Ongoing Clinical Trials for Post-acute COVID-19 Syndrome
Currently, there are 10 clinical trials investigating various treatments for post-acute COVID-19 syndrome, a condition where symptoms persist or develop after the initial COVID-19 infection. These trials are taking place across multiple European countries including Poland, Spain, Germany, Netherlands, France, Greece, and Italy, testing a range of medications from existing drugs repurposed for long COVID to novel therapies specifically designed to address persistent symptoms like fatigue, cognitive impairment, and respiratory difficulties. (Also known as: Long COVID, Post-COVID Syndrome, Post-COVID-19 Condition, Post-Acute Sequelae of COVID-19)
Clinical trial locations
- France
- Germany
- Study on Anakinra for Patients with Long COVID and Ongoing Respiratory Symptoms
- Study on the Effects and Safety of Ginkgo Biloba Extract in Patients with Cognitive Impairment After COVID-19
- Study on the Effects of Vidofludimus Calcium for Patients with Post-COVID Syndrome
- Study of Vericiguat to improve physical function in patients with Post-COVID-19 syndrome with or without chronic fatigue syndrome
- Greece
- Italy
- Netherlands
- Poland
- Study on the Effects and Safety of Ginkgo Biloba Extract in Patients with Cognitive Impairment After COVID-19
- Study of Allopurinol to Reduce Cardiovascular Events in High-Risk Patients with Heart Disease and Long-COVID Syndrome
- Title: Study of tianeptine effectiveness in treating cognitive symptoms (brain fog) in patients who have recovered from COVID-19
- Spain
- Study on Anakinra for Patients with Long COVID and Ongoing Respiratory Symptoms
- Study on the Effects and Safety of Ginkgo Biloba Extract in Patients with Cognitive Impairment After COVID-19
- Study of Plitidepsin Treatment for Adults with Post-COVID-19 Condition
- Study on the Effects of Plitidepsin for Adults with Long COVID Symptoms
Study of Allopurinol to Reduce Cardiovascular Events in High-Risk Patients with Heart Disease and Long-COVID Syndrome
This trial, conducted in Poland, is investigating whether allopurinol can help reduce cardiovascular risks in people with high cardiovascular risk factors who have experienced long COVID. Allopurinol is a medication commonly used to lower uric acid levels in the blood, but researchers believe it may also help protect the heart and blood vessels.
Main inclusion criteria: Participants must be between 40 and 70 years old with blood uric acid levels above 5 mg/dl. They must meet at least one high cardiovascular risk condition, such as having a calculated 10-year risk of heart disease death above certain thresholds, documented history of stroke, heart failure, poor blood flow to legs, irregular heartbeat, or diabetes/high blood pressure with organ damage.
Main exclusion criteria: People currently taking allopurinol or similar medications, those with known allergies to allopurinol, severe kidney or liver disease, active cancer, pregnant or breastfeeding women, recent major surgery, unstable medical conditions, or inability to provide informed consent are excluded.
Study focus: The trial will compare participants receiving allopurinol tablets with those receiving placebo over approximately 5 years. Researchers will monitor whether allopurinol can prevent serious cardiovascular events such as heart problems, strokes, or the need for heart-related procedures. Regular check-ups will include heart examinations, blood vessel assessments, blood tests, blood pressure measurements, and monitoring of long-COVID symptoms.
Investigational drug: Allopurinol works by blocking an enzyme that produces uric acid in the body. In this study, it is being tested for its potential cardiovascular protective effects in high-risk patients with long COVID.
Study of Plitidepsin Treatment for Adults with Post-COVID-19 Condition
This Spanish trial is evaluating plitidepsin, a medication originally derived from a marine organism, as a potential treatment for persistent symptoms experienced after COVID-19 infection. The study will compare plitidepsin with placebo to determine its effectiveness and safety.
Main inclusion criteria: Participants must be 18 years or older with documented evidence of previous SARS-CoV-2 infection at least 90 days before study entry. They must have at least 3 symptoms affecting at least two different body systems that have lasted for at least 2 months, started at least 90 days after COVID-19 infection, and cannot be explained by another medical condition. Participants must have significant limitations in performing regular daily activities.
Main exclusion criteria: People below 18 or above 65 years, those unable to provide informed consent, individuals with severe mental health conditions, current participation in other trials, pregnancy or breastfeeding, active cancer treatment, severe heart/kidney/liver disease, uncontrolled diabetes, organ transplantation history, or substance abuse are excluded.
Study focus: The trial will last 90 days after treatment, during which participants will receive either plitidepsin or placebo through intravenous infusion along with several supportive medications. Researchers will evaluate physical activity levels, mental health, sleep quality, general well-being, inflammation markers, and immune system responses.
Investigational drug: Plitidepsin targets certain cellular processes that may be involved in the persistence of COVID-19 symptoms, with the goal of improving overall health and quality of life in people experiencing long COVID.
Study of Vericiguat to improve physical function in patients with Post-COVID-19 syndrome with or without chronic fatigue syndrome
This German study is testing vericiguat, a medication that helps blood vessels relax and improves blood flow, in adults experiencing ongoing symptoms after COVID-19 infection, including those who may have developed chronic fatigue syndrome.
Main inclusion criteria: Participants must be between 18-55 years old with confirmed mild to moderate COVID-19 not requiring hospitalization. They must be experiencing symptoms for at least 6 months after infection, have a Bell Score between 30-60 (measuring functional ability), show signs of blood vessel function problems, and have normal thyroid function. Women who can become pregnant must use effective birth control methods.
Main exclusion criteria: People below 18 or above 65 years, pregnant or breastfeeding women, those with severe heart conditions, severe kidney/liver problems, active infections, blood clotting disorders, mental health conditions affecting participation, or recent major surgery are excluded.
Study focus: The 10-week study will test different doses of vericiguat tablets (2.5 mg to 10 mg per day) compared to placebo. Researchers will measure changes in physical function using a standardized health survey, along with monitoring fatigue levels, muscle strength, and any side effects.
Investigational drug: Vericiguat works by stimulating an enzyme that helps blood vessels relax and improves blood flow, potentially helping people experiencing ongoing physical and cognitive symptoms after COVID-19.
Study on [68Ga]FAPI-46 to Detect Lung Fibroblast Activity in COVID-19 Patients with Long-Term Symptoms
This Dutch trial uses advanced imaging technology to study lung changes in people experiencing ongoing symptoms after COVID-19. The study focuses on detecting activity in cells called fibroblasts, which are involved in the healing process and can sometimes lead to scarring in the lungs.
Main inclusion criteria: Adults over 20 years old with self-reported complaints of difficulty breathing or extreme tiredness for more than 3 months after a confirmed COVID-19 infection. Participants are divided into groups based on their Fatigue Severity Scale scores.
Main exclusion criteria: People not experiencing post-acute sequelae of COVID-19, those without long COVID breathing difficulties or fatigue, individuals outside the specified age range, or those considered part of a vulnerable population are excluded.
Study focus: Participants will receive an injection of [68Ga]FAPI-46 solution, which helps highlight fibroblast activity during a PET/CT scan. The study aims to compare fibroblast activity between patients with ongoing symptoms and those who have recovered, providing better understanding of how long COVID affects the lungs.
Investigational agent: [68Ga]FAPI-PET/CT is a diagnostic imaging test that helps doctors visualize how active fibroblasts are in the lungs, which may help in understanding and managing long COVID symptoms.
Study on the Effects and Safety of Ginkgo Biloba Extract in Patients with Cognitive Impairment After COVID-19
This multicountry trial (Germany, Spain, Poland) is testing a specific extract from Ginkgo biloba leaves for people experiencing cognitive difficulties such as memory problems, attention issues, and thinking difficulties after COVID-19.
Main inclusion criteria: Participants must be 18 years or older with a diagnosis of post-COVID syndrome and ongoing cognitive problems for at least 2 months related to the condition. They must have objective cognitive impairment shown through specific tests measuring memory and executive functioning, plus mild to moderate anxiety or depressive symptoms.
Main exclusion criteria: Individuals without cognitive impairment related to post-COVID syndrome, those outside the specified age range, or those belonging to vulnerable populations are excluded.
Study focus: The 12-week trial will randomly assign participants to receive either Ginkgo biloba extract EGb 761® (240 mg daily tablet) or placebo. Tests will measure changes in cognitive abilities, memory, attention, anxiety, depression, and other symptoms at weeks 6 and 12.
Investigational drug: Ginkgo biloba extract EGb 761® is a natural extract believed to enhance blood flow to the brain and possess antioxidant properties that may protect nerve cells and improve cognitive function in people with post-COVID cognitive difficulties.
Study on Anakinra for Patients with Long COVID and Ongoing Respiratory Symptoms
This multicountry trial (Greece, Italy, Spain, Germany) is investigating anakinra for individuals experiencing ongoing respiratory symptoms after recovering from COVID-19. The study aims to assess whether anakinra can improve both physical and immune system health.
Main inclusion criteria: Participants must be 18 years or older with confirmed COVID-19 infection at least 90 days ago, symptoms related to post-acute COVID syndrome lasting more than 2 months that affect daily activities, and two specific conditions: impaired lung function tests and specific patterns visible on chest scans affecting at least 15% of the lungs.
Main exclusion criteria: Pregnant or breastfeeding individuals, those with severe allergic reactions to the study medication, significant liver or kidney disease, active infections requiring treatment, recent participation in other trials, certain heart conditions, uncontrolled high blood pressure, recent cancer history, or drug/alcohol abuse are excluded.
Study focus: The trial will compare the effects of taking anakinra (100 mg solution for injection) for either four weeks or eight weeks versus placebo. Researchers will monitor lung function, immune response, physical performance (including a six-minute walk test), and safety throughout the study.
Investigational drug: Anakinra works by blocking interleukin-1, a protein involved in inflammatory responses, thereby reducing inflammation and potentially improving respiratory symptoms and overall health in people with post-acute COVID syndrome.
Study on the Effects of Dexmedetomidine on Neuroinflammation in COVID-19 ARDS Survivors
This French trial focuses on patients who survived severe lung conditions (ARDS) caused by COVID-19 and experienced delirium during intensive care. The study investigates whether dexmedetomidine, a sedation medication, can help reduce long-term brain inflammation.
Main inclusion criteria: Patients must be between 18 and 75 years old with confirmed COVID-19 infection, specific genetic markers, history of intensive care for severe lung problems requiring mechanical ventilation and deep sedation for at least 24 hours, and must be alive 24 months after leaving intensive care.
Main exclusion criteria: Patients who have not survived COVID-19 ARDS, are not being weaned off mechanical ventilation, did not experience intensive care delirium, do not have severe neuroinflammation, or are outside the specified age range are excluded.
Study focus: The trial will compare two groups—those who received dexmedetomidine during intensive care and those who did not. At 24 months post-discharge, researchers will use PET-MRI imaging to measure brain inflammation levels and assess cognitive function through clinical assessments and brain scans.
Investigational drug: Dexmedetomidine is administered intravenously and works by acting on specific brain receptors to reduce inflammation and provide sedative effects, potentially offering neuroprotective benefits in COVID-19 ARDS survivors.
Study on the Effects of Plitidepsin for Adults with Long COVID Symptoms
This Spanish trial is testing plitidepsin for adults experiencing persistent symptoms affecting multiple organs after COVID-19 recovery. The study will evaluate whether plitidepsin can improve the functional status of individuals with this condition.
Main inclusion criteria: Participants must be 18 years or older with documented SARS-CoV-2 infection at least 90 days before joining. They must have symptoms of post-COVID condition affecting at least two organs, lasting at least 2 months and starting at least 90 days after initial infection. Participants must be unable to perform all usual duties or activities (grades 3 or 4 on the Post-COVID Functional Status scale).
Main exclusion criteria: People with severe illnesses requiring immediate treatment, history of severe allergic reactions to study ingredients, pregnancy or breastfeeding, current participation in other trials, substance abuse or alcohol dependency, mental health conditions interfering with participation, or inability to provide informed consent are excluded.
Study focus: Participants will receive either plitidepsin (2.5 mg) or placebo through intravenous infusion. The study will monitor functional status, quality of life, and any adverse events at approximately 10, 28, and 90 days after infusion.
Investigational drug: Plitidepsin is an antiviral medication that works by interfering with certain proteins in cells involved in viral replication, potentially helping reduce viral activity and improve symptoms in people with post-COVID condition.
Title: Study of tianeptine effectiveness in treating cognitive symptoms (brain fog) in patients who have recovered from COVID-19
This Polish study is investigating tianeptine for treating “COVID fog”—problems with thinking, memory, attention, and concentration that occur after COVID-19 infection. The trial will compare tianeptine with placebo to determine if the medication can improve cognitive function.
Main inclusion criteria: Participants must be 18 years or older with confirmed COVID-19 infection (proven by RT-PCR or antigen test), experiencing cognitive decline after infection, and scoring less than 26 points on the Montreal Scale for Assessment of Cognitive Function. Women who can become pregnant must use effective birth control.
Main exclusion criteria: People below 18 or above 65 years, pregnant or breastfeeding women, those with severe heart conditions, severe liver/kidney problems, major depression or bipolar disorder, recent use of antidepressants, active substance abuse, severe cognitive impairment, seizure history, or hypersensitivity to tianeptine are excluded.
Study focus: The 16-week treatment period involves taking tianeptine tablets (maximum 37.5 mg daily) or placebo orally. Researchers will monitor changes in thinking abilities, memory, mental functions, mood, sleep, and overall well-being. Brain function will be examined through various tests including PET scans.
Investigational drug: Tianeptine is an atypical antidepressant that works by modulating serotonin and glutamate systems in the brain, enhancing neuroplasticity and potentially protecting against stress-induced neuronal damage, with the aim of improving cognitive clarity in post-COVID patients.
Study on the Effects of Vidofludimus Calcium for Patients with Post-COVID Syndrome
This German trial is testing IMU-838, containing the active ingredient vidofludimus calcium, to see if it can help reduce inflammation and improve physical function in patients with post-COVID syndrome.
Main inclusion criteria: Participants must be at least 18 years old with symptoms consistent with post-COVID syndrome that started within 4 weeks of initial COVID infection and lasted more than 12 weeks. They must have moderate to severe overall disability (Bell Scale score between 20 and 60) and at least two specific post-COVID symptoms including fatigue, cognitive impairment, shortness of breath, or orthostatic/autonomic dysfunction.
Main exclusion criteria: Pregnant or breastfeeding individuals, those with severe allergic reactions to study medications, significant liver or kidney disease, recent participation in other trials, drug or alcohol abuse history, or other serious medical conditions that might interfere with the study are excluded.
Study focus: The trial will last up to 84 days, during which participants receive either IMU-838 tablets (45 mg or 22.5 mg) or placebo orally. Regular assessments at days 28, 56, and 84 will monitor changes in physical and mental health, fatigue, cognitive function, and other symptoms using standardized questionnaires.
Investigational drug: IMU-838 is an immunomodulatory drug that works by inhibiting a specific enzyme involved in the immune response, helping to decrease inflammation and potentially improving physical function in people with post-COVID syndrome.
Summary
The 10 ongoing clinical trials for post-acute COVID-19 syndrome represent a diverse range of therapeutic approaches, from repurposed existing medications to novel treatments. Spain hosts the most trials with four studies, followed by Germany with four trials (some overlapping with other countries), while Poland hosts three trials. Several trials are conducted across multiple countries, particularly the anakinra study spanning Greece, Italy, Spain, and Germany, and the Ginkgo biloba study covering Germany, Spain, and Poland.
The trials focus on three main symptom categories: cognitive impairment (brain fog), cardiovascular and respiratory complications, and general fatigue and functional limitations. Multiple studies are testing anti-inflammatory approaches, including anakinra, dexmedetomidine, and IMU-838, reflecting the hypothesis that ongoing inflammation plays a key role in persistent symptoms. Two separate trials are investigating plitidepsin, a marine-derived compound with antiviral properties, suggesting particular interest in this novel therapeutic approach.
The trials employ varied methodologies, with treatment durations ranging from single administrations followed by monitoring periods to continuous treatment for up to 5 years in the allopurinol cardiovascular study. Most studies use placebo-controlled, randomized designs and incorporate comprehensive monitoring including physical function assessments, cognitive testing, quality of life measures, and in some cases advanced imaging techniques like PET-MRI scans. These studies collectively aim to address the significant unmet medical need for effective treatments for the diverse and debilitating symptoms experienced by long COVID patients.
