Talking Tall Rounds®: Heart, Vascular & Thoracic Institute Perspective - Current State of COVID-19 and Vaccination

Podcast Transcript

Announcer:
Welcome to the Talking Tall Rounds series, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Dr. Eric Roselli:
Welcome everyone to our Heart, Vascular, and Thoracic Institute at Cleveland Clinic, Talking Tall Rounds podcast. Today I'm here with Jerry Estep, the medical director of our heart failure center at the Cleveland Clinic and the Department of Cardiology at the Heart, Vascular and Thoracic Institute (HVTI), and we're discussing the HVTI Tall Rounds event that took place earlier in January of this year, entitled The Current State of COVID-19 and Vaccination, and it's really a great event that brought together many of our thinkers from our Heart, Vascular and Thoracic Institute, as well as other areas within the Cleveland Clinic, because we work in a really multi-disciplinary and collaborative team to give us some update with an HVTI perspective.

Dr. Eric Roselli:
Our conference was led off most appropriately of course by the heart of our Heart, Vascular, and Thoracic Institute, Dr. Lars Svensson, who welcomes all of us and gives us an overview of where we've come, and he's done, I think, a really great job of leading our team over the last year-plus, interacting with the overall enterprise, and you know, one of the things that I've always really enjoyed about having Lars in a leadership role with us Jerry, is his transparency about what's happening.

Dr. Jerry Estep:
Yeah I know Eric, I agree. I think it was timely to readdress COVID-19, the implications, what we've learned, and what I very much like is, you know, including not only members of HVTI and cardiology, heart failure specialist surgeons, but bring in, you know, Steve Gordon from infectious disease and Dan Culver from pulmonary and really tackling a primetime problem with a team approach, which is what we do, and so yeah no, Lars set the stage beautifully.

Dr. Eric Roselli:
Yeah, excellent, and as we always do with the Tall Rounds, like anything, you know, the whole idea of Tall Rounds is bringing a bunch of people with different perspectives together, and anybody that's involved in taking care of patients know there's no way to do that better than to center it around a patient, and so that's what we start with. We have Haytham Elgharably, one of our newer staff cardiothoracic surgeons who has a particular focus on taking care of really complex patients with both heart and lung failure, presents a patient who is COVID-positive and needs urgent surgery.

Dr. Jerry Estep:
You know Haytham did a great job, he set the stage about the variable clinical course, we certainly know patients can be asymptomatic post-COVID, or mildly symptomatic, but it's those patients that have more severe illness that can land in the ICU, and their mortality has just been horrific, 39, 72 percent, and I think the consideration is many patients still need surgery, some elective, some urgent, and he really did a good job reviewing what's been published, and there's still a paucity of data that's out there, he did a good job highlighting what may seem like a low, for example, STS risk patient, have a complicated post-operative course, and so again, highlighting the approach we take involving cardiac surgeons, cardiologists, ID, pulmonary, and putting forth really a consensus statement to guide all of us in terms of how long should we wait to delay elective surgery?

Dr. Jerry Estep:
For example, 30 days from respiratory symptoms if it's truly elective, but urgent surgery, if possible, waiting 14 days, but being very sensitive to the CT scan and understanding the pulmonary complications and working as a team. So he really set the stage nicely and comes up with a real clear summary, take-home messages that I think will help many people out.

Dr. Eric Roselli:
Yeah, it's interesting to see over the last year how we've all sort of helped each other make sure that no one in any one position is panicking, you know? I mean we established protocols where we had set aside an operating room for COVID-positive patients in the event that we were going to need to be operating on a whole bunch of people that were infected in emergency situations. We didn't really see a ton of that happen, thank goodness, but we've been prepared and we've been continuously sort of very dynamic in the learning phases of this, and it's really been great to see how the critical care cardiology team has taken a lead in staying on top of a lot of the emerging therapeutics for dealing with COVID-19 and how it effects the entire body, not just the cardiorespiratory system.

Dr. Eric Roselli:
And Paul Cremer, one of our staff cardiologists who's very involved in both critical care and general cardiology and imaging, has taken a lead in this running several trials both internally with groups nationally as well, gives us a nice review of this. Can you maybe hit some of the highlights of this?

Dr. Jerry Estep:
Paul does, you know, involved from a research perspective, as you mentioned from an expert clinician perspective, does a great job reviewing the stages of COVID infection and where these therapeutics play a role and does a real good job reviewing the data surrounding remdesivir, neutralizing antibodies, Dexamethasone, steroid use, and addresses add-on anti-inflammatory therapies, and I think for us to be able to walk away and understand, albeit modest, but the benefits of remdesivir and perhaps the limited unclear benefits of these neutralizing antibodies, positions us to better care for patients. So Paul really puts it all together in a short amount of time and makes what can be complicated, very less complicated and very clear in a very thorough review.

Dr. Eric Roselli:
Yeah and I like the way he sort of finished with sort of some ideas about next steps and a lot of ... a discussion with sort of some unanswered questions and where all that's going. It's been really cool to see how well a lot of different centers have been communicating about the things that we're learning so quickly about all of this, and one of the things that we learned of course really quickly from our MICU colleagues was this issue of how the virus, especially in the hospitalized patients, of the effects to the thrombotic system, and we have the head of our vascular medicine department, Scott Cameron who is a leading researcher in platelet function and dysfunction, discussing what we've learned a bit so far about the incidence and outcomes in patients who have thrombotic events associated with COVID-19.

Dr. Jerry Estep:
You know Scott did a great job highlighting that these thrombotic events certainly are more common, but it was nice to see what we've been practicing with the use of prophylactic anticoagulation, even in the absence of venous thromboembolism for hospitalized or ICU patients is appropriate, and you know, he goes above and beyond that and reviews, really highlights, the lack of evidence to support post-discharge anticoagulation, and he does a very good job highlighting the unanswered questions, which really does set the stage for investigation on whether low molecular weight or un-fractionated heparin is better or worse, and the role of platelets and platelet inhibitors.

Dr. Jerry Estep:
And many people think, well maybe aspirin has a protective effect against thrombosis, and he reviews that data, and it doesn't appear to have a protective effect, and so much to learn from Scott as usual with a great review of COVID-19 and thrombosis.

Dr. Eric Roselli:
Yeah, aspirin seems to be ... nice old drug that keeps getting a lot of undue attention maybe.

Dr. Jerry Estep:
And it is funny that you laugh because you know, aspirin use or misuse, I should say, is one of the current controversies in cardiovascular management, and certainly the intent of this podcast is not to get into those details, but I think we have a low threshold to recommend aspirin, and I think it's nice for him to include those concepts and to be clear, as the evidence is right now not supportive of mitigating, minimizing thrombosis post-COVID with aspirin use, but we do use aspirin.

Dr. Eric Roselli:
I'm sure if there's any guests who are neurologists listening in, you know, they're probably happy about that, and then we switch gears to discuss some of the patients who are most severely affected with respiratory problems related to COVID-19, and you know, we've done a lot of work in the last few years of really working to get our Pulmonary Institute team and our cardiothoracic team, especially our lung transplant and lung failure team to focus on developing better protocols to handle patients with really advanced-stage respiratory failure, so that we could help the medical service to understand what we've learned over the several really decades of use with ECMO and how to apply it in the patients with respiratory failure and the ideal situations.

Dr. Eric Roselli:
And I think what we've learned just in the last few years of how we take care of people that present maybe with really severe PE or other respiratory failure, we were sort of set up to learn pretty quickly about how to manage those advance-stage patients with COVID-19 pulmonary failure, and James Yun who is one of our lung transplanters, and who by the way, his wife is also a pulmonologist who takes care of patients with really advanced-stage respiratory failure, they are kind of a dynamic duo there, he gives us a really nice discussion about the role of respiratory ECMO and lung transplant for patients with COVID-19.

Dr. Jerry Estep:
Yeah, one of the things I liked that James did, I liked many things he did, he put forth our respiratory ECMO guidelines in a clear way, and he goes over the 15 patients in this setting of COVID using ECMO in 15 as a bridge to recovery or a decision that was 11 of the 15, and then we're asking ourself, is there a role of transplant in those that develop end-stage lung disease, or in our arena, end-stage heart disease, and goes over, you know, these case ... series of four patients where ECMO was used as a bridge to lung transplant, and some of the lessons learned in highlights, I think merit reviewing. Multi-organ dysfunction and multiple infections is typical in prolonged ECMO therapy in this patient population, I guess, should be anticipated.

Dr. Jerry Estep:
And I think timing, there's a limited transplant window, if you will, in terms of the projected benefits and these patients can have not only multi-organ failure, subsequent infections from being in the hospital. So he highlights those key concepts and I think it remains to be determined, you know, longterm outcomes, but he really sets the stage for consideration of something like lung transplant for these select patients.

Dr. Eric Roselli:
Yeah I think we've even transplanted another one since this discussion, so a lot to learn here, great to get sort of an early discussion of what we've done with these severely affected patients out there as soon as possible. I've been involved in just some email threads with friends from different centers that are involved in this, and there's been some sharing of ideas, hopefully sooner or later we'll be able to pull together some bigger numbers and get a better understanding about how to refine those kind of decision-making processes, but that was an excellent review and again, it's all about sort of bringing a bunch of people together when we're dealing with a complex problem and we have to move fast to sort of come up with solutions.

Dr. Eric Roselli:
We took the lead here in our center to help address this question about what do we do with patients who are in the late phases of recovery after having a COVID infection and about the late effects. I think that it'd be really nice for the audience to hear the full discussion, but can you give us a little introduction to the talk that we're going to hear that you gave on January 6th?

Dr. Jerry Estep:
Yeah, I had the privileged really to represent a large group, as you mentioned, representation in our group put this together from pulmonary ID, internal medicine, rheumatology, psychiatry, neurology, what we're learning is, is that as patients recover from active infection, many, and to be quite honest it's most, may have symptoms or multiple symptoms, including vague symptoms like fatigue, breathlessness, chest pain, and there's been some publications along those lines which I highlight, and so for us in HVTI, recognizing that these symptoms may have an underlying cardiac or cardiovascular involvement, we wanted to really position ourself to manage this growing patient population, and there's been now a number of publications that highlight after COVID infection there can be inflammation in the heart, inflammation in the lining around the heart, the pericardium, mild pericarditis has been certainly reported, and at the microvascular level coronary disease involvement, and as Scott mentioned, the potential for vascular complications.

Dr. Jerry Estep:
And so getting together to form this recovery clinic, and we actually have a brick and mortar true clinic at Independence where advanced practice providers are triaging appropriate patients to the different subspecialists, but within HVTI we've put forth a really fantastic effort to put focused evaluation and screening on those with potential cardiovascular complications, and so patients will be seen by a general cardiologist, or a sub-specialist who will look at baseline EKG, echocardiogram, a good physical exam, and then further phenotype, if you will, whether they have problems related to arrhythmia or heart failure or pericardial or vascular.

Dr. Jerry Estep:
One of the things I'm excited about is understanding the true incidence, or longterm cardiovascular implications. So we're positioning ourself to certainly identify patients, be clear if they have cardiovascular complications or not, those with symptoms, and then offer the appropriate treatments, and then I think we're going to be positioned nicely to highlight what is the true incidence of these different diseases. So it's been an effort that's been fun to be part of, and within HVTI, Mina Chung from EP and we have clinical cardiology representation from Heba Wassif and sports cardiology, even these young, healthy athletes can develop post-COVID complications and Tamanna Singh and Michael Emory, and then others in heart failure imaging and vascular medicine.

Dr. Jerry Estep:
And so just a fantastic group, we have our smart sets built out, we have easy access into our clinics, but working appropriately with a large team to understand issues outside of the heart and vascular realm. So we're fantastic ... excited about this launch and look forward to help caring for these patients.

Dr. Eric Roselli:
That's awesome Jerry, I mean you did this so quickly, they picked the right guy to do it. Let me ask you a quick question for the audience. You know we've seen the number of hospitalized patients, the numbers have come down, especially recently which is fantastic, I've paid attention all along to what the mortality rate's been for hospitalized patients and you know, early it was closer to 15%, now we're in the sort of single digit range, so we are seeing a lot more people survive even severe presentations of the disease, who should we refer to a clinic like that? Should it be anybody that was affected? Should it be people with certain risk factors? Should it be everybody who was sick enough to be hospitalized? How do we decide who to send there for a workup?

Dr. Jerry Estep:
You know I think that's a fantastic question, and you know, in our website, which you can go to, HVTI Recovery Center, you know, COVID Recovery Center, we want to see patients that had COVID. Now I think we're learning not everybody had a positive test, right? Many weren't tested, but if patients felt like they had COVID or you knew they had COVID and they're having persistent symptoms, and it's 28, 30 days from their active infection, chest pain, shortness of breath, fatigue, heart palpitations, exercise intolerance, they were once able to work on the treadmill, now no longer, we want to see these patients, because they may have a cardiovascular problem that needs attention, it needs to be diagnosed and addressed.

Dr. Jerry Estep:
And so we want to see patients with persistent symptoms, the ones I mentioned, you know, typically four weeks after their infection. Now you made a good point in that there are patients that are higher risk to have more severe complications, and we certainly recognize those are patients with preexisting hypertension, heart failure, certainly those post solid organ transplant, and so patients who have preexisting cardiovascular disease, hypertension, heart failure, I'll throw in AFib, and if they had COVID and want to ensure they're stable, we're happy to see those patients as well.

Dr. Jerry Estep:
So it's a two-fold patient population, they had COVID, thought they had COVID, have symptoms, want to make sure it's not cardiovascular in etiology, we'd love to see, and those with cardiovascular disease that had COVID and want to ensure that they're doing okay, we're very open and happy to see.

Dr. Eric Roselli:
Very good. We'll establish I'm sure, a really nice database and be able to provide some research to guide others about those longterm effects going forward. We then move forward in this Tall Rounds event to also hear about other enterprise research efforts from Dan Culver, one of our pulmonologists and intensivists who's taken a lead in this from an enterprise standpoint, and also gives us a bit of an update on where we stand with vaccines, although that's already changed in a matter of weeks.

Dr. Jerry Estep:
Right, you know Dan does a good job setting the stage, reviewing the several completed inpatient trials performed here within the Cleveland Clinic system and highlights the outpatient trials and those that are starting, so you know, close to 20 trials and highlights, and reviews our COVID registry which is just robust, positioning us to understand implications of COVID and best treatment, and what I really like that he did, he gets into the details of this mRNA vaccines, and we certainly are hearing Pfizer and Moderna and now Johnson and Johnson, and he shows what we know, and I think many of us now are understanding that it's high efficacy, right?

Dr. Jerry Estep:
95% and we certainly appreciate a booster is needed, but he defines what we don't know, and I think these are the next steps related to durability post-vaccine. Effect on transmission post-vaccination. So Dan nicely puts it together, if you will, not only highlighting where we're at as it relates to vaccines and trials, but where the focus needs to be, if you will, moving forward.

Dr. Eric Roselli:
Yeah that was a great presentation by Dan, and it really kind of flows really nicely into the final presenter from the group who has been the chairman of our Department of Infectious Disease now for several years, Steve Gordon, who's clearly been involved with this and Steve has done just a fantastic job over the last 15 months of being a voice of reason, like Dr. Fauci I think, you know, Steve has made sure that we're updated on the current knowledge and not panicking but well prepared for what's to come, and has just been a fantastic sort of a pillar of infectious disease care for us here, through this whole thing, so it was really nice to wind down the program by hearing Dr. Gordon's discussion of the infectious disease forecast of what's to come and what we can look forward to this.

Dr. Eric Roselli:
This is an appropriate talk for us to share and after you and I are done here, our listeners will be able to hear that discussion from Steve Gordon, talking about his forecast. If any of you are interested in seeing the entire Tall Rounds and the opportunity to get free CME, please join us for the online, you can watch both the slides and the speaker discussing them, as well as a panel discussion at the end of this talk, just like all of our Tall Rounds, the complimentary CME, something we're happy to provide, not only in this currently virtual educational environment, but will be a long-lasting educational product for those of you going forward, gives an opportunity to give a front-row seat at the Cleveland Clinic to participate in our very exciting and well-attended and progressive teaching program.

Dr. Eric Roselli:
Jerry, thanks for talking with me today on our Talking Tall Rounds event, and I look forward to doing one of these again with you in the future.

Dr. Jerry Estep:
Eric, thanks for having me, participating in the Tall Rounds was fun and this was equally fun, and hope to be asked again.

Dr. Eric Roselli:
Awesome, thanks man.

Dr. Jerry Estep:
Thanks buddy.

Dr. Jerry Estep:
Thank you Dr. Svensson for the opportunity on behalf of our working group to help define our approach to establishing a recovery center to better understand these patients that acquire and are recovering from COVID infection, and certainly I think we have all appreciated that patients with underlying cardiovascular disease, namely hypertension, coronary artery disease, and those with heart failure with reduced EF, in addition to those on immunosuppression like after a heart transplant, these patients are at higher risk for major complications during their acute COVID infections, felt that one in four patients hospitalized have cardiovascular involvement, and certainly a mortality as high as 40% for those that develop cardiovascular complications.

Dr. Jerry Estep:
Where there's a real opportunity to better understand the longterm sequelae relates to potential cardiovascular screening, and when you look at the reported symptoms and signs that patients are presenting with, two to three months after infection, many of these may have an underlying cardiovascular explanation. We've learned from our colleagues in Rome, Italy that had a nice JAMA research letter this past year, demonstrating the frequency of symptoms as exemplified on the right-hand side of the screen, during the acute COVID phase, and certainly those post-COVID.

Dr. Jerry Estep:
This was a little over 140 patients, 60 days after the acute infection, and you can appreciate that certainly the majority of patients, a little over 80% had at least one symptom present a few months after, and the most frequent symptoms being reported include fatigue, dyspnea, and chest pain. Now there's an effort to better phenotype the underlying reason as to why, and I feel that there's potentially a significant cardiac contribution to perhaps some of these persistent symptoms.

Dr. Jerry Estep:
So I've listed here the potential cardiovascular involvement in patients recovering from COVID, from myocardial, pericardial, myopericardial, coronary, and we've heard from Scott the potential vascular implications, and certainly we've learned from publications, and they are evolving, data sets where as high as 60% have evidence of active cardiac inflammation months after original COVID infection, and when you look at cardiac biomarkers like elevated troponin, it can be as high as 75% of patients that are in the recovery or convalescent phase, but certainly much to learn in terms of what are the implications.

Dr. Jerry Estep:
Several weeks ago I was asked to help organize the HVTI Recovery Center efforts and similar work was being done and supported by our colleagues in 4C so we have aligned, if you will, related to developing this post-COVID center of excellence and it includes a number of sub-specialties and efforts as exemplified here from pulmonary, neurology, cardiology, psychiatry, functional medicine. This is an important opportunity for us as an organization to perspectively define the outcomes of these patients that are recovering in terms of potential research. Kristen Englund has taken the lead from infectious disease with colleagues in 4C, Chris Baubich and Bill Lago, and Mina Chung's been instrumental in representing our cardiovascular medicine efforts.

Dr. Jerry Estep:
So really it's a collaborative effort both from leveraging resources in the family health center, this is actually going to be a launch with an actual clinic supported by APPs and coordinators in February 1st in 2021 upcoming, and again, at the family health center, and we are in alignment in terms of our efforts within HVTI to best triage our patients that end up having disease outside of the cardiovascular realm, and Michelle Biehl and Samar Farha have been instrumental in this working group from a pulmonary perspective. Now the rationale to focus in on the ... from a HVTI perspective are listed here, I've mentioned the implications of underlying cardiovascular disease and the prevalence of active inflammation by cardiac MRI and biomarkers, and we've learned that myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and there are concerns that subclinical or possibly overt cardiovascular abnormalities may be related not only to cardiomyopathy phenotype, but the development of cardiac arrhythmias or vascular abnormalities.

Dr. Jerry Estep:
And so I think us grouping together, we're best positioned to understand the longterm sequelae of post-COVID-19 on the cardiovascular system. So we're ... set up a website which will be launched hopefully in the next week or two, we have a clear aim to evaluate and screen patients for post-COVID cardiovascular complications, and offer a personalized plan to deliver cardiovascular care, and importantly to check and screen for symptoms and signs and appropriate referral for those with respiratory and/or neurocognitive changes, so we'll leverage the recovery center's efforts, and our patient population's going to be related to those that are post-COVID-19, whether they did or did not require a hospitalization, but have ongoing symptoms that may have an underlying cardiovascular etiology.

Dr. Jerry Estep:
Again this is four weeks after their original infection, and we're very open to those with preexisting disease to ensure stability of their cardiovascular status. Patients will be seen by a general cardiologist, or a cardiology sub-specialist, they'll undergo EKG for those that are symptomatic or evidence of biomarker elevation and echocardiogram, and we will be reserving additional diagnostic testing relating to cardiac MRI or cardiac pulmonary exercise testing, rhythm monitoring, chest CT, duplex testing, based on symptoms and signs and keeping with clinical standards, and our aim here is to understand the longterm cardiovascular implications and we will be pursuing and treating patients along the lines of clinical standards.

Dr. Jerry Estep:
So here's our HVTI CVM working group with representation from electrophysiology quality, clinical cardiology, sports cardiology, heart failure, imaging and vascular medicine, and we've aligned with HVTI's scheduling in our triage HVTI referral line, to ensure that patients are being triaged ideally first to clinical cardiology, but certainly those patients that have underlying heart failure are welcome to be seen in the heart failure section, and those with underlying arrhythmia or syncope or presyncope seen by our EP colleagues, vascular medicine, and certainly known athletes or those that engage in intense recreational activity be seen by our colleagues in sports cardiology.

Dr. Jerry Estep:
And so the monitoring goals are to understand patient volume and encounters based upon e-consults. We have implemented an effort to ensure we capture patient-reported outcome measures and by use of specialty care pathways and smart-set utilizing, we think this is going to best position us ... for us to understand the cardiovascular disease burden clinical outcomes, and so when you take a step back, this slide's courtesy of Kristen England, assuming from a conservative perspective 10% of all positive ... COVID-19 positive patients, certainly looking within Ohio and the Cleveland Clinic system and including caregivers, we're anticipating several thousand patients potentially eligible to benefit from these services.

Dr. Jerry Estep:
So I appreciate the opportunity to provide this update and we look forward to this very important multi-disciplinary launch. Thank you.

Dr. Steven Gordon:
I'm going to talk about what I call the frameworks of intervention to stop the pandemic. Just briefly as Dan mentioned, vaccination is the gateway for heard immunity, and then talk about other things, what I call the disruptability index, in particular with healthcare in something that you don't like to do, forecasting. So I think it's nice to put this into perspective, we hear from groups that this is just like the flu, this is just not like the flu, but if we compare SARS-CoV-2 to other respiratory pandemics where we have data, you can see that it's very closely aligned in terms of transmissibility and severity with the 1918 worldwide pandemic, and it's worse that obviously some of the other flu pandemics we're seen, and so I think that's important to underscore that there's no question that this has caused a lot of morbidity and mortality.

Dr. Steven Gordon:
The other thing is from the epidemiology point of view, which informs our decisions and also where we're shooting the vaccines, is this epidemic curve, which we call this reverse-L, so this means of course, fortunately children and young people are relatively spared from the most severe outcomes including death, and that's also the reason why obviously as Dan mentioned, kids were not included in any of these vaccine trials. The other thing we're learning about is why are children particularly more protected, a lot of this looks to be that they have a much more robust, what we'd say innate immune response than adults, potentially related to more recent exposures to the other non-pandemic COVID strains, but this is still being worked out, but we are very happy for this, to be honest.

Dr. Steven Gordon:
Because if children were dying, this would have a much different face globally. The other thing that we like to look at is the mortality impact, and again as was already mentioned by Dr. Estep, you can get COVID-19, not be hospitalized, still have severe sequelae but mortality is something obviously that we focus on, and I'd like to ... like this side because this compares epidemic deaths per 1000 people on the top, and the epidemics we're including include the opioid use disorder as well as HIV, so for me this is my third epidemic that I've experienced in my career.

Dr. Steven Gordon:
And you can see that COVID-19, about three per 1000, similar to what you would say we're seeing in the opioid use disorder, about similar to HIV pre-treatment, but not at the levels of Spanish Flu. Now as epidemiologists we like to adjust that for years of productive life lost, so this takes into account whom is getting infected, and again, because of that L-shaped curve we see, is that COVID-19, you can see the total life years lost is not as bad as the Spanish Flu where children were ... and young adults were affected. HIV obviously also primarily untreated was a disease of relatively younger population, as well as our opioid use epidemic in terms of overdoses.

Dr. Steven Gordon:
So just different ways of adjusting for the impact. The other thing that we learned, and this comes from ... many of you may recognize this who are into what we would say safety in terms of this Swiss cheese model of avoidance and error, when we look at what we've done for the pandemic, we put in what we would call non-pharmacologic interventions at the individual level, so that's our own what we do, distancing, hand hygiene, how our own behavior is, as well as societal interventions, so these are things that government reigns down in terms of no-fly orders or things of this nature, but in the end, as Dan has mentioned, we believe that the biggest impact is going to be widely distributed, effective vaccines globally to put an end to this pandemic, and we've entered that era.

Dr. Steven Gordon:
And it's interesting when we talk about the politics of vaccination, this is a long-standing, how could I say, issue. I like this book by Eula Bliss, and on the cover you can see this is the mother dipping ... Thetis is dipping her infant son Achilles into the river Styx because she had angered a god, and knew that he was going to go after, potentially, Achilles, so this is also important because if we think about passive immunization, it is the maternal-fetal antibody transfer that occurs that protects those children again from other vaccine-preventables during that first six months. So again, this is the global WHO goal in terms of ending the pandemic.

Dr. Steven Gordon:
I don't want to get into the details, as Dan mentioned, we're fortunate to have the two mRNA vaccines, and you don't need to be a scientist to know which curve you want to be on in terms of avoidance of vaccination. I do want to point out there was not a single arm dose, people have talked about one arm being effective, so it's very difficult to make those calculations in terms of protection on one vaccine, this is becoming important because as you know, the UK now is deciding on vaccine policy whether to interrupt that second dose to provide more first doses in light of the mutation.

Dr. Steven Gordon:
We've all learned and we've been fortunate ... I've been schooled by Dr. Culver in terms of the research is that this is also about science ... implementation science, but also about ethics, and this has never gone away from medicine, and this is something that we're blessed with at the clinic to have open, transparent discussions as well as experts. I also want to talk about this because we're seeing right now a Tale of Two Cities, I've gotten a lot of emails, let's say, of colleagues and wanting the vaccine, why am I in line, and then that contrast to other parts of our population shown here, including the African American, the less educated, elderly, where, "Not for me," and so as Dan mentioned, this is a Tale of Two Cities, we have to address that as we move forward, especially in light of the fact that if we have more transmissible virus, that number of herd immunity is going to go higher and not lower.

Dr. Steven Gordon:
Don't want to spend too much time on this, but you know, as an RNA virus obviously in use to HIV, mutations are readily available, coronaviruses don't mutate as quickly as HIV fortunately, much bigger genome, but also has a polymerase, but these, what we call variants of concern, VOC, is now in the new lexicon, the UK isolate was the first to be identified, this is what I call multi-resistant ... I mean multi-mutation, so it's got 14 mutations, eight in the spike, and three that are probably important, including the one that's been associated with more affinity into the ACE-2 binding, so stay tuned to this, this becomes important because the transmissibility appears to be more probably increased viral load, in terms of not reemergence or reinfections, but this, I think, is the one reason for policy to accelerate getting vaccine into arms.

Dr. Steven Gordon:
And again, you know sequencing has occurred throughout, the UK had led sequencing globally, they've sequenced probably two to three times the number of isolates that we've done in the states, which is about 51,000. As you know we have identified this VOC in the states, which is not a surprise given the prevalence of the strains in the UK, and the travel patterns, and we're all used to that in terms of mapping how the pandemic spread are facilitated by airplanes, not necessarily spread on airplanes, but airplanes being like mosquitoes driving people incubating to all parts of the world.

Dr. Steven Gordon:
So I think this has become important, that just shows that the horse is probably out of the barn, so to speak, and that it's no surprise we're going to find these variants all over when we begin to look for them. So I want to pivot to disruption, because you know, this has been preached by our leaders at the clinic as long as I've been in here, disruption creates opportunity, and this is an interesting book by Scott Galway which is a pretty good read. So if we go outside of healthcare, if you look at where the growth and market capitalization, you're seeing the big four here, Google, Microsoft, Facebook, and Apple, and of course Netflix because that's what a lot of people have been doing, streaming, and they were set up for this, they had already invested in what we call their data farms in terms of that last mile of delivery of services, so they were prepared for this, not that they created this.

Dr. Steven Gordon:
That other curve is not the epidemic curve of COVID, that's the hiring of Amazon, and so the jobs are flowing there and we know we have that center in Warrensville Heights which is also busy. So what we're learning in supply chain as well, potentially, is moving from what we would call just-in-time, which was the mantra, even for here, to maybe just-in-case, and that is making sure we have the ability, whether it's ventilators, machines, masks, that we still have locally-sourced operations, even if it costs more. The other thing is, let's be wary, because you know the Amazon, the Googles, they figured out a lot of things, and then they're going to where the money is, and two big pockets of the federal government where we spend a lot of money, where they're not quite there yet are education, and for those of you paying college tuitions for kids staying in your basement I think you probably are wondering what the value is there, as well as healthcare.

Dr. Steven Gordon:
And so this includes us, as efficient as we think we are, and what they point out in the book is that opportunity increases when there's a dramatic increase in price with no accompanying increase in value or innovation, that honor in margin, and although I think we think we're innovative, there are many that would still look at healthcare and say it hasn't justified the increase in price, similar to what you're paying for your liberal arts educations.

Dr. Steven Gordon:
And then to put this into play, many of you are aware, new algorithms, I think one of the issues obviously has been testing availability, and us saying that only RT-PCR is the gold standard, but in defacto you need to push out, what we would say, less sensitive, less specific testing such as the antigen testing, and CDC is kind of moving in that direction in terms of here, but this creates what we would say opportunity, so now you have companies pushing out molecular testing in the household for COVID, and as I said, who's good at that, what we call that last-mile delivery? Amazon or Google, so boom, they can get the product there, they can get the medication there as needed, and then I become the Uber driver, they need me, but ... so let's not kid ourselves, and this won't stop at COVID, because if you're having tests being done at home for ... molecular tests for COVID-19, why not for other things?

Dr. Steven Gordon:
And so we can see where this may be going. Okay so finally forecasting, and I'm going to define the end of the pandemic going back to Kubler Ross's model of stages of grief, denial, anger, bargaining, depression, and acceptance. So at the acceptance where we define now COVID-19 becomes a part of our normal life, similar to what we think about flu or the Browns losing or winning. So we will reach herd immunity, that is to say 60 or 90% of the population, hopefully through vaccination and not through natural infection, the pathogen may evolve to become less lethal, similar to say the other strains, OC43 strains of COVID-19, that may happen. The pathogen may disappear, similar to SARS-1 or become dormant. I wouldn't bet on that, it's really unlikely where there's animal reservoirs that you're going to ever eliminate a pathogen from humans.

Dr. Steven Gordon:
The only time that happens is like with smallpox where there is no animal reservoir, or humans will evolve to become resistant, which probably could happen, but that's going to take a long time, so we're hopefully putting our money on Dan's vaccines, but the other thing to remember is this is not going to be the last spillover pandemic, there has been what we would call anthropozoonotic and zoonotic transmission that is from minks to the workers in ... the mink workers and back and forth, so this has already occurred, resulting in the culling of 17 million commercial minks, and remember, most of our new and emerging infectious diseases over the past few decades have come from animals, and so hopefully we are now going to be prepared for the next thing that will occur in terms of platform and surveillance.

Dr. Steven Gordon:
And I'll leave on a quote from Osler, "Humanity has but three great enemies, fever, famine, and war, of these by far the greatest, by far the most terrible, is fever." Thank you.

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