Still Here, October 25: Links and transcript

Summary

Low-dose naltrexone (LDN) has been an oft-discussed off-label drug to help improve quality of life for people with Long COVID, myalgic encephalomyelitis, and other chronic illnesses. This week, co-hosts Betsy Ladyzhets and Miles Griffis talk with podcast producer James Salanga about an Australian clinical trial looking at LDN as a potential drug for people living with Long COVID and ME. Also in this episode: the latest COVID-19 numbers, and a new survey of around 70,000 people in China looking at Long COVID, reinfections, and more. 

Find our podcast on Spotify, Apple Podcasts, Pocket Casts, Amazon Music, iHeartRadio, or listen below and jump to the start of the podcast transcript.

Jump to a specific part of the transcript:

• Intro
• COVID-19 trends
• Australian low-dose naltrexone clinical trial
• Research
• Outro

Still Here is an abridged version of The Sick Times’ newsletter, which publishes weekly.

Mentioned in this episode (in order of appearance):

• The Sick Times: National COVID-19 trends, October 22
• CDC wastewater dashboard
• Biobot wastewater risk reports
• WastewaterSCAN dashboard
• Nature: Daily briefing: COVID protections eliminated a strain of flu 
• CDC: Vaccination Trends | Respiratory Illnesses
• U.S. free COVID tests: COVID-19 Testing   
• The Sick Times: Clinical trials explore how Low-Dose Naltrexone could help people with Long COVID
• The Sick Times: For people with severe Long COVID, medical care is out of reach
• The Lancet: Regional Health — Western Pacific: Long COVID facts and findings: a large-scale online survey in 74,075 Chinese participants
• The Lancet: Regional Health — Western Pacific: Long Covid is a significant health crisis in China too 
• Research Square: Long COVID and associated outcomes following COVID-19 reinfections: Insights from an International Patient-Led Survey

Additional audio in this episode: 

• Rude Mechanical Orchestra: Which Side Are You On? (orig. Florence Reece) 
• Pixabay: Thunder and the beginning of rainfall

Your support helps The Sick Times continue to chronicle the ongoing Long COVID crisis.

Transcript

Intro (0:00) 

[Instrumental snippet of theme song, the Rude Mechanical Orchestra’s rendition of “Which Side Are You On?” begins playing.]

James Salanga: This is Still Here, a podcast from The Sick Times.

Miles Griffis: I’m Miles Griffis.

Betsy Ladyzhets: And I’m Betsy Ladyzhets. 

[Instrumental ends]

Betsy: We’re the co-founders of The Sick Times. 

James: And I’m James Salanga, Still Here’s producer.

Miles: Many public health authorities are ignoring the ongoing COVID-19 pandemic.

Betsy: But here at The Sick Times, we’re not. So we’re bringing you the latest Long COVID news and commentary each week.

Miles: Without pandemic denial, minimizing, or gaslighting.

James: This podcast is an abridged version of our newsletter. 

Betsy: And each week, we share the latest on Long COVID and COVID-19 levels in the United States. 

James: Then we talk about one or two of the stories that have published on The Sick Times website this week. In today’s episode, we’re looking at clinical trials that are testing out low doses of naltrexone, or low-dose naltrexone, to formally see its impact on Long COVID.

Miles: And we’ll also share some of what is happening with Long COVID research. In today’s research update, we’re looking at a study published in The Lancet, looking at Long COVID facts and findings in China after surveying nearly 70,000 participants over one year.

James: And now, let’s get to our COVID forecast.

[Sound of thunderclap and light rain]

COVID-19 forecast (1:10)

Betsy: So our COVID forecast this week is decent news.

We are still in a bit of a lull in between the summer surge this year and what everybody expects to be a winter surge, likely starting in the next few weeks, but it has not started yet.

Wastewater data from the sources that I look at, and hospitalization numbers, test positivity numbers, all show continued downward trends across the US.

However, it is important to note that even when we have these kind of lulls or lower spread periods between surges, there is still a lot more COVID-19 going around now than there was in the real true lows, which I think of as like spring and summer of 2020 in some places, and also spring and early summer of 2021, when everybody had just gotten their first round of vaccines and before we had the Delta variant really spread in the United States.

So if you look at, for example, wastewater data from WastewaterSCAN, which has been collecting samples and tracking the coronavirus at sites across the U.S. for quite a while, their data really show that even though we’re at a lower period now, coronavirus levels are around the same or a bit lower than this time last fall. They are still about 10 times as high as early June of 2021.

Coronavirus levels in wastewater are a proxy for cases. They’re not a perfect equivalent. So there could be other factors that we don’t fully understand yet kind of contributing to that increase of the baseline over time.

However, based on what we know at this point, I think it’s still pretty safe to say that these kind of consistently higher wastewater levels do mean a consistently higher background amount of COVID spread.

James: I think the other thing that probably contributed to the massive jump in our lulls is just the removal of mask mandates as COVID mitigation policy has just gone more and more down the drain.

Miles: Yeah, I knew there was that interesting study that looked at — it’s been reported a couple times, but looking at how we eradicated a strain of influenza during early, you know, more stringent mitigations.

And it just shows how much you can mitigate and get rid of these diseases and viruses and protect communities. So it’s — yeah, it doesn’t have to be this way. It doesn’t have to be this high and put people in this much danger at all times.

Betsy: A lot of public health experts will sort of point to the fact that hospitalizations are consistently much lower than they used to be to, like, discredit what we see with the wastewater data and say, “Oh, well, there’s not as much severe disease.”

And I would say to that, “There may appear to be less severe disease, but we’re also tracking this less consistently than we used to be.”

Hospitals used to have to, like, COVID test everybody who came in. And now most facilities are not doing that. And in addition, we continue to have very little to no real-time tracking of Long COVID.

So hospitalization and death is not the only “severe” outcome from a COVID infection, those are just the things that we have more easy access to data on.

Also, as we’re kind of heading into this winter, um, I was recently looking at our vaccination numbers so far. That’s not great either.

Only around 11% of U.S. adults and a much smaller number — I think it’s like 4% of children — have gotten their latest COVID booster so far this fall. And there was also a recent study from the CDC looking at routine childhood vaccinations for students who are in kindergarten across the US, and they also found that those rates have been going down.

Not great indicators, to put it mildly, about interest among many people in the United States in getting vaccinated for all kinds of diseases, not just COVID. And so that really could create other public health challenges.

Miles: You can also find out more about the way we develop our COVID trends on our website.

James: And just like last week, [I] want to put out another reminder for U.S. folks that you can still get your four free rapid tests for a household at covidtests.gov.

And after a quick musical break, we’ll talk about the clinical trials that are going on now to study the impact that many doses of a well-known drug used for treating opioid addiction could have on alleviating Long COVID.

[Instrumental segment of theme song plays]

Australian low-dose naltrexone clinical trial (5:40)

The SIck Times: Clinical trials explore how Low-Dose Naltrexone could help people with Long COVID

James: So as I mentioned before, today we’re talking about clinical trials, specifically looking at low-dose naltrexone, also known as LDN.

While naltrexone is more well-known for its use in treating opioid addiction, using mini-dosages off-label to treat other diseases isn’t really new.

Betsy and Miles, why don’t you tell us a little bit about the history of low-dose naltrexone, or LDN, as a treatment?

Betsy: Yeah, so LDN has been used for a while now, kind of off-label, for a variety of different chronic diseases. People often use it in this context in pretty small doses.

There’s really a lot of self-experimentation that folks often do with their doctors to figure out the dose that works for them. 

And research suggests, you know, at higher doses, like, the original use of this drug was to be an opioid blocker. [While] the low-dose version appears to help reduce inflammation, help modulate the immune system, help reduce chronic pain, other things of that nature.

Um, and so it’s been used since the 1980s for diseases including myalgic encephalomyelitis, or ME, which shares a lot of symptoms with Long COVID, and for which — a lot of people with Long COVID also meet the diagnostic criteria for ME.

It’s also used for chronic pain, Crohn’s disease, multiple sclerosis, HIV, and rheumatoid arthritis, just to name a few.

Miles: So more recently, LDN has come up in communities for people who have Long COVID. Anecdotally, there have been people who have benefited from it — since we posted this story, we’ve seen comments from a lot of readers talking about their experiences with LDN.

There’s been a lot of readers who said that it helps, um, provide some relief for their symptoms, while others have sort of shared that it has done absolutely nothing for them.

It is just something that we really do need to look into. And so this is great that these clinical trials are happening. Hopefully, they will provide more information about why they work for some people and why they don’t work for others.

So a lot of clinics are now prescribing LDN to people with Long COVID, specifically with these Long COVID clinics. And yeah, it seems to be a pretty popular thing.

I know RHTM Direct, which is a company that offers telehealth for Long COVID, it’s one of their options. And it seems to be one of the first drugs that more open-minded providers who maybe aren’t working at Long [COVID] clinics are prescribing.

I recently just started seeing a new cardiologist at the recommendation of other people with Long COVID in my area. And after doing a bunch of different tests for cardiac issues, the first thing she recommended is LDN.

I’d been on it two years ago, I took it for like six months and titrated up. It’s really important to titrate up because it can have side effects. So you start with like one milligram or less, and then you sort of titrate up to 4.5 or 6 milligrams.

Some people go higher, it just sort of depends, but it takes a long time to sort of get there. I wasn’t noticing a huge difference, but I’m open to trying it again — it’s been a couple of years now, so who knows?

I think one issue that patients do face with it is that it can be expensive because it’s off-label. So for me, it was like $50 a month to get, which is pretty expensive.

So after taking it for a long time and not really seeing any results, I decided to go off of it.

So we’ll see what it’s like now. But I think that’s a pretty common experience because it’s not covered by insurance and these things, your patients are generally paying out of pocket.

So clinical trials like this will hopefully help that. If they do work for some people, if they do work for people with Long COVID and ME, then hopefully it’ll be covered so that it is a more affordable solution because people with Long COVID and ME spend so much on different supplements, all these different cares. 

James: Hopefully these clinical trials just make it so that LDN can be more accessible for folks to try out.

And researchers have been taking note of the experiences of people living with Long COVID, um, other patient experiences, which is why there’s now these clinical trials looking at LDN.

And so Dr. Meg Mundell, who’s the journalist working on this story, specifically focused on the Australian LDN trial, which itself is focused on people living with Long COVID. So it’s tracking a more expansive list of symptoms and builds on previous research about Long COVID, ME, and Gulf War illness. 

And so how is that research informing the design and aims of the Australian LDN trial?

Betsy: Yeah, so, one of the kind of advantages of this specific trial, which is going on at Griffith University in Australia, is the researchers behind this trial have been previously doing research into the underlying biology of Long COVID and ME, looking at things like [the] immune system and neurochemical signals, just trying to understand the diseases better.

And they found in an MRI study that there are similar neurochemical imbalances in the brains of people with Long COVID and ME, as well as issues with natural killer cells, which are a part of the immune system and also have a similar faulty situation going on in people with Long COVID and ME.

And the researchers found in doing a, like, microbiology study that LDN could specifically help to address this issue with natural killer cells — they could help with, basically, a chemical reaction going on that would unlock blocked channels for the cells and allow calcium back into the cell, so fixing a signaling pathway that’s been broken.

So now that they understand this potential biological mechanism better, they’re testing it with this clinical trial.

So it’s cool to see that kind of process of research, like, building from this more underlying pathobiology kind of study that is really trying to understand exactly, “How does this treatment work?” and, like, “How does it potentially help with certain symptoms?” to now collecting data from a broader group of patients.

And so the current trial includes about 100 people with Long COVID. But the next phase of the trial is also going to include people with an ME diagnosis, I believe, including people who had ME pre-2020.

So that’s also helpful in terms of including different patient groups and understanding that compare-contrast factor that Miles mentioned of, like, why is this helpful for some people and maybe not so much for other people?

James: One thing that The Sick Times has reported on as well is the fact that these clinical trials or just any kind of research, is really — can be really tough for people with severe ME, severe Long COVID to participate in because of the travel requirements, a lack of masking requirements, a whole slew of things.

And so for, you know, this Australian LDN trial, how have the researchers aimed to increase accessibility?

Miles: So the study is targeting these patients who have experience with post-exertional malaise, also called post-exertional symptom exacerbation or post-exertional neuroimmune exhaustion.

Um, this is a big hallmark feature of ME and can be a pretty common Long COVID symptom when you have a more severe presentation of Long COVID or ME. Again, it makes it really hard to do simple self-care tasks.

So getting to a clinical trial, which usually require[s] multiple visits, possible risk of infection, et cetera, is really difficult. So what this study is doing, they’re allowing people to participate from home — they mail out medications and the symptoms are tracked online.

So this is one way that I think a lot of clinical trials, especially with something simple like testing an oral drug, can do. You don’t have to go into a clinic. I think it makes it — logistically, the trial has to do a lot more, but they should treat their patients really well.

And this is one way to really include more people and, and offer more look[s] into severe ME because severe ME is almost always left out of studies.

Um, yeah, so the researchers, they also partnered with a pain specialist and an anesthesiologist, Dr. James Jerman, who’s been prescribing LDN to fibromyalgia patients for a decade, consults with patients over the phone, so this is a cool step and it’s great to see that this is happening in more Long COVID research around the world.

James: Yeah, I think it’s really huge that they’re making an effort to include people with more, um, severe forms of these diseases because like you said, it’s common that those folks are left out of these studies or just left out of research and contributes to their conditions being understudied, uh, just because there isn’t as much of an effort made towards accessibility.

So it is really important that this is something that it sounds like the researchers have given a good amount of thought to.

And to your point earlier, Miles, talking about how LDN is typically titrated up, the Australian study is a double-blinded randomized controlled trial and patients are starting on 1.5 milligrams daily, titrating up to four to six milligrams or the maximum tolerated dosage, whichever they hit first.

And so researchers anticipate that their early data should be out by early next year.

And like Betsy said, the next phase will be specifically looking for people with ME, including people who have had ME since before the pandemic.

You know, we’ve talked a lot about this one study. What other LDN stories are currently happening or are kind of on the horizon?

Betsy: Dr. Meg Mundell, who’s a writer and journalist based in Australia, primarily focused on this study just because there are some interesting aspects about it, like the pathobiology research and the inclusion of people with more severe symptoms.

But there are several other LDN trials going on around the world.

So that includes also a randomized controlled trial in Canada, looking at, specifically, fatigue in people with Long COVID who have ME-type symptoms.

There’s a study going on in Spain focusing on people with fibromyalgia and one in the U.S. at Harvard University, looking at how people with ME respond to LDN or mestinon, which is another drug used for an autoimmune disease.

So it’s cool to see, like, multiple trials going on for, kind of, the same drug at once.

I think when the data start to come in for these, hopefully, it will help us to really have a better picture of how well LDN works on average, and also hopefully a better understanding of for whom is it a better treatment. So that maybe providers can be more specific in prescribing it, rather than just like everybody trying it, when, for some folks it doesn’t have as big of a benefit for them.

Miles: Yeah, I think the last sort of point, like when we look at these different clinical trials, drugs like this, like, offer relief. A lot of the times they might help us find out what the root cause might be, but they’re not, these aren’t like cures.

These are sort of things that will provide better quality of life, hopefully, for some people and hopefully tell us more about the pathophysiology, and the pathobiology of the disease.

So they’re encouraging steps forward, but I think sometimes when people outside of the Long COVID community hear about treatments, they think, “Oh, great, this is a cure. You’re fine now.” And it’s important to sort of talk about all these potential treatments as offering relief, but not a cure.

James:  Offering that context is really important to, you know, not mischaracterize things like LDN as silver bullets, for example, but to also mention, like you said, that they do offer, they can offer, relief.

And so it’s not, as if it’s anything that’s, like, snake oil, but it’s important not to over- or understate what it’s actually able to do.

Betsy: Yeah, developing novel drugs, which some researchers are working on, it takes a long time.

And so it’s helpful to know, like, what repurposed drugs or what symptom management strategies can folks use in the meantime. So this is really a good example of that.

James: Yeah, and that wraps up our top story for this episode. And so next, we’ll hop to our research update.

Research (17:40)

[Miles’ voice echoes the word “Research” accompanied with a horn sound excerpted from the theme song]

Miles: This week, we’re looking at a new study that was in The Lancet: Regional [Health] — Western Pacific. It focused on an online survey of nearly, I think it was, yeah, over 70,000 people.

Um, and it found that reinfection with SARS-CoV-2 was associated with milder symptoms, but led to a higher incidence and severity of Long COVID.

The researchers say that, to the best of their knowledge, it’s currently China’s largest publicly available Long COVID epidemic survey and has worldwide applications.

So a few findings from it: Women were more likely to have Long COVID. We’ve seen that validated in a lot of other studies in the past as well, as well as other diseases like myalgic encephalomyelitis, ME.

The most frequent Long COVID symptoms in the study included fatigue, memory decline, decreased exercise ability, and brain fog or cognitive dysfunction.

Another interesting thing this study found was an increase of, um, susceptibility to other, um, infections, whether they’re bacterial or viral. So they pointed out a certain type of bacteria, as well as the influenza virus.

So that’s kind of an interesting finding that I think has been sort of talked about within the patient community and the Long COVID community, about being more vulnerable to different infections.

Betsy: Yeah, I mean, to me, the thing that’s notable about this study is not necessarily, like, the findings themselves, because of a lot of this, as Miles was saying, is information that has already been shown by other research, but more the kind of location and scale.

Like the authors mentioned, this is the largest study in China for quite a while. And it includes a pretty large sample size and also looks at reinfection.

And so I think it’s helpful, both to have, kind of, another study showing this potential risk of reinfection that has come up in a few studies, but still kind of needs more research to understand, like, exactly what’s going on with areas like the immune system. 

As well as the location — I think we’ve had a couple of international writers do stories for us that reflect this concern globally of, like, some people in non-,like, U.S., Europe, kind of think of Long COVID as a, like, high-class kind of disease or as something that only happens in these like higher-income Western countries.

And so I think it’s always worth highlighting when we have these studies that show like, no, this really is a global problem.

Miles: Yeah, researcher Dr. Ziyad Al-Aly wrote a commentary on this.

He says, “The features of Long COVID in China mirror those observed in studies conducted in other parts of the world. This underscores the consistency of Long COVID features across national borders, cultures, and healthcare settings.”

That quote stuck out to me when I read his op-ed on it, and I think it just shows that, if we know that the number now is over 400 million people affected by Long COVID around the world, this shouldn’t surprise us that this is in all these different countries.

But I think it’s worth highlighting when we do find these [studies] because it is so often overlooked and intentionally minimized and people talk about it as if it doesn’t, [as if] people aren’t talking about it in other countries, but we don’t know that. 

A lot of people are. There’s a lot of different groups [worldwide].

And if there’s, you know, not a lot of education about Long COVID, even in the United States, places with even less public health infrastructure and resources really aren’t educating about the long-term effects of COVID-19. The more we see these types of studies, um, I think it’s important to uplift them, and, and show people how this is a global issue.

James: I really like the points that you’ve both made about, you know, the fact that there are countries where there may be less public health infrastructure or even less research infrastructure to do even, like, a wide scale survey like this.

And I think it also highlights the fact that, you know, Long COVID and COVID are equity issues, that there are, you know, countries that had less access to the vaccines when they first rolled out that still have flagging vaccination just because of that lack of public health infrastructure.

And so, you know, we just still don’t have a really complete picture of the, you know, continuing impacts of COVID, including Long COVID, around the globe and just thirding that it is really important that we emphasize these studies and just anything that adds to that broader picture of the impact of COVID and Long COVID.

Miles: I guess my last, like, takeaway point from this is that they talk about reinfections, you know, they say they’re milder and then can lead to more severe presentations and symptoms after.

And they also sort of highlight, like, how little we still know about reinfections.

Like, this is something that is still really emerging, but we saw a pretty similar conclusion, um, in the Patient-Led Research Collaborative preprint that we wrote about a couple of weeks ago also showing that reinfections are worsening symptoms and quality of life of people and leading to worse outcomes.

This year, especially, sort of has been of the year, at least, sort of exploring what reinfections are doing and we’re showing that it’s just not good things.

James: Yeah, yeah. And I mean, it is helpful to have more and more data, but it is, yeah, I mean, hopefully it is something that provides more impetus for people to actually acknowledge that COVID is serious. It’s not like the flu, it’s not like a cold.

And it is something that we continue to grapple with and deal with, but it doesn’t mean that things have to be this way, even though they are right now.

Outro (23:07) 

James: And on that note, that is all we have for you this week. You can stay up to date with The Sick Times’ newsletter and coverage at thesicktimes.org, where you can also find the links to all the stories and the studies that we have mentioned in the podcast.

[Instrumental theme song excerpt plays underneath the rest of the podcast]

Miles: We’ll continue reporting the information you need to better practice care.

Betsy: Solidarity with everyone still here. 

James: This podcast and The Sick Times are supported by you. You can help us keep this work going by donating on our website. 

Still Here is a production of The Sick Times, a nonprofit newsroom chronicling the ongoing Long COVID crisis. 

Our theme song for this episode is the Rude Mechanical Orchestra’s rendition of Which Side Are You On?, originally by Florence Reece. You also heard a snippet of cellist Joshua Roman’s song “Immunity.” I’m James Salanga and I produced this episode. Our engagement editor is Heather Hogan. Sophie Dimitriou designed the cover art for our podcast, and Miles Griffis and Betsy Ladyzhets are your co-hosts and The Sick Times’ co-founders. 

Thanks for listening.