The COVID-19 pandemic created many diagnostic challenges for clinicians and laboratorians world-wide. Even during the relatively quiet "off-peak" periods of acute COVID-19, there remain the challenges of helping the large group of patients left with the shrapnel of "long COVID-19." This webinar will focus on the cardiovascular elements of acute COVID-19 and long COVID-19 with an emphasis on how deployment of known cardiovascular biomarkers can help aid in the identification, risk-stratification and treatment of patients.
- Identify the cardiovascular elements of acute COVID-19
- Explain how cardiovascular biomarkers can help with the risk-stratification and treatment of patients
- Identify the cardiovascular elements of long COVID-19
- Examine the consequences of pandemic-related access to care on cardiovascular patients
Presented by: Dr. Sean Xavier Neath
- Minute 00:50 – Introduction
- Minute 02:50 – Cardiovascular complications from acute COVID-19
- Minute 07:10 – The role of biomarkers in diagnosis and care
- Minute 08:45 – Troponin measurement
- Minute 13:45 – Natriuretic peptide measurement
- Minute 16:25 – D-dimer measurement
- Minute 20:30 – Anticoagulation algorithm
- Minute 21:45 – COVID-19-related thrombosis
- Minute 23:35 – Long-term health consequences of COVID-19
- Minute 37:20 – Q&A
Mary Beth: Hello and welcome. My name is Mary Beth [inaudible] from McKesson Medical-Surgical. Today's presentation is being recorded. To submit questions, please locate the Q&A panel in the lower left corner of your console.
Today's presenter is Dr. Sean Xavier Neath. Dr. Neath earned his PhD and MD from the University of Chicago. He completed his internship at Mercy Hospital in San Diego and his residency at the University of California, San Diego, where he is currently a faculty member in the Emergency and Urgent Care Medical Department. His research interests include application of novel biomarkers in the diagnosis and management of acute medical conditions. Please join me in welcoming Dr. Neath.
Sean Xavier Neath: Thank you very much, Mary Beth, and thank you all for joining us for what I hope will be an informative discussion about the cardiovascular effects of COVID and how a number of currently available biomarkers can help in the workup and management of these patients.
So briefly, my disclosures. I do have consultant relationships with several biotechnology companies working in the development of biomarkers for acute disease states, as well as in the quality assurance process for existing tests. The opinions in this talk are uniquely my own and do not necessarily reflect the views of my institution, any corporation, or regulatory body.
And hopefully, we'll have plenty of time for questions, so feel free to enter them at any point during the talk and we'll get to as many as possible at the end of the talk. Our goals here are to review acute COVID-19 with an emphasis on its myriad cardiovascular effects. Obviously, COVID, as we all know, affects multiple systems in the body, and the cardiovascular system is not spared.
I'd like to discuss the utility of biomarkers and the diagnosis and management of these issues. We'll spend some time talking about some cardiovascular elements of long COVID and long COVID in general. And finally, looking at the global impact, the consequences of the pandemic itself, and pandemic related access to care for cardiovascular patients.
By now, I'm sure most of us either have had or are intimately familiar with acute COVID-19. Most bouts of COVID, in our experience last about 5 to 10 days. And for most patients, an uneventful recovery. Other than the small subset that go on or have protracted symptoms. Now, we've thought somewhere in the very beginning, we think of this primarily as a respiratory disease, but it actually has a pretty profound impact on the cardiovascular system. And we'll be focusing on this during the talk.
There's an interplay, obviously, between the heart and lungs. They both occupy the thorax. And so, the respiratory and cardiovascular components of acute 19 are interwoven. It turns out that the risk factors for cardiovascular effects from COVID are actually similar to those for previously existing heart diseases, such as heart failure and acute myocardial infarction. And it's principally older patients, obesity, diabetes, patients with kidney disease and certain other risk factors.
The acute COVID myocardial injury is thought to have a lot of potential factors that are all playing in together. There's direct viral toxicity of the virus at the level of the endothelium. There is a release of inflammatory cytokines that wreak their own havoc on the body. And probably one of the biggest regions of concern is this issue of thrombosis and vasculitis that occurs in all the vasculature, but concerningly in the pulmonary vasculature.
Additionally, for many people, there's an autoimmune response in the context of COVID, which creates a fourth layer of complexity, all of which lead to a number of cardiovascular sequelae. Heart attack obviously being a major one. Now, cardio infarction of concern, but a number of other equally important issues such as injury to the ventricles resulting in heart failure, viral myocarditis, inflammatory responses, and other issues.
Now, as I mentioned, patients with pre-existing cardiovascular conditions are at higher risk to experience severe COVID. But that does not mean that somebody who is not previously healthy for some certain reasons that we've not fully elucidated can develop pretty severe cardiovascular issues with COVID. The patients who are hospitalized with severe COVID have a higher rate of cardiovascular complications during and after their hospital stay. And that includes heart attack, heart failure, the thrombotic events, and myocarditis.
The fact that COVID can cause myocarditis and pericarditis is not limited to patients with previously existing heart disease. We actually see a fair amount of it in relatively young people. Now, these cases typically are mild and concerningly manifest as chest pain in the patients. They go away with the end of the viremia and the host response to the virus for most patients. But in others they can cause complications.
As we mentioned, heart failure is an issue both with acute COVID and then the sequelae of COVID. Stroke, ACS, and arrhythmias such as atrial fibrillation. A patient who has a propensity, for instance, for paroxysmal atrial fibrillation is going to have an increased risk of atrial fibrillation events during their illness. All of these can cause patients with preexisting conditions to have a relapse of their underlying cardiovascular conditions, worsening quality of life.
This scheme shows kind of where the various insults can occur for the cardiovascular complications. The virus itself replicates fairly freely for usually the first week of illness, sometimes less, sometimes more. And then there's an antibody response, some of which is a bit maladaptive and can cause the autoimmune or the inflammatory conditions that I briefly mentioned earlier.
Finally, myocarditis and heart failure can be seen as a rare but serious complication of the mRNA COVID vaccines. So, at the population level, the vaccine protection from COVID is generally outweighing the risks. Of course, if you're that patient who's had some vaccine related side effects, there's little solace to you. But in general, we're much better off getting the vaccination than not getting the vaccination.
Now onto the world of biomarkers and how they play into the management and the diagnosis and the care of patients with COVID. There are a number of already existing and well-known cardiovascular biomarkers that have prognostic utility in COVID patients. Cardiac troponin, now available in the US for at least a couple of decades, is a necrosis marker. And while we think that primarily as a marker of heart attack, it is a strong signal of damage to the heart in a variety of mechanisms and it's useful to track in patients with COVID related chest symptoms.
The nature of peptides such as BNP or NT-ProBNP performed very similarly in the diagnosis of superimposed heart failure. We'll talk about that a little bit. And perhaps one of the very useful biomarkers with this interesting virus is D-dimer. D-dimer in this case is a thrombosis marker. And I'll make the point several times during this talk that there is an unusual amount of thrombosis clotting type dysfunction going on in COVID. So, D-dimer provides a sentinel alert that there is no adaptive response in that regard.
So, these three markers can be utilized to risk stratify patients as soon as the emergency department, but certainly, during the hospital stay with COVID. And there's fairly good research that shows that a troponin level or a D-dimer level that's twice the upper limits of normal is associated with severe risk for severe COVID.
There's recommendations that troponin should be measured in hospitalized patients with COVID and that repeat testing be performed if that initial result is abnormal to delta, it or to trend it, and/or if new clinical criteria arise. So, there are patients who enter the hospital with shortness of breath or pulmonary dysfunction from COVID who really have no initial suggestions that the heart is involved.
But unfortunately, as the disease progresses in some individuals can develop these. So that is an indication for retesting. So, these markers are dynamic. They follow at this change in the patient's process, reassessment should be made.
In non-critically ill COVID patients, there are troponin elevations that are seen, but there's an acceptance of what truly is an abnormal level. So, levels of up to three times the upper limits of normal often will indicate prior cardiac disease or myocardial ischemia related to respiratory failure rather than myocardial ischemia related to coronary artery blockages.
So, this is another schema of that representative troponin elevations. A healthy person with mild COVID, no prior cardiac disease should have a troponin that is normal and certainly not above the upper limits of normal. Patients with chronic cardiac disease will have oftentimes a troponin that goes anywhere from one to three times the upper limits of normal.
When we start seeing these higher elevations of troponin, we're concerned about patients with having a small MI, maybe a Type 2 MI and exacerbation of underlying heart failure. And we'll talk a little bit later about pulmonary embolism. That's what the PE stands for. There is myocardial stress that occurs when there's a clot in the lungs and the troponin can be a signal for that.
Finally, very, very high elevations, uncharacteristically high for that patient or well above ten times the upper limits of normal, indicates that there could be a myocardial infarction and other types of cardiac ailments, such as myocarditis or a [inaudible] type syndrome.
Now, this slide is actually old but very still useful data that shows when a patient is admitted to the ICU for a respiratory disease, let's say that their troponin level is actually predictive of their potential mortality. So, on the bottom axis, we see troponin levels and then the estimated probability of death. Troponin elevations tell us two things, two forms of badness, if you will.
That the patient has a near-term, short-term mortality, risk of death around the time of the ICU admission. But unfortunately, additionally, they have a substantial increase, long-term increase in risk of death due to that troponin elevation. So, making the case here that troponin elevations in general in the context of any acute illness, but especially COVID, are harbingers of potential for outcome.
So, this is kind of an extensive little laundry list of where the troponin may be tracked around the various patients, types of COVID patients in myocardial injury. We do see patients, especially with chronic heart failure who have a baseline chronic troponin elevation. We call that troponin anemia that is usually stable from patient to patient and then increases dramatically or increases noticeably during an exacerbation.
The acute troponin on the right side of the diagram has both ischemic causes and non-ischemic causes. So, when we get too focused in on troponin as an ischemia marker, we forget that a number of other things can cause troponin elevations. Essentially, anything that causes myocyte damage death will release troponin into the system. So, Type 1 MI, which is the big one, the STEMI, that type of thing. Certainly, will cause an increase in troponin in the various forms of Type 2 MI from hypoperfusion of some sort, shock, hypoxia, tachycardia all can lead to an elevation of troponin.
But a number of non-ischemic causes, as we've discussed, can also cause that. So, there's a number of features such as the myocarditis we discussed, pulmonary embolism, but also types of direct toxicity on the cardiac myocytes. And it can be as simple as a cytokine storm, a maladaptive immune response unleashing tons of interleukins and other factors that actually directly damage heart tissue. All of this can be tracked in terms of the amount of damage and the time of onset with troponin fairly effectively.
I'd like to move to the next biomarker here, which is the natriuretic peptides. Now the natriuretic peptides should be measured if heart failure is suspected on clinical grounds, and this is fairly important in many patients. And the subpopulation I'm particularly thinking about now is the elderly, where there's just a large baseline prevalence of heart failure.
And one of the things that we often do in critically ill patients who are hypotensive, their blood pressure has dropped. They have SIRS, they have sepsis, irrespective of whether it's a virus or bacteria. Fluid resuscitation is also frequently used as a major treatment modality. One of the problems comes in patients with existing heart failure who develop it during COVID is carefully monitoring for fluid overload and how to manage this.
And so, the natriuretic peptides have shown themselves to be very useful for this. The natriuretic peptide that we use the cutoffs for non-critically ill patients, they actually have a high positive predictive value even in patients with pneumonia. So, differentiating pneumonia from heart failure is an area of interest for me because heart failure exists in about 10% of cases with pneumonia exist at the same time. And obviously, the management changes when there's superimposed heart failure.
There is a caveat to the use of natriuretic peptides. The tools have to be used with a certain degree of savvy in patients with ARDS, acute respiratory distress syndrome, or septic shock. In these patients, the subset of the extremely sick, there is an overwhelming hemodynamic compensation. And it's very tricky and very difficult to rely on natriuretic peptides for that assessment of decompensation. This is an area where the bedside echo is potentially much more near-term useful.
So, as I mentioned, elucidating superimposed heart failure is a very important place for the natriuretic peptides. Pathophysiologically, BNP and NT-ProBNP levels are increased due to release of a pro-hormone that both of them share, and this is due to stretching of the heart muscle due to increased volume and pressure.
And that can be not just with left ventricular dysfunction, but right ventricular dysfunction, which is why we see an increase of the natriuretic peptides in a very, very bad pulmonary embolism where there's a right ventricular pressure overload associated with that.
So then onto D-dimer, which has become a very useful tool during this pandemic. Physiologically, D-dimers are generated by the cleavage of fibrin monomers, and they signal actually indirectly that there's been thrombus formed because of the nature of fibromyalysis that follows that. So, there are fibronectin products indicating that there's an excessive amount of thrombus somewhere in the body.
In the very beginning of the use of D-dimer, D-dimer was used and still is used for the diagnosis and monitoring of disseminated intravascular coagulation or DIC that's associated with sepsis or shock. And something that was picked up pretty early in the COVID pandemic is these patients were developing really high degrees of coagulopathy that we didn't typically see in other patients with severe influenza who were in the ICU or other types of pneumonia, certainly not at that level.
And the coagulopathy that we see in these tracks very well with the D-dimer. D-dimer is very informative, very elucidating into this particular hematologic aberration. So, the D-dimer testing tells us about the pathophysiologic aspects of COVID in the individual and gives us risk assessment for guidance on the intensity of anticoagulation for patients who are admitted.
So, this is a comparison of survivors versus non-survivors in the use of D-dimer levels. And we see that patients with COVID-19 have progressively increasing D-dimer levels compared to non-survivors. And even with relatively severe COVID requiring hospitalization if you are a survivor, you don't seem to develop this maladaptive thrombosis state and D-dimer levels tend to stay relatively normal.
So, the SARS-CoV-2 virus has a high affinity for endothelial cells, and it induces a condition that's nicknamed endotheliitis, which is basically inflammation of the endothelial lining of the vasculature. And many people working in the field posit that this explains why D-dimer levels are higher in COVID pneumonia than typical pneumonia.
So, this little attack, and I think I've got a diagram of this in a couple of slides, this little attack into the alveoli, into the pulmonary vasculature is fairly unique in terms of the intensity that we see with COVID as compared to similar viruses. And we discussed that the patients with COVID-19 have the increasing D-dimer values which tracks with survival.
So, it is strongly recommended in most of the guidelines now that in hospitalized patients with COVID, monitoring of coagulation parameters help predict deterioration. They help guide therapeutic measures, including the intensity of anticoagulation. One might think, well, let's just blanketly cover all admitted COVID patients with intense anticoagulation. Obviously, that clearly comes with its own side effect risk profile.
So, we want this to be as targeted as possible, we want to identify patients who are at high risk for thrombosis by both their clinical criteria, their medical history, but also by their D-dimer levels. So pharmacological prophylaxis of venous thromboembolism is recommended for all patients hospitalized with COVID. And then further, more intense anticoagulation or even thrombolysis is individualized based on risk factors of D-dimer and other laboratory and ultrasonographic findings.
So, this algorithm is cut off after the second thing, but it's from uptodate.com, which is one of the premier online references that most hospitals and most clinicians are aware of and are using something similar to this. So, when we have patients admitted with COVID, we've developed various order sets through the pandemic that are increasingly reassessed and honed.
And obviously, anticoagulation was missed during the first part of the pandemic because we simply weren't aware of this unique physiologic process that the virus does until we started seeing a number of patients die from pulmonary embolism and other somewhat unexpected degree of complications from thrombosis.
So now if there is definite evidence of ischemia or infarction, the patient either proceeds to thrombolysis or a therapeutic dose of anticoagulation. If they're already on an anticoagulation, they should continue it. And then if they're admitted to the hospital, at least prophylaxis for venous thromboembolism should be considered and then more aggressive anticoagulation if needed.
At the cellular level, this is a relatively busy diagram and I think it's useful because it shows that COVID is just so brilliant in attacking different parts of the physiology and creating havoc at a number of different levels. So, we see that here at the endothelial level, we're looking inside the blood vessel wall, for instance, there's a result of the endothelial injury either directly from the virus or cascades down. We've got clot formation, platelet adhesion, and a number of other factors that lead to the catastrophe of both peripheral thrombosis and intrapulmonary micro thrombosis.
This is a sort of a drill down to one of the initial things about the angiotensin-converting enzyme that was elucidated. Not forgetting how many months or years ago in the pandemic, but relatively early on, it was elucidated that the virus spike protein binds to the angiotensin-converting enzyme receptor leads to the activation of an intermediary protein that promotes externalization of phospholipid onto the outer plasma membrane.
And phospholipid is sticky and nasty in this situation triggers platelet activation, resulting in that thrombosis, that micro thrombosis inside the alveoli as well as thrombocytopenia, since the platelets get consumed in this process of adhesion further worsening bleeding complications in these patients.
This is a more detailed diagram looking at the components of the pulmonary thrombosis mechanisms, which are I'm not going to say unique to COVID, but certainly, much more powerful in COVID than in other respiratory viruses that we've typically encountered. So, we've got endothelial dysfunction, we've got immunothrombosis, NETs, which are neutrophil extracellular traps released by the neutrophils.
So, we've got our own body maladaptively releasing things that make the problem worse. Then there's a platelet direct stimulation by the protein, the variant envelopes or the plasma membrane and direct activation of complements. So, you see, this is a perfect storm to create clots in critical parts of the lungs that are already compromised by hypoxemia, by existing viremia, by pulmonary disease. Hence all the difficulties we've had in managing the critically ill COVID patients who progress to this level.
Taking a little switch here, I'd like to talk about the long-term health consequences of COVID-19. And this has been relatively difficult to define and arbitrarily, the eight-week mark, two-month mark has been instituted because most people symptoms resolve by then, frankly. So, we need some sort of way to look at the Gaussian distribution of this.
So, the post-acute sequelae of SARS-CoV-2 or long COVID, as we everybody refers to it, obviously defined by the Centers for Disease Control as a broad range of symptoms, physical and/or mental that developed during or after COVID continued for at least two months and are not explained by an alternative diagnosis.
And so, we do obviously see people who have had COVID, but who have myriad other problems. And ferreting out whether this is an exacerbation of their anemia, their multiple sclerosis can be a little bit difficult in somebody who was previously healthy, who has brain fog, fatigue three months out from COVID, that is pretty much screaming long COVID. And then the diagnosis is a little clear. Interestingly, long COVID potentially is now considered as a potentially disabling condition for a patient under various criteria.
This diagram looks at the incidence of myocyte injury. That's probably a little out of place, belongs a little bit earlier in the talk. But as patients get sicker, the bottom line is as patients get sicker, the percentage of those patients who have myocardial injury increases. So, we look at all survivors, non-ICU patients. There's still a little bit of myocardial injury, but not a lot. But by the time you're in the ICU and/or your survival has decreased, you've had greater than 50% chance of having myocardial injury.
So back to a little journey there. Back to the long-term health consequences of COVID. What I kind of alluded to earlier, is what is an acceptable time frame? Different people feel differently. Time courses actually vary from person to person. Fatigue is perhaps one of the things that we see quite frequently across the board. People without medical history, young 18-year-olds coming in three weeks, a month after COVID.
And then also appearing are shortness of breath. The chest discomfort, in my experience recently has tended to decrease. And I don't know if this is a different feature of the variants or how our various treatment or diagnostic modalities. Cough. Cough persists after almost every viral illness in some patients for a certain period of time.
And it's one of the major presentations to primary care, urgent care is a residual cough, often worse when lying down after an illness. COVID is no exception to this protracted cough, and that does not mean the infections carrying on after two weeks. And this is obviously something that the antigen tests can help clarify because people are horrified when they go out in public three weeks after their COVID and their cough is brewing. And actually, people are horrified out in public now with their cough and any sort of cough frightens people.
And then finally, things such as anosmia typically resolves fairly quickly in patients who have it. And this would be one of the things. So, if your anosmia is proceeding well after two months, then that's the suggestion of somebody who's got long COVID. And in my experience, people do not have all of these long COVID symptoms. They may have one, they may have a couple. Very rarely do they have all of them.
And I think some of it gets at what are the underlying risk factors for long COVID. This is still a work in progress, still being elucidated. And the existing respiratory disease going into COVID with bad history of COPD, for instance, is one risk factor. Some studies have shown that if you have a high viral load earlier in the disease and/or a long hospital stay, then your risks of long COVID have increased.
And then the other risk factor is type 2 diabetes. Patients with type 2 diabetes tend to have an increased risk of long COVID. And then one of the more interesting things is a reactivation of Epstein-Barr virus. And so, we see reactivation of viruses after COVID. I've seen many cases of shingles occur after acute COVID, which is a reactivation of zoster, and then reactivation of Epstein-Barr virus, which is associated with mono, is actually associated with patients developing long COVID symptoms.
So, well this is I mentioned still a work in progress, at least we're going to be able to identify patients with risk factors for development of long COVID. And perhaps these are patients that in the clinical setting you might want to really reinforce getting boosters, avoidance, that type of thing. Because it's one thing to have COVID for 5 to 10 days, it's another to be chronically fatigued for months afterwards or to be short of breath.
So, as I mentioned, the organ system targets of COVID and the corresponding diagnostic biomarkers. Long COVID rarely causes a protracted myocarditis, but it is worth checking cardiac markers in a patient with a chest pain component that persists after acute viremia is supposed to have been gone 10 to 14 days. Patients who have had a particularly bad bout of COVID and then show some signs of concern for either deep vein thrombosis or worsening lung conditions merits checking a D-dimer on these patients as well as some of the other studies. This is not the end of the workup. It's just part of it.
So, chest pain is really quite frequent, even in minor cases of COVID. And this applies obviously to acute COVID, but it can be slow to resolve in about one-fifth of patients. And this, in my opinion, is potentially both from irritation of the heart, but also the lung and the lining of the lung. So, we historically have known that in the post-viral period from a number of viruses, common cold viruses, influenza, that there can be irritation of the pleura, the lining of the lung, and that can cause chest pain, thoracic pain, pain with deep inspiration that persists after the initial illness.
But in patients who are short of breath with this presentation, it is useful to at least do initial screening with natriuretic peptides to see if new onset heart failure has developed. Obviously, an older patient who has had such an insult of COVID that requires hospitalization even if their heart was thought to be normal function before, may have had something that tripped them off with the cardiac damage into acute heart failure.
And this is where even prior to getting an echocardiogram or a stress test, you can get a cardiovascular biomarker much more readily that will at least heighten your awareness that this patient may have that risk. And as I mentioned, D-dimer should be used to evaluate patients at risk for hypercoagulability.
Finally, I'd like to look at some of the cardiovascular issues from delayed care, and this has been a huge part of the pandemic. I'm sure some of you have faced this either yourselves or with your elderly parents or with friends. Fear of COVID exposure has kept patients from seeking emergent care in the ER or even routine care in the PCP offices. That's from the patient side, and that's a reasonable fear.
But obviously, if your diabetes is out of control and you're not doing anything about it because you're afraid of getting COVID, you have to look at the overall risk benefits equation. So, one still needs care even in these type of settings. And in general, health care settings were not large areas of transmission of COVID but that fear is real and it's still, still very much persist. I have patients who are reluctant about coming in with lacerations, with other types of things because of fear of catching COVID.
On the medical side, on our part, routine care visits were canceled either because practitioners were sick, staff was sick, deployed elsewhere. The medical center wasn't set up with PPE, which was a big problem for a long period during this pandemic to not be able to see patients because you don't have the ability to protect yourself.
A number of these visits were turned into virtual visits, which, in my opinion, would be like a half approach towards care. Not great in terms of lack of face-to-face, but perhaps better than nothing. And this combination of issues with the health care system led to a delay in diagnosis, misdiagnosis, or obviously sometimes completely undiagnosed nowadays.
And then let's look at a particular cardiovascular. One of the things with heart failure patients is that they do require monitoring surveillance by their primary care team or cardiologists. Or if they have one, a sub-specialist cardiomyopathist and heart failure progresses when not managed right. It's kind of a balancing act of all the medicines to make sure that you don't damage one system, trying to keep the heart squeezing.
So, what's happened is we've seen a number of heart failure patients whose disease has slowly progressed due to lack of intervention and management, or who decompensated patients with heart failure who were relying on getting their weights just in the doctor's office, don't have scale at home, lack of timely intervention.
So, these things have certainly, certainly gotten better in the last year. We are not back to pre-pandemic levels of participation in health care and routine health maintenance. We have a backlog just like any other business. We have a supply chain issue with the number of people who've had their cholesterol checked, their blood pressure checked, a number of factors that have made this very, very difficult to come out of the pandemic and start to stabilize our health care system.
Who are the patients who are not getting timely care? Well, it can be anybody, but elderly patients are particularly at risk. They have decreased mobility. And to begin with, the fear, the phobia of COVID was rightfully very prominent among elderly people. I had a patient not more than two days ago who I diagnosed with COVID, and he looked great. He would be an outpatient with a heart failure. He's on an anti-arrhythmic.
And he goes, a year ago if you had told me, given me this diagnosis, I would have thought I was a dead duck. But now I'm like, going to be able to probably be fine with this. But the events that still persists, the patients with heart disease, obviously, hypertensive patients, patients with a previous history of stroke, particularly thrombotic stroke, people who are predisposed to thrombotic diseases, and the list goes on and on.
So, in summary, we've looked at a number of features of COVID, both in acute chronic COVID and then sort of some health care system issues with long COVID. In terms of how this disease, this virus that we think of or historically thought of as a respiratory virus has some profound impacts on the cardiovascular system that should not escape the minds of clinicians. And hopefully, is on our radar now with all of us. And hopefully, this has provided a little bit more information about some of the science behind it, the direction we're going, and hopefully, how we can more optimally manage our patients.
So, with that, we have plenty of time for questions. So, I hope to be able to get through as many of them as possible. And I thank you very much for joining, and I will take it back to the moderator to get some questions.
Mary Beth: Thank you, Dr. Neath. As a reminder, you can submit your questions about today's topic in the Q&A box on your console. The first question we have submitted here is, are the symptoms of clot formation similar after receiving the COVID vaccine?
Sean Xavier Neath: So, symptoms of clot formation in the leg or in the lung, that might be similar. Now, the prevalence of clotting disorders after the vaccine are significantly lower. And presumably, that's due to the absence of this uncontrolled viremia going on. Now, the vaccines obviously have side effects. All vaccines have side effects. But as I alluded to earlier on the whole, almost all populations are better off having the vaccine in terms of their risk of hospitalization, their risk of death than not having the vaccine.
So, can the vaccine cause immunogenic thrombus formation? Yes. Is it significant enough to warrant any subgroup not having the vaccine? No, in my opinion. Should it be on the minds of clinicians when patients come in with complaints? Yes. And one thing that I don't think we did very well in the beginning after the release of the vaccines was disregarding patients symptom post-vaccine.
Some of them can be serious. Not very many. Most vaccine related side effects can be bothersome, but not necessarily serious. The other thing that happens and happened frequently and still happens is patients contracting COVID in the short period after the vaccine and the vaccine taking the hit for that, which of course, is just bad statistics. But in summary, the symptoms of any sort of clot, if it's severe would be the same.
Mary Beth: Thank you. Our next question also related to the vaccine is how soon after having COVID should one receive the COVID vaccine or booster, and how soon after having COVID can you receive any vaccine?
Sean Xavier Neath: That's a good question. And there are some consensus guidelines out there. A short wait is indicated. A lot depends on the patient's risk factors. So, somebody who's high risk, who hasn't had the vaccine ever should certainly get it at some point near term.
The immediately convalescent period is not a good time to be getting any vaccine. And this is kind of standard practice that if the immune system is currently under challenge or currently under assault, vaccines should be deferred. Once things have stabilized a little bit, then you use the risk benefits for that equation to decide on vaccine administration.
Mary Beth: All right. The next question. Have we seen a decrease in the number of patients with clotting with the more recent COVID variants?
Sean Xavier Neath: So, I don't know if the data is fully teased out about that because controlling for the effect of prior exposure to the virus, immunity from the virus, immunity from the vaccines and the - so we're seeing patients who are now having COVID with the variants. And for many patients, it's their second bout.
So, it's difficult to tell if the decrease in thrombosis that we're seeing is related to the variants or if it's just related to better overall personal immunity to COVID. But I think at some point, we'll have some data from some nicely done epidemiologic studies to tease that out, but I think that will take some time. Personally, there could be reports out there. I'm just not aware of anybody having weighed in definitively on that.
Mary Beth: Okay. The next question. How often are you seeing COVID relapses in patients that have pre-existing conditions?
Sean Xavier Neath: So, I think here it's useful to make the differentiation between relapse and reinfection. Reinfection certainly does occur. Immunity wanes. We've probably all known somebody who's been reinfected with COVID, which was pretty interesting. In the beginning of the pandemic, people thought that reinfection was not going to be very likely, but it's a thing. And so, reinfections do occur.
Relapse to me indicates that somebody was getting better, but then worsened during that same illness, during that same index illness. And a perfect example of that is the relapses that we're seeing with Paxlovid, which presumably is due to Paxlovid, although it could be just a relapse of the disease. The relapse component in patients with pre-existing diseases is generally not seen because historically we haven't really had amazing treatments for it.
Now, with the monoclonal infusions, we had very few patients presenting with relapse type symptoms. With Paxlovid, I'm seeing it a little more, and perhaps that's due to how the five-day course was chosen that we maybe haven't completely eliminated in viremia.
Our patients with preexisting conditions more likely to have relapses. I think that's a fairly safe assumption. These are people, particularly ones whose immune systems are complicated, those who are on immunosuppressive, those who have immune system defects, which go without saying that those people are at risk for relapse from any infectious illness.
Mary Beth: Thank you. What types of symptoms have you seen most in patients that have long COVID, and why do you think they're so broad and wide-ranging?
Sean Xavier Neath: So, I would say fatigue and brain fog are probably the most common reported long COVID symptoms to me. And I have a feeling that there's probably something to this reactivation of Epstein-Barr virus, the mononucleosis virus that's associated with it. Those of you that had mono as a youngster or as an adult probably remember that profound sense of fatigue that's associated with Epstein-Barr virus infection. And so, when you reactivate it, it's like Groundhog Day. You have the same feeling over again.
Now, why they involve all systems? Well, I think that's related to the physiology. COVID just affects every organ system in the body. I had a nurse friend text me a patient, picture of her husband just today with this morbilliform rash. And she goes, did this really happen with COVID, which is something she hadn't seen? But obviously, COVID affects the skin, affects the heart, affects the lungs. And so, patients who for some reason or another develop long COVID in one system will potentially have it in just about any.
Mary Beth: All right. And the last question we have today is, have you seen patients coming back to the emergency department and doctor's offices at pre-pandemic levels recently, or is that level diminished?
Sean Xavier Neath: So, the emergency departments in the US are currently jam-packed and this was a pre-pandemic phenomenon. We had a couple of couple of days, couple of weeks maybe, I don't really remember like ghost town scenarios in the EDs when people were just afraid to come out.
But by and large, the EDs have remained busy through the last half of the pandemic and are even busier now.
And I think what we're sensing is that delay of care and the effects of delayed care, complicated patients coming through, and then the return to care and there's just a wide variety impacting the ED is, of course, hospitals. When EDs are full, hospitals tend to be full. This is a big problem.
Primary care offices are also currently backlogged with a lot of people. You can think about like people on this call right now listening to this call, how many of us have faithfully attended our annual physical in the last couple of years? Those spotty things have happened and now everybody's going back. Everybody wants to go back.
And on the other side of the storm is the large number of burnt-out nurses who have left the field, a number of physicians who have scaled back their hours and/or retired early. We're facing this where they call it quiet quitting that a lot of other industries have faced.
So, there is a return to the ED and PCP offices that is trying to be at the pre-pandemic level. And the question is, is there a capacity set up for this? So, there's some catch-up going on. I think things will stabilize. It will take some time. We've got a lot of work to do. And I think that we're starting to see some normalization in health care. But just like so many other industries, there's just a huge backlog of things that need to be done.
Mary Beth: Thank you, Dr. Neath, and thank you to our audience today for attending this webinar. If you'll please take a moment to review our disclaimers. And then we also invite you to view our upcoming webinars by visiting our website mms.mckesson.com-educational-webinars.
In closing, I'd once again like to thank Dr. Neath for sharing his expertise with us today. And thank all of you for attending. Have a great rest of your day.
Webinar originally aired on September 7, 2022
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