Podcast: The challenge of long COVID

The global pandemic: Three years later

Three years after we first began forecasting the trajectory of the COVID pandemic, we bring together IHME experts to discuss the ongoing effects of COVID and where we go from here.

In today’s episode, Dr. Sarah Wulf Hanson and Dr. Celine Gounder share their research on long COVID – its symptoms and paths to recovery, and who is most likely to be affected. 

 Listen as a podcast

Key takeaways:

• There are two main categories of long COVID:
  1. Those who were severely infected early in the pandemic and have residual organ damage, like lung scarring or heart damage.
  2. Those who had mild infections initially and later developed more significant symptoms like fatigue, shortness of breath, and cognitive symptoms like brain fog and memory loss.
• The second type of long COVID is becoming more common, and there are still big questions about what causes it mechanistically, making it more difficult to treat. There is growing evidence that it may be autoimmune-related, but with only three years of data, much of the cause is still unknown.
• Who is at highest risk of long COVID?
  • Women are at much higher risk of long COVID than men.
  • Children and young people under age 20 have much lower risk than older people. 
  • Black, Hispanic, and Native American people are at higher risk for more severe illness, and therefore more likely to have residual organ damage. 

This transcript has been lightly edited for clarity

Pauline Chiou: Welcome to this edition of the Global Health Insight podcast. I’m Pauline Chiou in Media Relations at the Institute for Health Metrics and Evaluation. In this podcast, we’ll be discussing long COVID with IHME lead research scientist Dr. Sarah Wulf Hanson and Dr. Celine Gounder, clinical associate professor in medicine and infectious diseases at NYU’s Grossman School of Medicine.

She’s also editor at large of Kaiser Health News and a senior fellow at the Kaiser Family Foundation. Thank you to both of you for being on this podcast.

Dr. Celine Gounder: It’s great to be here.

Pauline Chiou: Dr. Hanson, let me start with you. You’ve done so much research on long COVID. Remind us what long COVID looks like and what the symptoms are.

Dr. Sarah Wulf Hanson: It can look like many different things, actually, which is why it’s so complicated to study and to understand. It can affect pretty much any body system. So some of the most common symptoms we see with long COVID are fatigue and shortness of breath and cognitive symptoms like brain fog or loss of concentration and loss of memory. But it can also lead to GI symptoms or headache or insomnia or skin rashes.

It can really manifest in in many, many different ways in the body. So we see some symptoms that are really common. Post-exertional malaise is another really common symptom. But we also see some other, rarer symptoms associated with it as well.

Pauline Chiou: And Dr. Gounder, it’s so perplexing because as Dr. Hanson had mentioned, it’s sort of a range of symptoms. What are some of your big unanswered questions about long COVID?

Dr. Celine Gounder: Well, I think, first of all, it’s helpful to break it apart into two big categories of long COVID. So you have the people that got COVID pretty early in the pandemic before we had vaccines, who had very significant organ damage, in particular to the lungs, to the heart, to the kidneys. And so it’s damage that occurred at the time they had that initial COVID infection where they were probably in the hospital for that.

And that damage is just not reparable. It’s not curable damage. And so that might include scarring of the lungs. It might include heart failure, kidney failure. So that’s sort of one category of long COVID. The other category of long COVID are people who might have had a fairly mild infection, relatively mild infection at first, but then develop more significant symptoms later on.

And that’s the kind of long COVID we’re seeing much more now frequently. And that type of long COVID in particular, we are not as clear as to what is causing that mechanistically. And so that makes it more difficult really to treat and manage that kind of long COVID.

Pauline Chiou: Well, have you been able to make a distinction between what long COVID looks like from pre-Omicron infections as opposed to Omicron infections?

Dr. Celine Gounder: It’s less about Omicron or which variant per se and really more about did somebody have any kind of immunity prior to their COVID infection, prior to developing long COVID. So the people who had no immunity, it’s really people in the first year or two of the of the pandemic who got COVID, might have had COVID pneumonia, COVID infection of the heart or kidneys causing failure of those organs.

And we’re seeing much less of that kind of COVID. Now, it’s other manifestations of COVID, for example, the just general inflammation, the blood clots, those kinds of aspects of COVID that we think are causing the symptoms, the disease of long COVID now.

Pauline Chiou: Dr. Hanson, I’m curious to know if you’ve seen any disparities in long COVID after doing your research of over 1.2 million people in 22 different countries, are you seeing differences in terms of who’s impacted more: men or women, and differences in race or age groups?

Dr. Sarah Wulf Hanson: So we are in our data. We look at any cohort data, follow-up data from around the world that follow COVID patients over time. Currently, our analysis includes data from the first two years of the pandemic, and we’re updating that this year for all cases. And what we’re seeing in those data is a very clear disparity that women have a much higher risk, about twice the risk as men of developing long COVID and children and young people under age 20 have about half the risk of men.

And so we are seeing those clear differences. The risk across age is mostly defined by the severity of the infection. So if severity increases with age of the initial episode, then the risk of long COVID would also increase. But a mild case for young adults versus a mild case for older adults, we’re not seeing a clear age pattern there.

It’s mostly a difference between men and women that we’re seeing a large disparity.

Pauline Chiou: Dr. Gounder, piggybacking off of what Dr. Hanson just said, do you know why women are at a higher risk of long COVID than men? And why it seems that children are a bit more protected from long COVID?

Dr. Celine Gounder: I think this is also why, you know, going back to what I was describing about the two big categories of long COVID, the long COVID that results from organ damage during the infection versus this later long COVID that you can get even after a mild infection. It is important to tease that out a little bit, because if you think about who’s going to have severe organ damage, who is at risk for that, it’s going to mean older people, men actually more than women, and racial minorities.

So Black, Hispanic, Native Americans have been at higher risk for more severe illness. And that’s probably a reflection of higher rates of underlying comorbidities like diabetes, obesity, high blood pressure, and the like. But if you focus in on the long COVID that people can get even after a mild infection and the type of long COVID that’s more common today, now that people have immunity prior to having a COVID infection for that group, we do see that women are higher risk, and that is probably because there’s some sort of autoimmune component here, which is where your immune system turns against the body itself, and that somehow the COVID infection is leading to the body’s immune system turning against itself.

And this is an area where we still have a lot of questions as to why and how that might be happening. Is it you know, is the infection completely gone or not in those settings? Is this entirely dysfunctional, inappropriate immune response, or is there even something else that we’re not quite sure of yet?

Pauline Chiou: And for the children, do you have any thoughts on why children seem to have a lower rate of long COVID compared to men, as Dr. Hanson was saying?

Dr. Celine Gounder: Well, children are at lower risk for severe COVID, so that’s certainly protective. And we typically don’t see autoimmune illnesses develop until a bit later in life, usually more commonly middle age. And so it’s probably a function of just severity of illness and maturity of the immune system.

Pauline Chiou: And for people who are dealing with long COVID today, each case can be different. What’s the best way for individuals to navigate the systems and to live with what they have at the moment?

Dr. Celine Gounder: The challenge is we don’t really have very good treatments for long COVID. It’s about managing symptoms more than anything else. And so, if you have shortness of breath, that might mean you need supplemental oxygen or pulmonary rehab, where you work with somebody to improve your breathing, strengthen muscles over time.

If what you’re dealing with is blood pressure problems, a lot of people who have long COVID will have difficulty standing because their blood pressure will drop when they stand. And so that might require things like really trying to stay well hydrated too, taking certain medications to support your blood pressure, using compression stockings, and those kinds of things. So it really depends on what symptoms you’re experiencing, what we have to offer.

The other thing is that a lot of people who have long COVID also have social and financial needs, and so it’s really important that the care of long COVID patients includes assistance from social workers, case managers, people who can help them navigate the system, whether that’s applying for disability, or it could be food stamps, it could be supports in the home to help you navigate cooking or bathing, or all of those basic things that we all have to do for ourselves.

Pauline Chiou: There’s still so much we need to learn about long COVID for the people who have it now and who have been suffering, they want to have an end to like, when is this all going to be over? Is there a way to even get some clarity on that question?

Dr. Sarah Wulf Hanson: We do see a recovery pattern of long COVID cases from the first two years of the pandemic and from that recovery pattern. We estimate that the majority of long COVID cases do resolve, but also that about 15% of long COVID cases still have symptoms out a year from those follow-up studies. And so we’re currently unclear how many long COVID cases go on to become chronic.

Pauline Chiou: And Dr. Gounder, what’s your experience and what are your thoughts in terms of answering a patient’s question who says, Doctor, how long is this going to last?

Dr. Celine Gounder: It really depends, again, on the type of long COVID. So is it the severe organ damage that would have occurred in the setting of a severe COVID infection? Most of those occurred in the first year or two of the pandemic. Some of that is permanent damage. You know, once you have permanent damage, heart failure, kidney failure, damage to the lungs, some of that is not reversible, will not improve over time.

For people who develop that form of long COVID, that’s probably immune-system-related and can happen after even a milder case of COVID. We have less information on that, and it may be reversible and  may improve in certain settings. But remember, we’re only just now hitting year three of the pandemic. And so we have only that much information.

And so it’s really hard to say at this point.

Pauline Chiou: Dr. Hanson, in your research, as you looked across the globe and looked at the data, was there anything that stood out to you in terms of differences between countries or regions?

Dr. Sarah Wulf Hanson: One thing we noticed early on when we were gathering data is that anywhere that COVID patients are followed up long term, long COVID was present and seen in the data. So, you know, early on it was wondered, oh, well, is this only in certain areas or certain at-risk populations? But really, anywhere it’s looked for, it is there.

And so geographic variation, we do see a little bit of it in the data, but it’s unclear so far how much of that is noise in the data versus differences in the population level, risk factors in data like previous autoimmune diseases or other comorbidities perhaps. So it’s unclear right now exactly what the geographic variation is. There likely is some, as with all diseases, but right now not enough data to really clarify what are the differences.

Pauline Chiou: Well, there’s so much interest in long COVID and and how to find solutions for people who are suffering with it. We put out the question on social media for people to ask us anything to pass on to both of you. So let me start with Annie. Annie has this question for people who test positive for COVID. Does taking Paxlovid or other antivirals reduce the risk of developing long COVID?

Dr. Gounder, do you want to start with that?

Dr. Celine Gounder: Sure. And this is being actively studied through NIH-funded trials right now. There is some preliminary data that would suggest that taking packs of it does indeed reduce your risk of going on to long COVID. So as an antiviral, it is blocking the viral replication cycle. And so if you have, say, a dysfunctional autoimmune response, it’s being triggered by the infection.

If you can stop the infection, stop the viral replication, it makes sense that taking Paxlovid might reduce your risk. There are drug interactions that preclude the use of Paxlovid, but those are quite rare, and in almost all instances you can manage that risk by just holding the regular medication, a patient’s regular medication that might be, for example, a medication to reduce cholesterol.

You can hold that medication for a couple of days while somebody is taking Paxlovid and then restart. And for health care providers who might be listening, if you Google IDSA, the Infectious Disease Society of America and Paxlovid drug interactions, there’s a nice explanation there as to how you can manage those drug interactions.

Dr. Sarah Wulf Hanson: I agree with Dr. Gounder and also kind of anything like accelerator vaccination that reduces the severity of the COVID episode would reduce the risk of long-term symptoms, too.

Pauline Chiou: Let me ask a follow-up to this question, because Paxlovid is a prescription antiviral and it’s not available everywhere. It seems to be available more in the high-income countries. So what’s the solution to get it into the low- to middle-income countries where long COVID, as you had mentioned it, you see it everywhere?

Dr. Celine Gounder: Well, it’s a great question. And even within the United States, you know, one of the wealthiest countries in the world, we see disparities within the US as to who has access. We see disparities by geography, by race, by income. And so there really need to be intentional efforts made, one to make the drug available in the country through perhaps reduced pricing.

But then also, even once you make it available in a country, how do you distribute it? And in the United States, we have a program called Test to Treat, which rolled out perhaps a year or so ago now, in which there was a federal government initiative to try to scale up testing, particularly in underserved communities, but linking that testing with prescribing of the medication on site at the same location where you’re getting your test.

So you can imagine that might be places, for example, like retail pharmacies in New York City. We’ve also had mobile vans going to underserved neighborhoods to try to provide on-the-spot testing and treatment. But it really requires not just supply of the drug, but a plan to distribute the drug.

Pauline Chiou: Absolutely. It goes hand in hand.

Dr. Sarah Wulf Hanson: I also want to just note real quick that not everyone can take Paxlovid. So even if there is full access, it can’t always be prescribed in every case or can’t be tolerated by everyone.

Pauline Chiou: Dr. Hanson, is it because of the age and the weight restrictions and comorbidities? Okay. So that’s a great point to make. Not everyone can take it. We have another question from someone named Ms. Scarlet, and Dr. Gounder. I'll give this one to you and Dr. Hanson. Let us know if you want to weigh in on this.

How is the diagnosis made for long COVID, and what is the opinion on metformin for long COVID?

Dr. Celine Gounder: So this is a great question. And this is not like, say, a heart attack where we have blood tests, we know what it looks like on your EKG. There's not a test for long COVID. We basically add up the evidence. So did you have a COVID infection that we know of? Was there a lab test showing that you had COVID?

Do you have the symptoms, signs that would be consistent with long COVID? Do you have the risk factors that might put you at higher risk for long COVID and so we sort of add up all of those pieces to make a diagnosis. And I think that actually makes it very challenging because people then question it, whether it’s maybe sometimes health care providers themselves.

It could be the federal agencies when you’re trying to apply for disability, it could be your employer who is questioning, well, how do you know that’s really long COVID? And so I think that can make it very difficult on patients with respect to metformin. Metformin is a medication used to treat diabetes. And there was a study published recently in preprint from The Lancet that showed that people who took metformin were at lower risk of developing long COVID than people who did not take metformin.

And there was a 42% reduction in long COVID, which was pretty significant. It was not a huge study, but it does seem to be a real signal. And so if you think about one of the risk factors for both severe COVID and long COVID is diabetes, and you’re giving somebody a medication that manages diabetes, it makes sense that that would help reduce your risk of developing long COVID.

Dr. Sarah Wulf Hanson: Yeah, no, nothing to add, really. I think we all wish that there was a biomarker or clear diagnostic criteria for long COVID, but it is, yeah, looking at the full symptom profile and kind of excluding other reasons for the symptoms at present.

Pauline Chiou: All right. Let’s move on to the last question. It’s from Ru, and Ru asks, Has anyone tried PEMF or pulse electromagnetic field for long COVID? And this person says it actually fixes the issue. But you’re both the doctors. So, Dr. Hanson, tell me what you think.

Dr. Sarah Wulf Hanson: Well, I’m not a medical doctor, so I’m more on the data side. And we all want a clear diagnostic test or biomarker. We all want a silver bullet to cure long COVID. And there’s just nothing so far, no evidence of anything that cures long COVID across the board.

So I’m keeping my eye out for successful treatments, but haven’t seen anything that cures long COVID.

Pauline Chiou:
Dr. Gounder, have you heard of this as a possible solution? PEMF.

Dr. Celine Gounder: I am not really that familiar with pulse electromagnetic field therapy or PEMF. I know that from the NIH clinicaltrials.gov site, which is where clinical trials are required in the US to be registered if they’re receiving NIH funding, there has been at least one trial that has been funded, but from what I can tell, they haven’t actually started enrolling any patients.

So, you know, I don’t think we really have any data to support that as a treatment at this time.

Pauline Chiou: So this is a call for more research, more data. And thank you both for your own work and your insight today. Dr. Sarah Wulf Hanson and Dr. Celine Gounder. We really appreciate it.

Dr. Celine Gounder: My pleasure.

Dr. Sarah Wulf Hanson: Thanks so much for having us.

Related resources:

• Research paper: Estimated global proportions of individuals with persistent fatigue, cognitive, and respiratory symptom clusters following symptomatic COVID-19 in 2020 and 2021
• JAMA study: women twice as likely as men to develop long COVID
• Long COVID May Catalyze New Treatments for Chronic Pain and Fatigue
• Supporting Kids With Long COVID as They Head Back to School