Homeroom with Sal & Tom Inglesby, MD - Tuesday, September 8
Welcome to the Homeroom livestream. We have a very exciting conversation planned, but before we dive into that, I'll give you my standard announcements. First of all, just a reminder that Khan Academy is a not-for-profit organization, and we wouldn't exist without philanthropic donations from folks like yourself. So if you have the time and the generosity, please go to khanacademy.org/donate, and gifts of all sizes make a huge difference.
I also want to give a special shout out to several organizations that have stepped up over the last few months. Khan Academy was running at a bit of a deficit even before COVID, and then you can imagine, our traffic has been 2 to 3X of what it typically is. We've been trying to accelerate a whole bunch of programs and content and ways to support teachers and families, so special thanks to Bank of America, Google.org, AT&T, Fastly, and Novartis for helping us fill that gap. But we still are running a gap, especially for next year. So any support that can be provided is very much appreciated.
So, with that, I am very excited to introduce our guest, Tom Inglesby, who's the director of the Center for Health Security at Johns Hopkins University. Good to see you, Tom.
Great to be with you, Sal.
So health security seems to be a very relevant topic right now. (laughs) And maybe a good place to start, you know, I don't want to be flip about a serious thing. Where are we in your mind in this COVID journey? We're obviously six months in. People, you know, I remember, back in March, people kinda like were saying, maybe it's just going to be for a month or two, and then it's back to normal. Obviously, that hasn't been. How are you looking at it?
Yeah, I think, I mean, we're in the middle, I would say. We're definitely not through it yet. I think in some places in the country, we're probably still at the very beginning because the number of people who have antibodies to the disease is very low in some places, particularly in counties that aren't very populous. In some cities, they've really gone through it, like New York City. There are some parts of the city which have really experienced terrible disease; maybe 40, 50% of the people have been exposed, but that's a real exception. Most of the country hasn't been exposed. Most of the country is still susceptible to this, but the numbers are coming down slowly in the last month, and I'm cautiously optimistic that if we continue to act in this way and don't completely change our behavior once September starts, that we could keep moving in this direction until hopefully we get a vaccine.
And before we jump into vaccines and even possible therapies, I would encourage everyone watching, please put your questions on Facebook and the YouTube message boards for both myself and Tom. I will ask as many of those questions as possible. And we're gonna be talking about, obviously, this COVID journey, vaccines, therapies, and also just how does that interface with how we live our life, especially in things like university campuses, which Tom is also an expert on.
Before I even jump into the vaccine conversation, you mentioned at the level of antibodies in the population being very important. Obviously, antibodies are things that can tag pathogens as they come into the body so that your immune system can respond to them. Does COVID work the way that many other things do? I've also read things that, you know, people might think that the antibodies might not last, or they might not be as robust as necessary to, even for someone who's had COVID, you know, they might be able to get it again.
We don't know enough about it yet to say. I think that's an important, very important point. We have some studies that say that people are protected at least as long as four months, but in practice, we've seen, so far, very few repeat infections. So I think four months, three to four months, is probably the minimum for most people. The maximum level of protection might be pretty long; we just don't know yet. We haven't had enough time to study it. But it's a great point; we don't want to give people the impression that just because their antibody test is positive that they should be fully confident that they are immune to it. We don't know that for sure. We do think it probably provides protection, but we don't want to be overly confident this early in the science of the response.
But that sounds quite hopeful. As you mentioned, there are very few cases, there are a few, but very few cases of repeat infections; it seems like at least four months. And you know, this is all about your point earlier about the antibodies being a sufficient number of people having them in a population; it's all about this herd immunity at some point if enough people have it. So, going on to vaccines, which is, I guess, one way of getting people antibodies faster or in a broader way, where do you think we are on that journey? You know, you hear some places like Russia, and I think we've heard out of China, too, that they've been administering some form of a vaccine. There's talk in the US about potentially accelerating some of those. How do you think this is going to play out? Do you think what we're hearing out of Russia or China is real and credible, and do you think the US should accelerate those types of efforts, or do you think it's gonna play out slightly slower?
Yeah, I don't think we should accelerate what we're doing in the US. I think it's difficult to know what's going on in China and Russia because there's not a whole lot of information being provided about how they're using their vaccine candidates. I think Russia, there's a study that's come out that shows some early evidence of blood markers of potential immunity, but we don't have any real clinical data; we don't have the results of clinical trials yet from Russia, and the Chinese clinical trials we know some about, but we don't know enough about. So, they're presuming, if they, in truth, are actually beginning to vaccinate a lot of people, that is something we wouldn't do in the US. We would proceed more cautiously.
In the US, the plan is to—right now, there are three candidates that are in kind of the lead in terms of being furthest along, and they're all three, in the middle of large phase three clinical trials, which is the important, you know, kind of final, important phase of a trial. If those candidates look like they're safe and effective at the end of those trials, that's when we would begin to start using the vaccine on the public, but not before that. It would be unsafe to do that beforehand, and the US won't do that. I have confidence that the US won't do that. There is pressure on the system, you can feel it. If you read the newspaper, you can see that there is pressure to move as quickly as we can, but I do think that the regulatory agencies are gonna follow the right path and make sure the trials are completed and we know it's safe and effective before we use the vaccine.
And I really want to understand, I want folks listening to understand, kind of the pros and cons of this. So where we are with these three potential vaccines, and it seems like there's many coming down the pipeline, is we're entering phase three. Phase three is these large-scale tests to once further validate that people are getting antibodies, that they're actually getting immunity in some form or protections against the virus, and that it's also safe. What do you see as the downsides of, let's say, you know, several of these phase three trials, I believe were already, you know, several weeks into it or a month or more into it? What if they're already seeing, hey a lot of antibodies, and we're not seeing people have some weird side effects; what is the negative of moving forward with them?
Well, the negative is that we could, people could have very serious adverse reactions to the vaccine. I think early on, these trials will include up to 30,000 people each. And we know from other vaccines that serious reactions from vaccines can sometimes occur at a frequency that's much less common than one in 30,000 or one in 10,000. Sometimes, the more serious vaccine side effects take many people to expose, and so it's really important to be careful and not to make judgments on the basis of a few hundred people or a thousand people and to get as much vaccine safety information as possible.
We also could have a signal early on that suggests the vaccine is working, but when enough people are studied, it becomes clear that that was a matter of chance. And we certainly don't want to begin to vaccinate a large number of people with a vaccine that doesn't work or isn't safe. And so I think there's pretty strong unanimity in the public health community that these trials are moving along quickly. Hopefully, they will begin to show the results over the course of the fall that show that it's safe and effective. And then we can get onto the business of vaccinating, but we shouldn't be doing that before. This is a vaccine that will go into potentially millions, tens of millions of healthy people. And so we really gotta be sure that we know what's in this vaccine, we know it's safe, and we know it's gonna work before we move in that direction.
I mean, it makes a ton of sense. I mean, have there been cases? I'm sure there are, 'cause phase three trials are designed for this purpose where things looked pretty promising at the early parts of the phase three trial. And then as you got into month three or month four of it, I don't know how long they typically last, but as you get into the later stages of it, they say, "Oh, wow," you know, "one out of a hundred people are getting XYZ."
Yeah, sure. There've been plenty of cases where it took some time before the adverse effects began to show up. In the way, one good part of trials or one really important component of it is something called the data safety monitoring board, which has set up at the beginning of the trial and which peaks into the data somewhere along the way. And they decide ahead of time. Once we get our first hundred cases of COVID in our study participants, we're gonna peek into the data, just this small group of people. And we're going to look at it. If it looks like the vaccine is so effective, that it would be unethical to continue that it's just, we need to give this vaccine to people. It is so incredibly effective and appears safe. They'll stop the trial, and that'll be the end of that. And then we'll move on to, you know, FDA deliberations and they'll review the information and move on.
Similarly, if they look at the data, the first 100 cases of COVID that occur in the trial, and they say, "This is really unsafe. There's a safety signal here. This is not working as planned." They'll stop the trial. So we do have a check along the way to make sure something isn't so overwhelmingly favorable or overwhelmingly unfavorable. But if it just looks like the study needs to continue, it's not at one of those two extremes, they'll close the data back up. They won't say a word about any of it, and they'll let the trial continue. And then we'll look at the results when it's completed. And that probably will be sometime this fall. By the time there are enough patients for this trial to work, enough people have to get COVID, and we have to see whether those patients were people who were vaccinated or people who are unvaccinated.
I mean, it makes a ton of sense. I mean, so what you're saying is there's a natural mechanism within the phase three trials that if something is just looking amazing, and they'll just weigh that against kind of the public health of not acting. It's a natural mechanism that is, you know, well established in the scientific community. It doesn't have to be kind of forced.
Yeah, it's built into the trial. Yeah, absolutely, it's built into the trial ahead of time. They understand, they know the statistics ahead of time, they've thought about it. So they peek into the data. There's a committee, which is external to the FDA, it's not part of the companies. It's a group of highly respected scientists; they look at the data together, and they make a judgment. And then they will either stop the trial, which occasionally does happen. Something is so overwhelmingly positive or so dangerous that it will be stopped, but most likely, the trial will continue, and we'll get the results at the end of the phase three study.
Very helpful. There's a lot of questions coming in. You know, this first one, I think it may be as the other side of what we're talking about. We're talking about it's important for us, you know, to take the time to make sure that the vaccine is safe. There's the other side where people might, we know some people are afraid of vaccines, even when it is deemed safe. So this question from Facebook, Rosana Ground Intellect Villaflor says, is there any possibility that a vaccine can still make someone sick with COVID-19? I guess there's two ways to interpret that question. Can the vaccine itself make them sick or can someone who's gotten the vaccine later get sick? And then there's a second question. Well, let's just say they're, you know, so what is the mechanism? I know there's multiple ways that you can vaccinate someone. What are the promising candidates and how are you seeing whether, you know, the vaccine itself could make them sick or will truly be, you know, 100% protection, or might it be something like the flu vaccine where it's something less than that?
Yeah, there are a number of different vaccine approaches that are being pursued. Some of them use a little bit of genetic material from the virus. Some of them use a protein that the virus creates. Some of them use an inactivated form of the virus. There's different kinds of approaches to making a vaccine. And in this case, in terms of, can it make you sick? The vaccines that are being used here, none of them will have a risk of giving you COVID, none. But they could have side effects that make you sick. I think we usually, you know, we talk about mild or moderate side effects from vaccines. People could have a fever; they might have a sore arm. They might feel lousy. We don't know yet whether these particular vaccines will make people feel bad or how long they might make people feel bad. There's usually a range within the population. Some people get a bad, you know, have maybe a fever and feel badly; some people feel nothing. So we'll have to see at the end of the results of these trials what percent of people felt badly and with what specific symptoms, and we'll get that information when these trials are completed.
And the second question was related to remind me, Sal, was--
It's the one, let's say the vaccine; what you're saying is it is gonna be safe. (indistinct) We're talking about either pieces of the RNA of the vaccine or the proteins that are produced because of it, or a kind of killed version of the vaccine. So it's not like these are gonna be live vaccines that can make you sick. But the second part is so no one's going to get sick from the vaccine or get COVID from it. What's the confidence level that, you know, is it possible that we have a vaccine that gets through phase three, let's say January or February, but you know, it's 20% effective, not 100%.
So what the FDA has said is that they would like at least a 50% effectiveness for this vaccine. So they've put that out. And I'm hopeful that we'll do better than that, but 50% effective compared to what we have now would be a great benefit in protecting 50% of the population from the vaccine would be a huge improvement. Vaccines have, you know, some vaccines are in that range. The normal flu vaccine could be as low as that or less in a given year. But other vaccines that we have are super effective and maybe in the high 90s. We won't know for this vaccine until we get through trials, and there may be a big range. The first vaccine may come through, and it might be 50%. The second one gets through the system a month later, and it's 80%. We're not going to know the answer to that until we get through the studies. But even 50%, I would say, it would be something that would be a real improvement.
The other thing, Sal, is that we should anticipate that there are gonna be changes as more vaccines come online. As you said before, I think there's something on the order of approaching 30 vaccines that are in human trials with the big three that are in the lead. But over the next six months, we may have a whole number of vaccines that get through the system and that are safe and effective, but have slightly different profiles. One vaccine may be better for elderly people. One vaccine may be restricted for people who have certain kinds of underlying conditions. We just don't know yet. So we're gonna have to be somewhat flexible. The first vaccine might get approved, and then a second one may come along and be a little bit better and people wanna switch over. There are a number of things that could happen.
And just to make sure we’re this right, 50% efficacy would mean that 50% of those who get the vaccine are going to be immune? Is that what 50% means?
Yeah, it would be protected from infection. It doesn't weight. There's also another measure of vaccine, which is, does the vaccine prevent spread or transmissibility, which is a second factor which we will be looking at that everyone will be... The results will help us look at that. But I think the first measure that's most important is does it protect 50% of people from getting infection?
I see and then there could be benefits above and beyond that. Those who still get infected might have a less severe infection. They might be less likely to spread it as well, which are other things that you can measure.
Absolutely, right.
And so the timeline that we're looking at, you know, in a previous livestream, you know, we had Dr. Fauci on, we had Bill Gates on other knowledgeable folks. You know, we're in this world where the government has kind of taken a bet with several companies where we're already starting the production of some of these vaccines while they're in phase three. So that if we hope that in January-ish timeframe, maybe December, January, February, some of these get through phase three, there's already some of that vaccine there for us. How do you think this could play out, in kind of our best case scenario? Let's say one of these first three candidates are looking, or maybe hopefully more than one of them are looking pretty promising. And we already have that we've been manufacturing them for several months. What's it going to look like as we go into 2021?
Okay, so a couple of thoughts on that. The first is just how fast are we gonna be able to get vaccine into people? And it depends a lot on when the trials end and what combination, which of the vaccines, if hopefully more than one, as you said, get through the system. Moncef Slaoui, who is the pharma leader who's been brought into the government to run Operation Warp Speed and is focused, you know, 100% on vaccine development, has said that he's hopeful that by the end of February, as many as 40 million Americans will have been vaccinated. That's his hope; I'm sure it could be moved up. It could be moved back, depending on what happens on the trials.
That's just one kind of milestone just to put out there from someone who's quite knowledgeable about what's happening. But even let's say that that is true. Let's say that there are 40 million people vaccinated by February; presumably they will be people who are at highest risk from both from their profession and from their age or underlying condition. So that would be 40 million Americans, let's say, who are in those categories. That will diminish the risk substantially for obviously for that group. If the vaccine is as effective as we hope it is, it'll diminish the risk substantially for that group. But also, it will begin to diminish mortality for the country in a way that we can see, because you know, the people who are at highest risk of hospitalization, intubation, and dying from this disease will begin to be covered first.
No matter what happens though, no matter how fast we're gonna vaccinate, we're gonna have to live with this disease at some level for some time, because we're not all gonna be able to be vaccinated at the same time. Even if all of the vaccines deliver, there's gonna be over a period of time that we kind of transition into vaccination. There will be some people who decide not to get vaccinated. I hope that that number is low if we do have a safe and effective vaccine because I think the more that we're vaccinated, the less likely we're going to see big outbreaks. And over time, I think it will be kind of like not like a black and white switch that comes on or off, but kind of more gray. Over time, the risk of big outbreaks will begin to decline over the course of 2021. It will depend on the speed of how fast we're able to manufacture vaccine, how quickly we're able to get it into people's arms. But hopefully, our people's lives will begin to look closer to normal over the first half of 2021.
And we'll still have to live with it in the background. It'll continue to be background noise in our lives, I think, for a long time. We're gonna need to continue to have rapid testing for people who have symptoms of COVID. Hopefully, there'll be fewer and fewer. We'll need to isolate them when they're sick. We'll need to do many of the things that we do now, but they'll just be less frequent. There'll be less risk overall, much more ability to return to normal for most people over time.
A question here, really interesting one from Facebook, Geo Choudry is asking, is it possible that in the time it takes to develop a vaccine, maybe the virus will mutate? Obviously, we have a different, you know, we have a mutated version of the flu every year and we have new vaccines. Is there something about COVID that where we don't think this is gonna happen or it might happen?
So far, the evidence is that while there are changes to the virus that are occurring, there are different lineages around the world. The lineages are still relatively stable enough that it looks like a vaccine that works for one will work for all. So, at this point there does not seem to be any kind of divergence that will make the vaccines ineffective. It's a possibility over time. And it's also a possibility that getting back to the level of immunity and how long it lasts. It's a possibility that vaccination will be effective for a period of time, but that we'll need to re-vaccinate in a year or two or three. We just don't know yet because we haven't had any time. So there are different possibilities in our future, but so far, the good news is it looks like the vaccines that are being created will work for all lineages, if they work.
So it sounds like an optimistic scenario would be things start to somewhat normalize in the spring, summer of next year. Although that's kind of still optimistic. That would be if we are able to get 40 million folks in the US alone with the vaccines, you know, the February, March timeframe. And then obviously, you need to get many more to get true herd immunity. And I wanna go... These conversations always go a lot faster than I expected. I definitely want to get to the idea of school closures and universities, but the one last question about, you know, things that make the virus itself less scary. You know, the other track is on the therapeutic side, you know, how do we make the virus less deadly, less likely to do permanent harm to folks? Where do you see our journey there? I've heard things like, you know, some of these anti-inflammatory drugs, you know, the steroids, you know, preventing the cytokine. My wife's a rheumatologist, so I hear a lot about this. Where do you see that line of reasoning going over the next eight, nine months?
So, so far the therapeutic that's had the greatest benefit has been oral steroids, something glucocorticoids or steroids that the medicines we use for all sorts of common inflammatory diseases. And that's had a pretty substantial benefit in people who are intubated, the sickest people. It showed as much as a third reduction in mortality, which is pretty dramatic for one medical intervention. We have an antiviral, which is from Remdesivir, which is a much smaller benefit. It's kind of, it's believed at a benefit, but not as substantial one. And so far, you know, everything else is still in trials. There are antibodies that are engineered antibodies that are being studied. And hopefully, we'll know by the end of the year, there's a lot of hope that they might also reduce mortality, perhaps used in combination with other medicines, like Remdesivir or Dexamethasone. So hopeful that those things will also contribute to overall lessening mortality. We're learning things about the care of patients in the intensive care unit about trying to, you know, either turn them over in a way that improves their oxygenation, or trying to avoid ventilators for longer if possible, because that makes it a little bit more difficult to care for people and to have good outcomes. So I think if you look at the overall way that people are cared for, with this disease in the US, there has been a clear improvement over time. And hopefully that will continue to get better as we have more things come through the system.
But, you know, if I read between the lines, it sounds like that's good. And we have to be doing that as much of that as possible, but it's really going to be the vaccine that will normalize things unless we have some kind of unexpected breakthrough on the therapeutic side.
Yeah, even if we have a breakthrough in the therapeutic side that's dramatic, it's not really going to change unless it was available to everyone. And, you know, it's hard to imagine conditions in which it would dramatically change the pattern of spread of the disease. It could change the outcome perhaps dramatically, but not the overall course of the pandemic. That's gonna require a vaccine.
Right, and there's a world where the, you know, if we had proper therapies, the disease might not be, as you know, might be like the flu, but it sounds like we're far from that type of situation.
At this point we are.
It wouldn't be everyone wouldn't have access. So going to the school opening and closures, and especially on the university level, you know, last week we had the chancellor from the University of Illinois Urbana-Champaign on, and they're doing a very interesting operation experiment where they're doing, the whole campus is getting tested every three days. They had developed their test where they can get it within hours, at 24 hours at most. They're doing really strong contact tracing. What do you think about that? Do you think that is a solution for the next nine or 10 months? Or do you think that, or you will wait and see?
Well, I think we're going to find out, hopefully in the next couple of months, because schools are taking a wide range of differing approaches and some schools are really only testing sick kids and sick faculty members, people who clearly have symptoms and others, like you just said, are taking kind of the other, you know, kind of the opposite pole—testing before arrival, testing one, three, five days after arrival, a contact tracing. My instinct is that those schools with much more testing and with really close contact tracing are gonna do much better, just like in the rest of society, that's kind of a closed microcosm of society. We don't know for sure, 'cause this has never been tried, but I think we will learn, hopefully, you know, in the next month or two. And so that universities that have taken a kind of a virtual approach in the first semester, hopefully it become pretty clear what the best practices are for going in January. Right now, I think there hasn't been data. I think the CDC has said they didn't recommend approach. They didn't recommend testing base symptomatics on arrival. I think many universities have decided to do that anyway. And we'll see if it's effective. And if we have the bandwidth to do that, that's the other challenge, is that some universities have incredible S and T, science and technology within the university and can build those systems while smaller schools may struggle to be able to get that kind of testing at that frequency and that, you know, that extent.
If you know what I'm sure you're advising the leadership at Johns Hopkins, but if you're a university president right now, I guess you have three options. You can say essentially pretty much distance learning or a little bit of hybrid, but, you know, that's kind of the safest option. Option two seems like what University at Illinois is doing, which is still, you know, very aggressive and obviously, you know, places like Johns Hopkins obviously have the capacity to do, I would imagine similar types of things, or, you know, I guess the more laissez-faire, which I already get a sense that, or maybe not laissez-faire, but you know, just following the CDC guidelines. Where would you be on, I guess one of those first two options is my gut sense of where you would recommend.
I think at this point, just from the initial few weeks of university experiences, or even now it's up to a month in some places as you know, athletes have come back, I would lean in favor of really extensive testing on arrival. And then with some frequency over the course of the semester. It may be too much, and maybe we can pull back from that as we learn more. But I think there've been a number of colleges and universities where we've seen that doing less is not a good option, and where schools have had to be closed. Colleges would be closed after two weeks of being opened after they've had hundreds of new cases.
And, and so you would... if you're a university president you would rather open and do the aggressive testing than just, you know, stay distance learning?
Yeah, I think at this point, in terms of overall virtual versus in-person, I think some parts of the country have had a community incidence, which is pretty low, like for example, many places in the Northeast, their overall daily incidents of cases in that particular city is somewhere in the order of three, four, five cases per day, per 100,000. Other parts of the country, the incidence of disease is more like 20 or 30 or 40 or 50 cases per day, per 100,000. That's a very dramatic difference. And so what I hope is that university towns, college towns, the communities around them are able to drive their numbers down to a low enough incidence where the arrival of students is not a threat and doesn't threaten to kind of be a resurgence and the town itself isn't a threat to the students. The kind of the imbalance. Right now, I think there are, if you draw from across the country, we do have a lot of places right now, which have very high incidence, and those students, if they're gonna come across the country to a town, then I think that university has a real obligation to test them and make sure that they're not bringing in kind of higher risk for that community. So I would say, it's a long answer to say, in some places, I think it was reasonable to open and other places where the incidence is very high, it was probably higher risk, and I'm not sure I would have done that.
Yeah, and I realize we're already out of time, this is super helpful. You know, just last thoughts on, I mean, it sounds like, you know, we're hopefully all fingers crossed that the vaccine research, the phase three trials, and then the distribution works over the next six, seven months. It seems like the most likely scenario. If you were, you know, emperor of the universe right now, would you just be kinda banking on that? Or are there other things that you think we could do? You know, there's some stuff that's maybe a little bit water under the bridge, obviously, if we had better contact tracing, if we had better testing earlier on, but are there other things that we could do that could give us a more likelihood of getting to normalcy faster?
Yeah, I mean, there are other parts of the world, which are much closer to normal. I mean, I would say no country is acting completely normally now. And probably every country has a level of economic downturn and challenge and societal challenge, but there are parts of the world where they've had very few deaths in the last couple of months, very few cases in the last couple of months, and they're doing the things that we're doing, but they're doing them with more collective buy-in, with more unity of message. I think we've just had kind of a messy six months where some states have acted one way, some states have acted another. We've reopened quickly and then had to shut down again. If we kind of continue on what we know, which is physical distancing, universal masking when you're outside and near other people, avoiding large gatherings, basic hand hygiene, stay home when you're sick, get tested if you're ill, do the things we talked about in this half hour, I think those things will go a very long way. Even if we don't have a vaccine, I think we can get closer to normal, and other countries have done that. So I think if we keep moving in that direction, even before we have a vaccine, we'll be doing better.
Awesome, well, thank you so much, Tom. This was a super useful update on where we are in this journey. It all makes a ton of sense; thank you for this.
And thanks for having me, Sal.
All right. Well, thanks everyone for joining. I hope you got as much out of that conversation as I did. Special thanks to my wife for cutting my hair yesterday. It was getting a little bit outlandish, but it's still looking a little bit odd. But I also wanna encourage everyone for joining us tomorrow. We're gonna have a conversation about the SAT, with Dave Travis, who is the leader of our test prep work on Khan Academy, for those of y'all who know where the official practice alongside the college board for the SAT. So that's going to be really interesting to talk about all things SAT. So look forward to that, and I will see you tomorrow. Everyone, please stay safe and listen to whatever everything that Dr. Tom Inglesby just told us. See you tomorrow, bye-bye. (chime sound)