long COVID clinical trials

Long COVID is getting a lot of attention. Is that translating into clinical trials?

The bottom line is always treatments. Long COVID has brought a ton of interest to post-infectious illnesses. Researchers are asking whether they are actually autoimmune diseases, how big of a role coagulation or gut microbiome problems play, if viral reactivation is driving symptoms, or if the glial cells have gone bananas or … it goes on and on.

The bottom line for patients, though, is treatments. Since we haven’t gotten a handle on the core problem or problems in long COVID, it’s too early to expect someone to be working on a new drug for it, but old drugs in new bottles (i.e. drugs repurposed to treat long COVID) – that’s something we would expect in spades – and that’s happening. The more eyes on a disease, the more possibilities that should crop up, and as you’ll see long COVID has gotten quite a few drug companies thinking that they have something to offer.

Another hope was that long COVID would change how the medical world sees fatigue, exertion intolerant, and pain-producing diseases like chronic fatigue syndrome (ME/CFS) in such a way as to allow the testing of more serious drugs. For a variety of reasons – a heterogeneous patient population, lack of a biomarker, a reliance on symptom assessments, the fact that ME/CFS usually debilitates in an invisible manner but does not kill – all these factors and probably more have left ME/CFS out in the cold regarding high potency immune drugs.

Despite the fact that studies have shown that people with ME/CFS are considerably more functionally impaired than people with very serious diseases like heart disease or multiple sclerosis, they’ve been cut off from the high-level immune and other drugs that serious diseases typically get.

As this survey shows, at least with long COVID, that’s changing. Despite the fact that we don’t know what’s causing long COVID, expensive, high powered drugs are being trialed in long COVID, and sometimes in quite large studies.

So are drugs that one wouldn’t ordinarily associate with long COVID or ME/CFS, like low-dose antipsychotics that may help with neuroinflammation, statins, a Japanese anti-inflammatory drug, a xanthine derivative, and a myasthenia gravis drug.

Lastly, several trials are large enough to actually give some solid answers about treatment efficacy – something that’s been lacking in ME/CFS. As the biological similarities between ME/CFS and long COVID pile up, one would think drug companies will be more and more willing to give ME/CFS a shot if their drugs or treatments work out in long COVID.

One thing we don’t see yet – new drugs trying to get at Epstein-Barr virus reactivation.

Immune Drugs

A Stem Cell Trial in Long COVID (!)

Treatment of Long COVID Utilizing Autologous Stem Cells

This was a shocker – at least, to me. The last I heard about stem cells in connection with ME/CFS was at least ten years ago when Dr. Cheney was trying them out. People in this small, 20-person study are going to get 150 million ATCell™ “autologous adipose-derived mesenchymal stem cells” (and they won’t have to go to Mexico to do it). In fact, the stem cells are going to be gathered via liposuction from each individual and then expanded in the lab.

This U.S. study from American CryoStem Corporation is going to assess a bunch of interesting factors (lactate dehydrogenase (LDH), prothrombin time/partial thromboplastin time (PT/PTT Coagulation factors II), Troponin, D-dimer, Fibrinogen (Coagulation factors II), estimated glomerular filtration rate (eGFR), urinalysis and spot protein creatinine).

It’s expected to start in April 2023. People in the placebo arm will be allowed to try the stem cells at the end of the trial (nice!).

Bringing in the Big Guns

Impact of Monoclonal Antibody Treatment on Post-Acute COVID-19 Syndrome

Monoclonal antibodies cancer

Antibodies against cancer. (Image fr. Ramujana-original-raster-Wikimedia-Commons.gi)

Now we’re talking. Monoclonal antibodies are all the rage in many diseases. These powerful and expensive drugs can target and turn off specific factors in the immune system. They’ve been talked about in ME/CFS, but except for a perhaps underpowered Rituximab trial, have never received a shot.

They’re going to get at least a preliminary shot here. This 260-person casirivimab-imdevimab trial at the Intermountain Medical Center in Murray, Utah used an antibody that worked well to both treat people infected with earlier variants and reduce the incidence of infection. This trial isn’t aiming to get rid of long COVID; instead, by giving it early in an infection, it’s trying to reduce the incidence of long COVID later.

If the trial succeeds, though, one might expect the RECOVER Initiative to do as it did with Paxlovid – and follow up with a trial in long COVID.

Autoimmunity Take II: The RSLV-132 Trial

Phase 2 Study of RSLV-132 in Subjects With Long COVID

RSLV-132 is a “fusion protein” that’s designed to remove RNA that’s apparently escaped from the cell. We think of RNA – ribonucleic acid – as an essential component (mRNA) of the cell – but in autoimmune diseases such as Sjogren’s Syndrome,  it escapes outside of the cell and accumulates in the blood, where it triggers inflammation and ultimately the production of autoantibodies and autoimmune disease. RSLV-132 mops up the RNA in the blood and apparently did well in a lupus trial.

The 70-person study has been underway at centers across the U.S. since 2021 and is about to end soon (March 2023).

The “Mop Up” Trials

Plasmapheresis gets trialed … in long COVID in France…

Effect of Plasmapheresis on Clinical Improvement and Biological Parameters of Patients With Long-haul COVID (PLEXCOVIL)

I could see some hackles raising. Plasmapheresis … isn’t that like the next big thing that we’ve been talking about it in ME/CFS for several years? Yes, indeed. In fact, several very small studies suggest it may be helpful.

By filtering pro-inflammatory cytokines and/or autoimmune markers (such as adrenergic receptors) out of the plasma, plasmapheresis hold promise for ME/CFS. It’s long COVID, though, that’s going to get the first somewhat major plasmapheresis trial. Teeth gnashing aside, if this – and two other trials – are successful, it should boost interest in ME/CFS.

This 60-person French trial at the Hôpital Européen in Marseille, France should be starting soon.

And Spain…

Plasma Exchange Therapy for Post- COVID-19 Condition: A Pilot, Randomized Double-Blind Study

This prospective, randomized (1:1), double-blind, placebo-controlled study plasma exchange trial is going to include six two-hour sessions. It began last year and is expected to end in April 2024.

As Well as Immunoadsorption

Repeat Immunoadsorption Post Covid ME/CFS

This is another “mop up” approach that’s being looked at in ME/CFS – and is getting a chance in long COVID. This small German study (n=20) is for people with long COVID who have high levels of the adrenergic autoantibodies Carmen Scheibenbogen’s been studying for quite some time. They know that people with long COVID have high levels of these autoantibodies (yet another similarity with ME/CFS) because they’ve been testing them (paper to be published). The immunoadsorption technique mops up these autoantibodies. This Berlin study begins in August of this year.

None of these trials are going to be particularly big; these “mop-up” trials aren’t getting the big bucks that some of the monoclonal antibody trials are, but with 130 patients, the numbers are starting to add up. We should know a lot more about the efficacy of plasma exchange in long COVID over the next year or so – and if it works in long COVID, there’s no reason to think it wouldn’t in ME/CFS.

Berlin Cures…? Could BC 007 Help With Long COVID and ME/CFS?

Good Drug … Good Company

Study to Evaluate the Efficacy and Safety of Ampligen in Patients With Post-COVID Conditions

They used to say about Ampligen and its manufacturer – good drug/bad company. The drug remains the same, but the company has been remade and what a difference that has made. After decades of derision and missed steps, Ampligen is now being trialed in several different cancers and is due to start an 80-person, randomized, double-blinded, placebo-controlled long-COVID trial in March.

Longtime ME/CFS Drug Ampligen Gets Its Shot with Long COVID

Canada Goes Big in RECLAIM Long-COVID Study

RECLAIM: Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial (RECLAIM)

There are trials, and then there are 1,000-person trials! In this case, Canada has done something very interesting. They’ve developed a Canada-wide clinical platform to methodically assess treatments for long COVID. The US has RECOVER; Canada has RECLAIM (Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial).

My guess is that the two drugs named are only some of the treatments that will eventually be assessed. In any case, Canada ‘s testing two drugs no one else is.

  • Ibudilast is a drug mainly used in Japan which has some intriguing properties: it’s an anti-inflammatory that vasodilates the blood vessels (check), has neuroprotective effects (check), inhibits platelet aggregation (check), and even suppresses microglial cell activation (check). Good for Canada to give this drug a try.
  • Pentoxifylline is a xanthine derivative that’s used to treat muscle pain in people with blood vessel problems and peripheral neuropathy (interesting!). Inexpensive and readily available, pentoxifylline also inhibits the pro-inflammatory tumor necrosis factor (TNF-a) that Nancy Klimas is trying to beat down in Gulf War Illness and ME/CFS with etanercept.

The trials are beginning this month.

STRONGER! With Statins?

Statin TReatment for COVID-19 to Optimise NeuroloGical recovERy (STRONGER)

Atorvastatin or Lipitor – the most commonly prescribed drug in the U.S. – went generic long ago and is also readily available and affordable. It inhibits the production of cholesterol. So why devote a 400-person trial to it? The funders hope this 18-month (yes, 18-month) trial will help improve cognition and reduce neuroinflammation. Indeed, atorvastatin was recently shown to have neuroprotective effects and reduce microglial activation in mice. There’s more.

Atorvastatin also made good in the gut in some intriguing ways. By elevating butyrate levels (low in ME/CFS) and reducing leaky gut (present in ME/CFS), it may have found another way to reduce neuroinflammation.

This interesting study is going to use cognitive tests and brain MRIs to assess its effectiveness. Who knows? Statins might be a class of drugs that help a bit. Given their affordability, they might be a nice option.

The STRONGER Australian study has been underway and should be wrapping up in the spring.

A Biologic to the Rescue?

Temelimab as a Disease Modifying Therapy in Patients With Neuropsychiatric Symptoms in Post-COVID 19 or PASC Syndrome

You can tell we’re (people with ME/CFS) in a different world when a 200-person biologic trial pops up in long COVID. Temelimab may have the coolest brand name (Imjudo – take that overactive immune system!) going. It’s a monoclonal antibody that targets a protein found on the human endogenous retrovirus.

HERV proteins can trigger inflammation in the brain and damage the neurons, and have possibly been implicated in long COVID, ME/CFS, multiple sclerosis and other diseases. Elevated levels of this protein found in the white blood cells of COVID-19 patients have been correlated with T-cell exhaustion and other immune issues. Plus, the protein has shown up in the brains of people with COVID-19 who died.

This Swiss study began in August of last year and is expected to wrap up in August of this year.

The POTS Contingent

Efficacy and Safety Study of Efgartigimod in Adults With Post-COVID-19 POTS 

Efgartigimod (better known as Vyvgart) is used to treat myasthenia gravis – a disease people with ME/CFS have some acquaintance with via Mestinon (pyridostigmine bromide) which is also used to treat that disease. It’s also used in lupus, Sjogren’s Syndrome and … COVID-19-caused postural orthostatic tachycardia syndrome (POTS), which is common in ME/CFS as well. That’s the group this small 42-person Illinois study is targeting. It began in September of last year and is expected to wrap up in November of this year.

Something Very Different

Zofin to Treat COVID-19 Long Haulers

Zofin is using trying to use exosomes to alter immune functioning in long COVID.

Zofin is using trying to use exosomes to alter immune functioning in long COVID. (From Kalamedits – Wikimedia Commons)

Zofin is a new drug derived from amniotic fluid collected at childbirth that contains extracellular vesicles that can attach to cells and deliver microRNAs to them. Zofin contains microRNAs (miRNAs) that target the ACE2 receptor that the coronavirus enters the cells through. If the ACE2 receptor – which is found in cells across the body – has been gotten messed up by the coronavirus, Zofin could help return it to health. The interesting thing about the ACE2 receptor is that small studies suggest it’s messed up in ME/CFS as well.

Organicell, the small Miami drug company that produces Zofin, jumped on the long-hauler pandemic quickly and by December 2020, reported it had treated 6 patients, all of whom reported significant benefits.

The 30-person, randomized, double-blinded, and placebo-controlled trial began in April 2022 and is expected to last until April 2024. It’s taking place in sites in southern California, Houston, and Miami.

Brain / Nervous System

Anesthetizing the Fight/Flight System Back to Normality?

Dual Sympathetic Blocks for Patients Experiencing Sympathetically-Mediated Symptoms From Long COVID

Stellate ganglion block sounds almost too good to be true… Simply anesthetize the area around the stellate ganglion and watch the sympathetic nervous system (fight or flight system) calm down – reducing pain levels, improving sleep, gut functioning, cognition, and definitely feelings of well-being.

The thing is that anecdotally it appears to have worked with some long COVID patients in Alaska.  The really nice thing about this 40-person trial is that you don’t have to go to the far North to try it out. This trial is taking place in Hudson, New York and it just got started.

Bye-Bye Fight or Flight? Hello Better Blood Flows? Stellate Ganglion Blocks, Long COVID, and ME/CFS/FM/POTS

Anti-depressant or Anti-inflammatory? The Lithium Study

Low-dose Abilify helps some. Another anti-psychotic is under trial. So are psychedelics. These are brain chemistry-altering drugs and studies suggest that brain chemistry is altered in ME/CFS/FM. If Jarred Younger and his neuroinflammation hypothesis is correct, it’s probably been very altered, so why not explore more brain-altering drugs? We don’t even know the mode of action of many of these drugs.

How about Lithium, for example? Lithium is prescribed for manic depression and comes loaded with an impressive array of potential side effects (diarrhea, vomiting, poor coordination, tremor, frequent urination, sleepiness, muscle rigidity, and hypothyroidism) if the dose is too high. This Buffalo study, though, is using low-dose Lithium and is giving it a shot for its anti-inflammatory effects.

This 40-person trial University of Buffalo trial started in November 2022 and is expected to last until June 2023.

The Paxlovid Study

A Decentralized Phase 2 Efficacy and Safety Study of Nirmatrelvir/Ritonavir in Adult Participants With Long COVID

This “Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled study” (the more descriptors the better) RECOVER Initiative Paxlovid trial is looking for “100 highly symptomatic” long-COVID patients. This antiviral trial, which hopes to squash any remaining viruses in the body, comes on the heels of a study showing that people taking Paxlovid had a 40% reduced risk of coming down with long COVID.

Plus, you get to take part in Akiko Iwasaki’s study which will analyze the treatment effects.

The decentralized study begins in May and does not require site visits, and participants in Connecticut and New York who meet the entry criteria can enroll. It is designed to make it convenient to participate. The study drugs will be delivered to the participant’s designated address.

A Stimulating Study

Addressing Cognitive Fog in Long-COVID-19 Patients

Feeling foggy? Less alert? How about some stimulants. How about an old-time stimulant? Dextroamphetamine is used to treat ADHD (common in ME/CFS/FM), and narcolepsy, to enhance cognition in college students worldwide, as an athletic performance enhancer, and recreationally as an aphrodisiac. The study leaders state the drug is “known to reduce cognitive impairment in other chronic medical conditions, such as Inflammatory Bowel Disease”. What’s not to like?

It’s also a “Schedule II controlled substance that has a risk for abuse, tolerance, and psychological dependence”. This lower dose (10 mg/day for 12 weeks) study also includes “a digital behavioral tool with an embedded health coach” arm that helps with relaxation and coping. Participants will be closely monitored for side effects.

This University of Pittsburg Medical Center study will begin in February.

Tonix Tackles Long COVID

One thing you have to give Tonix – the maker of TNX-102 – they don’t lack confidence in their drug. After several setbacks (wrong doses, COVID-19) and numerous trials, they’re still hammering away at fibromyalgia, and, in the midst of all that, they’ve started a 470-person long-COVID trial.

Tonix Launches Decisive Fibromyalgia Treatment Trial Plus Big Year for Fibromyalgia Drugs?

My prediction – this pain-reducing and sleep-enhancing drug is going to succeed! If this company is willing to throw tons of money at a big long-COVID trial after all the problems with the FM trials, it must be very confident of its drug.

This phase 2, 14-week, double-blind, randomized, parallel, multicenter, placebo-controlled study wins the prize for the most descriptors (6) thus far. It began in August 2022. If you experience widespread pain, you’re eligible for this trial.

It’s underway in many sites across the U.S. (Check the website for locations).

A Different Kind of Stimulation

Trial of Auricular Vagus Nerve Stimulation in Painful Covid Long

Lauren Stiles, the founder of Dysautonomia International, thinks vagus nerve stimulation is going to be big in POTS and ME/CFS – it just needs more study. It’s going to get more study – not a lot – but more – in this 30-person trial at the Service Centre d’Evaluation et de Traitement de la Douleur (eg. The Pain Assessment and Treatment Center Service) in Paris.

A POTS Drug for Long COVID Patients with POTS

Ivabradine for Long-Term Effects of COVID-19 With POTS Cohort

There’s not much to say about Ivabradine except it makes sense to try this POTS drug in long-COVID patients with POTS. The authors must think so – they’ve opened a 250-person trial.

Find out more about this “comparative cohort, nested, randomized, controlled trial” – which forgot to give its location but which appears to be based in Bethesda, Maryland – here, and learn more about Ivabradine here.

Low-dose Naltrexone for Post-COVID Fatigue Syndrome

LDN was shown long ago to work in fibromyalgia, but it’s taken years to get an LDN trial underway in ME/CFS. What happens, though, when tens of millions of people come down with long COVID? Big LDN trials start popping up.

This 160-person trial is going to blow the small LDN fibromyalgia trials out of the water and that’s a good thing; it’s way past time for a nice hearty trial of this compounded drug to get underway.

This double-blinded, randomized trial is getting underway at the BC Women’s Hospital + Health Centre, Vancouver, British Columbia. Now, if we could just get a dextro-naltrexone trial underway, we’d really be sitting pretty.

Antidepressant or Cognitive Enhancer?

Vortioxetine for Post-COVID-19 Condition

Who knows what vortioxetine is doing or will do? Cymbalta – another “antidepressant” – was able to reduce pain in people who were not depressed. Could vortioxetine do the same for people with brain fog? This Toronto, Canada group apparently thinks it might. Another immune modulator, it does, after all, have anti-inflammatory effects.

Stating that vortioxetine is “an antidepressant with established pro-cognitive properties“, they hope it will improve cognition as well as general functioning, well-being, motivation, energy, and even sleep. They’re excited enough about its prospects that they’re going to try it out in 200 people.

This randomized, double-blinded, placebo-controlled study started in September 2021 and is expected to last until this month.

Stimulate Your Brain … From Home!

Home-based Brain Stimulation Treatment for Post-acute Sequelae of COVID-19 (PASC)

Will it be the next big thing? Currently, you have to go to a clinic or hospital and get the electrodes placed and set just right to get your brain gently stimulated to relieve your pain or improve your mood. Home kits are now coming available, and if they work … talk about a brave new world where you can potentially plug in for a while and emerge a healthier person.

This 40-person 1-month trial will attempt to improve the problems with executive functioning (ability to sustain attention, slowed information processing speed, etc.) via 30-minute sessions of low-intensity, home-based transcranial direct current stimulation (tDCS).

This Harvard study was due to end up in July of this year.

A Beta Blocker for Long COVID?

Post-Acute Sequelae of Coronavirus-19 (COVID-19) With Dyspnea on Exertion And Associated TaChycardia TrEatment Study (PEACE)

Metropol succinate – now there’s something different. Stuffthatworks reports that metropol succinte (Tropol XL) has been rarely tried but has “overwhelmingly positive reports” from those who have tried it. Forty-five percent of people who tried it reported it worked “very well”.  Metropol succinate is a beta blocker that’s often used to treat high blood pressure and chest pain.

This 20-person Hackensack University, New Jersey trial began in March of last year and is expected to last for several years.

The HOT LOCo Trial: Flooding the Brain with Oxygen 

Given how much attention hyperbaric oxygen treatment (HBOT) has garnered in fibromyalgia and ME/CFS it was no surprise to see a HBOT trial show up in long COVID. The Isreali’s have led the way – now we need outside groups to take HBOT on and that’s what this study will do.

This 80-person, randomized, placebo-controlled, double-blind, phase II trial from the Karolinska Institute in Stockholm, Sweden began in Sept. 2021 and is slated to finish in Sept. 2023.

  • Contact: Hyperbaric unit  +46812394680 ; Anders Kjellberg, MD –  +46851775212    anders.kjellberg@ki.se


A few of the supplement trials are shown below.

The Cannabis and Hemp Trials

Cannabis gummies

Finally, a few cannabanoid/hemp studies. We could use many more…(Image from elsa olofsson – Wikimedia Commons)

Chronic fatigue syndrome (ME/CFS) and fibromyalgia should simply be awash in Cannabis trials that aim to find a cheap and simple help for these diseases. There’s little doubt that Cannabis can help with pain and sleep and may even help with cognition, yet Cannabis trials are rare, if they’ve happened at all.

Two long-COVID Cannabis/hemp trials are underway – a cannabidiol trial in New York and a 111-person hemp flower extract trial at the Bateman Horne Center in Salt Lake City, Utah.

Sea Urchin Eggs For Better Health?

Passing over the question of how one harvests sea urchin eggs, this 60-person placebo-controlled, randomized Argentinian study notes that they are anti-inflammatory, have antioxidant properties, and have been used in eastern medicine for a long time.

Supplement Trial Digs Deep

Immulina Supplements on Inflammatory Biomarkers Correlated With Clinical Symptoms in Patients With Long COVID (PASC)

This University of Mississippi Immulina trial is notable for its size (120), its scope (blood inflammatory biomarkers, memory T cell, memory B cell, and antiviral antibody titers), and the fact that its principal investigator, Gailen Marshall, has long been associated with ME/CFS and is one of the ME/CFS experts involved with the RECOVER Initiative. The trial is just beginning.

University of Mississippi Medical Center

  • Contact: Donielle D Drakes, MBA    601-496-7821    ddrakes@umc.edu
  • Contact: Denise Montgomery, MT(ASCP)    6018155374    dmontgomery@umc.edu
  • Principal Investigator: Gailen D Marshall Jr., MD, PhD

 Energy Enhancement with an NAD+ Booster

Clinical Trial of Niagen to Examine Recovery in People With Persistent Cognitive and Physical Symptoms After COVID19 Illness 

Another 100-person trial, this double-blinded, randomized, parallel-group, placebo-controlled Harvard trial will examine whether Niagen, an NAD+ booster, helps with long COVID. It’s currently underway.

The Poo Study

Fecal Matter Transplant for Post-acute COVID-19 Syndrome (FMT-PACS)

Of course, there was going to be a poo study, In fact, I was surprised not to see more fecal matter trials. This 60-person Hong Kong, open-label, fecal transplant study is now underway.

Coming Up – the RECOVER Trials

Finally, we should see trials that will attempt to improve autonomic nervous system functioning, exercise intolerance, sleep, and cognition from the RECOVER Initiative.

Last BIG (Little) Donation Update!

Hot air balloon piggy

The drive is ending on a high note – looking at the many different clinical trials ahead.

Yes, this is (finally) the last blog of the donation drive. We thought we’d go out on a high note – looking at all the clinical trials coming up. Thanks to everybody who has supported us during this long drive.

This, too, is a long and rather exhausting kind of blog to write and undoubtedly to read, but how rich it is in all its details and how much I learned doing it.  Hopefully, you got something out of it – I certainly did writing it – and if you did please support us if it’s appropriate for you to do so.



A BIG thanks to the 320 people who helped make Health Rising's fundraising drive a success!

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