going to like in two thirds of the time, we're going to raise twice the money. We're not going to go into January this year.

40:11I know. I know, Vincent. We're going to – I want to get it on a quarterly system. I want to start doing – so next year, you're going to get October, November, December. So just to sort of shift things. So folks, then you have to give early, give often. And you know, everyone gives you the money in December, Vincent. January is a dry month anyway. Really? Yeah. Parasiteswithoutborders.com, folks. Click on there. We're going to double your money. We're going to help support Microbe TV. You know, as I like to say, if you like what we do or you just want us to keep doing it, whether you like it or not.

40:43Yes, we'd love you to support us either way. And this would really help us a lot if you think it's valuable for us to continue doing science programs. Thank you very much. Fantastic. It's time for your questions for Daniel. You can send yours to Daniel at microbe.tv. Amy writes, thank you for all you do. Huge fan and longtime listener. Daniel, with the greatest respect, I think you overestimate the ability of patients to change physicians if they find them behind the science or falling foul to government misinformation. In certain communities, there are so few doctors that all meaningful choice is removed unless you can afford to travel.

41:21Medicare patients are particularly vulnerable. Advocating for my elderly relatives to get quality medical care is a constant struggle. The ignorant responses I received from the doctor's offices in 2021 during the COVID pandemic were particularly alarming. I'm sad to report it's worse now as low Medicare reimbursements lead to high physician turnover and demand quickly outpaces supply. Cost is also a factor. Each new doctor test treatment is another copay. And if you can only afford a high deductible health insurance plan like myself, this can quickly become costly. You fight so hard for health equity.

41:57I hesitate to submit this feedback lest I sound ungrateful because Clinical Update and TWIV give me the tools I need to advocate for myself and my family. I'm very appreciative. Now, Amy, this is well taken. And don't, you know, don't apologize for sending this. I spent actually early part of my career, right? My first job was Helena, Montana. And then I was a primary care doctor in Colorado up by the Wyoming border. So I – and then was a hospitalist up in Alaska. So I've definitely been in underserved places where it's challenging. So yeah, no, it is tough. Sometimes you end up in a place and that's your choice and that's your doctor.

42:39and it is tough because what do you do if that doctor is actually giving you bad information, giving you bad guidance? So yeah, my default is if you can change doctors, but I appreciate that is not something everyone can do. So, you know, hopefully send people, send those doctors to TWIV, have them listen. You know, if they're saying stuff that runs, you know, afoul of the truth, then advocate for what's true, advocate for good care. But yeah, I think, you know, we can also start, you know, you talked about we've got a Democratic senator, right, and head into Washington. Maybe we could do something to fix this system and really improve access for the folks that need it.

43:23Really, maybe we can do something about the health inequity that we've got here. Barbara writes, a Malay person, avid vaccine supporter, and TWIV listener, ever since being introduced by a friend during my second COVID infection at age 65. Yes, I took Paxlovid. Thank you for all you and Vincent do to keep everyone safe. Influenza A was rude enough to infect me before I could get my seasonal flu shot. Symptoms began 924, positive home test 926, started Tamiflu. I'm still working on regaining stamina and otherwise seem to have no complications. My questions are as follows. One, should I get a seasonal flu shot even after having flu A?

44:05If so, how long post-infection should I wait? Two, I got a COVID booster M next spike in June. I plan to get another COVID vaccine at an appropriate time. Should I wait the full six months for my last shot or should I try to get one sooner? based on the idea that the next shot I get should be more protective of currently circulating variants. I have basically no underlying conditions except for a tendency towards diverticulitis and stress due to caring for my mother with dementia who lives in a memory care unit. Yeah. All right, Barbara. So, you know, first off, someone gets the flu. Do we still recommend that they get a flu shot?

44:43And we do because that's, you're going to get one particular type of flu. It might be H5. It might be H1N1. Actually, that's what we're seeing a lot of circulation at this point. Not H5, but H1, H1N1. But still, you might get, you know, flu B. You might get the other type of flu. So yeah, wait a couple of weeks. Wait till you're feeling better. Go ahead. Get your flu shot. That's what we tend to recommend. Now, the COVID, right? The COVID shot. Basically, and we'll maybe get into this a little bit later, but, you know, it isn't that have to wait that six months. It's that, you know, we look at the antibodies, we look at the risk of having symptomatic COVID-19, so the disease, and that protection, that reduction really tends to drop after about six months.

45:30It doesn't go away completely, right? There's still, as we've talked quite a bit about, the T cell effect that might endure a little bit longer, but it really drops. And so as it's been more than a couple months, it's fine for you to go ahead and get a COVID shot. You don't need to wait. And we're starting to see COVID activity. We're seeing COVID activity. This might go right into the holiday season. So go ahead, get that flu shot after a couple of weeks, get the COVID shot at the same time. I think that's absolutely fine. Kathy writes, I've been a faithful listener since the start of the pandemic.

46:00I'm so appreciative of what you do at Microbe TV. Especially love your clinical reports and have learned so much. Thank you. I have a question about timing of flu and COVID shots, given that I'm three weeks post-op from a hip replacement. I'm taking Celebrex, baby aspirin, and several doses of Tylenol daily, and I'm concerned if I get the shots now, their effects on my immune system would be dampened by the drugs. Is that a reasonable concern, or should I go and get the shots? I'm also concerned about adding additional inflammation into my system right now, so early in my HIPS recovery process.

46:33Thank you for your insight and expertise. Yeah, Kathy in Seattle. Well, you know, I don't think that the Celebrex, the aspirin, the Tylenol is going to have a significant impact on your immune system that's going to prevent you from getting the benefit from the shots. And, you know, it's always a balance, right? You're going to get a little bit of inflammation from the shots, but you will get a lot of inflammation if you end up getting flu or COVID without that degree of protection. So reasonable to go ahead and get those vaccines. You don't want to have the rudeness of flu infecting you or the rudeness of SARS-CoV-2 getting you sick before you get your vaccines.

47:11Heidi writes, I plan to get an influenza vaccine soon and am considering the mRNA M-Flusiva vaccine, either that or I plan to get the high dose this year. I understand the mRNA can be manufactured quicker, so it might be able to better match the strains that we will see this season. Does the mRNA vaccine and the regular protein-based vaccines protect against the very same strains? Is there an advantage of one or the other? Okay. So Heidi, this is a great question because it's going to allow us to sort of talk a little bit about that. So the mRNA has the ability to be better, you know, better matched because they can, you know, within 60 days, you can end up with a new mRNA vaccine.

47:50That's sort of the science of it, but that certainly is not the regulatory side of it. The mRNA vaccine, flu vaccine for this season. It's done. It's approved. And it's actually the same makeup as the cell culture or the recombinant protein flu shots, right? So it's going to have the H1N1 influenza A Missouri. It's going to have the influenza A Darwin H3N2. And it's going to have the influenza be Victoria, Pennsylvania, where your egg-based are going to be similar. The A's are the same, but the B is going to be a Tokyo, right? So even though there's this theoretical ability, if let's say suddenly we realize we totally got the match wrong, the mRNA within 60 days could be revamped, but somehow we need to have a regulatory environment that would allow that.

48:46Now, what about approval? Who can get the mRNA shot, right? So the mRNA shot basically was approved for flu A and flu B, approved for use in persons 50 years of age and older. And then it got this indication for persons 65 years and older under accelerated approval based on immune responses. And they actually have this new, right? continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial, right? It's kind of a new thing that was put there. Now, you mentioned that you're thinking about either I'm going to get the M-flu SIVA, so the mRNA flu shot, or I might get the high dose.

49:30So I'm thinking you're 65 or older. We haven't really done any, as mentioned, right, in that approval, we haven't done any efficacy trials comparing high dose to the M-Fluceva. So it's all basically looking at antibody levels at this point. So, you know, you're sort of a little on your own there. Do you go ahead with the recommended high dose or the recommended senior type? Or do you say, boy, 25 % higher antibody levels compared to the standard dose and consider that mRNA? I guess also if you're very reactogenic with mRNA vaccines, it's another consideration. That's definitely a good point because, yeah, as we've noticed, the M-fluceva, the mRNA flu shots, can give you more reactogenicity.

50:15So you're going to notice it, you know, if you're a person that reacts to the mRNA vaccines. And Steve writes, thank you so much for doing all the work you do to produce TWIV. I have been a listener since mid-2020 and a supporter for a few years. I really enjoyed the science of the stats and weather reports. You will be happy to know my favorite temperature is 82F28C. In the latest clinical update of 2nd October, Dr. Griffin said, I thought Dr. Griffin said that COVID vaccines should follow the flu model, i.e. once a year. Did I hear that correctly? Or should we continue with a COVID vaccine every six months?

50:51My wife and I are COVID virgins and would like to keep it that way. Thanks for all your work. I would like to know if there are any updates to the mRNA flu vaccine. Okay. Well, I think we hit the flu vaccine, the mRNA one. So that's good. It's kind of up there. But let's talk about this. So what is this story? You know, and remember, as I mentioned, we live in a regulatory environment. So I actually went, I'm going to paste in, what is the FDA approval for the current mRNA shots, right? So we'll talk about Comirnaty. I'll leave a link. It's basically the same for the others. So Comirnaty, that's the Pfizer BioNTech.

51:27This is approved, and it's approved to be administered as a single dose. You get it. And the only exclusion is you can't have gotten another dose within the last two months. So that's sort of interesting. So you go ahead, let's say it's November, because it is, it's November. Get a shot in November, early November, 5th of November. Maybe this will be the 7th by the time you hear this. And so then November, December, January, February, March, Now it's April, and there's a lot of COVID activity. As I've mentioned, the shot that you got this November, if you were to get another shot in the spring, again, you're going to get that 50 % reduction in, you know, clinically attended COVID-19, also some reduction in the severe outcomes.

52:15So the science is still there. But, you know, that's sort of the packaging. The packaging now is this one shot, but there will be certain high-risk folks. And just realize that six months from now, there's potentially a reason to go ahead and get a second shot. That's TWIV Weekly Clinical Update with Dr. Daniel Griffin. Thank you, Daniel. Oh, thank you. And everyone be safe.