From the DevelopingEM Archives: Dr. Ben Wyler, New York City, June 2020

The following interview is presented in collaboration with DevelopingEM: A Conference with a Conscience. The interview was recorded last year, and published on June 1, 2020. The original publication can be seen on the DevelopingEM blog here. For an unedited transcription of the dialogue, please scroll below the video.

In the interview, Dr. Ben Wyler discusses the realities of a pandemic-worn New York City as of June 2020, creating a time capsule for us as we move forward with vaccinations.

Mark Newcombe: Welcome, everybody! Just to fill you in, I'm talking with Ben Wyler. Ben is an Emergency Physician with an interest in travel medicine. He is currently working in New York, which is going to be interesting for all of us, and during our 2020 conference he subbed in at the last minute to give a presentation on COVID-19. And it was a pretty sobering presentation. I think it woke a lot of us up to what we would be facing when we got home. After... Perhaps even some cynicism about the whole illness and I certainly probably had not gotten myself all over this topic, so it was an incredibly useful presentation and it would just be sort of interesting to follow up with Ben: to see how things were in New York and Ben's also got some perspectives on what the future holds. So, firstly, Ben, how are you?

Ben Wyler: Doing good! It's nice to finally sort of be getting back to some semblance of normalcy after, you know, this initial wave of just tons of patients and really kind of a stressful period. And then followed by a sort of, you know, the calm after the storm where a lot of people were discouraged from coming in, so the ER was pretty empty, and now this week it's sort of feeling like we're getting back to business as usual. Still small numbers of COVID patients coming in, but certainly not like anything we were seeing, you know, a month ago.

Mark: Yeah, right, well that's good news! It sounds like things weren't quite that way when you got back from Colombia, so I guess we broke up the conference in like the end of the second week of March, which feels like a year ago but it's only two months ago. Just remind us: where you returned to, and what hospital you're working in, and what it's been like in that 60 or 70 days since the conference?

Ben: Yeah, I work at two Mt. Sinai hospitals that are both on the Upper West Side of Manhattan. The timing of the conference was really pretty uncanny because the day that I arrived back, Mt. Sinai imposed an international travel ban [, a] work-related travel ban, followed by banning any travel outside of the region for work, so we were all sort of, you know, confined to the City and anticipating this big wave of patients that was gonna be coming. But, the city didn't go on lockdown until March 22nd, and so there was still another week and a half where, you know, if you went out, bars and restaurants were full, the subway was packed, people were sort of going about their usual life. And, you know, looking at the numbers, it still hadn't quite sunk in the reality of the situation. The day that we went on lockdown, New York had around 10,000 confirmed cases (New York City). And three weeks later, we had 100,000 cases. So, it all hit us very quickly, you know. That 10,000 we were seeing: small numbers. Then, for several weeks, the numbers were just getting bigger and bigger every single day and, you know, I think the fear level was also rising with that. We kept having to move into new clinical spaces. So, the pediatric ER was basically taken over with COVID patients, the city was opening up new locations: the Javits Center and the USS Comfort, which ended up not really being used very much, but there's talk about... There's a cathedral next to one of the hospitals where I work and they were talking about opening up basically the floor of this church to use as a ward. They were opening all kinds of spaces that previously had been used for other reasons, as COVID wards in the hospital. And there was a sense of not knowing when this was gonna stop and whether we were gonna be spilling out patients, gonna be spilling out into the streets. And so there's a lot of anxiety. One of the particular things that I remember, you know, I was particularly focused on, was the issue of ventilator capacity, because you know, I had done some back of the envelope calculations, and I was almost certainly convinced that we were gonna exceed our capacity. We didn't have really clear, you know, numbers on what our capacity was for projections, but just seeing the rate at which things were increasing, I was really worried that we were gonna run out of beds, and worried about what that was gonna entail in terms of having to allocate beds, deny beds to patients, having to split vents, and trying to be prepared for that because I didn't want to, you know, walk into work one day and find out "Sorry, we have no vents," and then, you know, have young people coming in respiratory failure and having nothing to do for them. [Mark: yeah] So, and then, you know, PPE was one of the other things that was a concern. You know, we went, from the time that I gave the lecture where WHO was mostly talking about this as being a droplet transmitted infection and we really weren't taking very extreme precautions. I mean, we were wearing masks, but we were for the most part, had patients that were suspected COVID and we were only putting the masks on to go into the room to see them and, you know, donning gowns in between, but we weren't wearing masks the whole time in the department. And that very quickly evolved to, you know, maximal PPE, and then concerns about our supply of PPE, so pretty quickly we got to the point where we were wearing face a mask and eye protection, or an N-95 respirator and eye protection continuously throughout the shift, and then taking some additional precautions if we were doing... If we were intubating, or going in to see a patient that we had a high suspicion of being COVID, but really, the whole ED at some point became sort of the hot zone where we just had to assume that everybody had COVID and we didn't have a great system for cohorting the suspected COVID patients separate from the non-COVID patients because we were just limited in terms of the space that we had.

Mark: Yeah, it sounds like it's been busy, and exhausting. And, this last time I spoke to Ben about two weeks ago, he had a pressure sore across his nose and he was looking pretty tired, but he looks better today so it's good! You spoke to us at the conference about the disease, and you knew a lot about it at that time. Were there things that really surprised you about dealing with it clinically, to what you knew back then?

Ben: Yeah, you know, the first thing I think was just the fact that this is a very contagious disease. I don't think I had appreciated that quite as much. You know, the idea that this is an airborne transmitted disease and living in a city where, you know, we just have incredible density of population, so it's really hard to distance from people. So, when you're walking out on the street, you know, the streets are often packed and you're shoulder to shoulder with people and I was taking the subway to work, you know, well into... Up until about the first week of April, and the subways would be packed and so, you know, realizing that this virus can persist on surfaces for several days and that there's airborne transmission, you know, I think was a surprise. And it didn't really hit home until we started seeing cases rise and realizing, you know, how easily this can spread. And that includes people, you know, at work. You know, staff: physicians, nurses, respiratory therapists, getting sick on the job and realizing that even with the precautions that we were taking, that, you know people were getting sick.

The second thing is, I think, until you have been through an epidemic like this, wrapping your head around what exponential growth looks like and feels like is really hard to do. So, you know, again, going from in a matter of three weeks, from 10,000 patients to 100,000, it's just really hard to fathom, you know, how quickly things get out of control with that kind of growth. And, because there's about a 2 week lag from when you impose these kinds of distancing measures until you actually see the effect of that, you know, there's a lot of anxiety that comes with, you know, realizing that you... The whole city's gone on lockdown, and yet the numbers just keep growing and growing and growing. And so there was a point, you know, I think this was around the time that we went on lockdown, that I did a back-of-the-envelope calculation. We had about 10,000 deaths globally at that point, and I calculated that in a month, if we had not implemented, you know, these kinds of measures, or if they were ineffective, we would have over 1,000,000 deaths. So, that was just something that I think really started to hit home as the numbers started to rise.

And then the third thing, is that this disease is clinically very different than I think what we thought of in March. You know, all of the talk about it was describing it as an ARDS syndrome, which, you know, I think we all have experience with and, you know, thinking of primarily the treatment being respiratory support, and PEEP and early intubation. And, since then, we've learned that it's really largely, I think, a vascular disease. That, you know, there's a lot of endothelial damage, and activation of coagulation cascade, and thrombotic disease, and cytokine storm that has-- leading to end-organ dysfunction. And so, you know, we started to see sort of early on that this wasn't just acting like an ARDS. We'd see people that came in, satting 70% and breathing at a normal rate, not in any distress, and starting to get hearing these reports about, you know, on autopsy finding microthrombi in small pulmonary vessels, and started becoming aware of that. And it changed our practice: we went from sort of early intubation for hypoxia to being more tolerant of hypoxia, proning patients more, focusing more on these thrombotic effects, but there were also some real, you know, a lot of surprising asymptomatic infections or presentations that were unexpected so... I guess on the side, I don't know if this was asymptomatic or if there's some way to connect this, but we had several case where we would get a CAT scan for a patient with right lower quadrant pain to look for appendicitis, and find that they had appendicitis and ground glass opacities at the bases of their lungs. So, realizing that there were a lot more infections out there than what we were looking for was part of that. And then we would also see patients with things like encephalopathy, patients- young patients- presenting with strokes, with heart attacks, with PE's... So, some of these thrombotic complications or secondary effects of just the cytokine storm was really sort of shocking in terms of the disease. And now we are finding out in children, who we thought were mostly asymptomatic, that there's a Kawasaki-like syndrome that these kids are getting. So, this is really a different disease than anything that I've seen before or can recall studying in medical school. It's a really unique clinical entity.

Mark: Yeah, it's fascinating to hear that, I guess, we've been relatively lucky here in Australia, so we just don't have the experience with this end of the illness to any great degree, which is amazing. But, to hear what your clinical experiences have been, it's absolutely fascinating. It must be difficult, looking out from an epicenter, to try then to step back and think about the whole globe, but what do you think the main challenges are for, you know, a wider perspective outside of an epicenter, where the disease prevalence is maybe a little less, but we've still gotta deal with cases, and...

Ben: I'm actually, unfortunately, really worried about the global perspective with this disease. You know, early on, (when) China and South Korea were two of the countries were hit early. And [they] seem to have done a pretty incredible job of, you know, containing it, largely through really expansive testing and contact tracing and taking advantage of technology, using things like cellphone data or public surveillance to be able to identify, you know, potential contacts. You know, Europe had a big wave and has seen a lot of the mortality from this disease, but they've- a lot of the countries have really brought their curve down and have, you know, much smaller numbers of cases right now. It's hard to generalize about the United States, I think, because there's so much heterogeneity in terms of how different states are approaching this. You know, New York is looking pretty similar to Europe in terms of their ability to bring down the cases. Some of the other states are taking a less dramatic approach, and so we'll see, you know, what effect that has. But, you know, the hotspots in the world right now are largely countries like Brazil and India and Pakistan, Bangladesh. And these are countries that, you know, still are having a growing number of cases every day. So, have not been able to even, you know, even get their cases to plateau. And, they're countries that have much fewer resources in terms of, you know, hospital resources or testing resources to be able to either treat sick patients, or be able to do the epidemiological control and tracing that would be needed to try to mitigate the impact of this. And so, the other thing is that these, you know, these are largely urban countries that have a lot of poverty and really poor housing and, you know, tight quarters in these urban environments. And that's really just, you know, a hotbed for transmission of infection, so... You know, I know, you have some of that in America. I know, you know, I've looked at the numbers for Brazil. I don't really know what's going on on the ground there. I have been in touch with people in Peru, because I've done work there in the past, and I can say, you know, I think it varies a lot depending on the setting. I've been hearing from a colleague in Cuzco, in the mountains, who says that they really took the lockdown seriously. You know, all the businesses were closed, they locked down very early, and he's not seen a lot of cases. But, I know that Lima, you know, the capital, has seen a lot of cases, and Iquitos, which is a city of half a million people in the Amazon, which is not accessible by road, has been, from what I understand, really a catastrophe. They haven't had the hospital capacity to care for patients, and even haven't had enough oxygen in some cases to be able to treat some of the milder cases who just need supplemental oxygen because it's really hard to get resources there. So, you know, I think, depending on the resources that are available and the housing situation, those are gonna be two things that really determine how bad this is. I'm very worried about south Asia because all three countries in South Asia are seeing an increase in numbers and this is a region with 1.7 billion people, so the potential for it to, you know, really cause catastrophic outcomes there is really, you know, a big risk. And Africa, you know, the numbers coming out of Africa aren't that high, and I don't know how much of that is because of limited testing. You know, African countries do tend to have younger populations, which may, you know, limit some of the mortality there, but they also have high levels of poverty. The poverty I think is one of the things that is gonna have the biggest impact. This was true in New York as well. You know, I was lucky to be working in Manhattan because all the other boroughs in New York got hit much harder than we did and, you know, the areas that I work, as bad as it was, it wasn't anything compared to other parts of the City where, you know, there are poorer households, a lot of them multi-generational, or where people live with multiple roommates in small apartments and have to commute long distances, you know, on public transportation. So, all of those things I think were factors that led to much worse outcomes in those areas and I think that's gonna end up being true on a global scale as well.

And then, you know, the other thing is there are gonna be second order effects of this. So, the impact on economies, on food supplies... I worry about some of the places where locking down really, you know, in terms of what that means for livelihood for people, and for food supplies is gonna- could lead to a lot of, you know, second order problems.

Mark: Yeah, it's certainly unprecedented in the US and an unprecedented time for the world. It's an interesting thing to talk about, but perhaps not to think about for too long. We are gonna try and talk to some of our colleagues around Latin America in the next few weeks. Interestingly, I just had some contact from some of the pre-hospital and inter hospital guys and girls from Chile. Their critical care capacity in Santiago is now maximized, so they're looking for advice and support on moving patients to peripheral cities that are already receiving critical care. So, you know, a very advanced system that is, you know, at a point where they're looking at options that they wouldn't normally count on and so, now there's strains being seen even in an area that's dealt pretty well with the illness by all accounts. So yeah, we're gonna try and talk to Ana Paula and perhaps Manrique from a different perspective in Costa Rica in the next few weeks, which will be interesting. You've talked a little bit about the supportive care-- is there anything on the horizon in terms of focused therapies that you think are gonna be useful? There's already prominent people taking certain focused therapies, whether that's a useful thing or not, but what's your perspective?

Ben: You know, when I gave the presentation at Developing EM, I think, you know, I sort of glossed over it and said there's no proven therapy and unfortunately, I don't think we have- I don't think we're in too much of a different situation right now. You know, the drug that's gotten the most sort of attention has been Remdesivir, and the large Gilead trial, about three weeks ago they reported positive results from it, and they sort of gave the headline numbers, but there still is no published study, so it's sort of hard to scrutinize that to know what to make of it. But, you know, the numbers that they published were that it reduced the time to a significant clinical improvement, from about 15 days to 11 days. And that was their primary endpoint. So, they showed that, and they stopped the trial early actually, on the basis of that. And they also reported mortality data, that it reduced mortality from about 11.8% to 8%, which is, you know, pretty significant, and this was in a fairly severe group of people. You have to be a little bit careful, you know, interpreting this, when all they're reporting is the headline numbers. So, I'm sort of cautiously optimistic and have to assume that this wouldn't have gotten as much public attention if somebody hadn't, you know, sort of looked at the data, but I'm anxiously awaiting the publication of that study. I don't think that this is gonna be a game changer. I mean, it certainly helps- anything that we can do for the majorly ill is gonna be majorly helpful- but this is gonna be IV therapy, I don't know how much capacity we're gonna have to provide this to people around the world. Some of the other things that there is some, you know, I think there is growing awareness of or there may be studies coming up: anticoagulation, particularly Heparin, seems to be helpful in preventing some of the end organ damage from this thrombotic process, and there have been some small studies that suggest there is a benefit there: a mortality benefit. There's a lot of investigation going on now with some of these inflammatory modulators, so the IL 6 antagonists, tislelizumab I think is the one that has been the most studied. And giving steroids to patients, sort of in these later stages, and we just don't have enough data on that yet. There's studies going on with convalescent plasma, which is actually one of the big things. Mt. Sinai is doing a lot of things on convalescent plasma, but no big published studies on that. I'm a little bit skeptical that anything that addresses- you know, we sort of have therapies that are antiviral therapies and therapies that are immune modulating or preventing some of the downstream complications, and so you know, in these severe patients, I think they're already past, you know, a lot of the viral replication, and it's really the immune phenomena and the downstream effects that are causing a lot of the pathology, so I'm a little bit skeptical about the ability to have a big impact on mortality at that late stage, and I'm hopeful that we're gonna find some drugs that can be given early in the course, that are, you know, small molecules, cheap, that can- could be even taken prophylactically.

And, among those, I think the three that I am sort of the most intrigued by: hydroxychloroquine obviously is the one that everybody has been talking about and some prominent people have been taking. I will disclose-- I am actually working on a- I'm part of a randomized control trial giving hydroxychloroquine prohylactically to healthcare workers to see if there's any benefit. So, I think that is probably the place that it will have benefit, based upon what we know about how it works, but there's not been any good data showing benefit for patients that are already sick enough to be hospitalized. So, hopefully we will have in a few months, you know, some data on that. The second one is zinc, which is sort of interesting because it's been shown for to help with other corona viruses in people: you know, common cold is a corornavirus, and you know, there's really good data shown for the common cold that if you take it early in the course, it leads to more rapid resolution and it really, it's the same mechanism that would be expected to work for this. So, that's something that could potentially be available and, easy for, you know, a large number of people to take with relatively few safety risks. And, the third one, which is interesting because it's sort of come full circle, are ACE inhibitors, so early on, you know, they were proposed as being beneficial and the thought was because it's an ACE 2 receptor that the virus binds to, that if you, you know, block the receptor... It turns out that ACE inhibitors don't act on ACE 2, only on ACE 1, and then there was a concern that they actually up-regulate ACE 2, so that they could be more harmful. But, there are two fairly large retrospective studies that looked at people with hypertension on ACE inhibitors versus other anti-hypertensives and it found that they have lower mortality, adjusting for, you know, other conditions, the people who are on ACE inhibitors. So, you know, that's another one that you can imagine that maybe it has some effects on the vasculature and because we think this is a vascular disease, we think that it could be protective through that mechanism, but you know, again, these are retro- limited-size retrospective studies. So, but those are the ones that I'm sort of most interested in and keeping an eye out, you know, for larger studies and more data.

Mark: Interesting stuff! I guess the million dollar question is- or, the future would seem to be some sort of vaccination strategy that maybe has significant problems developing a vaccine. You know, you hear talk of 12-24 months, and staying partially locked down for that entire period, and... Do you think that we will see an effective vaccination against this crazy virus?

Ben: You know, I wish that I knew. If I had to bet on it, I'd guess that we will eventually, but, you know, the fastest that any novel vaccine has been developed was four years, and that was for a mumps vaccine. So, the idea that we would be able to do this in 12-24 months, you know, geez, I'm really hopeful that we can. I know that they're working on multiple steps of the vaccine development sort of in parallel rather than in series and they have something like 20 or 30 candidates that they're looking at across the globe. So, and there are some features that I think are fairly promising. They pointed out, you know, the problem with influenza, the reason why we need a, you know, a flu shot every year is because there is rapid mutation and this virus does not appear to be mutating rapidly. So, in particular, the spike protein, which is the target for a lot of these vaccines, you know, seems to not be mutating very much. So, I think that that's hopeful. You know, in the absence of a vaccine, we're gonna- Assuming that there's a way to get robust immunity, you know, it's either it's sort of a race between the vaccine and naturally getting to that point by people just getting infected, and I agree with you. I think, you know, the degree to which we can slow the spread over the course, you know, this is gonna take a couple years, what it's gonna cost us to be able to do that: economically, psychologically, socially, politically... It's hard to imagine that we can maintain the level of restriction that we've had the last few months, for that kind of time frame, so... If it's a year, you know, it's probably worth it, but I think at some point it's a race between natural spread of the virus and ability to involve the vaccine. The worst-case scenario is that there is not a way. We don't find a vaccine that gives long-term immunity, or that natural immunity ends up, you know, not being long term. And if that's the case, we could end up with a seasonal disease where this, you know, goes in waves through the population like influenza does. I don't think that's likely, but all of this is speculation. I think that's, I mean, I think an effective vaccine is the greatest hope that we have right now and it'll be interesting to see, you know, with the global community working on this and devoting the resources to that, how quickly we are able to come up with one.

Mark: So, for those of us who like attending international emergency medicine conferences, what do you reckon the next 12 months looks like? Do you think there will still be... ?

Ben: I can't imagine that we're gonna be going to, at least in the next six months, that we're gonna be going to any international conferences, and I would say probably- you know, I would be surprised if we are in the next 12 months. You know, at some point it comes down to risk tolerance. You know, there's personal risk tolerance, institutional risk tolerance, but, and, you know, collectively, as a group, you know, the degree to which we can sort of take precautions to reduce the risk, but I think that there's probably gonna be enough work to do on the home front, and enough concern about, you know, risk from air travel and large gatherings that, you know, that until we have a vaccine or until we have high levels of herd immunity, I don't think it's gonna be likely that we're gonna be taking that risk.

Mark: Yeah. I guess we're always looking to the future here at DevelopingEM, and we're having conversations with colleagues in Africa about 2022 and we need to stay positive and, you know, I'd be very disappointed if we weren't able to have the type of face-to-face meeting that we're known for, because I think that's where most of our benefit comes from.

Ben: Yeah, I completely agree!

Mark: I'm looking for presenters for 2022, there's probably gonna be a smaller pool to choose from. Are you happy to give a hopefully historical presentation on COVID-19 somewhere in that time?

Ben: Yeah, absolutely! I'd be honored to do that. That would be great. You know, it's interesting-- I'm actually reading a book right now that's sort of "lessons learned," a historical perspective looking back on SARS (Mark: right!), and it's interesting to see that, you know, we didn't really follow the lessons that were learned the last time. I think this time's gonna be different. I think there are gonna be a lot of things that change once we get through this. And this isn't gonna be the last pandemic threat that we see in our lifetimes, but, you know, hopefully the last pandemic that actually, you know, gets out of control like this one did.

Mark: Well, mate, thank you for that! It's been awesome chatting with you again, and be safe and we'll chat again soon!

Ben: Yeah, great talking to you!