Find answers to questions about RECOVER Clinical Trials

The ongoing symptoms of COVID can present everyday challenges to the millions of people who have Long COVID and their loved ones. RECOVER research aims to understand the long-term health effects of COVID and study possible treatments for people with Long COVID.

Participation of people from many different backgrounds in research drives:

• Effective treatments by ensuring results benefit people and their loved ones who are most affected by Long COVID
• Improved trust in research through meaningful participant and community connections
• Better research by providing opportunities to people to participate in impactful research now and in the future

This is high priority goal. The RECOVER clinical trials team is partnering with patient and community representatives, including through NIH CEAL, as well as the RECOVER National Community Engagement Group to reach communities of people who have historically been underrepresented in research. In addition, a track record for enrolling diverse participants is a key criterion for trial site selection

The RECOVER phase 2 clinical trials are the next steps for the RECOVER Initiative, and will focus on small groups of participants to test potential treatments for symptoms of Long COVID. (The number of participants in RECOVER trials will vary, but a typical phase 2 trial or trial arm has between 100-300 participants.) Each person who participates in a trial will be randomized to either receive a potential treatment or an appropriate control, such as a placebo. The phase 2 trials, which assess safety and effectiveness, will test at least 11 potential treatments for Long COVID.

Learn more about RECOVER clinical trials

In the observational cohort studies, participants share their health information so researchers can identify and learn as much about Long COVID as possible. Participants in studies don’t receive study interventions or medicine, but such studies can help researchers identify possible treatments for Long COVID to test in clinical trials. The observational cohort studies, which will follow participants for several years, may also tell us about the longer-term health outcomes following COVID-19.

Learn more about RECOVER studies

Although each of the clinical trials are studying different study interventions, or possible treatments, participants in all of the clinical trials will be asked the same set of questions about their general health and well-being. Participants may be asked to provide blood, stool (poop), or nasal swab samples for the RECOVER Research Biorepository, a secure storage place for samples that could help researchers make important discoveries about Long COVID and possible therapies. Collecting and comparing information across the clinical trials can help us understand how and why Long COVID affects people differently.

The RECOVER research team is committed to sharing what we learn. Once the clinical trials are complete and the data has been analyzed, overall study results will be shared via the RECOVER website and newsletters. The clinical trial researchers will also present findings at scientific conferences and publish results in peer-reviewed scientific journals to share with other researchers and the medical community.

Sign up to get emails with the latest information about all RECOVER research, including the clinical trials

The National Institutes of Health (NIH) created the RECOVER Initiative to learn about the long-term effects of COVID. The RECOVER clinical trials are led by the Duke Clinical Research Institute (DCRI) which is the Clinical Trials Data Coordinating Center. Each clinical trial has principal investigators (PIs), or lead researchers, who oversee the research activities.

The RECOVER team includes patients, caregivers, doctors, community leaders, and researchers from across the country. Community partners from various backgrounds help make sure RECOVER research includes and benefits communities that are most affected by Long COVID.

Learn more about clinical trials leadership

RECOVER clinical trials are designed as platform protocols that allow researchers to study different study interventions, or possible treatments, at the same time. Each clinical trial will focus on a group of symptoms. Several study interventions may be studied within each focus area. Results from these clinical trials will help us better understand how to treat Long COVID symptoms.

Learn more about RECOVER’s platform protocols

The RECOVER clinical trials focus on symptom areas that Long COVID patients have reported to be the most burdensome and important to address. The symptom focus areas are:

• Autonomic Dysfunction: dizziness, fast heart rate, shortness of breath, upset stomach, or other changes in body functions that happen automatically
• Cognitive Dysfunction: brain fog, trouble thinking clearly, memory changes, slowed attention, and other symptoms related to brain function
• Exercise Intolerance and Fatigue: exhaustion or low energy that interferes with daily activities
• Sleep Disturbances: changes in sleep patterns or ability to sleep
• Viral Persistence: when the virus that causes COVID-19 stays in the body and causes damage to organs or the immune system to not function properly

A Request for Applications (ROA) was released in May 2022 soliciting ideas for interventions to address Long COVID. Clinical trial intervention proposals were reviewed by teams of scientists in the areas of interest, and patient representatives. These groups chose multiple interventions to be incorporated into an adaptive platform protocol, and NIH leadership approved the final list. In addition, the work of the RECOVER Initiative to date, including large observational multi-site studies and analyses of 60 million electronic health records, also served as the foundation for the trials design.

Patients were part of the Protocol Working Groups which developed the protocols, or study plans, for each of the RECOVER clinical trials. Each working group included doctors, researchers, and patient and community representatives.

Starting off, we plan to have 5 clinical trials, 1 for each of the focus areas. However, the platform structure of RECOVER clinical trials allows multiple study interventions, or possible treatments, to be studied within each focus area.

Learn more about RECOVER’s platform protocols

Depending on the treatment being studied, a RECOVER clinical trial could last for about 3 months to 12 months, including follow-up visits.

Enrollment milestones and updates to interventions will be shared via the RECOVER website and newsletters.

The current clinical trials are Phase 2 exploratory trials to study the safety and effectiveness of potential treatments in adults. The number of participants in RECOVER trials will vary, but a typical phase 2 trial or trial arm has between 100-300 participants.

Each clinical trial will have different guidelines for who can participate. In order to understand how and why Long COVID affects people differently, we want to include adults of all races, ethnicities, genders, and ages from across the United States.

Yes, a person who has been in the RECOVER cohort study can participate in a clinical trial, if they meet the clinical trial inclusion criteria and are near a clinical trial site.

It depends on the health condition and the clinical trial. The study team will ask potential participants about their health history to help them find out if the clinical trial is a good fit for them.

Yes. We want to enroll adults from many different backgrounds in places across the United States so we can learn how and why Long COVID affects people differently.

Participants must be fluent in English or Spanish to complete study surveys and other activities related to the clinical trials.

Yes. Participants do not need health insurance to participate in a RECOVER clinical trial.

Selected sites will recruit participants by reaching out directly to their patients and local communities. Potential participants will be able to discuss the clinical trial with the study team to make sure it is a good fit for them.

No. There will be no charge to participants. Any tests or study interventions that are needed for a clinical trial that are not part of a participant’s usual medical care will be covered by the study. “Usual medical care” is the care a participant would receive whether or not they are part of the clinical trial.

Yes. Participants will receive compensation. The study team will provide details about compensation when they review the study activities with potential participants.

Depending on the possible treatment being studied, RECOVER clinical trials may last for around 3 months up to 12 months, including follow-up visits. Potential participants will be able to discuss the clinical trial schedule and activities with the study team before enrolling to make sure it is a good fit for them.

Depending on the clinical trial, participants may be asked to take a study drug, use a device, or try other approaches to help researchers learn if the study intervention improves Long COVID symptoms. Depending on the trial, the control group might get a placebo, or they might receive usual care but no additional treatment.

Participants will be assigned by chance to an active study intervention group or to a control group.

• Participants in an active study intervention group are given a possible treatment that may help improve Long COVID symptoms.
• Participants in a control group are given an appropriate control, which is what researchers use as a point of comparison to learn how different study interventions affect participants’ health. The appropriate control may include a placebo, which looks like the study intervention but should have no effect.

Participants in a control group are valuable contributors to research studies. Without a control group to compare to the study intervention group, researchers would not be able to learn how well a possible treatment works.

Participants will be asked to give blood, stool (poop), and nasal swab samples. The study team will review the clinical trial schedule and activities with potential participants so they know what to expect and they can decide if they want to enroll or not.

The samples, or biospecimens, will be used for research on COVID and the long-term effects of the virus that causes COVID-19, and may also be used for research on other health problems. Blood, stool (poop), or nasal swab samples collected in RECOVER clinical trials will be securely stored in the RECOVER Research Biorepository. Participants’ data and samples stored in the biorepository will not include any information that can personally identify them, and researchers cannot easily link any identifying information to the data or biospecimens.

Possible risks include side effects from the study intervention, risks associated with blood draws, nasal swabs, or other study activities, and loss of privacy. However, every effort will be made to minimize these sorts of risks. There may also be risks from participation that we do not know about yet.

We do not know if participants will benefit from taking part in a RECOVER clinical trial. The information learned from this research may help you, your loved ones, and other people with Long COVID in the future. Participants in RECOVER research can help:

• Their loved ones and community members learn why and how COVID and Long COVID affects people in different ways
• Researchers and healthcare providers find ways to treat Long COVID and help people live with fewer symptoms

Participant safety is a priority in all RECOVER clinical trials. Each study includes follow-up visits, safety assessments, and surveys to check on participants’ safety and well-being throughout the clinical trials. Patient safety is always prioritized in the conduct of clinical trials. RECOVER trials will follow standard best practices for monitoring participant safety. The outcome measures will be different for each trial and will be summarized in the protocols. Measures will be taken along every stage of the trials and at every participant’s visit to assess any issues of safety or adverse events. Study participants will also self- report any concerns to their study site. In addition, safety data are monitored on an ongoing basis by the Data Safety Monitoring Board. An aggregate safety report will be submitted per FDA guidelines, as required.

Like most clinical trials, RECOVER has several groups that work together to protect participants’ safety, rights, and well-being, monitor the research, and track progress. These groups include:

• Protocol Working Groups: develop the protocols, or study plans, for each of the RECOVER clinical trials. Each working group includes doctors, researchers, and patient and community representatives.
• Data and Safety Monitoring Board (DSMB): reviews the clinical trial protocols, or study plans, before the study is implemented. During the clinical trials, the DSMB monitors the data collected in RECOVER research and how the clinical trials are working, and makes recommendations to correct any data quality or safety issues that may come up during the studies.
• Institutional Review Board (IRB): reviews research activities to make sure the rights and well-being of participants are protected throughout the clinical trials.

The protected health information (PHI) collected for RECOVER clinical trials may be given to others only as needed for reasons like monitoring the study, determining the results of the study, and providing required reports. When the clinical trial results are shared publicly, no information that could identify participants will be included.

The Informed Consent Form explains how RECOVER will use participants’ information and samples collected in the clinical trials. The study team will review the Informed Consent Form with potential participants so they know what to expect and they can decide if they want to enroll in the study or not.

The Duke Clinical Research Institute (DCRI) and organizations doing work on their behalf, such as technology providers, will have access to the data collected in the clinical trials. Any use of data for research related to the clinical trials will be monitored and approved by the DCRI and its partners.

Only the RECOVER research team will have access to participants’ protected health information (PHI). To protect participants’ privacy:

• We will follow state and federal laws that protect the privacy and security of participants’ information.
• We will not share participants’ identity and PHI unless it is required to protect their safety, the safety of others, or if they give us permission to share it.
• We will store records in a locked cabinet or on a password-protected computer.
• We will assign participants’ study information a code and keep it separately from their personal record.
• We will limit and monitor access to the data collected.

RECOVER researchers and study teams will make every effort to protect all participants’ safety, well-being, and privacy. Additionally, the RECOVER team partners with patients, caregivers, and community leaders from many different backgrounds throughout all stages of the clinical trials. Our community partners help make sure RECOVER research includes and benefits communities that are most affected by Long COVID.

Learn more about how patients and community members are engaged in RECOVER clinical trials