RICK WEISS: Hello, everyone. Welcome to SciLine’s media briefing on long COVID. I’m SciLine’s director Rick Weiss. For those of you not familiar with SciLine, we are a philanthropically funded, editorially independent, free service for journalists and scientists based at the nonprofit American Association for the Advancement of Science. Our mission is simply to make it easier for reporters like you to get more scientifically validated evidence into your news stories. And that means not just stories that are about science per se but any story that can be strengthened with some science, which—as I am fond of saying, pretty much any story we can think of can always be made better with some science. Among other things, we offer a free matching service that helps connect you to scientists who are deeply knowledgeable in their field and are excellent communicators on deadline. Just go to sciline.org, and click on, I need an expert. And while you’re there, check out our other helpful reporting resources.
A couple of quick logistical details before we get started—we have three panelists today who are going to make short presentations of about five or six minutes each before we open things up for Q&A. To enter a question either during their presentations or afterwards, simply hover over the bottom of the Zoom window. Select Q&A. Enter your name and news outlet and your question. If you want to pose your question to a specific panelist, be sure to note that. A full video of this briefing should be available on our website, probably by the end of today and a timestamped transcript within a day or so after. But if you would like a raw copy of the recording more immediately, just submit a request with your name and email in that Q&A box, and we’ll send you that link ASAP after the briefing today. We can also use the—or—sorry. You can also use the Q&A box to alert SciLine staff of any technical difficulties. OK. I’m not going to give full introductions to our speakers. Their bios are on the SciLine website.
I’m just going to tell you that first, we will hear from Dr. Alexander Truong, a physician and assistant professor of medicine at Emory University, who will start us off with an introduction to the medical indications of long COVID, including some symptoms and what’s known about risk factors for who’s most likely to develop long COVID. Next, we’re going to hear from Dr. Bhramar Mukherjee, a professor of biostatistics and epidemiology at the University of Michigan School of Public Health, who will speak about the epidemiological and other research methodologies that are being brought to bear to try to unravel what’s going on with long COVID and why it’s such a challenging syndrome to understand and how researchers hope to eventually overcome those hurdles. And third, we’re going to hear from Dr. Christian Sandrock, who is a professor of medicine and director of critical care at UC Davis, who’s going to focus on long COVID patient case care and the potential role of vaccines or antivirals or other medications to prevent or decrease the duration or severity of long COVID. So, with that bit of introduction, let’s just get started and over to you, Dr. Truong.
Introduction to the medical indications of long COVID
ALEXANDER TRUONG: Thank you so much for having me. I’d like to start talking about some things that we actually know about post-COVID syndrome. The official name for post-COVID syndrome, according to the CDC, is post-acute sequelae of SARS-CoV-2 infection, or PASC for short. There seems to be still a lack of definition of exactly what defines this syndrome. But the majority of us believe that it consists of persistent symptoms after the initial infection that lasts for about four weeks or more and that negatively affected patient’s function.
RICK WEISS: I’m sorry to interrupt you, Dr. Truong. But I’m not seeing slides, so I’m not sure if they’re meant to be up yet. And we can share them if necessary.
ALEXANDER TRUONG: Oh, let me make sure. I’m sorry about that. Can you guys see it now?
RICK WEISS: Yes. You just—there you go. Now you’re in.
ALEXANDER TRUONG: OK. So, again, there’s a lack of definition for what we’re calling this syndrome. But it seems to be consistent with symptoms that linger past the initial infection for about four weeks, and it’s inhibiting the patient’s ability to function on their daily activities or their work function. It seems to even be multi-organ, affecting both the brain, the heart, the lungs and multiple other organ systems. It’s seen in both patients who have been hospitalized for the initial infection and those who’ve never been to the hospital and may have mild disease. And it comes by a bunch of other names, including long-haul syndrome or post-COVID syndrome.
What’s also unclear is whether or not your risk for having persistent symptoms is associated with how severe your initial symptoms are. It seems that about 10 to 30% of patients who have had COVID will have lingering effects from it past four weeks. About 65% of these patients will return to their normal level of health two to three weeks after their initial infection, but a significant proportion will have continuous symptoms. In one small study of about 134 patients, 93% of patients who’ve been hospitalized for COVID had persistent symptoms two months past their initial infection. The average age was 40 and ranged anywhere from 19 to 84 years old. Twenty percent of these patients were on mechanical ventilation or an assisted breathing device, and about 4 to 1 were women to men.
It’s also unclear exactly what the mechanism of action or the reason why patients are getting persistent symptoms. Initially, it was thought that it was secondary to persistent inflammation in the body, where the initial infection caused the body to have increased inflammation and that it just lingers even though the active infection is no longer there. However, in our clinic population, we’re not quite seeing this, and we don’t see a correlation between inflammatory markers and persistence of symptoms. There’s also a thought as to whether or not there were persistent autoantibodies in the system, meaning that the patient themselves develop antibodies to some weird antigen that then cross-reacts or recognizes their own body as foreign and thus fights against the body. That, in turn, causes some of these symptoms.
There’s also a hypothesis there’s persistent viral reservoir, where there’s pockets of virus in the body that seems to be persistently leaking out viruses. And lastly, there seems to be a hypothesis that some patients have a condition where they’re producing excessive histamine or what, in the medical community, we are calling mast cell activation syndrome. And excess histamine can cause some of the shortness of breath and fatigue the patients have.
Again, some common symptoms that patients present with are chronic fatigue, where they’re feeling like they need to sleep during the day or they don’t feel rested after having a good night’s rest. They have also brain fog or memory loss, where they have trouble with remembering things or losing track of things or concentrating. They also have shortness of breath, as well as pain syndromes, where they have joint and muscle pains, in some cases chronic headaches. However, from this slide, you can see that the list of symptoms are pretty extensive. But the most common things that we are seeing is the fatigue, the shortness of breath, the headache and the memory issues.
The risk factors for having post-COVID seems to be associated with being female gender. However, this is little bit unclear since we know in the medical community that women are more likely to seek medical care than men. So, this may be a sampling error. There may be an association with how long you’ve been hospitalized or whether or not you required an ICU stay. However, again, in our patient population, we haven’t been seeing this association. There isn’t signal that says that the number of original symptoms you have when you are actively sick with your acute infection may predict how long you have persistent symptoms or how many symptoms you have post-four weeks from your infection.
We aren’t seeing many patients who have had asymptomatic infections initially, meaning that they had no symptoms when they were initially infected, and yet presenting with long symptoms—long-term symptoms. There doesn’t seem to be a clear correlation between races and age, and there doesn’t seem to be a correlation between the persistence of inflammatory markers seen on lab work. So, when we look at the studies, there should be a little bit of caution when we read these studies because a lot of these studies were done on patients who were hospitalized for their initial infection. In our clinic population here, most of our patients are patients who have never had to be hospitalized or never sought medical care for their initial infection. And thus, the data that we’re reading in the literature may not be reflective of what we’re seeing in our clinics.
RICK WEISS: Great. And you’re still sharing, so you can hit stop share on that. Thank you. Thank you for that, actually, very clear explanation of something that’s not very clear at all—so a good introduction to this topic. I’ll remind reporters that these slides will all be available immediately after or soon after the media briefing on the website here. But for now, let’s go over to Dr. Bhramar Mukherjee.
The epidemiology of long COVID
BHRAMAR MUKHERJEE: Thank you so much. And thank you for allowing me to speak on this epidemiology of long COVID, which is a daunting task. So, a growing body of literature is showing that a large number of people suffer from long-term effects of the SARS-CoV-2 virus months after the initial infection. Symptoms, as Dr. Truong mentioned, are wide-ranging and can include breathlessness, chronic fatigue, brain fog, anxiety and depression. Different health agencies have provided various clinical definitions for this condition, making it even more challenging to reach uniform conclusion across comparable studies that are generalizable. While the National Health Service in the U.K. defines long COVID as signs and symptoms that continue for more than 12 weeks after the initial diagnosis, the WHO defines it as conditions that occur usually within three months from onset and lasts for more than two months.
It is clear that we need credible evidence that provides us with mechanistic understanding, insights into targeted interventions and pathways to improved managed care of long COVID for all patients. And I would like to emphasize on this word, all. The epidemiology of COVID-19, and particularly long COVID, is complex due to the newness of this virus and its long-lasting effect involving multiple organs in some patients. In my brief remarks today, I would like to touch upon four such challenges—variation in defining the clinical outcome and study populations, risk factors and prediction models for long COVID—we have seen many of them, but whose data are we seeing?—the role of vaccinations and boosters and, finally, the need for integrated, harmonized, representative sample, data and careful analysis.
Last year we actually conducted a meta-analysis and systematic review of the reported prevalence of long COVID, curating 50 global studies. This figure that you see shows you a summary plot where estimates range from 10% to 80%. This wide variation in prevalence estimates is partly due to the heterogeneity of the studies that were being studied and the lack of rigorous definition of the outcome we were measuring. The pool prevalence was estimated at 43%, and 54% of hospitalized patient reported lingering post-COVID symptoms. Note that many of these studies and estimates were prior to vaccination rollout. More recent studies—for example, the one that I cite at the bottom of this slide, published in Nature this summer—estimated that about 8 to 17% of COVID-positive patients suffer from long COVID, with about 1 to 5% reporting debilitating symptoms.
With 615 million infections reported worldwide and many to come, the healthcare burden of long COVID is going to be substantial even with this latest prevalence estimates. With deaths not often being reported these days, this problem of estimating how many people in the world are suffering from long COVID has become more challenging and is going to continue to remain so. We need better survey instruments, surveillance and apps of our community to track the prevalence and progression of this condition. Though the overall prevalence has varied considerably in our study, our study also showed that the top list of problems or symptoms were more consistent, with fatigue and memory problems being the two top symptoms reported by long-haulers.
There have been several studies, as Dr. Truong mentioned, using classical statistical models as well as machine learning tools to predict long COVID. These are some of the commonly reported risk factors based on current data. Age, sex, pre-COVID health status, acute-phase COVID symptoms, immune profiles, internal changes in microbiome are hypothesized to be risk factors. The area under the curve for these prediction models have ranged from 70 to 80%. As we know more about genetics of COVID, I’m hoping that genetics will feature into this risk prediction model and the list will be expanded.
However, as was mentioned, whose data are these prediction models based on? People who are seeking care. The explanation of female sex being much more likely to have long COVID does not really match with our experience with male sex having much more severe conditions due to COVID. Women may be more likely to seek care. So, what we are going to do with this information? How should patients act with this knowledge? We still need the translation of these findings to prevention and care.
So, we are already interested in knowing if vaccines help with long COVID. They are doing a fantastic job in keeping us out of the hospital. There have been two main types of designs for these types of study. One is, when post-infection vaccines—do they help? And the answer so far available is that the effect is modest. However, for post-vaccine infection or breakthrough infection, the risk reduction seems to be larger, but probably also depends on time since your last vaccine. A VA study in Nature Medicine quotes the estimates to be around 15% risk reduction, whereas the Office for National Statistics in the U.K. provides an estimate of 41%. Again, we need more credible estimates of the role of vaccines on long COVID, particularly on the role of boosters and long COVID, as we have more and more follow-up data.
Finally, what are the different study design and sources of data that have helped us so far? Many efforts are underway to further our understanding of post-COVID conditions, including the recovery initiative from the NIH, OpenSAFELY data integration platform in the U.K. harmonizing longitudinal health care data, the Wellcome Trust COVID information survey, the long COVID support group surveys, the VA studies. I have listed some of the most common forms of study designs and data sources that we have seen on this slide. This pandemic has really shown us that the value of integrated digital ecosystems where your vaccine information, infection information, clinical outcome data over time can be integrated nationally. And the countries that have done it well have really helped the world with breakthrough findings. In this final slide, as a statistician, I would like to illustrate some of the cautionary notes regarding the current data, knowledge and analysis. I think that from observational data, to arrive at causal conclusions will be a huge leap at this point. We have to be very careful what are we talking about. Are we talking about relative risk with respect to a reference or control population?
Finally, whose data?—selection bias. Who is seeking care? That’s the data we are seeing. We are not seeing a representative random sample of the population. It was mentioned that long COVID should not be treated as a single syndrome. So, in prediction models, we may want to really focus on subtypes of long COVID. For example, people who are experiencing brain fog or memory loss should be treated differently than people who are experiencing respiratory symptoms. We have to know a lot more about genetics of SARS-CoV-2 in general, COVID-19 disease outcomes and long COVID. What is the role of repeated infections? If I’m getting infected twice, am I more likely or less likely to have long COVID? But most importantly, the studies that we have seen are really limited to certain selected population in selected countries.
We need global data, international data on diverse population. Because I do believe that how you collect data—that matters. And that matters the most in health equity and reducing disparity. If you have biased data collection, incorrect measurements, exclusionary cohorts, no fancy AI or email algorithm cannot really rescue you. They will be trained on biased data, leading to incorrect conclusion, influencing misguided policy and further increasing inequity and disparity. So, my plea will be to invest resources in long COVID studies—good, well-curated long COVID studies—which have global scope in all populations. Thank you.
RICK WEISS: Fantastic and really interesting, and a great plea at the end for what really science does best and the reason why we at SciLine are always encouraging reporters to look for that scientific evidence—because these things are very hard to disentangle unless the methodology is really carefully designed. So, thank you for that. And over to you, Dr. Sandrock.
Long COVID care
CHRISTIAN SANDROCK: OK. Perfect. Christian Sandrock—I’m an infectious disease and pulmonary critical care physician at the University of California, Davis. And the beautiful thing of going after Drs. Truong and Mukherjee is that they did most of the work for me. So, you’ll see a lot of redundancy in the slides, and I can sort of gloss over it. But I think I just want to highlight some of the stuff we really see here in our long-haul COVID clinic. It still bugs me that that name lingers, as I would prefer PASC—sits a little bit more nicely, but so be it. And that’s kind of where we’re at with naming, which happens. And, you know, Alex kind of highlighted this very nicely.
You know, we really try and spend our time in our clinic separating what’s acute and what’s post-COVID conditions. And, really, the reason for this is how we sort of not only see our patients in clinic and process them in the health care system, but this really puts them in different classifications for what their long-term trajectory is. And, you know, again, as Alex mentioned, these definitions are still open to debate. They’re not solid. We sort of look at approximately two to three months as a break point for a post-COVID condition. But again, and we don’t—you know, this is not a black-and-white condition that we see in our clinic. But this helps us separate our patients. It helps us set expectations with our patients that, you know, hey, it’s been about four months with you having symptoms; this is going to be a slow progress for you, as opposed to, hey, you’re only 3 1/2 weeks out from your acute infection. We still don’t quite know where you’re going to land. And that just really lets us put them in that category, overall.
And I kind of want to just highlight two cases. And this is a slide I’ve had, actually, through all of COVID. And this is kind of how we deal with these different patients. The first is a 76-year-old gentleman. And I’m not trying to torture you with a lot of medical acronyms, but you can see has hypertension, diabetes, basically is admitted to the ICU for hypoxemic respiratory failure associated with our COVID. They are put on a mechanical ventilator. They have a long hospitalization, on the mechanical ventilator for 50 days. They get a tracheostomy, multiple other procedures. Their hospitalization spans approximately almost three months. And then you see them in clinic, and they’re left with weakness, fatigue, depression, lethargy, decreased appetite, brain fog and forgetfulness. You oppose that to another person who’s in their 30s, no past medical history. They develop acute COVID. They actually have this—regular symptoms of a fever, aches, upper-respiratory illness. And then that progresses over the next few months to include, you know, ongoing fatigue, difficulty concentrating and depression. But that person never sought medical help and was an outpatient.
And the reason for us distinguishing these two is really that, you can imagine, there’s really a lot of commonalities between the ICU stay and the post-COVID syndrome, if they’re in the ICU. But we know that there is something unique with COVID, as we’ve sort of determined, because patients never see the hospital, as Alex showed in his data, and we actually know that they have a lot of these different symptoms. And, really, we have what’s called a post-ICU syndrome. And that is very similar often to what we see with PASC in the ICU patients. We, actually, here at UC Davis are starting to merge our post-ICU clinic with our post-COVID patients who had prolonged ICU stays because much of this overlap which we see here, whether it’s depression, anxiety, difficulty concentrating, fatigue, lots of sleep disturbances—that all sort of covers both. And we may see, for example, these symptoms in someone who was admitted with a prolonged hospitalization from influenza or sepsis. We also may see that from COVID. But we do have a large cohort of patients who didn’t have an ICU stay, sought no medical support, and they still have a plethora of symptoms that we’re noticing. So, this really—there is something very unique to COVID. We certainly know this now. But from a clinical standpoint, we want to separate both because the rehabilitation and the trajectory can sometimes be a little bit different between both groups.
So, where are we now? And, you know, since we’ve done this in the past, what are some of the things we’re seeing? And I think, you know, this was really nicely highlighted. And, again, a lot of my work was generally done for me already. So, we know that there’s obviously direct and indirect impacts of the virus causing these long-term symptoms. And as Alex mentioned, still difficult clearly defining what they are and what these symptoms really entail in full detail.
Now, Dr. Mukherjee did a nice job of talking about the vaccinations. So, interestingly enough, our incidents are really high still in the unvaccinated, which vaccines have been awesome at preventing critical illness and preventing hospitalization. But they’re not perfect. And right before we were on this call, we were talking about the types of patients we’re seeing. We actually have about 8% of our hospital beds are patients who are still testing positive for the SARS-CoV-2 virus. But very few of them are there with actual sequelae from the virus. They might be there as a trauma and they happen to just be positive on their testing. Or they might be here for a surgical procedure and they’re positive on their testing. So, we now have a lot more patients in our hospital who are admitted with other things who happen to also have COVID, as opposed to being admitted for COVID. And, you know, Dr. Mukherjee really did a nice job of discussing vaccinations. Really, what we talk about all the time is, prevention is really the only form of treatment. You avoid this disease, you’re not going to get long COVID. And that’s really the real focus. Vaccination is still probably the best.
But the next line, which I don’t have in there, which is really the bottom portion, looking at both psychological and physical symptoms, is that we try mitigation. So, with these patients, if you’re in the ICU with us, we’re going to do early mobilization. We’re going to do aggressive physical therapy. We’re going to lessen sedation. We’re going to try and get you out of the bed and make you more comfortable and more interactive in your care. We know the data with that and our post-ICU syndrome is really good when we actually get people involved in their care and lessen a lot of the sedatives and mobilize them. We’re going to do the same with our patients with COVID. And that’s something, for a period of time, I think we forgot in critical care. Early on, we were just trying to survive. And we didn’t really focus on those details. And I think now those are things we’d like to really focus on.
The other area, which I think is a little different, where we’re sort of going now in our clinic is really this impact on return to work. And when you look at this data, you know, 60% of patients cannot complete all their ADLs 30 days after admission from a hospital. Now, these are hospitalized patients. But really, that 60% still have limitations in their ADLs. That’s pretty impressive at 30 days. And that’s—I mean, it’s a little depressing, actually. And it means the level of care that they need and what support they’re going to need from both the health system and family is pretty profound. Sixty percent of our patients actually don’t report that they’re really not returning to baseline at Day 60. So, again, they may be better. They may be functional. They may be able to go to work. They’re not at baseline. And really what we’re seeing is this is a long process—so a lot of the data we’ve already gone over so far on this call. Many patients still have symptoms at nine months. They have symptoms at 12 months. They have symptoms at well greater than a year. So, we spend a lot of our time figuring out, what are those symptoms? What is the trajectory of those symptoms? Where are they going? How are they improving? We have multiple areas that we work up.
And, really, when we focus our evaluation on both diagnosis and treatment, it’s treating the things we know. So, if it’s predominantly physical, they have a lot of shortness of breath. We’ll look at cardiac and pulmonary testing. We sometimes will find limitations, sometimes we don’t. If we do find something that we can treat, we will certainly treat that. And then the last thing, which is really associated with the first bullet point, is that, you know, the need after their acute COVID and as they move into the long COVID is going to be pretty great. We also know that the readmission rate is relatively high. So, we’re seeing that the ability for them to come back to the hospital is relatively high. So, the impact on the health care system is still great even though we’ve seen patients, you know, get better. We don’t see a lot of acute COVID clogging up our health care system in our hospitals. We certainly know that they’re still, you know, taking up a lot of our clinic and our post-, you know, ICU care time. The last thing is some of the treatment stuff we talk about is, when we look at rehabilitation, this is something that we at least enroll them in eight weeks. That’s where the literature is sort of appearing that this is best.
As I mentioned, we have merged this with our post-ICU clinic and our post-COVID patients because our treatment is really the same in both of those groups. The one thing we do with our COVID patients is we take it slow. So, you guys may know the literature looking at distinct cardiac deficits with many patients with COVID. While we might have just weakness from your long ICU stay, we may push you a little harder than we will with someone who has COVID. And, really, it’s sometimes been hard to improve a lot of the cognitive deficits we’re seeing in our patients.
And the last thing is return to work. This is a big question that comes up in our clinic all the time when we see patients with persistent symptoms from COVID. And I honestly don’t have a great answer. It’s really seeing what we’re able to do, what their trajectory is with rehabilitation, how they’re feeling. But really setting an end point for when they can return to work has been extremely difficult. So, I think we’ve talked about future steps—it would really be nice, I think. You know, Dr. Mukherjee’s discussion on the clinical research, which is my last point, is really where we really need to look at these patients and study them. But they’re a diverse group of people, so it’s very hard to, you know, really target them appropriately. And with that, hopefully we’ll have some questions. So, thanks for your time.
RICK WEISS: Fascinating. Some great detail there. And I’ll just mention, ADLs—I think for those not familiar, I think we’re talking about activities of daily living. So, 60% having trouble with that is quite a remarkable number.
CHRISTIAN SANDROCK: Yeah, I tried to not have as many acronyms—sorry about that, Rick—but yes, things like brushing your teeth, brushing your hair, going to the bathroom by yourself, feeding yourself, those things.
What is being done well in press coverage of these issues, and where is there room for improvement?
RICK WEISS: Great. So, while we pull questions together from reporters on this briefing, I typically like to start with one question that I like to give all three of you in sequence, and that is just to speak directly to reporters with some advice in a way and to mention for each of you anything you’ve noticed in the way the news media have covered this syndrome that you think is either laudable and you want to point to or that maybe is a shortcoming and you’d want to let reporters know that here’s something that they could do better at as they cover this disease. So, I wonder if you could each address that question in turn, starting with you, Dr. Truong, if there’s anything you can think of that might be some advice to reporters on this beat.
ALEXANDER TRUONG: I think that the media’s actually done a really good job in presenting post-COVID syndrome, or PASC, and emphasizing how it’s affecting patients. I think that, as Dr. Sandrock has already mentioned, we really need to wave the flag on vaccinations, because I think prevention is the biggest key. And I think that a better push in the media would be helpful for that.
RICK WEISS: Great—and Dr. Mukherjee.
BHRAMAR MUKHERJEE: So, I think that the media has done a wonderful job in raising awareness and also making people feel that their voices are heard and this is serious and in the beginning part, when, you know, many people were dismissive because some of these conditions often you have after illnesses—so gradually, that information crystallizing, and the media has not given up and have continuously followed, and the community—the scientific community has taken it seriously and has not given up. So, that’s something I want to mention. Where I think that the media has not done quite well is often I see articles which struggle to strike a balance between alarmism and denial, that there is a—like, you know, there is a centrist point of view, that it is what is happening, and the science is still evolving. That does not mean—that’s not necessarily a bad thing because as we know more and we share more and we change our positions and that’s how you progress with the new disease. That does not mean that you should lose trust.
RICK WEISS: Right. One of those central tenets of how science works—everything is provisional, but it does tend to get closer to the truth over time. Dr. Sandrock.
CHRISTIAN SANDROCK: I think you guys highlighted it, you know, extremely well. I would say that, you know, when we first started managing our patients with long COVID, you know, approval was one of the biggest things. Recognizing this as a disease, recognizing their symptoms are real and they’re not crazy was one of our big tenets and probably the first thing we did in all of our appointments. Interestingly enough, that’s waned. We don’t need to do that, and I think that’s really a lot of what’s been discussed in the media. We know this is a real disease. We know this is a cluster of symptoms. We know it has a lot of, you know, similarities with chronic fatigue or, you know, myalgic encephalomyelitis. It’s really things that we know that there’s a lot of similarities. And that—you guys have done a great job and, you know, the media’s done a great job in explaining that.
I think the one area which I’d like to see more, but it might be just the lack of data, is around the impact of the health care system. We knew what that was acutely and how the ICU was overwhelmed and hospitals were overwhelmed. But now that we’re sort of coming out of the dust and we just have a large group of patients who are chronically ill and have chronic symptoms and can’t go back to the workforce, we’re still learning what that impact is, and that is—you know, the acute phase of COVID really limited our ability to get patients in for cancer treatment and so forth. I think this long phase is also going to do the same. And I think that’s—you know, if you couple that with all the burnout and everything else we saw, you know, we have no nurses, we have no doctors, we have no health care providers, and we have an increase in patients. This is something that we just haven’t talked about a lot, which honestly scares all of us. This comes up in—multiple times every day in every meeting I have. And I think that’s a big worry of ours, so…
What work is being done to get data on long COVID from diverse populations?
RICK WEISS: Scary prospect there. OK. Thank you. So, we’ve got questions coming in from reporters. I’ll start with some of these here. This is from Sheila Eldred, who’s a freelance reporter based in Minneapolis. What work is being done on getting more data from diverse populations? Is anyone doing studies right now that have a more representative group of participants?
ALEXANDER TRUONG: So, I can speak a little bit to that. There’s a larger trial right now called the RECOVER trial, which is a nationwide trial recruiting patients. There’s been a bunch of sites all over the United States. And that’s looking at a much larger population of both patients who’ve been acutely infected with COVID, as well as those who’ve had long-haul or post-COVID issues, looking at who gets it, who doesn’t, and what medications work or not. A lot of the stuff that—at least, speaking for our clinic, that we’re doing to take care of these patients are basically—are based on experience and not data. And so, these trials will help look at that.
BHRAMAR MUKHERJEE: Yeah. I think that, you know, places where they have integrated data systems. For example, in the U.K., there was a study on long COVID integrating longitudinal health care record data from 10 studies, and they had more robust findings. But it’s U.K. We are talking about U.K. and U.S., and our notion of diversity is never going to a global population. And the global studies I have seen are mostly survey-based studies, not really looking at clinical outcome, vaccination, and it’s all self-reported or not getting biomarkers. So, I think that the bias that I was talking about is not just in terms of race, ethnicity within U.S. and U.K. It’s really getting that international landscape together. And there are very few limited efforts.
What, if anything, can we say with confidence about long COVID?
RICK WEISS: OK. I have a question here from Nick Gerbis at KJZZ Public Radio in Phoenix. And this is a tough global question for all of you, but I think he’s making an astute observation from a, you know, journalist’s point of view. Given all the inconsistencies in definitions and data, what, if anything, can we say with confidence about long COVID? How does a reporter deal with that? Is it just a matter of a reporter having to define their own terms each time they’re writing about it, to make sure they’re being clear about what they are talking about? It’s a tough question.
CHRISTIAN SANDROCK: Yeah, that’s—I’d love to hear what everyone else has to say. You know, this is something we struggle with because, you know, again, defining when that begins, what that begins with, what cluster of symptoms is difficult. What we tend to look at is really just the commonalities. And there are some trends. You know, Alex did a nice job of laying out the symptoms, whether it’s fatigue, shortness of breath, headache. Those are some of the chronic symptoms. And regardless of the studies, those persist. The other is just the length of symptoms. So, whether you start at, you know, 30 days, 60 or 90 days as your trigger point for what it is, we know this lasts much longer than that.
So, if we’re seeing people clinically that are at month four or five or six, regardless of the study, we know they’re in that window of long COVID. So, even though there are some differences in definitions, we really try to look at the commonalities. You know, I think Dr. Mukherjee’s meta-analysis, which she presented, really showed a lot of the difficulties that it really is in getting these diverse studies together, having similar endpoints. I mean, I—when I saw that paper, I thought, good God, this is not a paper I’d want to write, because just the difficulties of getting those studies together is really hard. And that’s—that is the challenge. So, as clinicians—and again, I’m speaking as a clinician—we just try and get those commonalities the best we can together. But I’d love to hear what other people think of that as well.
ALEXANDER TRUONG: I think when you talk to the patients who are coming to our clinic, they do tell a very similar story. They do tell about an acute infection with—they’ve got a confirmed infection, and then progression of disease or symptoms, you know, one, two or three, six months after it. So, I think the timeline works. I think that what the media needs to understand is that it’s definitely real. And whether or not we’re splitting hairs as to whether symptom onset is at one week, four weeks, whatever the case may be, is not as important.
BHRAMAR MUKHERJEE: So, I also think that the standardized definition posed by the WHO has been adopted by many countries, and that was in October of 2021. So, things have been more homogeneous because there has been a consistent clinical case definition which was proposed. So, I think that trying to harmonize data in a uniform way across studies is very critical. But I think that we know that this is real, and there are some people who are struggling even beyond the 12 weeks and who are really, really going into six months and one year. As we have more follow-up data, I think we’ll have further classification in terms of time.
What should long COVID patients look for in support groups, and what should they avoid?
RICK WEISS: I think those answers are really helpful. Thank you. A question here from Tinker Ready from the British—well, actually, it used to be The British Medical Journal. Now it’s just BMJ, I think. Are there any tips for patients looking for support groups? What should they be looking for in a support group, and what should they look out for?
CHRISTIAN SANDROCK: This—if you’re OK with me answering, this comes up all the time for us, and I’m going to try—we’re supposed to talk about our biases regularly and be very conscious of, you know, micro and macro aggressions. And I’ll be very conscious of my anti-social media bias. I think, you know, for a lot of our patients, they spend their time on Facebook and other media groups. And, you know, it’s really hard to separate a lot of the things that are said by particularly other people in those support groups if they’re not live and they’re virtual or part of the social media.
What we really say is—almost as an absolute—is if anyone is saying this definitely works, this is awesome, it is a quick fix, it’s something that’s helpful, don’t go with it. That’s—you know, we know this disease is complex. We know we don’t have good answers. We know the science is evolving. If anybody says, this is a perfect fix and it’s going to work for you, we can’t really say that. We’ve already learned that, you know, what we might use for someone for shortness of breath with long COVID is very different than someone with cognitive impairment. I mean, they’re completely different treatments sometimes. So, to say there’s going to be one fix that’s going to help you, that’s a big red flag. And if you’re in a group where that is happening a lot, I would say jump ship. And it’s really—the second thing is one that has a lot of affirmation. I know that sounds really kind of cheesy, but if the group has a lot of affirmation of both what you’re going through and what the patient’s going through and their symptoms and their struggles with the health care system and their diagnosis, I think that’s actually a good group.
RICK WEISS: Interesting. Others want to weigh in on that?
ALEXANDER TRUONG: Yeah. I would also say that I’ve had a lot of patients who’ve been victims of scams from these groups, saying that if they pay hundreds of dollars for this concoction of vitamins or whatnot, they’ll feel a lot better. A lot of these patients suffer a lot. A lot of these patients are grasping at straws to try to figure out anything that can make them feel better and very vulnerable to these kind of scam. So, I would just caution within these groups, these social media groups, there are going to be people looking for victims and so just to be cautious about spending money on interventions that may or may not work.
RICK WEISS: Bhramar, anything to add there?
BHRAMAR MUKHERJEE: No, nothing to add. But I do know that, like, there have been many studies where people, for example, Black women, have felt invisible in getting care or being heard. So, they have formed their own support group, not necessarily for treatment or care but just to share that experience of being invisible. So, we have to think about all of those contexts into why people lean on certain social media groups. Yes.
Should public health officials emphasize prevention tools beyond vaccines, such as masking and testing?
RICK WEISS: OK. Question here from Amy Mathews Amos, a freelance reporter from Santa Fe. Given that prevention is the best treatment and that vaccines still allow breakthrough infections, should public health officials be promoting other tools for prevention more? For example, masking indoors, testing regularly, avoiding crowds—those tools, which were promoted early in the pandemic, seem to have been pushed aside, yet people are still getting sick. Puts you—a few of you on the spot for the policy world…
ALEXANDER TRUONG: I’ll take this on. I think it’s really difficult because we have to separate exhaustion from doing this to actual data. I think the data definitely argues that masking, social distancing, avoiding crowds help prevent infection, including COVID infections, as well as a bunch of other things like flu and common cold. So, I think that those things are important. Whether we do it all the time or we do it in strategic moments is still a question that we have to answer. Now the numbers of COVID, at least here in the South, have gone down. So, I advise my patients to be cautious at family get-togethers, big groups of people—no football games, no concerts and things like that. But in smaller groups, foregoing masks, things like that, may be helpful. Again, this should be a policy that waxes and wanes depending on what the epidemiology and the rates are telling us to do and not what, you know, social media or, you know, people’s exhaustion about wearing masks are telling us to do.
RICK WEISS: Others want to weigh in on that?
CHRISTIAN SANDROCK: I—the only thing—I mean, I want to highlight what Alex mentioned. And I think, you know, Norway did a nice job of this—is the constant risk-benefit analysis, right? There’s a population-based and an individual-based, and I think, you know, Dr. Mukherjee did a nice job of talking about the dearth of testing that’s now happening, right? So, we may not know what the true incidence is. And as that varies, our risk varies. So, translating that into our patients is always a challenge. So, it becomes a risk-benefit ratio. If you’re going to miss Grandma’s 80th birthday and this may be the last one she has with you, is that really worth it, right? And where does that lie for you, and where does that risk lie, based on the incidence of disease in your community? It’s very hard to do that. And we never did that on a national scale.
You can imagine if we had our discussion, either state-wise or national, the—you know, the benefits of going back to school and the risk of going back to school for our kids—right?—or having these large events canceled. We never really did that, so that’s not something that happens frequently. But that’s what we play every day on a public health, you know, stage, but also with our patients individually. And, you know, I think that’s just a—it’s a hard challenge, and I struggle with it greatly.
BHRAMAR MUKHERJEE: Yeah, I wish there were more random samples being collected from every nation so that we actually know the true prevalence. And when the prevalence is going up, we act accordingly. We don’t have to do it all the time. There is definitely a cost-and-benefit analysis. Right now I know many people who even refuse to get tested. They have perfect COVID symptoms. They don’t test. They quarantine. And so, we do not have a sense. In England, for example, the Office for National Statistics, they had a random sampling throughout the pandemic so that you had a pulse on when the true prevalence—it’s not dependent on whether people want to get tested or not. The true prevalence—I think that those are very important things if you want to translate those information into policy.
RICK WEISS: It does seem like in the—sorry?
BHRAMAR MUKHERJEE: No, but till then, you know, vaccination, vaccination. You know, what did I tell my daughter? Get vaccinated. Stay on top of your boosters. Take risks in a mitigated way. But going back to college—and there is really little that you can do.
Should long COVID patients to be concerned about negative effects from COVID boosters? And are there standard treatment approaches for long COVID?
RICK WEISS: It sounds like people, though, who may not be factoring this in as they make their decisions about vaccinations—a lot of people are hearing, oh, COVID seems to be going away. The symptoms seem to be mild. Maybe not everyone is taking into account this other issue that could actually and should actually be part of that risk equation. So, some other questions here. Let’s see. We have something from Scott Sayare, a freelance reporter based in New York. Is there any reason for long COVID patients to be concerned about negative effects of COVID boosters or other vaccinations. Separately, are there standard treatments or treatment approaches to PASC at this stage?
CHRISTIAN SANDROCK: We tell our patients here, and I’d love—I don’t know of any data that they really should be concerned with the booster. We don’t really have any data that suggests by getting the booster, your long COVID symptoms are going to be worse. And there are some small studies in cohorts that suggest it may get a little bit better, but we don’t really have data otherwise. And then as treatment modalities—I would say that there’s a few things we do universally. Excuse me. Of course, I’m coughing when I’m talking. But a lot of that would be, you know, around rehabilitation. And that’s both cognitive and physical. So, gentle, regular exercise, mobility all the time, any cognitive exercises you can do—so I know this sounds crazy, but our patients in the post ICU, or maybe if they’ve had a stroke—doing things, crossword puzzles, other puzzles, Sudoku, things like this, to keep your mind focused and to retrain are always helpful, regardless of what’s going on. So, this is a kind of some blanket recommendations we make across that population.
BHRAMAR MUKHERJEE: I agree that the booster studies are still limited and there is not concrete evidence. But one study I’d like to go to—it’s a recent study which shows that reinfections actually makes your long COVID symptoms worse. So, this is a study of 30 global countries, and it was a survey data and they asked whether it made symptoms worse or not. So, of course, self-reported and all kinds of biases, but still, 80% people said that reinfection made their long COVID symptoms worse. So, in order to prevent another infection, I think vaccination is important. And severe illnesses and what happens during the COVID phase is associated with long COVID, risk of long COVID. So, that also implies that you should get vaccinated and get booster so that the severe outcomes do not happen, leading to that pathway for long COVID.
ALEXANDER TRUONG: As for whether or not there is a treatment or a modality of intervention that’s helpful for all patient populations, I think that’s difficult to answer because it’s such a varied group of people. And as we mentioned before, it’s unclear whether the patients coming in with brain fog is having the same issues as the patients coming in with shortness of breath. And those are treated very, very different from each other. So, unfortunately, there isn’t a one-size-fits-all intervention that’s going to help everybody.
Is it possible to know if long COVID symptoms will be lifelong or temporary?
RICK WEISS: OK. Question from Tom Henry, who’s a reporter from the Toledo Blade—is there any way of knowing if long COVID symptoms are going to be lifelong or temporary but long in a person? What are the odds of them being lifelong?
ALEXANDER TRUONG: We don’t know, is the short answer. I think we’re way too early in this. I definitely have patients who have been infected in March of 2020 and have persistent symptoms for the last couple of years and there are patients who get better after three to six months. So, it’s really difficult to answer whether or not it’ll be lifelong or not.
CHRISTIAN SANDROCK: You know, if we look to the chronic fatigue—you know, the CFS/ME population, which is—again, it’s not the same. But if we look to that, as Alex mentioned, some will get better. Some are going to have a waxing and waning course that’s going to be really long, as in years. But usually you’ll see a trajectory where they’re slowly improving, but there’s lots of ups and downs as, you know, they have life and stressors and other things and various infections that are, you know, not COVID that show up. So, I think there will be a subset of populations that are going to have symptoms for a long time.
Are there race-based disparities in long COVID outcomes?
RICK WEISS: OK. This is a follow-up from Sheila Eldred in Minneapolis who had asked about diversity studies. If you had perfect data, would you expect to see racial disparities in long COVID? Is there anything that would lead you to believe there’d be differences based on race?
BHRAMAR MUKHERJEE: So, you know, I—we wrote a very initial paper on looking at race ethnic disparities in COVID-related outcomes—not necessarily long COVID, but hospitalization, ICU admissions. And so, the first paper was in JAMA Network Open in June or July of 2020. So, we did not know much, right? And we saw that there is—even after adjusting for potential confounders, there is a disparity. And Blacks were at higher odds of getting ICU admission and hospital admissions, and even after adjusting for pre-existing comorbidities and socioeconomic indicators and everything.
And then we revisited one—actually two years later, the same data, same population to see what has happened, if the interventions and vaccines and messaging have improved the situation. And what we noticed is that the absolute risk of hospitalization and severity in both populations have gone down, but they have not gone down at the same rate. So, the relative risk, the relative discrepancy still persists. And so, how do we tease that apart? And we did a lot of like, you know, modern weighting and causal methods to tease out—it persists. And how do we understand that and how we intervene that is a very important question, and for that we need more data. And also seeking care and delaying care is a very strong predictor. And often that happens with people of color delay in seeking care.
Would knowing the underlying mechanisms behind long COVID help treat the condition?
RICK WEISS: All right. OK. A question from Cecelia Smith-Schoenwalder—she’s with the U.S. News & World Report. She’s asking first what we know about the potential causes of long COVID. I know that your—in your presentations, at least listed through some that are of suspect, at least. But maybe more on point here, also wants to know, would knowing the mechanism behind long COVID help treat the condition?
ALEXANDER TRUONG: Yes, very much so. We’ve been searching for this holy grail to see if there is one mechanism behind all the symptoms or are patients who have post-COVID a heterogeneous or diverse population of pathologies. So, if there was one mechanism that could be treated and it linked all the different symptoms, that would be the holy grail of post-COVID care right now.
RICK WEISS: Are there any particulars any of you might offer? If one of those theoretical ideologies proved true, what’s an example of what would then be a treatment?
ALEXANDER TRUONG: So, for example, and we haven’t experienced this in our clinic, if we were—if it was true that this was all inflammation-related—and again, that is far from being definitive at this point—then maybe uses of anti-inflammatory medications, high dose NSAID, non-steroidal anti-inflammatories, or prednisone, which is a steroid, may be helpful. We haven’t seen that in our clinic. But if there was a certain mechanism that can do it, then maybe a treatment for it could help.
Is there anything similar to long COVID with SARS, MERS, or other coronavirus diseases?
RICK WEISS: Another question here—comparing to other similar diseases, was there anything similar to long COVID identified with MERS or SARS or other coronavirus diseases?
CHRISTIAN SANDROCK: That’s a great question. And I don’t think we have the n or the population number to really follow those patients out. I mean, SARS-CoV-1 was much more limited. And, you know, that was a beautiful example of how a very aggressive public health campaign and early recognition could limit spread. And I think the same for MERS-CoV. It’s—you know, there are some similarities with coronaviruses in general. So, you could suggest that it may be there, but I think the population numbers are too low. I don’t know what, you know, Bhramar and Alex think, but I think that would probably be my (inaudible).
BHRAMAR MUKHERJEE: Yeah, I was very interested in what is specific and authentic to SARS-CoV-2 versus other flu-like and flu-like illnesses. So, what we did—and this paper is going to appear quite soon, it’s being revised—is we sort of compared the diagnosis you get pre- and post-COVID diagnosis and then the diagnosis pattern between flu—if you had flu diagnosis—and then what happens pre- and post-flu in the same contemporaneous period of the pandemic, because we are generally having anxiety and stress and we have all going through like, you know, different time trends. And what we see, what is really fascinating about the uniqueness of SARS-CoV-2 is the binding with these multiple organs and particularly neurological brain fog, like, you know, memory loss—this we do not see in—like, we do see some respiratory complaints with flu follow-up, as a follow-up to flu and severe flu. But some of the neurological complications, some of the cardiovascular and circular system-related things we do not see. So, there is something really unique about—and Alex and Christian talk much more about this—that something binding with multiple organs which makes it very unique.
Does intense physical exertion after COVID infection increase likelihood of long COVID?
RICK WEISS: OK. I’m going to try to squeeze in one or two quick questions. I know we need to end timely at the top of the hour to—so patient care can continue with our guests. But there’s a question here from Kelsey Simpkins, a freelancer in Boulder. Many cases of debilitating long COVID are reported to have developed after a person recovering from COVID participates in some kind of intense exercise activity, such as athletes returning to training, going for an intense bike ride and so on. Is there reason to be cautious of physical exertion in the weeks or months after COVID infection to help prevent onset of long COVID? Any data that you’re familiar with on that?
CHRISTIAN SANDROCK: There is a little data, and Alex probably knows this very well. There is certainly some data that—and causative is—you know, we’re having this great discussion of causative reasons. There is some microvascular disease which can cause some limitations. We may see this on a pulmonary or cardiac level with some deficits, and by having aggressive physical activity afterwards, it may exacerbate some of these symptoms. JAMA had a couple of nice papers looking at Division One athletes, highlighting some of their cardiac dysfunction, which occurred up into 25% of patients who were largely minimally symptomatic, some of them asymptomatic with their COVID infection. So, we do, as a general rule, not push patients in the post-COVID period as much as we would, say, another patient. But, you know, what does that mean—a 10, 20, 30% reduction? That’s always open to debate and how we sort of use our rehab. We really try and have them limit and do heart rate monitoring, really not push themselves from that standpoint and from a symptomatic shortness of breath standpoint.
ALEXANDER TRUONG: But we don’t seem to have data that argues that exertion itself actually puts you at risk for having post-COVID issues. However, if you have post-COVID syndrome, we find that a lot of our patients, like Christian is saying, will wear out pretty quickly. And so, that’s why use of physical therapy, occupational therapy, speech therapy, things like that have been super helpful because they’ve learned how to push patients to a point where their endurance and strength builds but not push them so hard that they’re worn out and then have to take days to recover.
What are you most optimistic about regarding long COVID?
RICK WEISS: Here’s an interesting maybe penultimate question for you all from Damian McNamara, who is reporting for WebMD and Medscape. What are you most optimistic about at this point regarding long COVID? Nobody’s optimistic about anything?
CHRISTIAN SANDROCK: No, I mean, I think the recognition is awesome. But outside of that, you know, I’m trying to figure out something more.
ALEXANDER TRUONG: I think what I’m optimistic about is a lot less of my patients are coming in telling me that their other doctors are telling them that it’s all in their head or they’ll just get better. But I think that I’m really optimistic that we’re recognizing this as a real thing that is affecting patients and it’s leaving them debilitated. I’m also really optimistic that we are getting better and better at taking care of these patients, although we are still very, very much in the very, very beginning stages of doing so. We’ve been running our clinic since August of 2020, and since then we’ve made a lot of mistakes, but we’ve also had some successes and there are definitely patients who’ll graduate from our clinic. And I will tell you, at the beginning in 2020 and 2021, nobody was graduating from our clinic and they were all lingering and still having symptoms. So, I think that, you know, whether it’s because of physical therapy, medications, time, whatever it may be, we as a group in the medical community seem to be getting a little bit better at recognizing and treating post-COVID issues, but we still have a long way to go.
BHRAMAR MUKHERJEE: I think I’ll just end, this iterative process by which science learns has been inspiring to me from where we were and where we are now. And we have to recognize that these estimates that we are putting forward, the data that we are putting forward, are ultimately influencing policy. The Disabilities Act is being informed by what really happens to 2 to 5% people and this is their life. And so, I think the more we think about science and these findings really translating into people’s lives and we are seeing that in terms of influencing policy, the more optimistic I feel that it is not just science for science’s sake, it’s people.
What is one key take-home message for reporters covering this topic?
RICK WEISS: Fantastic. Fantastic answers. Just to wrap, we only have a minute left. I want to ask each of you in 10 or 12 seconds, just tell me one take-home message each that you want reporters to walk away with as they continue to cover this topic. What’s one thing you really want to leave them with as we close? Alex, I’ll start with you.
ALEXANDER TRUONG: I think there’s been a lot of bad things that’s happened with the pandemic, with COVID and post-COVID. I think what it has done is that it has brought the medical community, the research community, clinicians, scientists, laypeople all together. And we’ve actually—it’s been empowering to see how we move forward in helping to take care of not only the ICU patients, but the patients who have left the hospital and have lingering symptoms. My clinic, a bunch of other clinics across the country are in the process of figuring out how to take care of these folks. We are employing physical therapy, occupational therapy, neurology, cardiology and a bunch of different specialists. And it’s really been empowering to see all those professionals and laypeople come together into one unified approach to help a lot of our citizens.
RICK WEISS: Fantastic—Bhramar?
BHRAMAR MUKHERJEE: Yeah, I feel very inspired by the work that media has done in collaboration and in amplifying science. Some of the best epidemiological work and analysis have been done by data journalists. And I have become really integrated with public health communication and that being a main vocation and team. Right now I’m doing a fellowship in Cambridge on that. And so, I think I became a different person and many people became a different people about translation of their science and media has been very wonderful partners in amplifying that message.
RICK WEISS: Great—Christian?
CHRISTIAN SANDROCK: I would say—I mean, all excellent points. And I would say this is still a young disease from a disease standpoint. So, I think the data is going to change a lot. And I would say the take-home message is be flexible, because there’s going to be a lot of data changes and there’s not a lot we know. And, you know, we’re not going to get it right right away. So, just be flexible.
RICK WEISS: Fantastic. I want to thank our guests today for such an interesting and informative set of presentations and Q&A. This really helps move the ball forward in the journalistic front as you all work to move the ball forward on the medical front. As you leave today, reporters on this briefing, please do take the half a minute it takes to answer a short survey that you’ll get as you log out. It really helps us keep designing and scheduling these briefings in ways that are most helpful to you. I encourage all of you to check us out on social media, on Twitter, at @RealSciLine. Check out our website, sciline.org. And again, to our panelists, thank you so much for sharing your time and your expertise today. It’s such an important function and we really appreciate your help. We’ll see you all at the next SciLine media briefing.