Long COVID affects an estimated 10-30% of people who had COVID-19, causing fatigue, brain fog, shortness of breath, and dozens of other symptoms that persist for months or years. No FDA-approved treatments exist yet, though researchers are testing repurposed drugs and new therapies. Most care now focuses on managing individual symptoms and rehabilitation.
What's actually going on in research
Trials are testing antivirals to clear persistent virus, anticoagulants for blood clotting abnormalities, metformin to prevent long COVID from developing, and drugs targeting immune dysfunction. Researchers are also studying whether reactivated viruses like Epstein-Barr play a role, and testing physical rehabilitation programs tailored to avoid post-exertional malaise.
Antiviral approaches
Studies are testing whether Paxlovid and other antivirals can treat long COVID by clearing viral reservoirs that may persist in the body. Early results suggest benefit in some people, though effects vary.
Microclot research
Evidence shows abnormal blood clotting in many people with long COVID. Trials are testing anticoagulants and drugs that break down these microclots to see if they improve symptoms.
Prevention trials
Metformin, given during acute COVID, reduced long COVID risk by 40% in one trial. Researchers are testing whether other drugs taken early can prevent long-term symptoms from developing.
What to know before you search
Eligibility typically requires documented COVID-19 infection and symptoms lasting at least three months, with specific trials selecting for symptom types like fatigue, cognitive issues, or breathing problems.
What types of trials are currently open
- Antiviral trials — Testing whether drugs like Paxlovid can treat long COVID symptoms by clearing persistent virus from the body.
- Immune modulation trials — Testing drugs that calm overactive immune responses or target autoantibodies that may drive symptoms.
- Anticoagulation trials — Testing blood thinners and clot-dissolving drugs for people with evidence of microclots or circulation problems.
- Rehabilitation studies — Testing exercise and physical therapy programs designed to avoid worsening symptoms, especially post-exertional malaise.
- Observational studies — Following people with long COVID to understand symptom patterns, biomarkers, and what predicts recovery.
Recently added Long Covid trials
Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
Chronic fatiguing illnesses such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Fibromyalgia, and Long COVID are becoming a major global health challenge. They cause severe personal and social strain and have no proven, widely effective treatments. Although these conditions have different names, they share many symptoms: long-lasting fatigue that doesn't improve with rest, worsening of symptoms after activity (post-exertional malaise), difficulties with thinking ("brain fog"), poor sleep, and widespread pain. Increasing evidence shows that these illnesses also share similar underlying biological problems. These include ongoing inflammation, problems with the autonomic nervous system (which controls automatic body functions), poor function of the blood vessels, and reduced energy production in cells. Whole-Body Cryotherapy (WBCT) is emerging as a promising non-drug treatment that may help break these cycles. WBCT involves very short, controlled exposure to extreme cold (around -110°C to -160°C). This triggers a rapid response across the nervous, immune, and metabolic systems. The cold acts as a powerful stimulus, encouraging the body to reset imbalanced systems. A session briefly narrows blood vessels and then causes them to widen again, improving blood flow and supporting healthy vessel function. WBCT also appears to reduce inflammation, lower oxidative stress, and improve parasympathetic ("rest-and-recover") nervous system activity. Early studies in ME/CFS and related conditions are encouraging. Small trials have reported reduced fatigue, clearer thinking, and better autonomic regulation after a course of WBCT sessions, with good safety. Research has also shown changes in blood-brain barrier proteins after WBCT, suggesting it may help repair "leaky" barriers that can drive symptoms in ME/CFS and Long COVID. By acting on inflammation, blood flow, and nervous system balance at the same time, WBCT could offers a scientifically grounded and potentially transformative approach in understanding the mechanism behind observed treatment effect.
Observational Study With CICR-NAM as a Food for Special Medicinal Purposes in Post-COVID Syndrome (PCS)
In patients with post-COVID syndrome, changes in tryptophan metabolism, energy metabolism, and the gut microbiome may occur. In an earlier nutritional study, patients with COVID-19 recovered their physical performance more quickly when taking nicotinamide (vitamin B3). Patients who responded to nicotinamide also developed post-COVID syndrome less frequently. At the University Hospital Schleswig-Holstein in Kiel, special nicotinamide tablets (CICR-NAM) were developed that release the active substance selectively in the lower intestine and have been shown to be very well tolerated in several studies. Patients with post-COVID syndrome and documented tryptophan deficiency may therefore take one tablet (500 mg) of CICR-NAM daily for up to approximately 4 months as a food for special medicinal purposes within the therapy groups of the outpatient clinic for patients with post-COVID syndrome at the University Hospital Schleswig-Holstein in Kiel. This intake is far below the Upper Level defined by the European Food Safety Authority for lifelong daily intake (900 mg per day). Therefore, there are no safety concerns. CICR-NAM intake is intended to complement the therapy group programme by supporting energy metabolism.
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