Early Experience of COVID-19

Well, good evening and welcome everybody to the Royal College of Physicians in Edinburgh. My name’s Andrew Elder. And I’m president of this college. This is our second webinar on the theme of COVID-19. These are going to be weekly events. We’ve already got a programme, in fact, mapped out for the next few weeks. And I really want to start by thanking everybody who’s involved in the production of these, from the college officer who’s opened the college tonight, through our IT team, to Jeanette Stevenson, our head of education, professor Jeremy Hughes, who is our academic lead for education, and of course all our speakers tonight. All our talks are being delivered live tonight by WebEx.

And we’re using Slido.com– I’m sure most of you are now familiar with it– to record questions. The hashtag tonight is #rcpeCOVID19.

And as well as recording questions there, please submit ideas for other talks or indeed speakers that you would like to hear in the coming weeks. We won’t be able to answer all your questions tonight because I mean, there’s already about 50 before the meeting started. But we’ll endeavour to answer as many of them as we can and have some of our speakers do the same. We know you’re all very busy. We know that some of you are in different time zones around the world. But everything that we are broadcasting live just now is also going to be recorded and available on the web site.

And it should be on the web site in recorded form in about 24 hours from now.

I wanted to stress to you if you’re interested in getting CPD from this that you need to complete the online feedback form by next Wednesday if you’d like a CPD certificate. And you can find the link for that on the event page and on the website. These are the main housekeeping issues that I needed to outline to you. But there’s one other point that I felt it would be unreasonable of me not to comment on. And it’s similar to what I said last week. This is a clinical, educational meeting. And it’s also an international meeting.

But I’ve heard from many colleagues from trainee through to consultant over the weak, over the past week in the United Kingdom about their concerns, about two issues in particular. And that is the availability of testing and the availability of PPE and the effect that that availability has on both patient care and professional well-being and morale. All I wanted to say about that was that really my whole week is quite rightly been dominated by those issues. And the same applies to everybody who’s in a professional leadership position like this in the United Kingdom at the moment. We hear those concerns. We agree with them.

And I can sincerely say that I do believe that progress is being made to resolve them now. And I’ll update you in a similar way both online in my statements and here every week. OK, so onto our programme, every week we are going to have an international angle on the pandemic. And I’m really delighted that our international speaker tonight is Professor Brian Garibaldi. Brian is a fellow of this college. He’s also a colleague and great friend of mine. He– we’ve worked together on bedside clinical skills, really, in the United States and other parts of the world. But Brian is the medical director of the Johns Hopkins Biocontainment Unit. He is an associate professor of medicine and physiology at Johns Hopkins.

And he’s going to tell us this evening about Hopkins and Baltimore and Maryland’s early experience of COVID-19. So, Brian, thank you very much for contributing. We look forward to hearing what you’ve got to tell us. Well, thank you, Andy, so much. It’s an honour to be here. I wish I could be there in person, but thank you for your support and for everyone’s support. We’re going to get through this together, sharing our collective knowledge and our experiences and helping each other through this. So what I thought I would do today is tell you a little bit about what we’ve experienced here in Baltimore.

And I wanted to start a little bit earlier than our current experience by telling you a little bit about our biocontainment unit. So back in 2014, the federal government of the US decided to set up 10 regional health centres across the country that would be able to take care of patients who had viral hemorrhagic fevers like Ebola or Lassa or Marburg. But very early on, we realised that our units could be the front lines in taking care of novel respiratory pathogens or other emerging infectious diseases that we didn’t know of yet. And so for the last several years, our team has been working not only to get Hopkins ready, but also to try to get our region ready.

And we’re not only the regional centre for the state of Maryland. But we also serve five other states in our region. So for the last two years, we’ve been going out and helping other hospitals come up with what their plans might be both in terms of where they would provide care for additional patients with an emerging infection, what gear they would wear, how they would train their staff to be able to do that. And so this is really, for us, has been a several year process of preparing for the unknown and now leveraging that experience to try to take care of patients with COVID-19.

So our unit was called into action about 2 and 1/2 weeks ago for our first people under investigation in the United States and very quickly our first confirmed case. And just to give you a sense of what our unit is like, we have a four bed negative pressure airborne unit where each of the rooms within that unit is also negative pressure to the hallway. So we have several negative pressure rooms inside of a larger negative pressure unit. And that was the place where we took care of the first four patients who were confirmed at Johns Hopkins. But very quickly, we exceeded the capacity of that unit to be able to take care of patients.

And so we’ve migrated now our entire team into our medical intensive care unit. And our hospital is pretty fortunate in that when our new health care critical care towers were built back in 2013, the entire medical intensive care unit can become an airborne isolation unit. And you can do that in stages. So we started out with the four beds we had in the biocontainment unit. We then expanded to 12 additional beds in the medical intensive care unit. And as of this morning, we’ve now opened in the second half of the ICU. So we now have a full 24 bed intensive care unit that currently has 16 critically ill patients with COVID-19.

We also have a sister unit that we’ve been training with past several years that is a medical surgical unit that becomes an airborne isolation unit. And that unit was activated almost at the same time as our initial biocontainment unit. We were actually caring for patients who are critically ill in the biocontainment unit that I’m caring for four level patients on a sister unit. We have since exceeded that unit’s capacity, which is 20 beds. And we are now step by step turning each floor in our main hospital building into a negative pressure ward.

And again, we’ve been very fortunate that when that building was renovated right around the time of 2009 pandemic influenza that building was actually made so that each floor could become a negative pressure floor. So we are now expanding to our second floor in that unit. And we’re turning one of those medicine units into another intensive care unit in anticipation of having to open that unit sometime in the next three to four days. Our current plans here at Hopkins– we have about 400 cases in the state of Maryland right now. And that number is obviously on the rise. Right now we are taking all of the patients who are confirmed cases throughout our health system.

We have four hospitals in our region that are part of the Hopkins health system. So we have been transferring all of the positive patients both general medicine patients, but also intensive care unit patients to our hospital. So our number of critical care patients is higher than you might expect just for what’s happening in the community. But that’s because we’re really taking care of several different counties in the state of Maryland right now. But we do anticipate that we’re going to be stretched pretty thin in terms of our resources over the next couple of weeks. The hospital has been preparing for months to get ready for this. So our supply chain right now is doing OK.

We did not have an infinite supply of protective equipment. But we are OK for the next few weeks as people are looking to ramp up capacity and relying on other industries to help us figure out how we can repurpose protective gear from other industries to use in the health care. One of our concerns right now is capacity for ventilation for mechanical ventilation. We, going into this epidemic, had about 207 ventilators in our hospital, which included 65 trauma ventilators that were purchased back in 2009 for a potential surge during H1N1. We have since purchased or put in an order to get another 250 ventilators. And we expect that we may need to use them.

The trick, obviously, in that particular situation is where do we take care of those patients? Our hospital buildings were designed to have surge capacity for medical gas and electric. But we’re now in the process of relooking through those plants to understand where we can add extra beds. Most of our ICU, or all of our intensive care unit rooms right now are single rooms. But we’re looking into the possibility of doubling up patients, depending on the ICU headwall capacity in those rooms. So all those plans are in process as we’re starting to see the beginnings of the surge here in Maryland and now in Baltimore. I thought I would share a little bit about our clinical experience to date.

And I’ll say this with the caveat that depending on your viewpoint, the plural of anecdote is data or is not data. So please take everything that I say with a grain of salt because we’re still learning how to do this better. And we’re learning from people across the world about how we might change our policies and protocols to try to keep staff safe, but provide the best possible care. From a critical care standpoint, there are two things that I’ve noticed in the first 15 or so patients that I’ve taken care of. The first is that these patients, when they develop ARDS, tend to be very responsive to proning.

And so we’ve gone through a very early strategy of proning patients whenever their PDF ratio gets less than 150. And that has actually allowed us to fairly well oxygenate without exception all of our patients so far. We do have the capability to do ECMO, or Extracorporeal Membrane Oxygenation here. We have not had to put a patient on ECMO yet because we’ve been able to use proning and a relatively higher peep strategy to oxygenate our patients. The first few cases we’ve seen have been younger. And so to this point, we have not seen much in the way of multi system organ failure. It’s been a really single organ disease that we’ve been seeing.

And we’ve had a few patients who are now approaching a point where I think they’re going to be able to be liberated from the ventilator in the next 24 to 48 hours. But it’s not clear yet how quickly we’ll be able to do that. The other thing that we’ve seen is very impressive fevers. So our patients, who have become ill, have been having daily spiking fevers to 39 and 1/2, even sometimes 40. And for many of them that’s been really the beginning of their worsening oxygenation and their need for mechanical ventilation. And those fevers have continued despite antipyretics like acetaminophen, as well as cooling blankets. And that’s something that we’ve seen.

One aspect of care that I think has been incredibly helpful to us in the early going has been point of care ultrasound. Our institution is probably behind other institution. Or, I would say internal medicine in the United States is probably about a decade behind the emergency departments in terms of utilising point of care ultrasound for real time diagnostics. We have found in our early patients that point of care ultrasound is very predictive both in terms of figuring out if a person under investigation is likely to have COVID. So we’ve been very good so far at predicting which of our PUIs are likely to rule in by nasal swab PCR testing based on their ultrasound findings.

And we’ve also found that the extent of lung involvement on ultrasound has predicted progression to hypoximia and requiring mechanical ventilation. And so we actually have to move to get more ultrasound devices. We do have a lot of cart based devices for procedures. But we’re trying to mobilise a smaller fleet of handheld devices that could be on each one of our floors so that our physicians have real time access to ultrasound. And now the trick is trying to make sure that we spread out our capabilities since not all of our attendings are trained in ultrasound.

We’re doing some crash courses in just acquiring images, which can then be reviewed by someone with more experience because it’s actually– it’s fairly easy to acquire the lung images at least. It’s slightly more complicated to interpret them. So that’s something that I would encourage. If you have the skill set, be prepared to use it and think about how you can ramp up that capability in your own institutions right now. CT scans are hard to come by because the transport down to the scanner is difficult. And if you do take a patient down to the scanner, it closes off the scanner for a number of hours until that can be used again for non-positive patients.

That obviously may change as we have more positive cases.

We have been all in terms of our pulmonary division. So I’m a pulmonologist. And we have come up with a week-on-week-off schedule for our entire pulmonary faculty to cover our existing two ICU teams, but now preparing to staff eight additional or eight total ICU teams in these different floors that we’re now opening up. And so we’ve had just tremendous support from our faculty to be all in. And the other thing that we’ve done, which has been really impressive, is we’ve ramped up our telemedicine presence for outpatient visits. So before last week, only about 1% of our hospital’s telemedicine visits were for clinic visits where by telemedicine and now we’re up to about 40%.

And so that’s been a tremendous institutional effort. I just want to briefly say a little bit about therapeutics. We open today an adaptive trial with the National Institutes of allergy immunology. And what this adaptive trial is going to be is a multi-centre trial where we’re going to complete enrollment for one therapeutic across the country and then rapidly move to additional therapeutics once we’ve completed enrollment for the first round. So our first drug that we’ll be starting today is remdesivir. And so we just enrolled our first patient this morning to participate in that clinical trial. Additional trials that we’re planning are for IL-6 antagonist or blockers as well as convalescent serum.

The New York Blood Bank has just put out a call for convalescent serum in the US. So there is no serum available yet. But hopefully within the next two weeks that will be available as a compassionate use, but also potentially as part of a clinical trial. We have seen a lot of use of hydroxide chloroquine as first line therapy. And I’ve been struggling with this because I don’t believe the data is there yet to suggest that this should be given to all patients are at risk of progression. But unfortunately, I think it’s become almost standard of care in many hospitals.

And this is something that I think we need to study and we need to study quickly because we think that it’s a relatively well tolerated drug. But we’ve never given it in this context. So I do worry about that. And I would caution you to think about how you want to apply the evidence that’s available and whether or not you will be using hydroxide chloroquine in your hospitals and practises outside of the clinical trial. And I would say the same is true for some of the IL-6 therapies that are available. We have used several patients of the non-hydroxychloroquine.

We’ve also used one dose of tocilizumab, which is an anti-IL-six treatment, on a patient who is a transplant patient, who was very immunosuppressive and was doing poorly. So I think we just need to be mindful about this balance between wanting to be able to offer something but also trying to make sure that we gathered the right information over the next several weeks to months so that we have the ability to impact what happens throughout the rest of this epidemic. I think those were the main points that I wanted to cover with everyone.

I would like to say that this has been the most amazing experience of my career just in terms of seeing how everyone is on board and supporting each other and how every part of the institution has come together to really figure out how we can make it through as best as we can. And I hope that you’re having the same experiences in your institution. And I imagine that you are. But it’s a privilege to be a part of this and to hopefully make a difference in the early going. So thank you for allowing me to speak. So, Brian, thank you very much, indeed, for that.

And just to pick up on your very last point, yeah, I think the virus is shining a bright light on lots of things. And certainly, we are seeing exactly the same professional responses as you are with teamwork and compassion and hard work to the fore. There’s a whole lot of questions here. If I may just try and give you a couple, go in here about studies from Italy and the United States show that many COVID patients with PEs, plus or minus microthrombi in the lungs, do you think there are any special considerations for COVID patients regarding VTE prophylaxis or treatment?

And then a related question to that is the potential use of TPA in COVID patients given the finding of these lung microthrombi? Yeah, I think there’s a lot of concern that particularly in our sicker patients, we’re going to start to see this microvascular dysfunction. And perhaps, you might pick it up by sending very frequent DIC labs, which might be a marker of that microvascular dysfunction. We have been, as a matter of course, putting all of our patients on VTE prophylaxis. And I suspect many of your hospitals will have protocols to make sure that that happens.

But I’ve been more aggressive in terms of if our algorithm suggests that they just need mechanical prophylaxis, I’ve been perhaps a little bit more aggressive in using either enoxaparin or subcutaneous heparin just to make sure that we’re covering that base. I think this is an area where ultrasound potentially can be helpful as well in terms of being able to do frequent scans, looking for deep venous thrombosis. Because we’re going to be limited in terms of our ability to get CT angiograms for many of our patients just because of the time and transport and the difficulty in blocking off the scanner for an extended period of time.

We have not seen a patient develop additional either hemodynamic instability or worsening hypoxemia suggesting that they’ve had large pulmonary emboli. But I think we’re probably still pretty early on in our experience as the number of ICU patients that we’ve had. So I think I’m worried about it. We haven’t clearly seen it yet. But I’m also worried that we’re going to miss it because we’re not able to test for as frequently as we otherwise might. OK, and then a broader question we got here. It doesn’t sound like you’re quite at this point yet. But I know that ethics committees are a very strong part of most American hospitals at usual times.

Are there– in addition to a local hospital ethics committees looking at the difficulties that may arise when there’s a limit on the number of ventilators, let’s say, are there state wide committees or even national committees that are talking or thinking about broader guidance? Yes, there are. So I think locally, every hospital is beginning to think about what their strategies are going to be for allocating scarce resources. And the two that I’ve been involved– and I’m on the committee here at our hospital, too, that we’ve been discussing most intensively over the last week are ventilators obviously, but also blood supply. So our American Red Cross has had a drop in the number of donors.

And so we’re very worried that we’re actually running out of our ability to transfuse. So we’ve actually combined forces with several other hospitals in our state that have put together a list of recommendations to send to the governor’s office. This will probably be a state-by-state issue that’s decided.

And so we’ve come up with joint recommendations with several of the other large health systems in our state and are presenting that to the governor’s office this week to be able to actually enact some crisis management issues related to ventilator allocation, blood allocation, but also things like whether or not patients with multi system organ failure should receive cardiopulmonary resuscitation, or whether or not it would be appropriate to consider a DNR order perhaps not in line with what the family or patient might want in certain situations. OK, and then finally, Brian, if I may, there’s a few questions on the same theme. But I feel almost duty bound to ask because one of the questioners is an ex boss of mine.

That’s professor Sir Christopher Edwards. And he says, please give me your comments on the use of corticosteroids in the treatment of COVID ARDS, A-R-D-S, and particular methylprednisolone versus dexamethasone. Yes, there’s been a lot of conflicting reports about the utility of methylprednisolone or steroids in general in ARDS. The surviving substance guidelines put out their recommendations suggesting that it would be a benefit. And there was a single centre retrospective study looking at about 200 patients in Wuhan, China, where those who received methylprednisolone seemed like they had a lower mortality with severe ARDS. I would say that we’re still in the same points we are with steroids and ARDS that there probably is a role for it.

But we haven’t figured out how to identify the right patients to receive it. And so to date, we have not given methylprednisolone to our– we have now 11 intubated patients. We have not used methylprednisolone. And I think our centre is just very wary of using it because it’s a lympholytic drug. You need your lymphocytes to clear this virus. We know that the risk of secondary infections is high. I’m really worried about the possibility of myopathies and prolonged ICU weakness. So I think we need more data before we know what the real role is. Will we use it in slight cases?

I think we probably will at some point, particularly if we see patients who may be developing fibril proliferation related to their disease. So far, we haven’t seen that with the mechanics that we’ve seen on the vent. People are on very high PEEP, but their plateau pressures have not been high, suggesting the lung compliance is not as poor as we would expect. And I don’t know if that’s going to bear out that they’re not laying down as much collagen matrix or having as much diffuse cellular damage and hyaline membrane formation. But I think the jury’s still out. And we’re being very cautious here about the use of methylprednisolone. OK, well, Brian, thanks very much again for joining us.

I know it’s coming up to about 3:00 PM there. You hurried your lunch just before you spoke to us. And you’ll have several hours of your shift left. May I just thank you on behalf of the whole audience of joining us tonight. Thank you very much. Thank you. It’s been an honour. Stay safe, everybody.