TWiV 1350: 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 1350 recorded on August 20, 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. Daniel Griffin, New York, without a bow tie. I am upstate New York at a lake, so taking a little bit of a break. But when you said August 20th, I was just, oh, my gosh, like, where does time go? That's it. That's it. All right. Well, I'm not ready to give up summer, so I'm going to try to enjoy it a little bit longer. but I have a, it's a poem. This first part is a poem.

1:00I think there's a very similar quotation from somewhere else, but no one in my family seemed to remember this poem or I even tried AI. Can you imagine I checked with AI? Like, nope, nope. So here it is. And I think it's sort of appropriate for all the things that are going on. It is easy enough to be pleasant when life flows by like a song, but the man worthwhile while is one who will smile when everything goes dead wrong. For the test of the heart is trouble, and it always comes with the years, and the smile that is worth the praises of earth is the smile that shines through the tears. It's a good one.

1:39Yeah, for all the things that are going on. I will start off with some news, and I don't know if I put everything that was disheartening in here, but I try to cover some of the things that are going on in the world. Cholera outbreak sickens over 90 in Myanmar's biggest city, Burma, depending how you call that. At least 93 patients have tested positive for cholera at a single hospital in Myanmar's biggest city, officials said. It was an outbreak that began last week spread across the region. There are more than 180 people in the city, Yangon, who have been hospitalized with diarrhea, a common symptom disease.

2:17Dr. Nanda Nguyen, the head of the Yangon region, public health and medical service Department said on Friday, one 92-year-old man had died, he said. The outbreak is the largest strain on Myanmar's faltering medical system, which has been neglected under a junta rule that has prioritized weapons over health budgets. You know, I didn't put this in. I wonder what people were thinking when they put this in. Okay, do you know of any other countries that are prioritizing weapons over health budgets. Yeah, I do.

2:48This is the next one that really has me maybe kind of think of the poem, trying to somehow keep a positive attitude here. But this is basically defund the CDC. So in the AP, we have the article, the CDC has zombie programs. Congress funds them, but few people are left to do the work. CDC still has an Alzheimer's disease program. Congress appropriated$41 million to it this year. There's just no one staffing it. Isn't that crazy? I just, people, like, make sure you get the word out there. That's just, I can't imagine there's really people in our voting public who are okay with that. And then there's the agency's Office on Smoking and Health.

3:33Congress allocated$246 million for that, its staffers were cut too. Same for the epilepsy program, its sickle cell disease data collection operation, its rape prevention unit. So think of them as the CBC's zombie programs. They appear to be alive, at least according to legislation and congressional appropriations, but functionally they are dead or nearly dead because the CDC experts who did the work were laid off by President Donald Trump's administration or remain on leave, aid, but not allowed to do their jobs. All right, and this is a little bit of good news. Pushing against the tide of the anti-mRNA vaccine tide, Merck, Moderna's personalized cancer vaccine slows recurrence in phase three, setting up approval push.

4:25So Merck and company and Moderna, their personalized mRNA cancer vaccine has successfully lengthened recurrence free survival when compared with Keytruda for patients with high risk skin cancer. The phase three win sets up the partners to potentially seek accelerated approval. The Interpath 001 trial enrolled 1 ,137 patients who had previously had their cutaneous melanoma surgically removed and the patients end up getting this treatment sort of compared to others along with Keytruda or Keytruda alone. And I'll leave a link into that because this is exciting stuff. And I, you know, it's interesting.

5:11A lot of people thought that really was going to be where the big wins in the mRNA vaccine arena was going to come, but we're seeing it in other infectious disease vaccine technology or HAV. And I'm going to touch on the mRNA flu vaccine stuff. But cyclosporoc kaiatinensis. Remember when we were told that it's all over? It's all good now? Well, we're up to 15 ,716 confirmed cases, 11 ,841 additional cases still requiring confirmation. So what does that put us? 27 ,000 cases. This is compared to last summer, 1 ,180. So 20, 26-fold increase. So something's not going right. And those are the CDC numbers.

6:05a look at Michigan alone, we're at 13 ,909. Missouri has 1 ,950. 614 in New York City alone. And we'll leave in a link. We keep doing this. It's quite popular, the TWIP, Why is Cyclospore So Hard to Contain? We talk about how sticky those oozes and just how you really got to prevent the lettuce and other things from getting contaminated. it's really, you know, near impossible to get this stuff off despite my wife's best efforts. So, all right. Screwworm. In SIDRAP, I'm going to leave a link. There's a nice article, FDA grants emergency use authorization for another New World Screwworm treatment.

6:50And so the FDA granted emergency use authorization for Simherica Trio as another potential treatment for New World Screwworm. This is for puppies and dogs. This is the latest medication with emergency approval in canines. The FDA noted the scientific evidence indicates the benefits of Symperica Trio outweighs its risk. Now, Symperica Trio has been around since 2020. Symperica Trio has been FDA approved to treat heartworms, fleas, and ticks and dogs. It's available only through prescription from a veterinarian. An active ingredient in the medication, sarolanere, is an antiparasitic drug that has been associated with neurological complications, including muscle tremors, loss of coordination, seizures.

7:40So really, this is, you do this with your veterinarian. And I'll leave in a link to the FDA link where they have this approval. But what is in this trio. So there is therolanere, which kills fleas and ticks by blocking invertebrate gamma amitobuteric acid or GABA-gated and glutamate-gated chloride channels. So in the parasite, this action stops chloride iron flow, causing uncontrolled nerve firing, muscle spasm paralysis, and death in the target parasite. Moxydectin, I think we've talked about that before. This is a macrocyclic lactone antiparasitic drug. It binds to glutamate-gated, again, and GABA-gated chloro-channels in the nerve and muscle cells of parasites.

8:30Same effects, killing the parasites. And parantal, right, our favorite from pinworm. And this acts by depolarizing the neuromuscular blocking agent. Basically, so it mimics the neurotransmitter acetylcholine. and so it stimulates the worm's nicotinic receptors. It inhibits cholesterase. And so you end up with a sudden continuous muscle contraction. You get this spastic paralysis. The worm loses its grip and passes in the stool. Or in the case of, I would say, the maggots, the larvae, right? They're just paralyzed in rigor, basically. I like killing screwworm maggots. I don't feel bad in any way that they're paralyzed.

9:16All right. Ebola. Not going well, right? So from the Africa CDC, we have the press release three months into the Bundabugio Ebola. Did I do that? Bundabugio. Bundabugio. Yeah, I'm going to have to keep working on that. Bundabugio Ebola outbreak. Now is the time for decisive action. I think we've talked about we're farther. We're probably eight months in, actually, right? So we're seven or eight months, not just three. But I'll read the last couple paragraphs from this Africa CDC. The current outbreak is already the deadliest Ebola outbreak in the history of the DRC, the fastest growing Ebola outbreak on record, with a case fatality rate approaching 50%.

10:03It's now taking approximately one life every 30 minutes. Unless its trajectory is urgently reversed, its risks becoming the deadliest Ebola outbreak ever recorded globally. The world cannot wait for that project to become reality. Behind every number is a person, a family, a community living with fear and loss. These deaths are not inevitable. We call for a humanitarian ceasefire and save sustained access for healthcare workers, humanitarian responders, and essential supplies. We call on governments to lift blanket travel and trade restrictions that are not grounded And in science, such measures push people and goods through unmonitored crossings, disrupt supply chains, and make containment more difficult.

10:46This crisis is also a stark reminder that Africa must accelerate the local manufacturing of diagnostics, therapeutics, vaccines, and other essential health commodities. And I'll leave a link into that. We're up to confirmed cases, 5 ,105 confirmed deaths. About half that number, 2 ,400. And I put in a little map just so you can see, like, the DRC is really huge, right? It's really this, like, right in the heart center of Africa there. All right, measles. Basically, we added, like, another 100 cases just this last week, so we're up to 2 ,632. too. And I always go through this map every week. But I'm going to actually sort of point out this time, you can actually not only look at how many cases are local spread, how many are imported, and you can see not too many are imported.

11:44So that rhetoric that, oh, it's a worldwide problem, and they're just coming into our US, that's just, that's a lie. That's dishonest. This is our problem. These are mostly local cases, you can see looking at the map. But you can also click at another button, the MMR rates, and you get basically, you know, red's bad, blue's good, and you can see what the different vaccination rates are in the country relative to a lot of these outbreaks. So you can see places like Utah, New Mexico, you know, not great, and you got a lot of cases going on there. But it is interesting, you really have to zoom in, because this is really a granular issue.

12:24You know, if you have a local community, even if you're surrounded with all this good MMR vaccination rate. If your local pocket doesn't have high enough vaccination rates, you're going to get yourself into trouble here. It's big blue dots there. Big blue dots, right? Because we're now in thousands of these cases. And these are confirmed cases. Carolinas are the most. South Carolina has a huge amount going on there. Yeah. Kind of our big area at the moment. But we have a couple of interesting things in the measles section. And part of it, I think, is hopefully this is like us sort of educating, you know, this message we send.

13:05And so, you know, vaccines, right? Do vaccinated cases transmit measles? A systematic review and meta-analysis was published in Expert Review of Vaccines. So I think our listeners know the answer. but here this group reviewed evidence on whether vaccinated individuals can transmit measles and conducted a meta-analysis to understand transmission characteristics. I love this because they're going to look at the peer-reviewed and the gray literature and included studies reporting measles transmission events from vaccinated individuals. They meta-analyzed the data to calculate the median number of transmissions from vaccinated cases by measles burden, number of doses, and time since first and last dose.

13:49They identified 11 ,911 peer-reviewed, 22 gray literature records, and included 33 articles in this review. 70 individuals had received one or more doses of measles-containing vaccine-transmitted measles viruses, resulting in 237 secondary cases. Vaccinated transmitters in eliminated areas were older than those in non-eliminated areas. Additionally, 91 % of studies provided data on subsequent transmission generation, leading to 812 measles cases traced back to vaccinated individuals. So there's a couple things here. So one is that measles transmission from vaccinated cases, although relatively uncommon, must be considered because these can contribute.

14:38We've talked about the numbers, right? So on average, one person unvaccinated gets measles, transmits it to 20 people, probably takes 20 vaccinated people before you get one onward. So about a 400-fold reduction in transmission by getting vaccinated. But as we've said many times, vaccines prevent severe disease, but they don't prevent infection, and they do not prevent all transmission. now the article county district and community level measles transmission in the united states in 2013-2015 was published in nature communications now i think our listeners are well aware that about 26 years ago so back in 2000 united states declared measles eliminated in the last 2025 2026, more than 3 ,500 cases have placed that status under formal review.

15:31As these authors point out, vaccine hesitancy accelerated by COVID-19 disruption and misinformation has eroded the immunological buffers sustaining elimination. What they're going to say here is current surveillance compounds this threat because county-level vaccination aggregates structurally obscured the fine-scale susceptibility clustering where outbreaks originate. So they go through this really robust analysis. They assemble a nationwide multi-scale vaccination database. Look at 45 U.S. states and Washington, D.C., 2013 to 2025, 50 ,000 schools, 13 ,000 districts, 3 ,000 counties. They developed this transmission model to quantify epidemic risk across different spatial scales.

16:23Basically, what they're seeing is the way we currently aggregate, you're really losing the fine details. And instead, what we're seeing with this boundary misalignment, you've got well-vaccinated counties above threshold, but then you've got less vaccinated populations. So the spatial architecture of the U.S. measles vulnerability has fundamentally shifted. Transmission potential is super critical in schools, but invisible at the scale monitored by surveillance. So preventing measles re-indemnicity requires surveillance and interventions operating at school and district levels where imported cases can be intercepted before igniting sustained transmission.

17:05And I want to point out, when they say imported, They're not talking about coming in from Mexico. They're talking about cases being brought into that school. All right. We read this article in the New York Times, more U.S. parents opting children out of vaccine requirements, CDC reports. Now at a time when measles and other potentially deadly diseases are spreading, more American children are receiving exemptions, allowing them to attend school without the routine childhood shots that can protect against these illnesses. So roughly 4 % of kindergartners in the U.S. were given a non-medical exemption for at least one vaccine during the 2025-2026 school year, an 18 % jump from the previous year.

17:49This rise is the largest annual increase recorded in more than a decade. And this comes as a growing number of states look to loosen vaccine mandates or even do away with them entirely. And they've got some nice graphs we can really see, you know, going from this less than 2%, this is non-medical exemptions, really rising, you know, to 4%. This is really very concerning because measles is not a trivial disease. I don't understand why parents are letting their kids be susceptible. You know, if you look at they've got a second, it's not just measles that we're losing. Look at polio dropping down below the target.

18:34Whooping cough is dropping down as well. So that's pertussis. Daniel, what are people thinking? Well, it's tough because clearly, parents love their children. They wanna do what they think is best for their children. But there is a group out there that is misinforming, really preying on them for political and economic advantage. So they're being scared. They're being told, and we keep covering this, they're being told that the vaccines are dangerous, that, you know, 82 percent of women that get the vaccine end up with an abortion. I mean, that's not true. So, you know, we need to keep actually, you know, educating and sharing the truth because this billion dollar industry that's basically misinforming these parents.

19:21So they feel like they're doing the right thing by their kids. But unfortunately, they've been misinformed. Well, they have to start listening to other sources like this one, right? Yes, yes. You know, it's really funny, right? I remember when we were spending all this time trying to get people to stop smoking. And, you know, and as an infectious disease doctor, like it's bad for business if I can get people to get vaccinated, right? I mean, I see less sick people. I earn less, more people, you know, so it's really funny. Like here we are basically, you know, trying to put ourselves out of business.

19:54well there's a sidrap piece the threat of more expanded measles outbreaks looms with start a school and you know and for the the much older clinicians that than i um you know this this was always a problem you had you know you had measles but then you put all these kids together in the school and they point out here that schools are high risk settings uh schools are higher risk for measles and this is from zach moore the north carolina state epidemiologist and president elect of the Council of State and Territorial Epidemiologists. Kids tend to have more physical contact with each other than adults do.

20:29Classrooms are confined spaces. Also, particles of the measles virus can remain in the air for up to two hours after an infected person leaves an area. So as students move from room to room throughout the day, they can become infected, even if everyone in their own class is healthy. A pernicious aspect of measles is that its first symptoms resemble other respiratory illnesses and people are infectious. up to four days before you get that characteristic rash. That puts the onus on school nurses to know which students are unvaccinated or immunocompromised and to work with other health, public health officials to identify exposures in the event of an outbreak.

21:08Unfortunately, a percentage of the people who get measles will die, suffer life-altering complications, including blindness, hearing loss, permanent scarring of the lungs, intellectual disabilities, and other lasting neurological deficits. Additionally, the virus can erase pre-existing antibody cells and leave people vulnerable to other viruses and bacteria for years. So that's the risk of measles as opposed to these incredibly safe vaccines. So, all right. All right, flu. Let's talk a little bit about flu. I'm going to start off with the mRNA flu vaccine. So we have a JAMA medical news. In JAMA medical news, we have the article, What to Know About the mRNA Flu Vaccine, newly approved by the FDA.

21:56And actually, people are already getting their little alerts, hey, time to schedule your flu vaccine. So the FDA granted Moderna's mRNA-1010, the M. luceva influenza vaccine. So you end up with basically, you're going to sort of break this down. If you're 50 to 64, you've got traditional approval. If you're 65 or older, they have this accelerated approval. What is the story? Why the difference here? So it's based upon the study. So they've got this, we've talked about this study, phase three trial of this Moderna mRNA flu vaccine. They gave it to volunteers 50 years or older, and they compared this to standard doses, right?

22:41So So if you're 50 to 65, you're going to end up with a, you know, normally you would get the standard dose, 65 and older, you get the high dose. So here they looked at those folks, 27 % more effective than the standard dose. But they also looked at older folks. But the issue is, you know, how does this compare to the high dose, right? So we know from this trial, mRNA vaccine was as effective in participants 65 years or older, although we just don't know if it's superior to the high dose. uh so i'm gonna put that out there but i think there's a there's a sort of a a an optimism right 27 seems better than the high doses done to standard in the past so we're anticipating as we get the the ongoing phase three trial data um that we're going to actually find out um you know whether or not it's superior so what do you think vincent what are you going to look for this fall i know as a 50 to 65 year old individual i'm going with the mrna flu shot you yeah yeah Yeah, I would like to get the mRNA flu shot because I think it's likely to have greater antibody breath like the COVID vaccine does.

23:51But I don't know if it's going to be available this season. It's not available so far. Yeah, they actually, Moderna says it will be available. So it'll be out there. You know, give it a little. We're still in August, still in August. Summer's not quite over yet. You know, and we really sort of talk about end of September, early October as a target date. So it should, they say it's going to be available. So we'll have to keep everyone up to date. Well, I'm going to Europe at the end of September. So I need to get one in the beginning of September. So I'll have to get the traditional. Fingers crossed.

24:22We'll see what happens. Got a couple of weeks to go. All right. So this one is a preprint and I wanted to discuss it because it, you know, people are going to be a little surprised and try to figure out what's going on here. So Oseltamivir for critically ill patients with influenza, a randomized trial. oh, this is a Lancet preprint. So, you know, I read that first. And initially I'm like, well, boy, critically ill patients. This sounds like when they were trying the monoclonal antibodies and waiting until people had been sick for like a week or two and basically giving people an antiviral during the inflammatory phase.

24:54So I'm not going into a lot of optimism, by the way, but let's see what they find. So this group evaluated oseltamivir for five days, oseltamivir for 10 days, so Hamaflu for five days or 10 days, versus you don't get any antiviral treatment. And they're looking at critically ill patients aged 12 years or older with confirmed influenza, severe respiratory infection. The primary outcome is gonna be 90-day mortality. All right, so between March 1st, 2020 and March 13th, 2026, that's quite a stretch here, 442 participants were randomized to receive five days, 162 in that group, 10 days, 156 in that group, or no antiviral 124.

25:41So they stop. They've got a scheduled adaptive analysis where they basically five versus 10. So what is an adaptive analysis? So you stop. And then what you find at this point is going to predict what you do in the future. So they're basically five versus 10. It's, you know, there's this predefined inferiority threshold. They say, okay, at this point, what we find in our interim adaptive analysis. We're going to trigger cessation of recruitment, and then they're going to follow them at this point. So by day 90, 13.7 % in the no antiviral group, 19.8 % in the five day, 19.4 % in the 10 day pamphlet group had died.

26:25So that's quite a bit higher, right? So the median adjusted odds ratio for 90-day mortality was twice as high, so 2.13 for five days of Tamiflu, 2.17 twice as high for 10 days of Oseltamivir. So basically, you were better off not getting any antiviral. So for the five - and 10-day Oseltamivir treatments, the posterior probabilities for harm were actually 98 and 98.2 % respectively. So they basically say, hey, treatment with Tamiflu in critical of patients. It's not effective, and it's actually highly likely that it increases the 90-day mortality. So what's the story? I think a lot of people are surprised.

27:07One is, okay, it's too late, so I appreciate that maybe it's ineffective, but doubling your risk of dying? What happened there? So this data is from the REMAP app. This is like this ongoing trial looking at upper respiratory and lower respiratory tract infections. There's even an ongoing evaluation of biloxivir. When we get that data, Zofluza, we'll let people know. But the first thing I know, she can go through the tables and look at my first issue, like, is it too late? They enrolled patients that had about five days of symptoms prior to even being recruited into the study. So we're past what most of us think as the viral phase.

27:47And yes, I mean, the majority were already on high-flow nasal cannula or intubated. Subgroup analysis suggested higher probabilities of harm in patients with more severe illness at baseline, such as shock or proven bacterial infection. So, I mean, I was concerned about the antivirals being started too late, but the authors also pointed out something that really resonates with some of our discussions. They point out that observational studies of oseltamivir typically report only in hospital mortality. Now, the short-term mortality impact of critical illness actually continues to manifest after hospital discharge.

28:28Remember all those clapping everybody out and like, now it's all good? So they point out that this is why all-cause mortality after 90 days or out to 90 days is really the preferred endpoint for randomized trials in this patient population. So what were your thoughts, Vincent? I mean, I don't... First of all, if the viral phase is over, how could this have any effect at all? I don't understand, right? So it shouldn't help, right? It shouldn't have any benefit, right? It shouldn't have any... Yeah, but why did it harm? What was the harm issue? Yeah, I don't know what the harm would be. That doesn't make much sense to me.

29:07Because both populations are treated the same, with the exception of the antiviral. So I just don't understand that at all. Yeah, somehow Tamiflu is having some negative effect on these folks. But has this ever been seen before? No, and actually I think that was what sort of has surprised people. Because usually you're treating earlier. Usually you're just looking at in-hospital mortality or progression to the ICU. So you're trying to target in the first, you know, 48, 72 hours. But they're actually saying, like, maybe timing isn't even as critical. Maybe you need to look long-term. Maybe there's something, some long-term effect.

29:43And I think it'll be interesting to see, is this also what we see with biloxivir? I would think so. I think not. Yeah, I think there's probably something about a hama flu side effect. I hope so, because we do need to have at least one antiviral for influenza. But I think you need to use it early, right? That's always been what we've seen in the past. Get it within the first 48 hours, you see a decrease in people ending up in the hospital, etc. But, you know, people, they've been sick like five days before they even get like randomized, probably day six before they get their first pill, right? So, you know, a week too late.

30:20I don't understand why you do this trial at all if you're going to treat them so late, because that's just going to muddy the whole interpretation. You should give it early, but then you don't know who's going in the hospital, I guess. That's the problem, right? Well, it's interesting because this is actually considered standard of care, right? If somebody is like in the hospital, they get Tamiflu. If they're critically ill, they get Tamiflu. This is like the WHO list of meds. So they're actually, I think this is good to do the study to say like, is that good advice? I mean, I think if you give it earlier, it has an effect.

30:54It has a positive effect. But maybe this is telling us not to treat people in the hospital. I mean, do you treat patients in the hospital with flu without Sotamivir? So we certainly, if they're within the first like 72 hours, definitely do it. And actually, it has been pretty standard if they're sick enough to go to the ICU to get Tamiflu. So this would actually impact what people are doing. Yeah. Do we know how long after infection these patients are? Yeah. So they're at least five days after symptom onset before they even get recruited. So there's a nice table one. Yeah. No, I, you know, I initially saw like they're already in the ICU.

31:32You don't end up in the ICU in the first 48 hours. They're already advanced to high flow nasal cannula there. It definitely was too late to start treatment as we saw. I mean, it seems to me that if you have a over certain age population who test positive, you should just give them Tamiflu without waiting. I think that's the whole issue. And we tried to do this. Well, we actually successfully did this with the Medicare Advantage population is they, you know, you've got it home. You've got the ability to test. You've got the flu. You've got like a little box Tamiflu is in there. Bluetooth, it opens.

32:04You start. I mean, you want to start as soon as possible. What we're seeing here is if you wait clearly five, six days after your symptoms start, it's not helpful and actually looked like in this context harmful. So maybe the outcome is you do not give it to hospitalized patients. Well, I think you don't give it to maybe critically ill when it's been that long. But if someone gets sick, ends up in the hospital, they've only been sick for two or three days, we have good data on that. But they're going to say your good data didn't look at 90 days. And if you go out to 90 days, maybe you'll start to see this signal.

32:40Yeah. So I don't know if it's like... What does critically ill mean? Is that ICU or intubated? Yeah, ICU. ICU. Yeah. Okay. All right, RSV. We've got some more good data on nursevimab. So this is a first and second year outcomes after nursevimab immunization published in JAMA Pediatrics. Just give people context. Like RSV has historically been a huge problem. It hospitalizes 1.4 million babies around the world each year, making it the most common cause of hospital admissions for respiratory disease in infants. The virus kills nearly 46 ,000 babies under six months of age every year. You know, here in the US, historically, it's been the number one thing filling our pediatric, our children's hospitals in the winters.

33:34So here is a cohort study where they analyzed two nationwide matched cohorts using the French National Health Data System, including infants born in metro France before the 2023 and 2024 immunization campaigns. Infants receiving nircebumab were matched one-to-one to unimmunized infants. Both cohorts were followed for a year afterwards with an additional second year of follow-up. So this cohort study included 74 ,672 infants in 2023, 175 ,526 in 2024. These are little kids. So at baseline, the mean age was 4.5 months in the 2023 cohort, kind of 50-50, a little more male than female. The mean age in the next year, the 2024, also 4.8 months, so pretty young kids, among 37 ,366 infant pairs in 2023 and 87 ,763 pairs in 2024.

34:41The RSV, lower respiratory tract infection-related hospitalizations during the first year follow-up occurred in 0.8 % in the immunized, 2.4 % in the unimmunized, and then follow-up 2023, 0.5%, and 1.9%. So clearly nircevimab was associated with a lower rate of the RSV lower respiratory tract infection-related hospitalization, both in 2023 and 2024, with effectiveness estimates of 66 % and 72 % respectively. And associated with higher rates of hospitalization for ear, nose, and throat bacterial infections was observed. No significant association was observed for other outcomes. During the second year follow-up, no protective association.

35:31So you really, it's that first year that you're getting your benefit. All right, well, so that's the monoclonal for the babies. Well, what about vaccination for mom? So a nationwide program of bivalent prefusion F vaccination in pregnancy and protection against respiratory syncytial virus hospitalization in infants until age six months in the UK. A multi-center prospective test negative case control study was published in The Lancet Child and Adolescent Health. So here we're looking at mom getting vaccinated during pregnancy to protect the infants. In late summer 2024, the UK introduced the maternal bivalent RSV pre-fusion vaccine for all pregnant individuals at a gestation of 28 weeks or more.

36:18After an initial catch-up phase, the maternal RSV pre-F program changes into year-round delivery. Between September 2nd, 2025, January 1st, 2026, 1 ,356 infants were admitted to participating sites and screened for eligibility, 694 of whom were included in the primary analysis. So we end up with 429 RSV positive infants, 256 RSV negative infants. Median age was two months, so little babies here. Now, ethnicity data was available for 693 mothers, of whom 78 % identified as being of white ethnicity. The mothers of 161, so 38 % RSV positive infants and 66 % of the RSV negative infants had received the vaccine before delivery.

37:11So we ended up doing a calculation and basically the adjusted vaccine effectiveness for preventing infant hospitalization admission was 61%. So not bad. 76 % for three months. Yeah. Yeah. Yeah. Yeah. So, all right. Yeah, I'm actually hoping, I was talking to my daughter, Daisy, right, who's a pediatric ICU nurse, that this coming winter, I'm really hoping that this is going to transform her experience of what, you know, what they're seeing in the children's hospitals. Yeah, particularly in New York, I think we're going to have good uptake. All right, Vincent, our COVID multicolored curves, what do you see in there?

37:56Yeah, it's the little bumps now. There's a little, and they're little, right? They're still in the very low. They have not even quite entered the low. So kind of interesting, right? I mean, we're end of August. I mean, all of the lines for the different regions have kind of not continued to rise, right? Yeah. I mean, unfortunately, this date is a little old. It's like 8 slash 8 is kind of where we are. And people are reporting COVID now, right? You're seeing it? Yeah, we're starting to see a few cases, yes. You know, this data is a little behind. We have some issue about how reliable this data is that we've talked about.

38:37And unfortunately, we're having all this misinformation right about the vaccines, right, which is not going to help this winter. So we have this article here, which I will share in the New York Times. Trump officials falsely connect COVID vaccines to miscarriage. Prominent Republicans and others have claimed this week that the shots aren't safe for pregnant women, but years of data show otherwise. Thething misleadingly on old text messages of Dr. Anthony Fauci that were recently released by Republican centers, regardless of vaccination status, 10 % to 20 % of known pregnancies and in miscarriage.

39:17It's important as a baseline. This was true long before the pandemic, so rigorously conducted studies use these figures as a baseline to compare miscarriage rates after COVID vaccination. A British meta-analysis in 2022 reviewed 23 studies on COVID vaccination that cumulatively included about 118 ,000 people vaccinated during pregnancy. Another in 2023 reviewed 21 studies with about 150 ,000 pregnant women. Neither found an association with miscarriage. And the 2022 analysis found that vaccination was associated with a decreased risk of stillbirth. A more recent study published by the CDC and other researchers reviewed some 23 ,000 pregnancies among women vaccinated between December 2020 and June 2021 who participated in the agency's COVID-19 Vaccine Pregnancy Registry.

40:10The study found that the vaccinated pregnant women did not have more preterm births and perinatal deaths compared with the general population in 2019 before the pandemic. Now, important to put this in context, right? So they're scaring pregnant women, ultimately trying to get them not to get vaccinated. Now, nearly one-third of pregnant women who had COVID from January to June 2020 had to be hospitalized compared with 6 % of non-pregnant women of the same age. Pregnant women with symptomatic COVID were more likely to require ICU, mechanical ventilation, and specialized heart-lung bypass than non-pregnant women with symptoms.

40:50They also faced a 70 % higher risk of death. It's huge. Yeah. And we've got these, yeah. This is malevolent on the part of the Trump administration. I think the tough thing is they don't see it that way. I mean, they believe, They are misinformed. I mean, I don't think these prominent Republicans actually realize or knowingly are trying to put these pregnant ladies in harm's way. But there is this really vocal misinformation going on. And so they hear all this stuff. You know, they look at Fauci's. And actually, I looked at these text messages. They actually were reasonable. I mean, I hate when people say data free because nothing's really data free.

41:36but basically talked about like, you know, early on before we've done these studies, which we're now talking about, you know, if you're asked a question like, you know, should a pregnant individual get vaccinated? Is it safe? You've got to do these sort of risk calculations and say, well, we do know that during pregnancy, people are at higher risk. Vaccines historically have been safe. So I'm not sure it's a data free. I think going into it, you would be surprised to not see that vaccination against a serious respiratory illness was not going to result in protection. But why is it just Republicans that are doing this?

42:10The Democrats don't do it. It's just a political thing. And on top of that, the Republicans don't even understand the data. They're not qualified to make a statement on this. It's up to public health officials. I think that's really what's probably the most upsetting, is that we used to live in a country where there was the humility to defer to experts in a field. But here we have basically politicians giving health advice, thinking they can look at the data, thinking they can look at the information. It used to be we would say, let's get an expert who knows about this. Let's defer to them. Now it's, oh, if you're an expert, you probably have your own political agenda.

42:47But no, I mean, those of us in medicine and science, with rare exception, we try to be honest. We try to follow what the evidence dictates. No, the only outcome of this is bad and that people are going to get sick. In this case, pregnant women are going to get sick. 70 % get hospitalized, higher risk of death. This is just a ridiculous outcome. Yeah, no, it's terrible. It really is. All right. Well, I'm going to wrap us up with this was a viewpoint published in JID, Journal of Infectious Disease, Beyond the Acute Illness, Three Myths About Viral Respiratory Infection. and I liked this, and I'm going to leave in a link.

43:31So they start off with this introduction, a trained marathon runner can't run more than three miles weeks after a SARS-CoV-2 infection. An elementary school teacher struggles through the school day for months due to fatigue after catching a bad cold floating around. A septuagenarian is unable to return to her home and garden after a short influenza-related hospitalization. While these stories used to be seen in isolation, the COVID-19 pandemic highlighted potential long-lasting consequences of viral acute respiratory infection. Despite increasing attention, critical gaps in understanding what these effects look like in real-world settings, who is impacted and how clinicians may best help patients recover fully remain.

44:15Here, these gaps are highlighted by exploring three common misconceptions. So number one myth is it's just an acute respiratory illness. So one widely held misconception is that these infections affect only the respiratory system. Some patients can develop long-lasting systemic consequences such as fatigue, cognitive impairment, and brain fog, or worsening physical functioning. And I would go on and say, or have heart attacks or have strokes. Myth number two, severe acute respiratory illnesses and long-term morbidity only occur in young children, older adults are the immunocompromised. And they go through pointing out, I mean, we sort of saw this introduction.

44:59I mean, we had marathon runners who like, you know, couldn't do this. My wife was a runner. She had trouble going up a flight of stairs for weeks after getting COVID. Myth three, we're providing needed care after the acute infection phase. Unfortunately, that's not true. We're falling down. We've got so many people, and just use long COVID as an example, really struggling for months to get into these specialty clinics. A lot of them have closed down because it just didn't allow them to make money in our capitalist model. I'll leave in a link, but this is a good article. I think it really resonates with that.

45:37We should be looking at 90-day outcomes in our interventions because it isn't just getting out of the hospital. It isn't just the 30 days. We see increased risks out 90 days and even farther in some. settings. All right, no one is safe until everyone is safe. We are in our ASTMNH fundraiser, right? So we're actually trying to do something special this year. We're going to create an ongoing Dixon-des-Pamiers One Health Lecture Series, and we're going to announce this at the American Society of Tropical Medicine and Hygiene fundraiser. We're going to continue to support scholarships for women from low and middle income countries to come to this annual meeting.

46:28We're going to sponsor the president's dinner where they're going to announce really more of a reception. I don't think you get dinner, by the way. And so we're hoping to actually get up to a maximum donation of$100 ,000. So go to parasiteswithoutborders.com, click on donate. This is really, I think, those of you that remember Dixon DesPommiers, I think this is really going to be a special way of remembering all that he did. It's time for your questions for Daniel. You can send yours to danielatmicrobe.tv. Mary writes, I'm a longtime listener to Clinical Update. I always look forward to Friday night or Saturday morning when the update comes out and again to TWIV on Sunday.

47:10I also listen to as many as I have time for of the TWIPS, TWIVOs, and all the others. I'm attaching a PDF of the backs of the two vaccination records my mother kept for us kids. I thought you might be interested in how recommendations in Oregon changed over the decades, especially the ones for polio. The top form is from 1961 when I was 11. The bottom is when I was 27 in 1977. My polio vaccination notes on the other side showed that I had a booster in 1961 when I was 11 and a cube in 1962 when I was 12. I remember having injections as well as does my older brother, but it's not in the record, so my memory might be faulty.

47:49My mother was a nurse, so she ensured we got whatever vaccinations were available, but I wonder if my record is missing injections or other boosters. I was motivated to check into my vaccination record because of the question another listener had with concerns about measles, immune amnesia. I don't remember when I had measles if it was before or after the polio vaccine. I checked with my older brother. He thinks he was about 10. So I would have been 8 plus or minus if we had measles at the same time, which would be very likely. If that's the case, then the OPV at least would have been taken after I had measles.

48:23So if these two OPV doses were all that I received, and if I had measles before OPV, is it reasonable to still consider myself protected? Yeah. Well, so one, this is great. Let's take a look at these cards, which are really, these are just neat. I would go to a museum, right, where you can see stuff like this, just the history of our public health. But no, Mary, what's interesting is the first one, which is 1961, there's no measles vaccine there. Right. Didn't come out till later, right? And then the next one, which is 77, then you have the measles, which are still the individual. It says you could get MMR, but they also still have the individual doses.

49:06Yeah, that's kind of neat, right? Measles, mumps, rubella. Yeah, so Mary, you're good. Did you have any comments? Because this is right up here. I'd be basically asking about polio. I like the fact that they have, they say, the sugar cube, right? Because that's going to be your sugar cube with the pink stuff on there, the oral polio. Yeah, I mean, you got the doses after measles. And as is pointed out here, polio circulated in the U.S. until 79. So it's likely you got boosted as well by that, you know, community circulation. So I'm sure you're okay. All right. So Gina writes, thanks to you and Vincent for your weekly reports.

49:49I've been listening since a friend at UC Santa Cruz, who is a professor of MCD bio, recommended the podcast to me near the beginning of the pandemic. You have been a strong voice of facts and reason, and I am grateful. My question is this. My sweetie and I, I think that's cute, isn't it? My sweetie and I provide some care for his mother, who is 86 years old and about eight months ago finished chemo after radiation and brain surgery for brain cancer. She had been getting treatment for brain cancer for about two and a half years. We masked the entire time to ensure we did not get her sick can create even more work for her already depressed immune system.

50:25We were so happy once she was six months out from her last chemo and was declared cancer-free. We stopped masking given COVID-19 levels have been so low. This week, you said COVID was starting to climb again. And sure enough, I checked our wastewater data, and this is the case in Santa Cruz too. What is a good decision point for us to start masking indoors again to protect my mother-in-law? Our decision to stop masking six months post her last chemo was a little arbitrary. And to make this question even more stark, as I was walking my dog this morning, I ran into a friend whose husband just tested positive for COVID this week.

51:00So the K-12 scores just started up 10 days ago. So I imagine we're about to see more cases here rather than this being a really small blip. Yeah, so the timing issue, you know, this is, you know, if you're out there and you run to your friend and your friend's husband just tested positive, well, I would worry about your friend testing positive or even being asymptomatic and you then having this exposure if you chat for too long. Schools, as we mentioned, that's always a concern as we go into the school season. We often see these rises. Also in the link I leave in, not only can you look at sort of nationally and regionally, but you can actually zoom into state level or as you mentioned, you can actually zoom in even more.

51:46It's kind of your threshold. Like, when are you willing to take the extra precautions? You know, someone who's older, someone who has cancer, someone who's been through chemo, you know, we're looking at a higher risk situation than just someone kind of the middle of their life for pretty bad outcomes, right? I mean, people still end up in hospital. We still lose tens of thousands of people each winter. Maria writes,

52:36facilities. While listening to you over the years, I've gotten the impression that you feel we as doctors are in part to blame for the current grievances of the public toward the medical community. Do you think doctors' communication skills are truly to blame? I apologize if I misunderstood and for getting defensive. I am just so demoralized from blaming myself for something that appears to be a systemic issue in healthcare. It's incredibly tough to continue absorbing the anger of patients. After that anger materialized into a threat to my life, I actually decided to quit patient care altogether.

53:11I share all of this to explain why I feel so passionate about this and where my bias may lie. Putting the blame on doctors' communication skills may miss the bigger picture. We've been witnessing a systematic destruction of trust in scientific institutions over the past decade. It's fueled by widespread and pervasive propaganda that's driven by forces greater than one individual or country. How can we possibly compete with an entire machinery of misinformation? Perfect communication skills won't allay the fears of a patient who refuses Tylenol because a politician said it causes autism. It won't help with someone who insists the COVID vaccine is the root cause of their laundry list of chronic medical problems.

53:53Taking the blame for our patient's skepticism is a bit of a savior complex. It ultimately does both ourselves and patients a disservice. If you made it this far, thank you for listening to my ramblings, and thank you and Vincent for everything you do. This is great. I think that I'm glad that we read this on the show because there's a lot in here. So one is, I think it's terrible, right? This is a physician who is no longer practicing because of how horrible this became. of basically the anger that patients are having turned up by political and misinformation people. Yeah, you're right. This is one of the things we're trying to combat is there is a widespread, pervasive propaganda campaign that is anti-science, it's anti-medicine, And it's aimed to undermine so much of what we've built over time.

54:58You know, it was interesting when, you know, that first email where it was, oh, my mom was a nurse, so of course I got all the vaccinations. We're actually seeing even in the nursing community growth in the anti-vaccine, anti-science. That's really disturbing. And it may be that there's a lot of changes that are even more than forget about the fact that physicians are now mostly employees of these large companies. And some of these large companies, there's a reason why I'm independent from UHG and Optum. it's because you know they don't want the exposure of promoting science when that might have a negative political exposure for them so yeah Maria you know you should personally not feel you know as though you've fallen down on the job I think we all need to work on science communication but not everyone wants to do that we have a lot of people who try to get them on the show and they don't enjoy this and they don't enjoy the death threats and all the anger that gets targeted at them.

56:05So, you know, I think it's really a shame that that anger has made it unpleasant for you to continue to be a provider. John writes, thank you. Vincent, before we go on, what are your thoughts? I mean, it's, we try to get everyone sort of out there to do science communication, but it can be unpleasant at times, right? Well, I think she's right that it's not all a failure of doctors to communicate. It is a failure in the healthcare system, right, which has been ongoing and now is getting worse and worse. But I do think that doctors have some role to play in communicating with, at least with their patients, right?

56:45And they have to learn what to communicate properly. And that's part of being a doctor, I think. I think you can't not have that. I do think the bigger problem is the destruction of healthcare, but that's also part of it. John writes, thank you, Vincent and Daniel, for your important, credible public health information. I live with my partner who has suffered from long COVID for almost four years. It is discouraging for both of us. She contracted long COVID about four weeks after we both had a bout of acute COVID, despite having three Pfizer RNA vaccinations. We've tried all the various suggestions to ameliorate the symptoms, including PEM, brain, that include PEM, brain fog, and some mass cell activation.

57:30Now we are attempting a trial of microdosing a GLP-1 agonist with some easy success, but it's too early to gauge the results. She's not in the current Scripps trial as we live in BC. I'm aware there is a current trial in Canada using two medications separately, Upadacinib and pyrifenidone with their usual therapeutic suggested dose. Do you have any current information about medication that may be effective, and do you have any update on the Canadian trial using upadacinib and pirifenidone? Thank you for the weekly updates. I look forward to your podcast each week. Yeah, John, no, I appreciate your writing in, and I'm sorry to hear about all the different symptoms, the post-exertional malaise, the brain fog, the mast cell activation.

58:16But yeah, there are a number of ongoing trials. It kind of took a while to get going, right? There was a lot of early on just sort of classified. As there are trials that come out that show their particular benefits, we will certainly include those in that last long COVID section. And Michelle writes, my daughter is pregnant with her first child due early November. We're trying to figure out a couple of vaccine questions. First, she needs to get a COVID booster in this third trimester, but the full ones are not yet available. She has only had COVID once, and that was in April 2025 and no booster since.

58:53Is she better off waiting until the fall ones become available or getting last spring's booster now as COVID rates in New York City are slowly rising? A second question, she's wondering whether to get a maternal RSV vaccine or wait until the baby is born to receive monoclonals. Any thoughts or recommendations? Thanks for all you do. As you probably can tell, my daughter and I have been listening to TWIV since March 2020. Oh, this is great. So yeah, let's walk through. So the first is COVID, what to do with the COVID booster. So she's going to deliver early November. So I think you're going to be able to get the COVID booster in September.

59:32So I think that's going to be good timing. You'll probably start seeing availability in the next week or two here. So COVID booster in September is great. flu shot, right? You know, you want to get that during the third trimester. So that's going to be great too. Probably they're already coming out now. So you're going to get that early September. Now here comes the question. So what's better? Part of this might be a preference and the other, it would make sense to do both if that was an option, right? So the maternal RSV vaccine, we've talked about data where that's about a 60, 70 % reduction in the child ending up.

1:00:11Also, you get protection, mom gets protection. So there's a lot to be said for mom getting the RSV vaccination. And then also, you know, if potential, I don't see why, well, this will be kind of an access and a financial issue. Why can't the baby also get RSV monoclonals as well? But I would start off now, go ahead, you know, in September, blue shot, COVID shot, RSV vaccine. That's TWIV weekly clinical update with Dr. Daniel Griffin. Thank you, Daniel. Oh, thank you. And everyone be safe.