RECOVER builds on current knowledge about symptoms affecting the lungs and heart
RECOVER researchers continue to study how SARS-CoV-2, the virus that causes COVID-19, spreads through the lungs and eventually impacts other body systems, such as the heart and nervous system.
As a pulmonologist (a doctor who cares for people with lung conditions), RECOVER researcher Jerry Krishnan, MD, PhD, spends a lot of time thinking about how COVID and Long COVID have impacted his patients’ ability to breathe.
Dr. Krishnan explained that SARS-CoV-2 uses the blood vessels around the lungs to travel through the bloodstream to other areas of the body. “SARS-CoV-2 is a respiratory virus that can spread anywhere else in the body,” he said. “It uses the lungs as a portal of entry, and it has figured out the secret code to unlock the door to the rest of the body.”
Some people who have COVID recover fully, but others have persistent COVID symptoms or develop new symptoms. People who have symptoms for at least 3 months are considered to have Long COVID, according to a definition of Long COVID developed by the National Academies of Sciences, Engineering, and Medicine.
Difficulty breathing is one of the most common symptoms of Long COVID. However, researchers can’t assume that all patients who have difficulty breathing have problems with only their lungs. “People can have shortness of breath for multiple reasons, including problems with the lungs, heart, bone marrow, and the brain,” said Dr. Krishnan, who is the lead principal investigator for ILLInet, the RECOVER study hub at the University of Illinois Chicago.
As RECOVER moves into the next phase of its adult observational study, researchers will continue to understand how Long COVID can affect specific areas of the body, including the heart and lungs (cardiopulmonary symptoms). Studying patients for longer will help researchers understand which Long COVID symptoms may persist or be more likely to resolve and whether any new symptoms or health conditions develop over time. Dr. Krishnan said that many questions remain, such as why some people experience a persistent cough. This next phase of the adult observational study will provide the time and opportunity to address some of these questions.
Researchers will also continue to explore how Long COVID can affect the brain (neurocognitive symptoms), symptoms related to the autonomic nervous system (the system that controls automatic functions like heart rate and breathing), and the relationships among different body systems, chronic (long-term) illnesses, and Long COVID.
“The lungs and the heart are very interconnected; there is blood flowing between the two constantly,” Dr. Krishnan explained. “We now know there are many cardiopulmonary symptoms associated with Long COVID, including shortness of breath, chronic cough, and heart rhythm abnormalities that can lead to dizziness and fainting.”
Common clinical tests help RECOVER understand changes to the lungs
RECOVER used the pulmonary function test (PFT), which is commonly used by doctors in routine care settings, to measure the lung function of people participating in the first phase of the adult observational study. Because this test was conducted with thousands of participants in the study, researchers can now examine a large amount of data to understand why people with Long COVID may have difficulty breathing. The PFT measures the following 3 areas of lung function:
- How the airways work to move air in and out of the body. Dr. Krishnan described these airways as the “plumbing” of the lungs and noted that people who have Long COVID may experience spasms of the airway rather than air flowing smoothly.
- Lung volume. Dr. Krishnan explained that Long COVID can cause lung scarring in some cases, and scarring can lead to smaller lungs.
- Diffusion. This is a measure of how effectively oxygen can travel from the airways into the blood. Problems due to lung scarring or damage to the alveoli (tiny air sacs in the lungs) can affect diffusion.
In addition to the PFT, RECOVER conducted many other tests with thousands of adult observational study participants. One test that researchers use to understand impacts to the heart and lungs is called the 6-minute walk test. This test, which measures how many times a person can walk back and forth between 2 points over 6 minutes, can help researchers understand how the heart and lungs are working based on how tired people become during the test.
RECOVER is also examining changes to lung structure through imaging. Some study participants received chest X-rays or, in some cases, high-resolution computed tomography (CT) scans. These images allow researchers to look for scarring or other types of damage to the lungs.
“One thing that is very exciting about RECOVER is that these clinical tests will help us to understand how Long COVID affects the lungs,” Dr. Krishnan said. “This information will help us to provide healthcare for people living with Long COVID.”
Addressing Long COVID through many types of studies
RECOVER is continuing its research studies to more completely understand the problems that Long COVID causes in the body while connecting these problems to the various symptoms people experience. The initiative is designed to address the impacts of Long COVID from many angles using different types of studies, Dr. Krishnan explained.
- The first phase of RECOVER’s observational study helped define what was happening to people living with Long COVID—including the risk factors that might make someone more likely to develop Long COVID and the symptoms that people living with the condition experience.
- RECOVER’s pathobiology studies are using biosamples collected during the observational studies—such as blood, urine, and saliva—to understand why symptoms exist. For example, a RECOVER pathobiology study found that people who reported common Long COVID symptoms, including cardiopulmonary, musculoskeletal (affecting the bones and muscles), and neurologic (affecting the brain and nervous system) symptoms, were more likely to have parts of the SARS-CoV-2 virus (called antigens) in their blood for a long period. Better understanding the root causes of symptoms can help lead to treatments and solutions.
- RECOVER’s clinical trials are designed to help understand how to help people living with Long COVID. By testing 13 possible treatments, RECOVER is able to build understanding about what does and does not work to manage symptoms.
“Understanding what and why is not enough,” Dr. Krishnan said. “We need to fix the problem, and clinical trials are key for building our understanding around how we can actually help people with Long COVID.”
The RECOVER-Clinical Trials (RECOVER-CT) program is exploring how to help people with various symptoms, including those affecting the cardiopulmonary system. The RECOVER-ENERGIZE Exercise Intolerance trial is studying whether a personalized cardiopulmonary rehabilitation program (a customized program designed to prevent symptom flare-ups) can help people improve their quality of life and ability to exercise. Two RECOVER-AUTONOMIC trials are also studying how to help people manage symptoms related to the autonomic nervous system and the cardiopulmonary system, such as fast heart rate and dizziness. Learn more about these trials and other clinical trials that RECOVER is conducting to test possible treatments for other types of symptoms.
Dr. Krishnan, who is supporting plans for additional clinical trials, shared that RECOVER-Treating Long COVID (RECOVER-TLC) will conduct trials to address cardiopulmonary symptoms. One example is REVERSE-LC which will test whether the drug baricitinib can improve a range of Long COVID symptoms, including heart and lung function.
