An expert panel mines the latest data to discuss the COVID-related issues on patients’ minds. Our specialists shed light on why surges wane, which measures truly enhance protection, whether masks harm children, why the vaccines confer different degrees of immunity, which populations need a third shot, and other considerations.
Good afternoon, welcome back to medical. Grand rounds on by walker, chair of the department of Medicine at UCSF. This is a kick off to our new academic year and so we will be back here with grand rounds Weekly for the next nine months or so. I hope you will turn this into your weekly habit were uh based on the experience we had with covid over the past year where sort of upping our game and got some fantastic sessions planned for you. Some of them will be Covid, some of them will uh will not be but the other really interesting issues in health care that I think you'll want to learn about and hear about from our speakers. Just a little bit of advanced notice today will be a covid session. We'll do another one on october 14th with our friendship to uh and I will chat for an hour. So put that on your calendar for october 14th next week we'll do one of our clinical problem solving exercises where we present an unknown to Robbie gay ha one of our superb clinician educators. The week after that on september 23rd we will do a session on the controversy over the new Alzheimer's drug with rita Red Berg, talking about some of the policy and FDA approval issues and Gil Rabinovich chief from neurology, talking about some of the clinical aspects of the clinical data On that drug the week after on September 30 will have Eddie Chang, the chair of the Department of Neurosurgery. Talk about his remarkable research on the really essence of speech and how human brain comes up with speech and what he and his group have done which is develop a speech neural prosthesis for people that are unable to speak and obviously it's gotten worldwide attention. So a lot of really interesting cool stuff coming up. But let's focus on today. I'm not going to spend any time going through why we're talking about Covid still when we signed off in May we were hoping that maybe we would be over the worst of it and maybe a ripple of Covid here and there. But clearly that has not been how the summer has gone. So I felt like it was time to bring together uh three of our favorite speakers to update us on where things are with Covid. I can be brief with their bios because you've met them before first will be George. Rutherford will give us a short talk on the state of the pandemic and this fourth Sir George is a professor in epi in bio stat and serves as medical director of our prevention and public health group and has been our go to person for all things Covid epidemiology for the last year and a half. We'll also have Peter Chin Hung Peter is professor of medicine in our division of infectious diseases at UCSF Health. He's also associate dean for regional campuses at the U. S. S. School of medicine and has been a go to person for us on clinical and uh other aspects of the pandemic as he has been for the media as has our third speaker, Monica Gandhi, who is professor of medicine, Associate division chief of the division of HIV infectious disease and global medicine based in Zuckerberg san Francisco general. She also directs the UCS of Gladstone Center for AIDS Research and is the medical director of the HIV clinic. So these are three absolute world class experts. No surprise that they have been essential communicators about the pandemic, both locally and to the media nationally and internationally. And so we're thrilled to have them here to educate us about what's going on and what's going on part. We will try to cover as much as we can in the next hour everything from the current wave to the schools to masking too, Delta two mu two boosters. So I'll talk fast, they'll talk fast If you have questions, please type them in the Q. And a will get to as many of yours as we can and if you have uh if you're just closed captioning is available at the bottom of the screen. So with that I will turn it over to George rutherford. Thanks bob. Okay, so I had hoped that when we had broken in in May that we'd be looking uh pretty good now. It's it's sort of good but not great and we need to be um uh this is going to continue to be a problem. We have had 1/4 surge since May in the United States and in in California as you recall back here in april and May, there was a surge in the upper midwest that probably really representative fourth surge. Although it may have been the tale of this sort of big winter surge. We did not see the same thing in California but have nonetheless had had to have had a surge in through july and august. The United States right now sorry, is running At more than 140,000 cases a day With more than 1500 cases a day, California. Is it about a little bit more than 10,000 cases a day. Uh and has clearly turned down the US has seemingly turned down. Although there's this kind of really jagged sought to tooth pattern two cases and it's a little unsure whether we can say this is a true turned down or not. The cautionary tale here is from the United Kingdom where they had a very similar pattern with a surge drop down across the summer. Late later summer surge, A decline which like we're seeing now. But then it went right back up again and I just want to say, you know, we need to be careful that this doesn't happen here in the UK65% of the entire population is fully vaccinated, whereas in the US right now this morning, 53% of the entire population is totally vaccinated. So we are at risk for this happening. And it's going to take some concerted effort to keep it from not happening. Uh Where cases going on now in the U. S. Well they're going all through the south, the southeast up in here into the lower midwest but also in the Intermountain west with states like Wyoming and Utah Nevada Idaho. Um And then even the sort of northern and eastern tears of California being uh quite heavily affected. And this is per per 100,000 cases in florida are starting to come down somewhat uh Which is most welcome. But it's um you know with the hurricane that's gone through and flooding and all those problems. It's unclear how that's going to affect the gulf coast. Um One thing that's come out is that this surge is affected Children. Uh These are data that just came out from from C. D. C. And they're showing a surge in 0 to 17 year olds out here in uh in august. But if you look by state and if you take this by the states into cork tiles the States, the quarter of the States with the lowest vaccination average vaccination coverage have the highest risk for E. D. Visits. Sorry this is for emergency department visits. I realized this is medicine grand rounds. Everybody thinks something else for emergency medicine. Emergency department visits. Um With 3.3 times higher odds and 3.7 times higher admissions in the in the states with the lowest levels of vaccine vaccination, California by the way is up in this upper highest tier uh here in California. As I said, this is a disease of the kind of the northern and eastern more tear with big surges in in del norte, in Siskiyou to hama Colusa, uh Sutter and yuba. And even down here in Kings County. But there's still, but there's a lot in Shasta. And some of these other big thing, the big population center in this part of the world is here in Reading. Um In the Bay Area, we're doing quite well, although contra Costa Solano are lagging behind somewhat, uh particularly Solano County. And in southern California ventura, Los Angeles Orange are doing well on a per capita basis. Overall the our sub e for California, the effective reproductive number is less than one. We have a test positivity rate of about 4.5% which is coming down. Um and we've had a flattening out of hospitalizations with only a 3% change over the last 14 days in the Bay Area. Um Only two counties have, you know, it's, it's, this is jumping around Alameda has declining case rates as du marin and and napa san Francisco itself Has had 70 more cases over the last over the last week. But everybody is doing pretty well. All this, our CBS except for a couple like in Solano are below our at our or nearer below one. The percentage of tests that are positive. Again, with the exception of Solano are all under four. Um And you can see how this tracks with the uh with the uh percentage of the population that, is that a first dose of vaccine. So erin Moran where its highest um this is where the uh one of the lowest for the uh percentage of positive. Okay. Um in California we've administered uh 46.6 million doses of vaccine. The we're flattening out here at around 75-80,000 doses a day. Um 65.8% of Californians have received one dose or more and 57 .4% have been fully vaccinated, which is by the way less than in the United Kingdom. In San Francisco, 79.5 have had one dose or more than 73.3 of every. This is of everybody including Children are fully vaccinated. And here you can see um the data for the uh for the greater for this is for California and the highest eight counties are all Bay Area counties. And then you get to imperial in san Diego. Um So that's all, I think that's good news. We're pushing although it's not kind of surging back up quite like we hope the vaccinations are indeed climbing the problem we're facing is delta. The delta variant. Uh and the delta variant is a big, big trouble. It's become essentially the only variants circulating in the United States and over here in region nine Which includes California as well as Arizona Hawaii, Nevada and the Pacific territories. It's uh 99.5% of all the all the ice islands that have been sequenced. So we've entered a phase where delta is completely overwhelmed everything else and it's not budging. So kind of what's going on just to summarize what's going on. The US there's the rise of the much more transmissible delta variant. Now it's almost 100% of isolates in the US. We have a problem with failure to vaccinate which is far more important than vaccine failure. We have a continued mixing of unvaccinated people with resultant transmission and I was um I saw that the Sturgis, Harley Davidson, annual motorcycle rally happened last last month in South Dakota. So that's probably not a good thing. We have had less than full of adherence to non pharmaceutical interventions. Uh We've had a failure to develop immunity and some immuno compromised individuals and this has led for a recommend led to a recommendation for an additional dose in the primary series of the mrna vaccines. There's some mixed evidence of declining vaccine effectiveness that's been temporally associated with the rise of the delta virus, it's unclear whether that's waning and whether first of all, whether it's anything at all, whether it's waning immunity or whether their escape mutations. And this has led to the whole discussion and a breakthrough infections which are still uncommon. Um But it's uh prompting likely to prompt action at the federal level. This is a study that was just published uh last week in the new England Journal from U. C. San Diego. Looking at vaccine effectiveness by month among health care workers. Um These are M. RNA vaccines so 94% 96% 96% 94% And then 66%. Um in july there's similar data from a number of places that have similar levels of declining vaccine effectiveness. However, um we're you know, we're still seeing most of the cases and people who are unvaccinated and most of the hospitalizations and people are unvaccinated. This takes us up to almost the end of july from Los Angeles County. Um The dashed line there people who are unvaccinated. These are infection rates and the dark blue line is the people who are fully vaccinated And it's actually 454.9 times higher in numbers of cases among the unvaccinated. Uh and hospitalizations are 29.4 times higher among the unvaccinated. And these are hard data from Los Angeles. So I think it's probably consistent with what we're seeing. So the U. S. Is considering recommending a third dose of mRNA vaccines. There are two issues. One is non responsive amongst solid organ transplant recipients and other immuno suppressed patients. And the second is this issue of waning immunity again, we'll have some discussion about that. Um There's a recommendation for an additional dose after the primary series for transplant recipients and immuno suppressed patients immediately. Um And then there's this discussion about a third dose for everyone else, 6-8 months after the second dose after their second dose, beginning on September 20. This would recapitulate the rollout from last winter with long term care residents and health care workers Being vaccinated first, then adults over 70 75 and over in the front line, The central workers next than adults, 65 and over all essential workers and some and some of those younger people with high risk medical conditions. Um Right now there's been opened up. There's an active discussion of whether this should just be for people to receive the Pfizer vaccine only and there's some interesting reasons for that. And meanwhile, for those of you who got J. And J vaccine, we're awaiting the results of the one versus two dose trial uh that they did and I uh at least at san Francisco General S. F. D. Ph has gone ahead and offered M. RNA vaccines to people who had a single dose of J and J vaccine. This is something that's evolving as we're talking. And then finally, where does this put us, this is the institute for health metrics and evaluation At the University of Washington there most likely scenario, which is the Middle one, Which is has 57% of Americans fully vaccinated by December 3031 and that mask uses roughly comparable over time. Um has this, you know, still not coming all the way down. This is these are case counts of, you know, tens of thousands per day. The worst case scenario. This is where where everybody stops wearing masks and the best case scenarios where we can keep masks on people. So we'll have to see how this plays out. This does not include in the models, it doesn't include issues of schools per se, which are a bit of a wild card as to how they'll play out. What I'm happy to say is that at least in my dealings with with a handful of school districts, including large school districts, there is very little in school transmission. Almost all the kids you have been found to be infected have come from um have been infected either in their families or in the community and not on the uh not in the schools per se. There are a handful that are, but it's only a handful. So I'll stop there and happy to hop back on uh when you stay stay back on George and let's bring on eater and Monica. So, and um let me start with you just to clarify its first terrific and sets us up beautifully for a whole lot of questions that will will will come, why does surges come down? You know, you hear talk that you've sort of reached a level of immunity but like really that and then you hear talk it's just fear of God. But like why did that start on that day and then why did the UK go back up? So do you have any good explanation for why it seems like these last 2 to 3 months and they always come down new york times had a really interesting article that said that all these delta surges around two month time frames. They go up, they go down, they go up, they go down uh and there was some population that it might be biological. I doubt that. Um I think that this is really I mean there's gonna be some biology to it obviously, but I think it's also behavioral, you know people wearing masks maintaining you know socially distancing but more importantly getting vaccinated and using this as a spur to get to get vaccinated. So it is what it is. And you know, I think we could go on and delta so transmissible that I think you could easily you know without any kind of if you did no abatement at all, they basically find almost everybody who was unvaccinated and get him and give him delta virus. So I think the fact that it's coming down bespeaks our efforts to control it. All right, let's turn to just say about that because I think it's really interesting to see the cases coming down in like you just showed in California in san Francisco but the cases came down in Missouri first and that's actually where they rose first. They banned a mask mandate. There was no capacity limits and there wasn't actually a lot of behavior change and their vaccines didn't go up that much as we would have liked. They did go up some there is of course a role of people getting infected. Natural immunity bringing cases down India had 4% vaccination rate in early March when the delta variant rose and George I wish it was vaccination. But unfortunately we just didn't have the vaccine supply there to provide everyone with vaccines. There was behavior change but it's 1.37 billion people, a lot of people in close proximity and of course it is a lot of some of it in lower vaccination rates, regions of the surge is coming down as natural immunity. So maybe completely dot there though in terms of Missouri. So if you say people didn't get vaccinated that fast and they get your and they didn't wear masks. So when it comes down, what is your hypothesis about what's going on that essentially there are people who get sick from it and go into the hospital but there are other people who have mild disease and get a noon and essentially when it take it does take some time it takes two months. This happened in India as well but immunity will bring down a pandemic. We all wanted to be through vaccination. Natural immunity you think is some sort of level of natural of immunity through natural infection? And that is why I agree with Monica to to that natural immunity has been underestimated. Maybe it's not as sexy or it's kind of taboo to talk about it. But I'm particularly struck by the contrast between michigan and florida for example, very similar demographics. But if you remember in michigan before the Delta search, they had that huge winter alfa surge with indoor sports. And then now people are like scratching their heads. You know, why is michigan doing so well generally speaking compared to very similar vaccination rate of florida. So that that speaks to that as well. Yeah. Let me ask one of the three of you is getting a lot of emails that's pinging. So if you can turn that off, that would be great. Uh let me start asked peter and Monica if you're anything like me, probably George to. You're getting a ton of calls from friends and family. Some something you've forgotten about and they have a question for you. Like what do I do this happened? So what is the most common question that you're getting from The people that you haven't heard from in 20 years? Uh and how do you how do you answer Peter Do you have one? Yeah. I mean the most common question is for me is should I travel. And I think that's, you know, people are itching the travel. They've been vaccinated. We thought the world would be open and we'd all go forth and counts. Specifically. A lot of people recently with mu in Colombia, they had booked tickets to go to Columbia and they are saying, should I cancel that trip to cartagena? And so I've been getting a lot of questions around that and what do you tell? I tell them? You know, um take your precautions. The level of disease in Colombia is not terrible. Um And it's just because there's mu there doesn't mean that, you know, if you're going to a seaside city, you take your precautions. You use your disease mitigation strategies. I won't necessarily cancel that trip. But again, this comes to like one of the points you're going to bring up, which is how do you live with the pandemic? How do you, you know, manage disease rather than live under uh infection fear. What about, what are you talking about the flight by the way? Are you are you convinced the flights are okay? I think the flies okay with multiple exchanges for uh our but what I'm worried about is the roots to the flight, The gate area, the concessions, the food court, the transport from the airport to the hotel, that's much more, You know, if people really want to be Versant flights sit by the window to non event. Um keep your mosque on for most of the time you're pre go to the bathroom before the flight and after the flight. But minimize going to the, you know the corridor and keep your head in one direction. Keep your head in one direction. Okay, George, who is sticking to say I'm going to say the real answer to your question has never turned down the opportunity to go to cartagena fabulous place. You know, one thing I would say about child being asked me to, you're absolutely right, like totally agree with both of you, that air exchange is excellent on the plane and I actually just because I have an unvaccinated younger child always put the vent on, so that just brings in more even though we're kind of cold and then I'll be a little more Maskey on the plane. So I when you travel on multiple international airlines, you actually need to kn 95. So You know, I think it's important to remember that not all masks are equal, can 95s are good masks um Double master good masks um So are like a two piece of cloth and a filter paper inside, so if he's unvaccinated my younger child and I'm going to be mask you with him. Mhm. So I haven't heard the term Maskey before. So let's get into mass keenness while while we're there, then we'll get, this is going to go everywhere. I need to peel back and talk about you at some point. All right, So you're being Maskey. So tell me what being you were taking a flight to new york a couple of months ago when the case when things were a little bit lighter. You're taking it today and your mask ear today. So exactly what does that mean? In terms of what mask and in terms of your behavior as it relates to the peanuts and a drink. So yeah, a couple of months ago, things were good. Things were so good between our friend and Delta. I'm so sorry the Delta happened and by the way it happened because we don't have global vaccine equity, which we can talk about later. And so so what happened is during Delta flights, I use a Delta flight. So we talk about the airline. No, no, very very clear. Plus Delta is better tv but lights during the Delta era. Is that what you're saying? I think you're frozen for me. Delta is an unfortunate name. It's like having a what do you want to name your airline right now. All right. We'll get back to Monica when she she reappears. Peter. Let me peel back to you for a second then maybe George as well. You so you mentioned it. What is it? Is it a scary into or something we really care about? So, I think from you. First of all it has a greek letter. So that already elevates us above other things like C. One to which doesn't even have a greek letter yet. Um it is a variant of uh interest designated by the w show not a variant concern yet higher level. And then the C. D. C. Hasn't said any variant of interest or consistent very low. All states have reported it as far as I know but much more common and very regional. So like northern part of center of south America mainly Colombia some Ecuador, You know maybe a smattering of other countries, maybe 40 but less than 1% of cases globally so far. And if new and delta went in a boxing ring, delta is going to win. If I had to be a variant right now in 2021 I'd want to emphasize transmissibility over vaccine invasion. Because so far they've only emphasised these variants only emphasize wanting for for gamma and beta. And like mu it's an lambda to some extent, it's like a little bit more vaccine envisioning. But Delta is like so transmissible that it makes all the other variants cower in fear colored the variant to rule them all. So so that the the idea is you might hear about you and maybe it is a little bit more able to evade immunity than Delta is. But as long as Delta is so much more transmissible than it than Delta is going to win the battle and be the main variant that we we see. Is that clear that mu is not that transmissible. You know I mean I think we probably don't know many things about mu but and that's being studied but so far so good. Um You know it's not clear if it's more transmissible yet. Although there were earlier reports in Colombia that it's already cresting and going down. So you know I'm taking it with a small grain of salt. It's clear it's not more transmissible as it never want. Like it's actually been here since january and delta was a little later and it hasn't been able to take it over. You're able to tell because if it was more transmissible because your delta, it's also not only the either the cross sectional snapshot, it's the tempo. So remember in March and May, delta was 5% and then the next month it was 50%. So the rate of increase was breathtaking which we haven't really seen with mu percy in India. We called it a wall. I mean it went it wasn't it wasn't but that's Delta has been out since january. I don't think it's going to rent. Okay, George anything what I had on on you know they're absolutely right. I mean you know the next letter is new in the greek alphabet. Alright. I thought that's that's in the hebrew alphabet but we'll get back to Monica. Uh you were by the way I just while while you froze, I checked Delta stock went down about five points. So when you when you were talking about a delta flight or you're talking you're talking about the virus a flight in the era of delta. Is that is that correct? Now you're on both of them. There we, there we are. Okay. Monica's ubiquitous. It seems incredible everywhere in one square. Why am I your Maskey? So why are you more Maskey? And what does that mean practically what are you actually doing? Yes. So I did fly in both times and I was, everyone was happily flying with the less Maskey between alpha and delta. So why have a couple of reasons to be to be more A conscious about the type of vascular right now. No one delta, you know, it's very extreme if you're have 60,000 people come in at once and have a lot and all the windows closed and have a lot of intimacy and have no masks and there's mixed vaccination and unvaccinated people, which is the provincetown outbreak. You could have a high breakthrough infection rate. That is as stressful as a situation on the vaccines that you can get. And no one, no one, there are seven hospitalizations. They all did find luckily no one died and it really is a stress test of how well these vaccines are working against. Um, it's severe disease now in normal circumstances where you're just doing what you're doing and you're not going inside and doing All of that with mixed vaccinated and unvaccinated. The breakthrough rate is, I mean, I know, you know, we all saw this New York times article, but it was compiling data from Utah from Virginia, from Washington State. And the breakthrough rate will always depend on your region. So higher rates of community transmission of higher breakthroughs. But it's one in 5000 and high incidence regions, somewhere like san Francisco one in 10,000. So, uh, today. Right, right. And as our cases have gone down, that will go down and so you have to decide what your level of comfort is without risk. I, as a health care worker actually have very little comfort with risk because I, because I had to go to work. But uh, if I weren't a health care worker, I was very comfortable with my parents being here with that low risk um, that they had, they were just here last week. But what we do inside is we do masks that are really been more proven to work. So, um, there was a large cluster randomized village level, uh, controlled trial. The Bangladesh RCT. It was performed among today. She was just in pre print last week. But the reason it was important as a compared cloth mask to surgical masks in a population level. So It's hard to tell like who knows everyone who's wearing it. They tried to increase use. But at least those over 50 were protected from symptomatic infection, but with surgical masks not cloth masks. So I would use a surgical mask. And actually bought these pink ones because so tired of blue. Um, and then, um and then if I really was in a high stress situation, like inside around a lot of unvaccinated people, I would actually put two together. I would put the this together with a cloth mask. We have done some research on how that really blocks out virus more or take a cloth mask and put filter paper inside of it. They're super easy to get on amazon. And you have two different mechanisms are repelling the virus electrostatic from the, from the filter type paper polypropylene material and then the cloth is a physical blockage. And that's what I do on my unvaccinated child on planes during delta. So just to be clear cloth close to you as a 60 surgical on your face, cloth, tight fitting cloth on top of it. It can be actually either way and I actually prefer the surgical on top because then I can reuse it because I do wear lipstick. Um, and um, and I, and sort of environmental concerns. But it's really the principles behind two things increased fit, so closer to your face, you would also tuck in the surgical mask and increase increased filtration by the two layers. So one of our colleagues has famously been writing about the concerns about the level of evidence from asking and some concerns about arm that mass can cause and kids, can somebody address whether they have those concerns. Do you wanna start or them to give it to me? I was like, and jorge being the first to our only, our only pediatrician here. So just having been on the American Academy of Pediatrics website this morning to answer this question for Buzzfeed, um, they say it's almost no situation. I mean if you have to be over two, okay, if you're if you're under too, there's a suffocation risk. Okay. Okay. Okay. We give you that one. Um, it's certainly some very developmentally delayed Children may have similar risks of suffocation, but for speech or language impairment, no evidence. Um, for Children with marginal lung function, no evidence that they harm you in any material way? No, no harm and not get not getting this disease is a huge help. Just to be fair though to those criticisms because I really do want to be fair that a lot of what this is based on is that let's please remember that the UK europe do not mask Children under 12 and the W H. O do not mask Children under five. So when various practices occur across a world, it is fair to question, do Children need it as much as adults? Even in the Bangladesh RCT was adults who benefited for symptomatic reduction in covid overview what's your what's your bottom line on the state of the evidence around kids and masking. So that mandatory, this sort of goes into the issue of mandatory masking in school. You know this is my bottom line on it is that I think that I want Children back in school. I don't think I've ever made a secret about that. And because of that I think it's best to have masks in school because I don't want distancing. Which is what why the California t. Ph said everyone masks when delta came out. Um And uh no distancing because that's the least effective of our strategies. There are theoretical benefits of course like just like sorry to use the word condom in the same word as school but condoms we've never tested but we know that condoms um you know block transmission. So there's physical science reasons to believe it. And um and I just want Children back in school. So I think I'm asking right now is totally totally valid. I do think that we need metrics to remove masks. Were mixed society. Not everyone loves their Children masked. And metrics that are based on how communities are doing is the right thing to do to remove them. Not just the metric of Children being vaccinated. And I also believe that we should be fair just like we were just fair about natural immunity. Peter we should be fair about what happens in other countries and acknowledge that not say oh it doesn't matter that other countries don't mask Children were the right people. We should acknowledge that variability. I mean I think everyone's talking the same thing which is that there are multiple strategies to protect kids in school. Now if the U. K. Is not masking they're doing other things much better than we are in lieu of not masking. So they're doing quarantining, contact tracing. A lot of testing in the U. K. We can't really have enough tests to deliver that uniformly. So I think when you read the headlines, U. K. Is using mass and schools, it's because they're using other uh disease mitigation strategies and it's you know to me it's all about swiss cheese. You have generation, you have sure if you can distance your desk, that's great. Um but if you can do robust testing, contact tracing and quarantining like the UK does, you know the mask is is relatively cheap and expensive and kids actually, from what I understand they wear it and they don't complain. Um That's what, okay and just to be clear minded when you talked about condoms, you're talking about HIV and you're talking you're not getting a condom over your face. I just really like that's why I was like eating doing that. We're mixing uses here. Never had an RCT of condoms because it's just basic common sense that George take in terms of peter mentioned the idea that other countries are doing more testing uh why are we not? You know I'm hearing reports out of Austria and Germany that it's you know there is absolutely ubiquitous. You know, Anderson testing everywhere you walk into the gym, you walk into the school, you walk into the supermarket. What's going on here to make that so hard? Well I mean other countries like Los Angeles test kids every week to go to go to school. Um uh And the U. K. Does this sort of modified quarantine? They have another word for it but they basically test kids every uh you know once every day to keep them in school. I think it's something exposed just to be clear if they've been exposed. Yeah exactly. Sorry? Yeah so I think it's I think it's something that we're uh you know that we need to use more of um I got a note today that to the state just ordered another seven million doses of seven million been ax now gets uh so we may have the supplies to do it. I think it's just been underutilized and we need to push on it some more. And if you were having a testing strategy for the schools or for your workplace what would it be? Would it be pcr would be the androgen would be twice a week once a week every day how would you work on how much money you have? Right? You know it's you know so if you're the balance you know nobody is unlimited research balancing resources with what you think is good enough efficacy to make a difference. What would I think that I think an engine testing is the way that is the way to go. And I'd probably do it two times a week or every, every, you know, every three days like that. I mean to me it depends on what else you have going on. So like at stanford they're doing and Jorge knows this because we want to talk to us together, but in Sanford they're doing once weekly testing I think. Um but they also have a vaccine mandates, so if you don't have anything else then you probably have to do more frequent testing to kind of be more reassured. Uh in general, I'd really like to agree with what you just said peter because I just do want to point out that san Francisco department of Public Health just put out data 33 minutes ago. Um that was breaking news that show really low rates of transmission in schools, just like George and said, even as we have started our schools august 16th was the date of um school opening here in SF USd, they don't do a symptomatic testing which is a decision that you made because of the, when we get into lower prevalence is you have a false positive rate. What they're doing is that they're doing the quarantine kids if they've had an exposure, what the private schools are doing right now is because they have plenty of been x, they will call test to stay, which I think is a really important strategy that if you've been exposed, you get an urgent testing. So to be able to stay in school and unfortunately SF USD has not yet done that and they're keeping kids out of school for 10 days. What I'm really hoping is that they'll take the seven million tests that you just said from the California DPH and please use test to stay strategies which are really successful around the country, boston's doing it, trying to do it at least UK has been doing it. We've had an exposure start by asymptomatic. Now exposure you test to stay. Yeah, I would like to ensure just one last thing, I mean that whole essay cluster randomized trial from the UK um situation is that one of the things that we do have, the reason why I think it's been so amazing in schools here is because the adolescents are so highly vaccinated too. So you have this a bigger wall of immunity around the kids under 12 in SF versus like many other places around the country Where they're doing less than 50% of the adolescence, whereas In SF It's like more than 90% can you really get and teacher mandate to manipulate for vaccines. I mean, I know you can test out, but that's essentially as much as you can trying to go towards a mandate for teachers, which if any, where there's going to be a mandate besides healthcare workers, it seems like that's where it should be and this this test to stay strategy. I mean, one of the things we're running into in healthcare workforce is we're telling people you have a sniffle, you got to stay home. Should we be going, should we be doing antigen testing on people and you had sniffle? You do an androgen test? If you're negative, it's okay to work. We need to stay at work. I mean that there was some real problems when we had some breakthroughs here in the general. So I mean that test to stay strategy and right now, what we're going through delta in any situation is a great idea and it doesn't need to necessarily be an issue testing. You have all the money in the world. You can do pcR testing. That's fine too. I do like an agent for the reasons you said that essentially it's more likely to say you're infectious, which is the entire point of why you would keep someone out of school is they could be infectious because a PcR test will give you one dead virus in your nose, remember that? And also it's cheaper. It's, you know, right away that upscale. Um, and yeah, and point of care, okay, let us switch to vaccine efficacy. Is it waning. Is it waiting for symptomatic isn't waiting for severe waning differently for Pfizer Moderna J and J for natural infection, a lot of stuff to cover and then we'll obviously get boosters. So somebody want to summarize what they think the literature shows in terms of is the vaccine efficacy waiting for both symptomatic and overall infections. George you hinted at this a little bit what anybody else want to weigh in on their take on the literature. I I can do this quickly. Is that I think that in general you have to divide it into like you said severe disease and symptomatic disease where you can get like a cold or flu. So let's go back to severe disease. I think the data is very consistent that that we are not having waning effectiveness against severe disease in general. And that means from the UK Canada the US there was a C. D. C. And new york study 20 time 200.2 times more likely to be hospitalized if you're in L. A. So lots of really unvaccinated people being in the hospital not vaccinated as much. So I think we have a good severe disease actually maps onto one arm of our immune system which is T cells and they tend to stay up for a long time. So then what's going on with more breakthrough infections? Um I do think the Pfizer vaccine because it was given three weeks apart at least in one study in a jam study comparing to Madonna had lower antibodies than Madonna and it could have been that shorter interval let alone Madeira is three times the dose. And then um and remember Israel where we're seeing most of this waning against mild disease only used fighter and then there was a Mayo clinic study that said that people who had more reinfections in the male clinic system if they got the Pfizer than the Madonna vaccine. So I think that three weeks apart, maybe too short. I think a lot of vaccine ologists were saying that even at the beginning you said that bob. So because of that it's possible that um that if you have the Pfizer vaccine you may be more likely for a mild breakthrough which is I think it's prudent to put back masks while we're in the delta surge in the inside setting. But whether we need to boost or not, I know we'll get into that. But I will say that mild and severe are different and they're armed by their protected by different arms of the immune system, antibodies from resells protect you against mild disease and they do wayne. The time is totally natural to what the immune system does. Those you'd be too you couldn't move have too much protein. And so it's normal for that to happen. And it really is mild disease, that severe disease being protected. So we have to talk about that. Okay, anybody want to add anything or disagreement. Yeah, I mean I I agree with Monica and I mean for me that data is very robust no matter how you slice and dice the pie that severe disease hospitalizations and deaths are spectacularly prevented by the current vaccine strategy. I am very intrigued by the idea of interval between doses and of course um you and the audience will probably remember that in the UK they they had no other choice but to delay the second doses. And they retrospectively looked at people who got the delay, those wishes people got in time and at the time I didn't really know what to make of the data because it was antibody levels. But they showed that the people who got the delayed had higher antibody levels and the people who got in the schedule. Yeah. Okay. So, uh, if you told me, so I'm 63 year old guy got fighter eight months ago. Um if you told me I could go to the Walgreens and get my booster. Now I would leave this call and get it because I still don't want even quote mild disease because it's quote mild disease that you know, you lose your sense of taste or smell for a month and you feel like garbage for several days you can transmit the infection although at a lower rate than probably lower rate than an unvaccinated person. Um, we don't know the probably of long covid. I'm Monica made some comments about what that is and maybe we have more information on that. I don't even want mild disease. If I can avoid it. When I hear people say the vaccines were never designed to prevent mild disease I don't really care what they were designed for if they did it before and they don't do it anymore. I want them to do it again. Unless the treatment carries some risk which as far as I can tell. The third dose carries next to no risk. So talk me out of why I should stay on the call if I got a call from Walgreens now that I can get my third shot right now. Monica. You wanna tell me why that's not the right thing to do? I think. Yes. So I think that it is a couple of reasons. So one is that essentially If you get your possibility of getting a mild breakthrough infection depends on the prevalence in your area and one in 10,000 is very low right now in San Francisco and uh and that will go lower with time as the case is coming down and it's just a temporary fix because it's really just treating like the antibodies coming up in your nose. But they're going to go right back down again. And what really matters is what's called your memory, your cellular memory, your B cells and your t cells are there. We know it well like biopsy people's lymph nodes and bone marrow and we know that these memory B cells are there. We know the t cells are there and if you see the virus again you'll fight it hopefully and your antibodies will come right back up. Second reason is really and we have to be fair about this right. Um When dr Tedros from the W. H. O. Reiterated yesterday um that please don't get third shots to rich people while we are waiting for just at least get 40% of people vaccinated in low income countries. He's speaking to the fact that 2% 2% of people in low income countries have been vaccinated in sub Saharan africa. And you can just argue that what you just said is saying you get a third shot americans get a third shot to prevent a cold. But there are people who are dying every single day in massive amounts because we have no global vaccine equity and the U. S. Is sitting on upwards at that by the end of the month of a billion surplus doses. It is geopolitically I just can't imagine how that's going to look for the for anyone. Um If we do this. And then the third thing that I really want to say is that and I can wear a mask right now prevent myself from being around someone where I can get a mild breakthrough. So I just need to wait a couple more weeks until those cases go down more and then it's going to be one in 40,000 chance. Um And finally again don't treat I would just take those severe breakthrough infections or 7000 in this country out of 173 million fully vaccinated figure out the demographics it's so easy. Are they all fight your patient Then give a divisor people? Are they all immuno compromised? Are they all 63 and otherwise healthier they are they 70 and have to medical conditions start with that group. And if they need to be in long term care facilities, older people immuno compromised people, multiple medical conditions start with that group while we're sorting it out. I want to share some thoughts on Monica's comments um as well too. And you know I'm sort of mixed about the booster shot. On one hand there are lots of other disease vaccination paradigms where we do a prime and boost and the prime is zero and one month and then the boost is like six months at six months, hepatitis B HPV etcetera. So it makes kind of sense biologically. But then on the other hand I'm looking at the data so I can I think it all depends on if you want to be proactive or reactive right now we're looking at data and everything looks good, you know, is that slide waning. And the older population for severe disease and hospitalizations and death in Israel Maybe 91% vs two in the 80's if you believe that data which hasn't been peer reviewed in the older population. Um you know, are we gonna do you know optimize immunization and that group nursing home residents, older individuals. So they don't get into something in the future, maybe that might be the solution. But regardless, you know, I agree with Monica about the optics, even though we might have enough vaccines to kind of, let's just lay out boosters for all. And I felt this way also because over the weekend, the Israeli Minister of Health started talking about 1/4 booster, 1/4 shot um, for the future. And maybe the green, the green past might expire after two or three doses and they could program it that way. So I think that gave me some more room for thought because again, if you think about antibodies going down to protect against mild disease, you probably have to get a boost every six months to really keep that up or develop a nasal vaccine. Yeah, George any any thoughts on this? Well, I mean, there's some enlightened, you know, there's there's global equity and there's enlightened self interest. We have a border with three million people who live on it, who are all unvaccinated. You know, that would strike me as something that would be within our kind of our purview to want to take care of that little problem before we start passing out their doses to people who don't really need them. Um, so, I mean, I think you can I mean, the global help, The global equity thing is fine and I fired Dr Tedros, I'd be saying the same thing, but I think if you want to look at from a purely us perspective, there are countries from which we have tremendous amount of immigration, including Haiti and the D. R. And Mexico. And you know, we should be helping them with their vaccination programs I think. And that's what really directly within our self interest I guess I'm still struggling with a couple of things. One on the equity side. You know, you could see the arguments quite clear morally. But same thing is true for the way we manage hypertension, diabetes cancer. We don't we don't say maybe we should that you're treating this cancer with this very effective, incredibly expensive chemotherapy and you're not doing that to people in India africa. So obviously the argument is somewhat different here that that somehow it's in our self interest at some level or in the world's interest to get everybody vaccinated? That's different than treating everybody's cancer. That's true, right. With the global pandemic. That's true because A variant will emerge like an emergent India with 4% of the population vaccinated, it will emerge elsewhere. So take morals and ethics out of it. It's a it's a public health imperative, don't you? I guess the question the question is is it really are we frame we're framing or versus and you know, we're talking about a billion extra doses, you know to to to use 100 million of them to give high ish risk people a third dose. Are we really in a material? Is this a symbolic act or is it really materially Going to change the nature of the risk of a variant over the next year and if I would give all 60 year olds and Mr 16 because that way we think it makes me feel better, obviously it's not all that I see myself as a sort of reasonable test cases where we draw the line, that's what that's what Israel did was really kind of mean that like I mean like draw a line because number one level looks really strange from the administration FDA saying one thing and one thing, it's embarrassing like we need to come together and just draw a line, if it's over 60 then do that and that kind of you get it all in that way, you know? But the line is it's got to be some what's the evidence behind the line. The line is that there is a risk level of a certain population, whether it's comorbidities or age or whatever that does say that the risk of a breakthrough is meaningfully can lead to a bad outcome in some way at a higher prevalence. I mean part of what persuades me here is that we're talking about something that is very low risk and very low cost and and you know, and so it has a different feeling trying to sort of figure out why not give it to people. I understand, but when I hear people say, you know, we should be concentrating. Sometimes I make the domestic argument, we shouldn't give it to a third dose for persons already been vaccine. We should concentrate on giving it to the unvaccinated. Trying to figure out like what does that mean? Like what are we haven't been concentrating on that for for six months but it's like bob. I do think one thing to not lose in the shuffle here is that you know, people who are immuno compromised your solid organ transplants need a third dose period over four. So they're gonna need more. Yeah, they need 1/5 peter, what is the evidence in terms of them getting their third dose and meaningfully creating how well is it working there too. So uh groups of evidence right now more studies are being done, one from France and then one from the Hopkins group, there's also one in University of Toronto, but essentially after the, if you are not supposed all about 50% of people who are more severely meal compromise with develop an antibody response and of those unvaccinated people if you give them a third shot About anywhere from 30 to 50% of that group will respond. So again, there's you know, 70, 50 to 70% of people who may not respond even after a third shot. So that's where the interesting idea about using monoclonal antibodies as bridge in some individuals might be interesting as well. Okay, we're gonna run out of time. I want to get to cover a few other issues in terms of efficacy and boosters. So how about Moderna? Let's say. Monica has agreed that it's over 60 let's say is the number who got Pfizer based on what we know about Moderna and some uncertainty about what the third dose should be. Should we hold off on them until we figure out what the right doses. I think we're trying to figure that out now. You're right. They're debating between 100 and 50 micrograms. The dose for the first two is 100 because there are two possibilities five indiana had higher antibodies and also the lower re infection rate in the mail client system which is the higher doses three times as high as 30 micrograms which spicer or it is that longer duration, Even one week makes a difference. Um and I think that I fundamentally have you ever had a vaccine that's three weeks apart. There's not a single vaccine, the only one month is minimum to prime the immune response. So I think it has a lot of duration. So to me it makes it seem like maybe it doesn't matter because when you get the booster fighter it's going to be waste based out from your second dose. But the madeira is interesting. There is some data that it really produces long lasting cd eight cells over time. So I kind of like Madonna. I got fighter. So what are you saying that Moderna might not need it because it may be produces longer lasting immunity either because we gave you a bigger dose than you needed or we spaced at an extra week. That's the question. I mean because when we can talk about antibodies and B cells and T cells. All right. But we really want to look at re infection rates. That's the clinical outcome. That's of import. Um, and that's why I'm asking everyone is asking the cbc please take those severe breakthroughs and tell us that they're all fights are tell us they're all johnson and johnson because johnson and johnson people always feel that they're being left out of the time. So let's let's get out of them are. So at this moment, if you were a modern a person, let's say you're 70 and you're you are at higher risk And the fighter people have gotten their vaccine boosters endorsed. You would say based on what we know now, I would hold off on moderna partly because you might still be better protected and partly because we don't actually know what dose we should give you. Is that accurate? Peter is that where you would be? No, I actually would. I think if you will in 60 and there's a booster approved. I might tell you to just go ahead and get it because I'm not sure when that data will come out and we're in the middle of get the and you get you get the original dose you get the third full on does even though it might be more than you need. Okay J. And J. Everybody with J. And J. Is like feeling like nobody's paying any attention to me. So so what should they do? And I you know there's a couple of weeks ago it seemed like it was a no brainer that if you got J. And J you probably get an M. R. N. A. And then a study did come out at least preliminary saying the second dose of J. And J worked pretty well. So what should a J. And J person think and do let me start with Peter. So I think one interesting study that didn't get a lot of press was a J. And J. Study looking at it was very small 17 people and and they followed them for six months and it was interesting because the antibody levels were it was horizontal. They didn't decline like Pfizer or Moderna. I thought I was very intriguing. And then of course there's a change. A study showing that the second shot uh increases antibodies. But that's not surprising. I think if I were J. And J. Person um you know I would I would uh you know do I would feel like what uh you know jangers probably many people believe J. And J. Is really conceptualized A two dose vaccine series not as one does. And that was mainly Pragmatic. Um so I would I would probably want them to get an additional dose depending on who they are. Especially if they are over 60, you would get a second dose of the J. And J, not an M. R. I know I would get any dose as a second dose but I'll get a dose. Um You know, there is mixing and matching studies that didn't talk about not J and J but with astrazeneca and it was you know, it was safe and effective. I'm getting this question all the time. So when I get it, because I don't know anything, I'm going to tell them what you told me. So, if you got J and J is your first dose and you're over 60 let's say, would you say you should get a booster? And they say, all right. Which of the three should I get? What would you tell them? I would tell them to get an M. R. N. A. Just right now from what I know, I mean, the M. RNA vaccines give you a code for more of a spike protein than J and J does. But again, that's more not not based on clinical data so far. And again, more speculative. But And then I know that mixing and matching is safe. You had to get one thing is one thing to wait on is the ensemble to which is the two dose johnson johnson, we're going to get there saying get data at the end of this month that is the two dose and it will be have been conducted during delta. So I probably hold out and wait for that. You tell them to wait for a second George. Anything you can do both, you know can hold you can hold out and get the M. RNA vaccine while you're holding out. Right? So there you go. All right. And and then maybe final question natural immunities. Some studies have come out and said it works pretty well. So how long is it working for? What are we seeing in terms of waning immunity for if you had your prior infection, let's say in 2020. I think the best study for me recently comes from Kentucky where they looked at people a year ago. In 2020 we got regular covid and they follow them in the same database. And if you were vaccinated you would, you know, or if you were a vaccine you were twice as likely to higher odds of getting re infected with covid. So what it says to me is that yes, you could get reinfected if you even if you got it before. And then number two um your your you know vaccines rule. But we knew that already. Um I think reinfection is not that commonly described. But at least in this Kentucky study. It's definitely a thing, there are some studies that illustrate that maybe it last year but there's 1000 full difference in some studies. And one individual response was this another two natural infection? I think some people, some people have a good some people have a vigorous antibody response and some people not so much and you don't really know who you are. So you could be at reasonably high risk. Just just just to be careful about that Kentucky study that may be on the list of how not to do case control studies. Because I was going to say that I wouldn't pull that out as the only study. There's plenty although it's quite compelling, I'll give you that. No, I mean to be really fair you have to look at the signs of studies in prospective studies. Some even show reinfection Rachel lower after natural infection. So again let's be fair. You really want to be fair when you present because then you'll be more trustworthy. You don't want to pull out like the badly done studies. So I would just say I don't think we know but I get one dose and that's my recommendation because there's so much data that you had a document if you had a documented prior infection based on what you know to you get a single dose of an Mrna Yes and that's what italy Germany spain France are all doing and they're smart. They think about immunology, they've been doing it for a long time. It works alright. We're out of time but I can't I can't help myself. We can go over minutes to just just last question, tell us what the six months life is gonna be like, you know, it's sort of the end game now is so hazy and you know, is there gonna be another surge coming or in the Bay Area are going to reach a point where the immunity actually is high enough to beat back Delta. What do you think? What are you telling people about the future? Uh George go ahead. Sure. I mean, I'd be um I think that it's I'd be curious what Monica and Peter think about whether we could see a works very any more transmissible variant the Delta. There are a finite number of amino acids that can that can substitute. I don't know kind of mechanically whether that's really going to happen or not. Um I think that well we we can reach herd immunity. Herd immunity remembers are not -1 divided by our not. So that they are not for Delta six. That means you have to get to 84% of everybody at least everybody over six months of age. Um So it's gonna take some substantial amounts of pediatric vaccination to get their Monica is absolutely correct. You have to add in the and peter to you have to add in the natural immunity unclear whether that wayne's or not, but it certainly seems like there's a wall and East Los Angeles and stuff where there's uh we're not seeing kind of ongoing outbreaks of disease. So I think that you know I think we're getting pretty pretty close um and I would if I had patients with we had prior confirmed disease, I tell them to get a single dose as well. I completely agree with that. But the point is if we can get to 85% immunity and real lasting immunity, you know, either from vaccines or from primary infection and it hasn't waned. You think based on what we know today that will be enough to exert considerable back pressure on cases and prevent a big surge in the future. But you're still worried about the next delta. That's even better than delta delta plus. Yeah. Yeah. But it's miller time then bob. Yeah. Right okay peter, what's your take on the future? Um You know, I agree with George. I'm probably a little more slightly more pessimistic that we won't necessarily reach herd immunity because we all borders, the supports in there. People moving in and out of san Francisco all the time and you know, I just don't know where they're coming from. I'm hopeful that that's the case. I I do think that this winter and particularly is going to lead to a lot of confusion with diagnostic tests because you're going to have influenza or Covid potentially or Rsv and you know you could have you know bypass that sniffle before if we still are seeing covid uh and and that will be very confusing to a lot of people but I'm also optimistic. Um and you know, if anybody is going to do it, we are going to do it in the Bay Area. Yeah. Monica. What's your last word? Yeah, I mean I always think about HIV and how it gets hemmed in by its mutations. I think really important principle of evolutionary biology's like what George said. You can't keep on going. You can't keep on going. This is a really transmissible variant. I am very hopeful that this is that variant that was the most transmissible. It's going to give a lot of people immunity who declined to get vaccinated. That's not ever how I'd want people to get immunity but it will. And I'm actually pretty hopeful. I don't think we're going to eliminate it ever. I'm sorry. It's going to be endemic but it's going to be low grade sitting in the environment outbreak here because this group decided not to get vaccinated of severe disease but it's going to calm down and it's gonna be this low level virus and I think this is going to be the last of it. All right. Well I hope that turns out to be right. I have to remember our conversation in May where we had a similarly optimistic outlook and the delta came along. So obviously this thing has to continue to humble all of us this time has gone on and uh, but let's let's keep our fingers crossed that we are getting to that level. Thank you the three of you. Fantastic and interesting and honest. And uh, you know, this is the best information that people can get out there. It's not perfect because information continues to evolve, but really appreciate you sharing that with us. Thank you to my team putting this together. You see them listed up there. We'll be back next week for non covid grand rounds. We'll do a clinical case present region, which will be fantastic with Robbie Gaia and we will go on from there. This will be posted on Youtube tonight. For those that didn't get a chance to watch, stay safe. And we will talk to you next week.
