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Post-Acute Sequelae of COVID-19 · The SHEA Podcast

• 0:09
  SPEAKER_01: Welcome to the Rapid Response Podcast brought to you by the Society for Healthcare Epidemiology of America, Shay, promoting the prevention of healthcare-associated infections and antibiotic resistance and seeking to advance the field of healthcare epidemiology and antibiotic stewardship.
• 0:25
  SPEAKER_01: I'm Dr.
• 0:25
  SPEAKER_01: Jennifer Hammerhan, infectious disease specialist at the University of Toledo, and I will serve as your moderator.
• 0:31
  SPEAKER_01: The discussion on the podcast does not reflect Shay's perspective, but facilitates communication of multiple perspectives and experiences as we go through this challenging time together.
• 0:40
  SPEAKER_01: Shay is excited to launch this episode of the podcast COVID-19 updates, what we know now.
• 0:46
  SPEAKER_01: Today's discussion will focus on post-acute sequoli of COVID-19.
• 0:51
  SPEAKER_01: Our speaker today is Dr.
• 0:52
  SPEAKER_01: Avindra Nath, Chief of the Section of Infections of the Nervous Center and Clinical Director of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health.
• 1:03
  SPEAKER_01: Thank you for joining us today.
• 1:05
  SPEAKER_01: Before we start our discussion, I would like to turn it over to Dr.
• 1:08
  SPEAKER_01: Cindy Prince to get us started with a brief news and guidance update for the week.
• 1:13
  SPEAKER_00: As of this recording, the WHO reports 159 million COVID-19 cases to date globally with 3.3 million deaths.
• 1:21
  SPEAKER_00: In the U.S., there have been 32 million confirmed cases with 576,000 deaths.
• 1:26
  SPEAKER_00: A research letter by Bayorski et al.
• 1:28
  SPEAKER_00: in JAMA described the antibody response in solid transplant recipients after the second dose of a two-dose SARS-CoV-2 vaccine.
• 1:36
  SPEAKER_00: 658 transplant recipients underwent serological testing to assess humoral immune response.
• 1:42
  SPEAKER_00: The authors reported that 46% of participants had no measurable antibody response after dose 1 and 2, 39% had no response after dose 1, but had a measurable response after dose 2, and 15% had a measurable response after dose 1 and dose 2.
• 1:59
  SPEAKER_00: In an analysis of those participants who were receiving antimetabolites, 57% had no response after dose 1 and dose 2, 35% responded only after dose 2, and 8% responded after dose 1 and dose 2.
• 2:12
  SPEAKER_00: The authors concluded that the majority of their study population had a measurable antibody response after the second dose of the two-dose vaccine series, but for those who had no response after dose 1, antibody levels were low after dose 2.
• 2:25
  SPEAKER_00: This indicates that a large proportion of transplant recipients remain vulnerable to SARS-CoV-2 infection even after two doses of vaccine.
• 2:33
  SPEAKER_00: In the Lancet, a multi-center perspective cohort study by Hall et al.
• 2:38
  SPEAKER_00: examined vaccine effectiveness in a large cohort of healthcare workers who were undergoing regular COVID-19 screenings.
• 2:44
  SPEAKER_00: This analysis views data from the CIREN or SARS-CoV-2 immunity and reinfection evaluation study in the UK.
• 2:52
  SPEAKER_00: 23,324 participants, all of whom work in publicly funded hospitals in the UK, were included.
• 2:59
  SPEAKER_00: Among participants, vaccine coverage was 89% as of the data cutoff period of February 5, 2021, with 94% of those having had the Pfizer vaccine.
• 3:09
  SPEAKER_00: Being unvaccinated was associated with prior infection, age, ethnicity, job type, and higher deprivation.
• 3:16
  SPEAKER_00: There were 14 infections per 10,000 person days in the unvaccinated cohort, compared to 8 infections per 10,000 person days in the cohort who were fully vaccinated plus at least 21 days.
• 3:27
  SPEAKER_00: Just over half of the unvaccinated cohort had COVID-19 symptoms, considered to be typical of the infection, while 14% were asymptomatic.
• 3:36
  SPEAKER_00: For the vaccinated cohort who were infected, 36% had typical COVID-19 symptoms, while 19% were asymptomatic.
• 3:43
  SPEAKER_00: The effectiveness of a single dose of the vaccine after 21 days was 70%, and of both doses plus seven days was 85%.
• 3:51
  SPEAKER_00: The authors noted that the B117 variant was the dominant variant in circulation during the study period, and thus the study demonstrated the effectiveness of the Pfizer vaccine against that variant.
• 4:02
  SPEAKER_01: Thank you, Dr.
• 4:02
  SPEAKER_01: Prince.
• 4:03
  SPEAKER_01: I now want to move into the discussion with our speaker.
• 4:06
  SPEAKER_01: Dr.
• 4:06
  SPEAKER_01: Nath, thank you so much for joining us today.
• 4:09
  SPEAKER_01: You've been studying post-acute sequala COVID-19 since early in the pandemic.
• 4:13
  SPEAKER_01: Can you tell our listeners what you've been studying, data that has come out of your work and key takeaways from what you have seen?
• 4:19
  SPEAKER_02: First of all, let me thank you for having me on your podcast.
• 4:23
  SPEAKER_02: So, yes, I'm very excited to share our experience, which is in some ways unfortunate because of the devastation that has occurred from the pandemic.
• 4:32
  SPEAKER_02: As you know, that the acute devastation is there with so many deaths taking place during the acute phase of the infection and the mortality rates are extremely high.
• 4:41
  SPEAKER_02: And we think that those people who survived the infection, they are the lucky ones.
• 4:45
  SPEAKER_02: Unfortunately, a large percentage of them continue to complain of a variety of different types of manifestations.
• 4:51
  SPEAKER_02: And this has been an area of great concern.
• 4:55
  SPEAKER_02: So even the US Congress now has appropriated$1.5 billion just to study this phenomenon because they realize that this is a huge issue within the United States and going to be a problem worldwide.
• 5:06
  SPEAKER_02: Because these symptoms are occurring in the younger population, and these are individuals who are the most productive members of our society.
• 5:13
  SPEAKER_02: But it's very complicated.
• 5:15
  SPEAKER_02: There's no one easy answer to these things.
• 5:17
  SPEAKER_02: There are a wide variety of reasons for having persistent symptoms and wide variety of manifestations of these post-viral symptoms.
• 5:26
  SPEAKER_02: So first one has to consider the fact that if you were hospitalized, maybe you had multi-organ damage and your persistence symptoms are due to either damage to the lungs or kidneys or heart or something of that nature.
• 5:39
  SPEAKER_02: And that once you've excluded that, then some patients may have underlying diseases that they were unaware of.
• 5:45
  SPEAKER_02: So it's quite possible maybe a person had thyroiditis or diabetes or something and they weren't aware of it and it just unmasked itself during the infectious process.
• 5:54
  SPEAKER_02: So that's a second group of patients.
• 5:56
  SPEAKER_02: Then you have the third group of patients who say, well, they were healthy all along.
• 5:59
  SPEAKER_02: And now all of a sudden they got these new symptoms.
• 6:02
  SPEAKER_02: And if you look at those individuals, you can further classify them into many different types.
• 6:07
  SPEAKER_02: So some that may just complain of you know loss of smell and taste, and they recover with smile and develop very abnormal taste sensations.
• 6:15
  SPEAKER_02: And then there are other individuals who will complain, may develop what is called acute disseminated encephalomyelitis, which means that they get inflammation of the brain and spinal cord.
• 6:24
  SPEAKER_02: So they can present with the sub-acute neurological manifestations.
• 6:27
  SPEAKER_02: And if you do an MRI scan of the brain, you'll see areas of inflammation in their brain.
• 6:32
  SPEAKER_02: There's some patients who will develop what is called as a hemorrhagic encephalopathies.
• 6:36
  SPEAKER_02: And so these individuals, if you do an MRI scan, you'll see that there's bleeding in the thalamus and inflammation there.
• 6:42
  SPEAKER_02: It's a totally different underlying mechanism for these two manifestations.
• 6:46
  SPEAKER_02: And then the others who might have small inflammatory lesions scattered throughout the brain, and they could be vascular in nature, small strokes.
• 6:53
  SPEAKER_02: Patients can develop bleeding as well as occlusion at the same time.
• 6:57
  SPEAKER_02: And so they develop microvascular disease and they could have long-term consequences.
• 7:01
  SPEAKER_02: And then you have a whole set of individuals that we call long COVID, where the MRI is normal, all the blood tests are normal, and they complain of a lot of different symptoms.
• 7:12
  SPEAKER_02: But most of the testing that a physician has available to them in their office is unrevealing.
• 7:18
  SPEAKER_01: Sounds incredibly challenging and certainly sounds like a huge variety of problems that can happen afterwards.
• 7:24
  SPEAKER_01: So, you know, I've read statistics as high as 10% in terms of the estimate of people who develop post-acute sequelive COVID.
• 7:33
  SPEAKER_01: Do you think that that is accurate?
• 7:35
  SPEAKER_01: And so overall, what percentage of people do you think are going to have problems and what people are going to have severe problems?
• 7:41
  SPEAKER_02: So it just depends on how you define these things.
• 7:43
  SPEAKER_02: I told you there's so many different types of manifestations and so many causes for these things.
• 7:47
  SPEAKER_02: So if you exclude the individuals where you can clearly define an underlying cause for their problem, then even at and say six months later, anywhere from 10 to 30% is the number.
• 7:58
  SPEAKER_02: Originally we thought the numbers are going to be low, but actually numbers are getting higher as we are collecting epidemiological data on these patients.
• 8:05
  SPEAKER_02: So it's a huge problem right now.
• 8:07
  SPEAKER_02: And six months is a long enough time.
• 8:09
  SPEAKER_02: Usually some patients will get better on their own.
• 8:11
  SPEAKER_02: But if symptoms last six months or longer, then the chances of recovery are greatly diminished, not eliminated, but greatly diminished.
• 8:18
  SPEAKER_01: And so while research has been reported that this can occur in all age groups and demographics, are there any specific populations that seem to be more prone to it?
• 8:27
  SPEAKER_01: And do we know why?
• 8:29
  SPEAKER_02: Yeah, so you're right.
• 8:30
  SPEAKER_02: We see it predominantly in women and the ratio we think is close to four to one.
• 8:36
  SPEAKER_02: And the age group is a little bit younger too.
• 8:38
  SPEAKER_02: So, you know, in their 30s and 40s is probably the mean age group.
• 8:43
  SPEAKER_02: Now, why is that the case?
• 8:45
  SPEAKER_02: I guess one way to look at it is that all autoimmune diseases are more common in women than it is in younger women.
• 8:52
  SPEAKER_02: So if this syndrome also has a strong immune component, then it's not all that surprising that we would see it in that demographic.
• 9:00
  SPEAKER_01: And should people seek medical advice from specific specialists if they believe they're having long-term sequelae of COVID?
• 9:07
  SPEAKER_01: Or how do you advise proceeding in these situations?
• 9:11
  SPEAKER_02: Depends on where you live and what kind of access you have.
• 9:13
  SPEAKER_02: So, you know, now most medical centers are establishing these COVID clinics, and these are multi-specialty clinics.
• 9:21
  SPEAKER_02: So I think that's the best place to go if you have access to them.
• 9:24
  SPEAKER_02: Some of my colleagues are telling me that those clinics are getting filled up and they have six months to nine months waiting list, and that just sounds so unrealistic.
• 9:32
  SPEAKER_02: I mean, you know, you have symptoms, you want to see somebody now, not nine months from now.
• 9:36
  SPEAKER_02: But my guess is there are going to be more and more studies ongoing on these patients.
• 9:40
  SPEAKER_02: There are going to be a lot of research studies embarking because the$1.00 is going to fund a lot of research.
• 9:45
  SPEAKER_02: A lot of it's going to be clinical research.
• 9:46
  SPEAKER_02: So I think I would suggest you get into these clinics or get into some of these clinical trials and enroll yourself in them because that's where you're going to get the best help.
• 9:54
  SPEAKER_02: But if that's not available to you, then you should see somebody because at least people can provide symptomatic relief.
• 10:00
  SPEAKER_02: They can exclude other diseases that could be underlying.
• 10:03
  SPEAKER_02: So there are a lot of things people can do, even the general physician can do to help you.
• 10:07
  SPEAKER_02: And so there's no reason to suffer in silence.
• 10:09
  SPEAKER_01: What do you see as the biggest challenges in treating these patients?
• 10:13
  SPEAKER_02: Yeah, so the first challenge really is the diagnosis, the proper diagnosis.
• 10:19
  SPEAKER_02: I think that's the biggest challenge.
• 10:20
  SPEAKER_02: So these patients are very frustrated because once they've, you know, had all the other underlying diseases have been excluded and they complain a lot of symptoms.
• 10:30
  SPEAKER_02: The physicians do all the testing that is available to them.
• 10:34
  SPEAKER_02: I can't find anything.
• 10:35
  SPEAKER_02: And so some will tell them, well, maybe this is all psychological.
• 10:37
  SPEAKER_02: And as soon as you raise that term, patients get very upset because I was doing perfectly fine before I had this.
• 10:43
  SPEAKER_02: Sure, there's a psychological component, but there is something more devastating happening to me.
• 10:48
  SPEAKER_02: I think that's the biggest challenge that we face as patients and as physicians, because physicians can't find anything wrong.
• 10:53
  SPEAKER_02: The patients have a lot of complaints, and they're also right.
• 10:56
  SPEAKER_02: They have a genuine problem.
• 10:57
  SPEAKER_02: The thing is, we don't have good testing available to us.
• 11:00
  SPEAKER_02: So that's, I think, the biggest challenge.
• 11:02
  SPEAKER_02: And so you're now beholden to research tests.
• 11:06
  SPEAKER_02: And research tests are not the same as clinical tests, they haven't been FD approved and they're available only in some research labs.
• 11:13
  SPEAKER_02: And so, you know, there's the challenge.
• 11:15
  SPEAKER_02: And then how do you validate these things and make them available to the general public?
• 11:19
  SPEAKER_02: And those things take time.
• 11:21
  SPEAKER_02: The second thing is if you don't understand the pathophysiology, what are you gonna treat?
• 11:25
  SPEAKER_02: So you have to treat people empirically.
• 11:27
  SPEAKER_02: So you say, okay, well, I think this is immune-mediated.
• 11:29
  SPEAKER_02: Okay, let me just try corticosteroid, let me try IVIG, let me try to lysimab or something like that.
• 11:35
  SPEAKER_02: And so, but you don't really know.
• 11:36
  SPEAKER_02: I mean, is this thing a placebo effect?
• 11:38
  SPEAKER_02: Did it really have a biological effect?
• 11:40
  SPEAKER_02: How long you should treat people and the people have different dosages they're giving them, different regimens they're giving them.
• 11:45
  SPEAKER_02: So you have no idea.
• 11:47
  SPEAKER_02: Undertreating them, over-treating them.
• 11:49
  SPEAKER_02: And so it has to be done in the context of a clinical trial.
• 11:53
  SPEAKER_02: I think that's the other.
• 11:54
  SPEAKER_02: So even common treatments that we give patients, it's true if you're really desperate, you're gonna try something, but enrolling in a clinical study can make a huge difference long term.
• 12:02
  SPEAKER_02: So I would urge everybody to, as soon as you find out where you can enroll in some clinical study or trial, you should do so.
• 12:09
  SPEAKER_01: So, Dr.
• 12:09
  SPEAKER_01: Nabbs, can you tell us a little bit about any clinical trials that are going on right now or that you're participating in?
• 12:16
  SPEAKER_02: Yes.
• 12:16
  SPEAKER_02: So we have clinical studies at the moment.
• 12:19
  SPEAKER_02: They haven't translated to trials.
• 12:21
  SPEAKER_02: I'm a principal investigator of two studies at NINDS.
• 12:25
  SPEAKER_02: The first one is to study patients with any kind of neurological manifestation of COVID or the COVID vaccine.
• 12:32
  SPEAKER_02: So that's the other problem, is now we have patients getting the vaccines and they're complaining of a variety of different neurological symptoms.
• 12:38
  SPEAKER_02: And so we want to understand that as well because that could shed clues on what's happening with these long COVID patients.
• 12:44
  SPEAKER_02: And then the second study that we're doing is screening patients online to who are complaining of post-COVID symptoms and trying to identify a subset of individuals who have symptoms that overlap with the chronic fatigue syndrome.
• 12:57
  SPEAKER_02: Because you know that that's another dilemma.
• 12:59
  SPEAKER_02: We have millions of people who complain of persistent symptoms after various kinds of viral infections.
• 13:04
  SPEAKER_02: And they also go from doctor to doctor and nobody knows what's wrong with them.
• 13:08
  SPEAKER_02: And so we've been trying to study those patients.
• 13:10
  SPEAKER_02: We collected a huge amount of data.
• 13:11
  SPEAKER_02: The problem with chronic fatigue syndrome is oftentimes by the time we see them, we don't know what virus initiated their symptoms.
• 13:17
  SPEAKER_02: With long COVID, we know what started it, right?
• 13:20
  SPEAKER_02: We know what virus started, and we can capture them early on.
• 13:22
  SPEAKER_02: So I think by studying them, it might shed light on the chronic fatigue syndrome, for which for years we've had no idea what to do with these patients.
• 13:30
  SPEAKER_02: And so this second study will bring in about 50 individuals who look like chronic fatigue syndrome and bring in another 50 individuals who had COVID but fully recovered.
• 13:38
  SPEAKER_02: Now, these chronic fatigue syndrome patients are also of multiple subtypes.
• 13:43
  SPEAKER_02: So that makes it even more complex.
• 13:44
  SPEAKER_02: We didn't talk about that.
• 13:46
  SPEAKER_02: But maybe this is an opportunity to describe them.
• 13:48
  SPEAKER_02: So some of them complain of predominantly cognitive difficulties and they may have psychological manifestation like depression, anxiety, or some people have psychosis.
• 13:57
  SPEAKER_02: And then there's a second group of individuals that complain of exercise intolerance or fatigue.
• 14:02
  SPEAKER_02: And so with a little bit of exercise, they can just get wiped out for the rest of the day.
• 14:07
  SPEAKER_02: And the fatigue can be not just physical, but can be cognitive fatigue too.
• 14:10
  SPEAKER_02: So I know several physicians who developed it and they say they can't even do telemedicine any longer because they get so exhausted.
• 14:16
  SPEAKER_02: And then there's a third group of individuals who develop dysautonomia.
• 14:20
  SPEAKER_02: So that means every time they stand up, their heart starts to race, or their blood pressure falls, or they can develop ball of bladder symptoms, sleep abnormalities.
• 14:30
  SPEAKER_02: And then there's another group of individuals that complain of various kinds of pain, chest pain and joint pain and stuff.
• 14:36
  SPEAKER_02: And so they are these subgroups of individuals, but they overlap.
• 14:40
  SPEAKER_02: They maybe have predominance of one versus the other type of symptoms, but they can have any combination of these things together.
• 14:47
  SPEAKER_02: So we want to study the pathophysiology of these subgroups.
• 14:50
  SPEAKER_02: And we think that we're going to find immune abnormalities.
• 14:53
  SPEAKER_02: We will probably find that there is persistent activation of the innate immune system, like for example, macrophages.
• 14:58
  SPEAKER_02: There's reasons to believe that we probably find decreased interferon responses and we may find T cell exhaustion.
• 15:04
  SPEAKER_02: And so if these hypotheses hold true, then for each of these abnormalities, we already have existing modes of treatment.
• 15:12
  SPEAKER_02: So that's the kind of clinical trials we would like to do so that we could give more targeted immunotherapies as opposed to putting people on, you know, prolonged corticosteroids or something like that, or immune suppressive agents that can suppress the entire immune system because you can't do that long term to people.
• 15:28
  SPEAKER_02: So that's the direction that we are moving in.
• 15:30
  SPEAKER_02: Now, there's you know$1.5 billion that's available now through Congress, and part of that is going to be used for clinical trials.
• 15:38
  SPEAKER_02: So there are going to be a lot of clinical trials popping up over the country.
• 15:41
  SPEAKER_02: That announcement for inviting grant proposals is supposed to come out in the near future.
• 15:46
  SPEAKER_02: So my guess is a lot of people will apply.
• 15:48
  SPEAKER_01: What impact do you think that post-acute sequality COVID may have on our healthcare system going forward?
• 15:54
  SPEAKER_02: I mean, it's already, if you look at it, I mean, our healthcare system can't handle it.
• 15:57
  SPEAKER_02: It's already breaking apart.
• 15:59
  SPEAKER_02: So you have all these patients they can't access care.
• 16:01
  SPEAKER_02: We didn't have enough physicians in this country to handle regular problems.
• 16:05
  SPEAKER_02: Now you got millions of people with new set of problems that nobody knows how to diagnose or treat.
• 16:10
  SPEAKER_02: So the healthcare system has already exceeded its capacity.
• 16:13
  SPEAKER_02: I mean, we are in the worst times we've ever lived on this planet.
• 16:16
  SPEAKER_01: Is there anything that you can recommend in terms of reducing the risk for developing these sequali or mitigating the impact?
• 16:23
  SPEAKER_02: Well, early diagnosis and treatment is key.
• 16:26
  SPEAKER_02: You know, the longer these symptoms go, the more hardened the immune system becomes, and it's very hard to reverse these things.
• 16:31
  SPEAKER_02: So I think empirical therapy early on, recognizing these things is going to be key.
• 16:37
  SPEAKER_02: And the best prevention, of course, is the mask.
• 16:40
  SPEAKER_02: You know, we think we're vaccinated and protected.
• 16:42
  SPEAKER_02: There's a variant coming out every day, and they're worse than the previous ones.
• 16:46
  SPEAKER_02: I mean, I've been vaccinated for quite some time.
• 16:48
  SPEAKER_02: I don't go out anywhere without a mask.
• 16:50
  SPEAKER_02: I mean, that's the best treatment.
• 16:52
  SPEAKER_02: But if you got the disease, unfortunately, then we gotta treat that.
• 16:55
  SPEAKER_02: But you know, you there's a chance you get reinfected with some of these things.
• 16:58
  SPEAKER_02: So you don't want that to happen.
• 17:00
  SPEAKER_02: You can't say I've got my disease now that I'm done.
• 17:02
  SPEAKER_02: That's not true.
• 17:03
  SPEAKER_02: You can get the darn thing all over again.
• 17:05
  SPEAKER_02: So I'd say an ounce of prevention is worth a pound of cure.
• 17:09
  SPEAKER_02: So wash your hands, wear the mask, do all the preventive things, you know, small price to pay for prevention of major consequences.
• 17:17
  SPEAKER_01: And I think you've certainly answered this to some extent already.
• 17:21
  SPEAKER_01: What are the knowledge gaps that we need to address through research on post-COVID squala in the future?
• 17:27
  SPEAKER_02: And there are huge gaps.
• 17:29
  SPEAKER_02: I mean, I mean, we don't understand the variability in the population as to why some people fall sick, some do not, some have long-term SQL A, some do not.
• 17:37
  SPEAKER_02: And the different types of SQL occur in different individuals, all these variety of different manifestations, why are these differences?
• 17:44
  SPEAKER_02: What the pathophysiology is, what the treatment is.
• 17:47
  SPEAKER_02: And there's a lot of research being done currently.
• 17:50
  SPEAKER_02: So we've made huge strides in a short period of time, but yet there are huge gaps.
• 17:55
  SPEAKER_02: It's going to take us a while to sort these things out.
• 17:58
  SPEAKER_01: Well, thank you very much, Dr.
• 17:59
  SPEAKER_01: Nat.
• 17:59
  SPEAKER_01: This was very enlightening.
• 18:01
  SPEAKER_02: Well, thank you for having me on the podcast.
• 18:03
  SPEAKER_02: It was a real pleasure.
• 18:04
  SPEAKER_01: Thank you very much to our speaker for sharing your perspectives and experiences.
• 18:08
  SPEAKER_01: This podcast can be accessed on Shay's online education center, Learning CE, under the Rapid Response Program.
• 18:15
  SPEAKER_01: You will also find resources such as the recorded webinars, healthcare facility outbreak preparedness, and the Shea COVID-19 town halls.
• 18:23
  SPEAKER_01: Please note that this podcast series will now air every other Thursday, and our next episode will launch on May 27th.
• 18:30
  SPEAKER_01: This concludes this episode of the Rapid Response Podcast.
• 18:34
  SPEAKER_01: Thank you for tuning in.