Find answers to questions about RECOVER Clinical Trials

Many people have health problems for weeks, months, or even years after getting COVID-19 – a condition called Long COVID. Ongoing symptoms of COVID can present everyday challenges to the millions of people who have Long COVID and their loved ones. The RECOVER Initiative was created to understand, treat, and prevent Long COVID and help people who are suffering.

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 a high priority goal. When selecting clinical trial sites, we look at each site’s history of enrolling diverse groups of participants. To reach people who have historically been underrepresented in research, we also partner with:

• Patient, Caregiver, and Community Representatives for RECOVER clinical trials
• The RECOVER National Community Engagement Group (NCEG)
• The NIH Community Engagement Alliance (CEAL)

In RECOVER clinical trials, participants may take a study drug, use a medical device, or try other approaches to help researchers learn how the possible treatment, also called a study intervention, affects Long COVID symptoms. The RECOVER Initiative’s 8 clinical trials will explore 13 study interventions to learn if they are safe and effective treatments for Long COVID symptoms.

Learn more about RECOVER clinical trials

In RECOVER observational cohort studies, researchers are studying large groups of people over several years to better understand who gets Long COVID and why, what symptoms people have, and how Long COVID affects their health over time. These longitudinal observational cohort studies do not give a treatment or medicine to participants or change their regular health care — participants keep living their lives as usual and share health information with researchers.

Learn more about RECOVER observational cohort studies

Although each of the clinical trials is studying different possible treatments, also called study interventions, participants in all RECOVER clinical trials are asked the same questions about their general health and well-being. Combining information across the clinical trials can help us understand how and why Long COVID affects people differently, and help us get answers for more people faster. Additionally, some blood, stool (poop), and nasal swab samples collected in the clinical trials will be sent to the RECOVER Research Biorepository, a secure storage place for samples that could help researchers make important discoveries about Long COVID and possible treatments. Participants’ data and samples stored in the biorepository will not include any information that can personally identify them.

We are committed to sharing what we learn. After the clinical trials are complete and the data have been analyzed, researchers will share overall study results via the RECOVER website and newsletters. RECOVER researchers will also present results from the clinical trials at professional conferences and publish results in peer-reviewed scientific journals to share with other researchers and the healthcare community. No information that could identify participants will be shared with the public. Sign up for the RECOVER Report to get emails with the latest information about all RECOVER research, including the clinical trials.

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, or lead researchers, who oversee the study plans and activities.

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

Learn more about clinical trials leadership

Eight clinical trials will explore 13 possible treatments across 5 areas of Long COVID symptoms.

Learn more about RECOVER clinical trials

Results from the RECOVER observational cohort studies and conversations with people living with Long COVID helped guide decisions on which symptoms to focus on in the clinical trials. RECOVER clinical trials focus on 5 groups of symptoms that Long COVID patients reported to affect their quality of life the most:

• 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 to collect ideas from researchers for possible treatments, also called study interventions, for Long COVID symptoms. The applications were reviewed by teams of scientists in the areas of interest and Patient, Caregiver, and Community Representatives. These groups chose multiple interventions to be included in RECOVER clinical trials and NIH leadership approved the final list. In addition, the work of the RECOVER Initiative to date, including large observational cohort studies and analyses of 60 million electronic health records, helped guide the plans for the clinical trials.

People with Long COVID were part of the Protocol Working Groups that developed the protocols, or study plans, for the RECOVER clinical trials. Each working group included doctors, researchers, and Patient, Caregiver, and Community Representatives.

Anyone can read the study plans on the Design of Clinical Trials page. Each protocol is also posted on the study web page along with other study documents. The study plans may change over time as we learn more. If a protocol changes, we will update it across the clinical trials webpages.

A total of around 3,300 adults will be enrolled across 8 clinical trials. The number of participants in each clinical trial ranges from 180 up to 900.

RECOVER clinical trials are phase 2 exploratory trials, which study the safety and effectiveness of possible treatments. A typical phase 2 clinical trial has between 100–300 participants.

Each clinical trial has specific guidelines for who can participate to make sure the study is a good fit for each participant. We want to include adults of all races, ethnicities, genders, and ages from across the United States to understand how and why Long COVID affects people differently, and to find possible treatments that work for people that are most affected by Long COVID.

Yes, a person who is in the RECOVER cohort study can participate in a clinical trial if they meet the eligibility requirements and they are near a study 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 activities and surveys.

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

Enrollment for RECOVER clinical trials is site-based, which means study sites will contact potential participants in their local communities. The study team will discuss the clinical trial with each potential participant to make sure it is a good fit for them.

No. There is 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 are 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, participants may be enrolled in RECOVER clinical trials for around 3 months up to 12 months, including follow-up visits.

Depending on the clinical trial, participants may be asked to take a study drug, use a medical device, or try other approaches to help researchers learn if the possible treatment, also called a study intervention, is safe and improves Long COVID symptoms.

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. An appropriate control may include a placebo or comparator that looks like the study intervention but has no treatment value.

Each participant in a RECOVER clinical trial is a valuable contributor to this research. Without control groups to compare to the active study intervention groups, researchers would not be able to learn how the study interventions, or possible treatments, affect Long COVID symptoms.

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 may be used:

• To check participants’ overall health
• To check the safety of the potential treatments being studied
• For research on COVID and the long-term effects of the virus that causes COVID-19
• For research on other health problems

Some blood, stool (poop), and nasal swab samples collected in RECOVER clinical trials will be sent to the RECOVER Research Biorepository, a secure storage place that could help researchers make important discoveries about Long COVID and possible therapies. Participants’ data and samples stored in the biorepository will not include any information that can personally identify them.

Possible risks include side effects from the potential treatment being studied, risks associated with blood draws, nasal swabs, or other study activities, and loss of privacy. However, we will make every effort to minimize these 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. What we learn from this research may help participants, their 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. The clinical trials follow standard best practices for monitoring participant safety and well-being throughout the studies. Study visits include safety checks and safety labs, and participants are regularly asked to complete surveys about how they are feeling. Participants are also encouraged to report any concerns to their study site team. In addition, safety data are monitored on an ongoing basis by the Data and Safety Monitoring Board. A report combining all safety issues will be shared with oversight groups and submitted per FDA regulations, as required.

There are several groups that work together throughout the lifecycles of the clinical trials to protect participants’ safety, rights, and well-being, monitor the research, and track progress. These groups include:

• Protocol Working Groups: developed the study plans, or protocols, for each of the RECOVER clinical trials. Each working group included doctors, researchers, and Patient, Caregiver, and Community Representatives.
• Data and Safety Monitoring Board (DSMB): reviews each clinical trial protocol before the study begins. Once the clinical trials begin, the DSMB monitors the data, or information, collected in RECOVER research and the progress of the clinical trials. The DSMB identifies safety issues that may come up during the clinical trials and also makes recommendations to correct any data quality issues.
• Institutional Review Board (IRB): reviews each clinical trial protocol before the study begins and reviews research activities as well as participant materials 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 safety and progress of the studies
• Determining the results of the studies
• Providing required reports to groups that monitor the research and safety of participants

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 teams 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, or information, collected in the clinical trials. Any use of data for research related to the clinical trials will be approved and monitored by the DCRI and its partners.

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

• We follow state and federal laws that protect the privacy and security of participants’ information.
• We do 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 store records in locked cabinets or on password-protected computers.
• We assign participants’ study information a code and keep it separately from their personal record.
• We limit and monitor access to the data collected.

RECOVER researchers and study teams make every effort to protect all participants’ safety, rights, well-being, and privacy. Additionally, the RECOVER team partners with Patient, Caregiver, and Community Representatives 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