Episode 2 - Latest Update on Urgent Virus Outbreaks, August 2023 Dialogue on Urgent Viral Diseases

Episode 2 - Latest Update on Urgent Virus Outbreaks, August 2023 Dialogue on Urgent Viral Diseases    

 This episode of Going anti-Viral features an IAS–USA Dialogue titled "Latest Update on Urgent Virus Outbreaks," which is a panel discussion held on August 1, 2023. 

Dr Paul A. Volberding from the University of California San Francisco serves as the moderator and welcomes three distinguished panelists: Dr Carlos del Rio from Emory University, Yvonne Maldonado from Stanford University and Dr Michael Saag from the University of Alabama Birmingham. discuss recent developments in COVID-19, MPOX, RSV, and HIV. This includes the the paradigm-shifting results of the REPRIEVE study, current hurdles in COVID-19 vaccination and antiviral treatment, and trends in RSV and MPOX. They also discuss the overall impact of COVID-19 on education and child development.

 00:08 Introduction and Panel Discussion Overview
 01:56 Discussion on the REPRIEVE Study
 05:59 COVID-19 Updates and Vaccination Challenges
 13:35 The Role of Antivirals in COVID-19 Treatment
 20:39 Future of COVID-19 Vaccines and Age Group Considerations
 27:20 The Importance of Transparency

28:18 The Need for Open Discussions on COVID-19 Vaccines
 29:47 The Existential Threat to Science-Based Medicine
 31:49 The Challenge of Testing for RSV
 33:11 The Potential Impact of RSV Vaccines
 36:45 The Ongoing Struggle with Long COVID-19
 42:46 The Increasing Cases of MPOX
 48:27 The Tragic Impact of the Pandemic on Education
 53:42 The Importance of In-Person Interactions
 54:10 Closing Remarks
 

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Produced by IAS-USA, Going anti–Viral is a podcast for clinicians involved in research and care in HIV, its complications, and other viral infections. This podcast is intended as a technical source of information for specialists in this field, but anyone listening will enjoy learning more about the state of modern medicine around viral infections.

Going anti-Viral’s host is Dr Michael Saag, a physician, prominent HIV researcher at the University of Alabama at Birmingham, and volunteer IAS–USA board member. In most episodes, Dr Saag interviews an expert in infectious diseases or emerging pandemics about their area of specialty and current developments in the field. Other episodes are drawn from the IAS–USA vast catalogue of panel discussions, Dialogues, and other audio from various meetings and conferences.

Email podcast@iasusa.org to send feedback, show suggestions, or questions to be answered on a later episode.

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Transcript

  Welcome to Going anti-viral, the podcast of the IAS-USA, a professional continuing medical education organization focused on HIV and other viral diseases. I'm Dr. Michael Sagg, Professor Emeritus of Medicine and Infectious Diseases at the University of Alabama at Birmingham and volunteer member of the IASUSA Board of Directors. 

This episode of Going anti-Viral features an IAS-USA dialogue titled, Latest Update on Urgent Virus Outbreaks, a panel discussion held on August 1st, 2023. Moderator, Dr. Paul A. Volberding of the University of California, San Francisco, welcomes three distinguished panelists, Dr. Carlos Del Rio of Emory University, Dr.

Yvonne Maldonado of Stanford University, and me, Dr. Michael Saag of the University of Alabama Birmingham. The panelists discussed recent developments in COVID 19, IMPOX, RSV, and HIV, including the paradigm shifting results of the REPRIEVE study, current challenges facing vaccination efforts and antiviral treatment for COVID, And current trends in RSV and IMPOX.

And with that, let's begin. 

Yeah, I think we can get started. Maybe let's just go around and order on my computer screen, Carlos. Thank you. Happy to be here, Paul. Thank you. Uh, Mike. I'm a professor of medicine and infectious diseases. Great. And finally, Yvonne. So, I'm a professor of global health and infectious disease. As always, welcome to the to the program at the risk of forgetting it.

There still is HIV. Right? And so I think 1 of the big stories in the last couple of weeks. Has been the reprieve study study showing that statins can help reduce the risk of cardiovascular disease, even in HIV infected people without other indications. Any of you want to just tell us a quick highlight of that beyond what I've just said.

I can get it started. Uh, we've known that statins are indicated like they are for most all people. Um, when they have risk of cardiovascular disease or score high on the cardiovascular risk calculator, but for HIV, there was a concern that early. Inflammation from HIV would potentially put people at higher risk for cardiovascular disorders, and maybe a statin might be indicated even when the risk calculator is low.

So Steve Grinspoon, Turner Overton, and others put together a study through the ACTG that was designed to take people over the age of 40 with HIV, but no other specific risk factors  for cardiovascular disease. So their cardiovascular. Relative risk over 10 years was 3 percent or less, and they randomized them to receive a statin therapy or placebo, and they enrolled roughly 7, 300 individuals, and it was meant to go on for quite a long time.

A few months ago, the data safety monitoring board stopped the study because the group who were receiving statins had lower rates of of hospitalization due to cardiovascular events and lower mortality. And they saw a wide enough difference that it hit stopping rules. And just this week in the New England Journal of Medicine, Greenspoon, Greenspoon  and his colleagues published the findings and they're really quite robust.

And on one level, a little bit surprising because I think there was genuine equipoise about. Should we be using statins and people who otherwise don't have an indication and, but it's clear that this is something that is going to change treatment. And my final comment is that, um, statins, we know help with cardiovascular illnesses, but there seems to be another.

anti inflammatory or some other benefit that it's hard to quantify. And it almost makes some people say, well, maybe we should just put, put in statins in the water supply because it helps people live longer, but that's the overall summary.  Great. And in full disclosure, I was on the DSMB for the data safety monitoring board for that.

So you're responsible for. Yeah. And in addition to everything you said, Mike, which is all, it's all great. Um, just a kudos to the, to the study, uh, uh, management and leadership for keeping this going as a huge study, very international and despite the emergence of the COVID pandemic, Thank you. They're able to, to maintain the integrity of, of this really large, uh, longstanding trial that I think, as you say, that does show, um, there's a real outcome, there's a real, uh, benefit.

And I think the, the message of, of statins for people with HIV and the, and the, and the underlining, uh, uh, of HIV as an independent risk factor. Uh, in addition to the usual ones is an important part of this study. So, uh, so really good. Um, yeah. I might add one other thing, Paul. I've never seen this from any study group historically.

Maybe you can give me another example, but I think they published 25 to 30 manuscripts around the study without really getting into its overall outcome  on all kinds of things and just a remarkable effort by the study team that I'm sure is going to continue. Absolutely different types of clots and other things that that contribute to this.

So, uh, so really good. Um, COVID COVID is still here, right? Um, in the Bay Area, we've heard in the last couple of weeks that cases are increasing in some neighborhoods. Um, and I haven't heard anyone saying that, uh, or suggesting that the disease itself seems more severe, uh, but it hasn't gone away. Um, well, we're so certainly here in the Bay Area, there are some data, you know, we're not keeping track the same way we were before.

But as you all know, we've been tracking wastewater data around the country and here in the Bay Area, we are seeing a bit of an uptick. So In our wastewater across the Bay Area and it's pretty much, it's, it's pretty widespread. I wouldn't say it's alarmingly high, but it's definitely up a little. Um, we don't really know why that is.

And if you look across the country at the different s uh, the different genotypes, um, they're really a mixed bag. So XBB one has been around, but it's starting to to drift down, and there's just a whole bunch of clusters of different XBB type sub variants that are just. That's tending to crop up now. The hospitalization rates have ticked up a little bit, but not much.

So I would say in the Bay Area here at Stanford, for example, we are seeing a few more hospitalizations, but certainly nothing  alarming. Obviously, it's unfortunate when people are hospitalized and across the country, the numbers are up a little. We're talking about maybe 5 to 7, 000 hospitalizations a day right now.

Across the country, so pretty low, but definitely higher than what we had seen earlier. So what that means in terms of waning immunity or the need for another booster, given that the we are pretty clear on the data that the current booster is not really affecting our current variants. Um, I think we're just going to have to wait for the fall variant.

I don't know, Mike or Carlos, what you think, but. I think we're probably going to have to wait for those fall fall boosters to come along.  So,  we're waiting  for the new booster to be to be announced, but you're suggesting that the number of the variance that we're seeing are actually still fairly complicated.

Are are we concerned that going with a single. A variant booster will be a mistake. I mean, there was some talk earlier about going to a to a bivalent booster to broaden. Well, you know, the the issue Paul is that that this vaccines were never designed and are not very good at preventing infection and we need to get me to get that very clear in our heads.

They're very good at preventing severe disease. They're very good at preventing hospitalization and death and the people we're seeing getting hospitalized and. And even dying today are people that have not even received their first bivalent booster. So I think, you know, as a nation, only about 16 percent of the population received the first booster.

We're talking about now a new booster. Well, my biggest concern is people are not going to take it. And that to me is the biggest challenge is we're talking here about the science, but the reality is  that vaccines don't save lives. It's vaccination that saves lives. And if we don't get people vaccinated.

We can have whatever booster with one variant or two variants or three variants is not going to make a difference if people don't take it. And even in people over the age of 65, only about 46 percent of them have received that bivalent booster. And, you know, they were already recommended to get a second one.

It's only about 10 percent of people have done so. So  I'm worried about our communication. I'm worried about how we're letting people know. And I'm worried about  the enormous. lack of trust in vaccines and code vaccines in particular that we currently have.  That is just people say, why should I get vaccinated anyway?

But let me jump in to push back just a little bit, Carlos, because we've also seen data that something like 98 percent of the U. S. Population, at least of adults, has either been vaccinated or has recovered from COVID infection and presumably both of those confer some degree of protection against severe disease.

Uh, is that gonna be enough to get us through the next? Uh, so there are a number of papers, Paul, around this area. We have a CDC Vanderbilt network with seven sites around the country, and we're looking at those house at household transmission in particular. But even if you look at the general population, The data are consistent that showing that, uh, interestingly enough, vaccination and infection are not as effective at preventing, uh, serious outcomes as the  combination.

So, being infected and vaccinated seems to be really the best. a way to prevent yourself from having serious outcomes. Um, but as Carlos said, we can't get people vaccinated or boosted, boosted, which is a real problem because what the other data that have been showing up very clearly is that the, um, the Omicron variants and all the sub variants just don't respond, uh, don't react to, they, they aren't, um, you can't prevent infection.

Very well or complications from them from the original or ancestral strain. So we really do need that booster strain and certainly whatever might be coming in the fall to really affect any of the variants that are coming out at this point. So the fact that I've been fully vaccinated and boosted and infected twice, uh,  remember, remember one of these dialogues, remember one of these dialogues that I mentioned hybrid immunity, I said, Paul, you need to get infected because you were one.

You were one, you were one of the people. People. I listen to you. I I did. I always do what you say, Carla. So I went out and got infected twice. Um, and let me just, uh, perseverate on this a bit. Uh, so I actually got infected twice and I think both were tied to, uh, to plane. Long distance, plane travel. Chai in my wisdom, decided not to wear a mask. 

The last time I traveled was a week ago and I wore a mask and I didn't get infected. Does that prove that masks work? And what do you think, Carlos? Well, masks for sure work. We know that. I mean, we all worked in with hundreds, if not thousands of these patients and in the health care system, you know, we and others have published data showing health care systems were incredibly safe.

We were really  Masked and gown, mostly the masking, I think in the eye protection. So it's very clear that it works. The question is on an individual basis. How does it work? Um, you know, it depends on how you wear your mask and who you're around and all of that. But, um. Masking definitely works. I think at this point, I think Carlos's point is very important.

We brought it up at the beginning, but it kind of got lost. Um, the question is, you know, we really need to get away from this idea that vaccines are going to prevent infection. We never set out to prevent infection. Obviously, it would be great. Many of us thought the virus itself would evolve to become a less virulent virus that we could just tolerate.

And then we protect the sickest people in our population. That's what we do with vaccines. All in all, just protect people against morbidity and mortality. And that's what the vaccines will do.  And so that's the message we need to get out because people say, well, I got vaccinated and I still got sick.

Well, good, but you didn't wind up in the hospital, or you didn't die. So that message has just kind of disappeared. Yeah, but I want I want to add to that. Moving on from vaccines, the other tool we have is antivirals, right? And we're not using them appropriately. Carlos, let me, let me jump in because Mike and I have talked about this before.

And I think on this, uh, on this, uh, these calls before, but, um, so the 1st time I got infected, I was pretty sick and I took Paxlovid and it. Seem maybe to make me get better quicker. Who knows in a one. The second time I didn't and did fine without it. Mike, where do you stand on packs a little bit? And Carl's raise this idea, but I wanted to draw you into the conversation.

Well, I think that it really the details matter.  This is a viral infection in the first 3 to 5 days. There's high level of our replication and then the immune response is really what generates our symptoms. So. At the time we're developing symptoms for the first time from an illness, the virus has been there for a while, churning.

And if, if someone can get on Paxilovir within the first four to 12 hours, that's when it's going to work the best. So if somebody waits three days, it's probably not going to have much effect. To that point, remdesivir,  which is used in the hospital on day seven, eight, by the time somebody gets admitted.

Does a little bit, but that's because the virus, the viral, uh, spike was days before, and it's just not going to work as well. So the timing really matters. So if someone, I think we should all be monitoring ourselves for symptoms. If we have symptoms test quickly, if positive get on Paxlovid, assuming no contraindication.

And, and get it on as soon as you can. What I think we're experiencing into Carlos's point, there's resistance. I don't know if it's so much among patients, the doctors  treat, and I haven't quite figured that out yet, especially treating early. Mike, I've even heard at the pharmacy, I've heard pharmacists on the phone saying, Oh, the doctor told you to take it, but I don't think you should.

I cannot believe that that is going on. In today's world, welcome to the world, I guess. Right. Um, so another, let me just make another point. And I don't know that we've proven this, but remember when we saw these patients at the very beginning, I remember taking care of these patients. We had a big tense because we weren't, we were so many, we couldn't be in the hospital and they'd come in and they say, I feel great.

I feel great. I don't want to enroll in any trials. And 2 days later, or 3 days later, they were really sick. So this really comes back to your point about treating early. Because what we know about early disease, especially among the, um, the, uh, uh,  the fully susceptibles is the virus doesn't hit you hard until about seven, five to seven days out, you really don't feel bad.

And we started figuring out to give people pulse oximeters. And when you measure their pulse oximetry in the first two to three days, when they felt fine, their pulse oxes were actually not good. So they didn't feel bad. But their, their pulmonary physiology was responding and then what happens is it gets kicked in later on and then they're sick and it's too late for the antiviral potentially to work.

Now, I don't know that I can't prove that, but that seems to be a pattern that we saw over and over again. Mike, do you want to comment? Yeah, I wanted, I wanted to say three quick things. One is about Paxlovid, uh, Bonnie, to your point. You, you can't, some people say, well, I'll just wait and see how I do. You can't do that.

You get, if you're going to use Paxlovid, use it early. The two other quick wrap up points from our earlier conversation. I think airplanes are perhaps one of the most unsafe environments now, not because of the airflow is great, but because people are on vacation, they get sick. They test positive. They say, I don't want to be sick.

On the road. I'm going to hop on my flight early and come back. So they fly while infected and transmitting virus. And, um, I would bet, unfortunately, some don't bother to wear a mask. The second, the second thing that I would add is going back to, does the vaccine prevent illness? And by my recollection, the original vaccine against the original strain actually did seem to protect against symptomatic infection.

It was that early thing. And then when Delta came along in the summer of 21,  that's when we lost control of preventing symptoms. If you remember the outbreak on Cape Cod, where 75 percent of people were vaccinated, but remember, remember Mike, the, the, again, those initial phase three studies, the Moderna, the Pfizer.

They were all designed to prevent severe disease hospitalization. We really didn't look at infection until later, and it was a surprise when we found it prevented infection, and we were all very happy, but you're absolutely right. That happened is that lasted a short amount of time, and because it went away by the summer, right?

But the reality is they still prevent some infection. They still have some, and I want to emphasize what Bonnie says. We have about 67 percent of the U. S. population has been vaccinated. And then we have a large percentage that also has been infected. Those of us that have hybrid immunity have actually pretty good protection.

Now, over time it wanes. It's very clear that over time the protection wanes. When you look, for example, at the current strains,  your protection after you've been boosted is about 30 to 40 percent. After 90 days is down to about 12%. So it wanes, but the protection against severe disease and death wanes a lot slower, except if you're over 65 and the older you get, the more rapid is going to wane.

So, going back to Pax Lovett, the emphasis, and you're absolutely right, we got to get people, especially over the age of 65, if they get infected, take Pax Lovett, not because they're not sick.  But because they have risk factors to getting sick and what you want to prevent is you want to treat them to prevent them from getting sick as opposed to treat them because they're sick.

And I think that's a little bit of a change in in the way we manage things. And we as physicians frequently say, well, you really don't need the sound about it. You're not as sick. Here you have to say you really need this antiviral because we don't want you to get sick. Your risk factors determine that you need this antiviral.

And that's a bit of a change that I think is causing the difficulties that we're hearing with people knowing when to prescribe it. So I, uh, I want to get back, uh, actually I want to get back and kind of close off, hopefully, the discussion of, uh, of COVID vaccine, because I want to get to some other... Yeah, let me let me just add 11 new.

This is brand new. This is brand new out this past week. There's an article in science advances where the group of Duke and the Fred Hutch and some others release data about a broadly neutralizing anti Corona virus.  Basically a monoclonal. But the hope is that not only might it work as Bivalamivimab and others did before and not lose its effectiveness.

The hope is that it could be developed into a vaccine that's, that produces broad neutralization. And that theoretically could get us back to where we were back in December, 2020 and early 21. So that's a. Hopeful comment about the future, sort of holy grail of, um,  HIV vaccines with bean abs as, as, uh, we, we toss the term around, uh, before we move on from vaccine, though, let me just ask, uh, what's the bottom line, uh, what's the vaccine that people can expect to, uh, hear about this fall, uh, when is it going to appear, uh, it's probably, does it work more and who should get it?

It's probably going to be an XPV vaccine plus minus the original strain. It's probably still going to be a vivalent with the XPV and the original strain. It's, it's going to be recommended, you know, strongly recommended for people over 65. I think it's going to be recommended that everybody gets it. I don't think they're going to say you don't need to take it.

But the reality is very few people aren't, you know, young people are unlikely to get it. We know that already from the current booster. But I think we need to make an effort. Those of us that see patients over 65 to really recommend they get vaccinated. What you said at the beginning, you're right. If somebody says to me, should I get boosted now?

I tend to tell them no. Wait until the new, the new, the new  vaccines emerge in the fall. But, but we are, uh, we're playing a bit of a guessing game because, you know, with, with influenza, when they decide what, what, what viruses are going to put in the vaccine, the three strains that are going to go in the vaccines, those strains stay pretty stable throughout the year.

Rarely do they change. COVID is like, you know, that on steroids every X number of weeks, the virus is evolving and producing a new strain. So we may think XBV is the right strain. Between now and the fall, there are many weeks. There may be a new variant that emerges that doesn't do, that we're not included in the vaccine.

So that to me is the biggest challenge, is that, is that we're paying, playing catch up. And going back to what Mike says, we need, you know, pan coronavirus vaccines, because playing catch up with these vaccines and trying to target the virus is not working. So let me violate my, let me violate my, uh, whatever I was saying and ask, um,  I'm going to ask the person who was trying to talk, um, to talk, uh, Bonnie, um, on the other end of the age spectrum, uh, you're a pediatric ID person.

Uh, will these vaccines be, will the vaccine in the fall already be approved for all age groups down to infants?  Uh, have we, have we learned the lesson of not testing new vaccines in all age groups? Well, so that's a, that's, I think we're still struggling with that, and it'll be really interesting to see how FDA and CDC come down.

I have talked to some of my colleagues and some of the policy makers, and I think they're struggling to figure out what to do with the adolescent age group. In particular, the younger adults who seem to seem to do well. I don't think there's any question. Well, in my mind, there's less of a question of whether children.

Under five, for example, should get vaccinated, although they are the least likely to be vaccinated. I think that's the group where we saw the most  morbidity in the over 12 year olds between 12 and say, 25 or so. That's where there was the least morbidity and we're telling. I think that's where people are struggling to decide, but I do agree with Carlos probably recommended for everybody.

But as you heard with RC, which we'll talk to about later, maybe shared decision making for sure the older individuals. But I think kids under 5, there's more of an argument because of the hospitalization risk. And I think the adolescence is still up for grabs.  I just want to say before we move on at all, that among the participants, we have a real hero of the, of the HIV epidemic, Margaret Fishel, has joined us, so, uh, welcome, uh, to the, to the call, Margaret, um, uh, great to, great to have you here.

Um,  So, uh, also in the last week or so, we've heard  continuing discussion, a big story in the New York Times, uh, this past Sunday on the origins of, uh, of SARS CoV 2. Um,  who wants to jump into that for a few minutes and tell us why we should care and what's your bet? Is this an animal virus that just kind of jumped in the marketplace into humans? 

Is it an intentional engineered virus to target, um, um, certain populations, uh, uh, subpopulations of Ashkenazi Jews and Chinese people? What, what, what's your, what's your reaction to this, to this story? So, yeah, I saw that article. And of course, David Relman here at Stanford has been a real proponent for getting this story straight.

I don't.  I think the article left us with a very nicely done article, but I think most people agree with what the article said is that we're probably not going to know absent additional information because the sources of information are not available anymore. They've either been deleted or they were never.

collected to begin with. So there are very good arguments for all three opportunities. That is, one is a true spillover event from animals, and there's very good evidence. If you can match strains from animals that flow very well through the lineage of the human SARS CoV 2. On the other hand, there's some bumps there that really can't be accounted for.

The other issue around a, you know, it seems like a very big coincidence. There's a viral facility near the market or in the same city as the market. And the question there is whether or not it was an intentional release, or whether there was an accidental release from an infected individual who worked at the lab.

And there's some really good data. Supporting  the way some of the genetic sequences look to be manipulated as if they were manipulated in a laboratory fashion. And it's a little complicated to go into that. But basically, some of those mutations generally don't occur in nature. Now. It's hard to know with coronavirus, what might or might not occur in nature.

So. It's we're, we're probably not going to know for now  whether we should know is really important because it does help us understand how we should be attacking the next wave of coronavirus. Now, what Mike brought up about a universal epitope is great, but we still need to understand whether spillover, how to predict spillover events.

And there are people who are modeling spillovers and where do you reach a particular level that might need to be intervened with? Um, these are going to be massive questions, though, even if we understand it. How do we address spillovers? How do we address lab accidents, especially outside the U. S.? Um, those are going to, we're going to need to mobilize a lot, and that's why those are so important.

I don't know what others think. And I, and I would add to that, that the reality is  that lack of transparency and lack of cooperation of the Chinese authorities And trying to, you know, not not be transparent and not invite, you know, international, you know, investigators right away to try to figure out what's going on only increases the suspicion and the concerns about this.

And we really need to work for for a world in which there is. True transparency and international collaboration. The, the, if we don't have that, this events will continue to happen and we will continue to have this kind of problems. The reality is we all need to work together to try to prevent this, you know, whether it's a spillover or a laboratory accident, there's a laboratory accident.

If we work together, we should be able to contain it. But trying to, trying to not disclose it and trying to keep it hush hush is not the right approach. And we really need stronger international regulations that will allow us to do that. That's all good. I'm being facetious here. But honestly, if we have a, if we have a government hearing about UFOs, we should be able to have a more open hearing about COVID vaccines.

And certainly, I would say they're at least equal, if not more important.  I won't  comment on the proposal of having a certain former Um,  Kennedy, uh, appointed to the CDC directorship, but, uh, let's let's pass on that political comment. Mike, I was going to say, as an end of one people of Ashkenazi Jewish heritage can get infected. 

Well,  despite what  junior he's, he's, you know, that brings up a really good point, Paul. And I know all of us have been dealing with this and the question and I'm monitoring this on the American Academy of pediatric side. We are seeing more and more.  Vaccine legislation anti vaccine legislation coming forward.

Fortunately, most of it has been knocked down, but there is more and more, uh, there are more and more efforts to reduce the power and influence of vaccination programs at the state level. Um, this goes hand in hand, of course, with, uh, care for certain sexual and gender minority patients where we've actually seen whole divisions of physicians fired.

from state, uh, and public community clinics and state and public universities fired for the kinds of work they're doing. So we are facing a real existential threat around the value of science based medicine. Um, and vaccines are just the spearhead of that. So I do want to, I do want to move on, but I think it's fair to say that as I understand that there's been a long history way before COVID of concerns about vaccines and various, uh, Doubts and conspiracies probably going back forever.

Um, so  nothing,  nothing new under the sun, but, uh, but really obviously, uh, really troublesome. And speaking of vaccines, Bonnie, um,  The new discussion this week, uh, has been RSV. Um, I find it, um, pretty confusing. It is confusing. It's exciting that we are finally focusing, but as Carlos pointed out before we started, you know, is it really a disease?

I mean, you know, and here's a great example. We've been tackling this on NVAC, on the National Vaccine Advisory Committee. We're trying to discuss this and the best use case for vaccination. Information is RSV. Here's a disease that kills 6 to 60 to 60 to 6 to 10,  000 adults over 60 every year that we never knew about because people didn't think about testing.

Because why would you test if you have nothing you can do about the disease? This brings me back to the days. Early of early HIV, where I advocated for testing pregnant women, and I was told, well, what would you do with that information? Nothing. So we have to have a use case for testing before we were able to do it.

So this has been a triumph in many ways to actually identify the source of. deaths and hospitalizations, 60 to 100, 000, adults over. Why did it take us so long to  turn our attention to  RSV? And because everyone thought it was a pediatric disease, right? We didn't, you know, adults get viruses, you know, people just think, well, there's some, something going around and it's hard.

It's very hard. To test for RSV. Now we have better methodology, but even as a pediatrician, the tests were terrible. They were DFA tests, you know, direct fluorescent antibodies. They were terrible, false positives, false negatives. It wasn't until we had much better, um, a PCR technology that was rapid that you could do a point of care that really even pediatricians were able to use it.

And the reason we were focused on it is because it's the most, it used to be the second most common. Now it's the most common cause of hospitalization in kids in the U. S. Two to three percent of kids are hospitalized, so we've always been focused on it. And because it causes more severe and acute symptoms in babies, with bronchiolitis being the main one, we were, we could intervene with, uh, with different, mostly with oxygen.

Again, the question of steroids has been put to bed, but for a long time we used steroids. Bronchial dilator. So there was a lot of intervention you could do that did not involve, um, you know, vaccines. Um, and so that was never really the case with adults because you have bigger airways, you don't have the same acute disease when you wind up with this more chronic manifestations.

So we just didn't recognize it. It's hard to test for. Pediatricians hate to have to deal with it because You know, not everybody has capacity to do the rapid testing that's required. And then what do you do about it? There's not a whole lot to do. So the vaccines are going to make a big difference. And the, the monoclones may also make a difference.

So let me, let me, uh, ask a question that I've, uh, sort of heard in, in, in reading about this, that some say, That the vaccines, first of all, there are several vaccines that are, that are coming out right? Um, and some of them apparently have only been tested, uh, for about a one year, um, uh, protection, uh, duration.

Others are being tested in, in trials for a three year, uh, protection. Should I take a vaccine, uh, that's only been shown effective in shorter term, should I wait until a longer duration? Uh, trial result is available. What's your what's your reaction to that bunny? Well, so as with most mucosal viruses, um, R.

S. V. We know a lot about the epidemiology and kids because that's the only thing we could study for the longest time. We know that most individuals, adults as well. can get reinfected year after year and yet RSV, there's two serotypes, A and B, they rarely mutate outside of a fairly limited number of small and unimportant, mostly unimportant mutations.

So the viruses have been remarkably stable and yet we get reinfected, all of us, every age group, year after year. So the idea that a vaccine works for a year makes sense to me because you're probably not going to get Long term immunity. And in the meantime, you can prevent the annual surge. If it turns out we have a vaccine that works for more than a year, then that's great.

But in the meantime, I would want to be protected in the average year.  I know that now that for here at Stanford, I'm sure others we've been testing our RSVP. RSV influenza and paraflu panels for years. And in adults, it is equal. I mean, we have just as many RSV as flu admissions to the hospital. It crowds out our hospitals.

We sometimes have to set up tents. It's been, and this is before COVID. So, The vaccine is going to be critical. Now CDC made the decision to recommend with shared decision making, which is kind of a bit of a  difficult thing to do because it means you have to consult with your doctor. That means the doctor has to make a decision.

And I think there were a lot of reasons for that. Some of it were they were worried that people might not want to get vaccinated and giving people more of an opportunity for them to make the decision. But certainly for people over 60, I would say absolutely get the vaccine. Because the risk is pretty high, um, that, that, um, that an individual gets medically attended disease and potentially hospitalization.

So whether or not we're going to need boosters, I don't think we're there yet. Some of these studies will be, will be helpful to look at. And it's also a testament to understanding the technology because For decades, literally decades, we were looking at the wrong version of the protein of the  epitope that we were targeting.

So it wasn't working and in fact it was probably exacerbating inflammatory responses to the vaccine. We haven't commented on long COVID and there's been, uh, there's been developments including trials now of the,  of the, of the neurocognitive effects of long COVID. Uh, so I welcome, um, some thoughts about that and also, um, kind of the long term, uh, effects, possible effects of, uh, vaccination, uh, and what, what the, what options people have for, uh, for, um, getting compensation for vaccine related injuries that, uh, anyone want to kind of tackle those things, uh, pretty briefly.

I'll start with long COVID. But I think that, you know, that finally, after. Long time, you know, the recovered cohort was established by NIH as a way to do this recovered recently published in JAMA. I think a pretty good paper trying to define long COVID. I think one of the challenges that we have is we don't have a definition.

And those of us working in HIV know that establishing a case definition at the beginning was critically important in trying to define the syndrome before we knew the cause, right? It was very important to have a case definition. Um, shortly thereafter, as you probably remember, then the case definition, there was a lot of debate among scientists about how do we modify the case definition?

How about, and that's when we added tuberculosis and that's when we added cervical cancer and HIV.  So the reality is the case definition is useful and in long COVID, we didn't really have one and furthermore, we still don't have a good biomarker. So there's no test that somebody can have and go to the doctor and say, you know, here you have long COVID.

Here's this test that shows the following. So,  so it's a lot of challenge to do a trial. When when you don't even know who you're including, right? Because the inclusion criteria is not defining the population. So hopefully with the new definition,  and that's why recover took a long time because they were trying to say, who are we going to study to begin with?

Now that there's a case definition,  you know, trials are going to be started with with antivirals and with other medications.  I think there are two,  there are two prevailing theories. Is it the virus? Is this persistent viral infection? And for that reason, you know, a study of  Paxlovid, a randomized trial with Paxlovid and long COVID is going to be conducted in which people are going to be treated for 15 days with their Paxlovid or placebo.

And those of us that are taking Paxlovid are wondering, how do you make a Paxlovid placebo? Because, you know, it's pretty easy to know that you're taking Paxlovid, right? Your mouth will know it.  And, and I haven't kept up exactly what's going to be done in this trial, but at some point in time, the discussion was, oh, we'll just get people, you know, you know, placebo, uh, uh, retinavir.

And I was like, oh, boy, I would have a lot of trouble enrolling somebody in a study. I'm going to give you a drug like retinavir as a quote unquote, the placebo. But, you know, I have not looked what the trial conclusion finally was. The second theory is that this is the immune system, right? That this is immune activation.

That is leading to long code. And the reality is good could be either or right. It could be both. It could be. We really don't know. And that's why this clinical trials are important, but also. The work that is very important is the work that Steve Deeks and others are conducting trying to understand the pathogenesis of the disease, because really, at the end of the day, until we understand the pathogenesis, we're not going to be able to really have a good therapeutic option.

So I am excited that clinical trials are starting, but I feel a little bit like. You know, I'm glad Margaret is on the call. I feel like the first study of, uh, you know, Zidovian  in the ACT original study, that's now how we're treating HIV today, but the ACT original study was, you know, was the beginning of a long road that eventually led to highly active antiretroviral therapy.

So I hope it doesn't take us that long to get to a good therapy for long COVID. But clearly, this is not, this is the beginning is not the end. And it's going to take a while to get there.  So, uh, back to RSV, there are a couple, um, of questions. One is, um, uh, one question was, uh, did, did the person hear rightly, hear correctly, uh, that, uh, we're recommending RSV vaccination for adults?

And I think the answer is yes, right? Yeah, so  I see. I saw that and I do think that, um, the one older adults, the one comment there about listening to the ACIP. It can be quite convoluted, but I do think it bears help. I mean, I've summarized it very briefly.  There is a fairly complex conversation around how to recommend for people, 60 and over.

And again, this is an adult world in pediatric worlds. We vaccinate everybody, because even though the risk for certain diseases is not very high, you're starting off with a very young population. Um, so we tend to vaccinate across all pop, all age groups and all healthy and unhealthy young children for diseases that may actually have low prevalence.

So it's a little different, I think, for adults,  but, um, uh, so I think the discussion was a lot more in depth around how to counsel what my concern is not. That everyone should get it, but that physicians may not have the discussion with their 60 patients, 60 and older, some of most of whom, many of whom may be at risk for disease.

And of course, we also don't have specific markers for who might be at highest risk. Certainly there are very high risk groups, but there are individuals who are at lower risk who may still get disease. I mean, it's a quite, quite highly prevalent.  Annual pandemic, right? So a couple of comments here. First of all, uh, it's been pointed out to me that is USA has recently had a course in long covid that's available online, which if you go to the to the organization's website, you can find a link to and also that Bonnie is going to be leaving a discussion for is USA soon. 

And we'll we'll notify you all of that at the end of this course on RSV. So we'll have a plenty of chances. And I like these comments in the Q and a from from  Amy Kressel, who says that that the discussion about shared decision making was really nuanced and important and actually gives us a.  Uh, direction to listening to that on, uh, on the YouTube channel.

So lots of sources of information. And if you want to hear that, uh, start, go to the YouTube conversation and start at 3 minutes and 13 seconds. And you can, you can hear that, uh, that conversation. So, uh, thanks. Thanks for the feedback.  And, uh, so we've, we've talked about, uh, RSV a bit, we've talked about COVID and HIV, um, Peter Chin Hong is usually our go to person for MPOCS, uh, but does anyone want to kind of hit, uh, latest updates on, on MPOCS?

Um, and I, Peter did. Let me give you  a couple of the updates. You know, we started seeing a surge in cases in some cities. We saw it in Chicago. We saw it in Boston.  It burned out very quickly. It didn't take off like we thought it was going to and I think in part is talking about. There's a certain degree of immunity from prior infection and from people that have been vaccinated.

The disease primarily still continues to be, you know, impacting, uh, men who have sex with men. And increasingly, and in almost every cohort, about 50 percent of those are persons living with HIV.  So the message continues to be, if you're a man, have sex with a man, especially if you're HIV, uh, co infected, you should get vaccinated.

The question is, does the vaccine offer full protection? And the answer is probably no. You don't get full protection from the vaccine. You get some protection, but you don't get full protection. If you're, if you have HIV,  You also need to be in antiretroviral therapy and be virally suppressed. The people that we have seen die of monkeypox or severely ill are persons who are not virally suppressed, who are not on antiretroviral drugs, and who have, have very, very, uh, low, uh, CD4 counts.

So, so again, emphasizing the importance of Of treating if you have HIV, but you're virally suppressed and you're you're, uh, you have a good city for account. You will your response to monkey pop to impacts is going to be no different than if you didn't. You're going to do just fine. When you're going to respond to the vaccine.

We are seeing internationally, you know, the disease continues to spread in Latin America there. You know, there they haven't vaccinated and therefore they're still. A fair number of patients and now we're seeing cases in China and, uh, and the outbreak of in China is again very problematic because of the lack of vaccines because of lack of take a very amount of treatment  and because of the enormous stigma that is associated with with this infection.

So, uh, you know, we're not out of monkey above impacts, impacts continues to be a problem. And I think what we. What we need to emphasize is that a lot of this illnesses, you know, a lot of diseases are disease of global significance. If there's a case of of impacts in Chicago, people in China should worry about it.

If there's a case of impacts in in Brazil, people in in New York should worry about it. And, you know, this, this infections should remind us that we live in this global community and through transportation and many other ways. We're not, you know,  geographic barriers really mean nothing to those viruses. 

So I'm on the ACIP MPOCS working group. We are still meeting, uh, unfortunately we had hoped to, you know, get some more recommendations. We're working on recommendations for the next steps for vaccination the  NIH to look at vaccine effectiveness. For example,  In a much more controlled setting, I think early on, some of the early estimates were  very good, but could be better because they were responding to the huge surge.

I think 1 of the concerns about the Chicago outbreak in particular. Is that, um, many, if not most of  the individuals who were had serious infection were actually vaccinated. And so we're digging deeper into understanding how many got 2nd doses. How how far apart from the 1st and 2nd dose was the infection.

All of those questions, because that's going to give us a better understanding is what's happening now in the community, especially the MSM community. Is well, I don't want to get the vaccine if it's not going to work. Um, and maybe the question is force of infection. That is how many partners did you have?

How far apart were the doses before you got infected? Maybe you didn't get your 2nd dose, etc. So all of those data we're going to need to really.  And fortunately, um, the government and most public health agencies at the local level are working with MSM communities in particular to get messages out for all of the summer events, the pride events, and all the summer events that happen to make sure that there are vaccine clinics set up, that there's good information for communities, as Carlos said, this is a very tight network that travel can, can travel, and so you can see Outbreaks,  small transmissions that occur in random settings as people move around, so this isn't over.

We were hoping it would be done. The question is, can we fight endemicity? Can we make it a non endemic disease? And that really depends on our ability to  just get that international message out because it's not just based in the US.  Let me just pass on a comment that, um, that Peter Chin Hung gave us, uh, before this, uh, this, uh, call today.

He says that,  uh, as Carlos has said that there are cases, uh, uh, increasing cases of MPOCS in China and East Asia,  and he talks about stigma and says that in China, uh, MPOCS is being used as a gay slur. Uh, and talks about the intersectionality with HIV. Uh, so I think, you know, the, the, the level of politics and this and the, and the concern that we have for, uh, for how that affects our, our patient population is, is, is a real one.

Uh, stay, stay tuned for that. Um, let me, uh, kind of at the, at the risk of  being political, but why not, um, ask Bonnie. So one of the,  Questions that were comments that we've heard in the in the news recently has been that  kids are still apparently suffering lack, you know, kind of difficulty catching up educationally because of the time  lost with the with the pandemic. 

And, you know, there's going to be a lot of. Kind of searching going back to see what would what did we do? What worked? What didn't work? Why did we do it? Why didn't we do it? This all, you know, we're going to be living with that for the rest of our lives. Um, comment about schools. Um, because, you know, here we have.

Um, some, some great natural experience, you know, uh,  with, you know, places where schools were kept open, largely places where there are closed, um, places where public schools were closed, where private schools were kept open. You want to just spend a couple minutes talking about, uh, what lessons we might have learned about, uh, about schools and the coven pandemic.

Yeah, it's been nothing short of a tragedy to see what's happened to our children, especially the health disparities, um, children who have no access to Internet, you know, outside of school, et cetera. I would say that we are a victim of the same fractured school district, uh, uh, policies as we did with this fractured healthcare systems that we have in the US.

So very early on the American Academy of Pediatrics, we worked with, I worked with the American Academy and we set up a document in June.  Of 2020, and then try to reinforce that 2021 to really try to make it clear that we thought children could go back to school and we set up a very, very specific set of guidelines that we thought schools could follow.

To send kids back to school and the academy, which is a non aligned group was accused of being political for aligning with a particular party that said school should be open. Now, when we wrote this, we wrote it to say, yes, schools can be open, but they need to take certain.  Precautions and then the reality, the harsh and sad reality is that many of the school districts were incredibly under resourced, whereas there were schools.

And I know here in the Bay Area, we worked with some of them. Schools were incredibly over resourced. They could test every day. They could. You know, isolated home or put people in hotels and we know that when schools were resourced, well, kids did fine and they were able to keep up. But the problem was that that that was related to your socioeconomic status.

And so schools that did not have resources just chose not to go down that route. And then it really became a political issue. Where, um, unions were afraid to go back to school for unclear reasons. And we really tried to get involved in a dispassionate way and trying to help the unions understand that they could go back to school.

But by then, I think the political forces had really taken hold and that led to incredible delays around the country.  In different school districts, applying different approaches. Now, we happen to also work with the top 2 school districts, not New York, but Chicago and Los Angeles and helping advise them on how to get back to school.

And they really did try to build in with donor support and other supports, because they were so big testing protocols to get kids and teachers back to school to feel safe. And in those situations, it's sometimes work. But it's such a heterogeneous, um, the school district's district, um, structure is still unclear to me.

It's very disorganized and I don't, I think they do the best they can, but there's no central way to address school district policies. And I think we should really learn from that. That certainly is how we have, we saw our health districts, um, suffer as well. And there's one comment in the Q& A, uh, about teachers in some areas not being considered essential workers, um, and the effects, uh, the, of that on teacher morale, um, being, being a lingering effect.

So this is obviously a bigger topic than, than we can, uh, that we can dig into, but, um, but clearly, uh, the pandemic has, has, has caused some searing effects on our society and we'll be, we'll,  we've probably lost.  of gains that we've made in the educational system. Some of these children are, it's not just mental health.

There's a lot of developmental issues and just school, school, um, uh, school based, um, approaches to trying to get kids caught up is just very heterogeneous. And I can tell you, even at the university level, at a university like Stanford and others, I've talked to colleagues around the country, their college students are still suffering pretty tremendous mental health distress.

Uh, from being away from college and and also having, uh, not had the social, uh, development that they've needed, even though during those years. So, let me just add to that quickly. We have we have to get people back in person. And it is very important that we we are social animals. We need to get together and we're still having problems of people, you know, coming to work and people don't want to go to work.

People don't want to go to class people. And the reality is part of the solution we have. Is really to to get back into into trying to be, you know, being in person. I think if human interactions, humans require human interaction. Great  again. Thank you. The participants for coming today. We had well over 300 people on on board. 

And thanks to the to the discussants as always a great, great group. And thanks, as always, to the staff and I S. U. S. A. for getting us together. Thanks a bunch.  Have a good day. Okay. Have a good day, everybody.  Thank you for listening to this episode of Going Antiviral. This podcast is for informational and educational purposes only and is not intended to serve as medical advice.

Opinions expressed in this podcast do not necessarily reflect the opinions of the IAS USA or its affiliates. To listen to more episodes of Going Antiviral, be sure to visit our website at IASUSA.  org.