New insights on Long COVID symptoms in adults highlight update to RECOVER study findings

For many illnesses, there is hope for recovery. In the case of COVID-19, the road to healing is neither a predictable nor straightforward one.

Long COVID is loosely defined as lingering or new symptoms present for 3 months or more following a COVID infection. With over 200 symptoms affecting all the body’s organ systems associated with Long COVID, the condition has baffled patients, clinicians, and researchers alike.

To better understand COVID-19 and explore why some people develop Long COVID, the RECOVER Initiative (Researching COVID to Enhance Recovery) began enrolling participants in 2022. As one of the largest studies in the world dedicated to researching Long COVID, RECOVER has enrolled nearly 30,000 participants across its observational cohort studies. These cohort studies gather information on adults, pregnant people, and children and are helping researchers learn more about how the COVID-causing virus, SARS-CoV-2, affects the body.

Most recently, scientists updated the research they previously conducted to explore Long COVID symptoms reported by participants in the RECOVER adult observational cohort study. The “2024 Update of the RECOVER-Adult Long COVID Research Index” was recently published in JAMA. In this study, researchers compared symptoms in people who had SARS-CoV-2, the COVID-causing virus, to those who did not. This comparison was then used to find symptoms most different in people who had COVID.

A total of 13,647 participants were included in the updated study compared to 9,764 in the original one. Having more participants to glean insights from enabled study authors to expand their research to examine 52 symptoms, while the original study explored 44.

Symptoms that were most different between people with and without SARS-CoV-2 infection included post-exertional malaise (the worsening of symptoms following physical or mental activity), fatigue (feeling very tired), brain fog (having trouble thinking clearly, concentrating, or remembering things), dizziness, palpitations (pounding or irregular heartbeats), smell or taste change, thirst, chronic (long-lasting) cough, chest pain, shortness of breath, and sleep apnea.

In addition, this research update classifies Long COVID symptoms into five clusters (as compared to four clusters in the original study). This is important because it shows that Long COVID isn’t a one-size-fits-all condition. While some people may experience a cluster of primarily respiratory symptoms (such as coughing and shortness of breath), others may struggle with changes in smell or taste.

This study is just one of many for RECOVER. So far in the Initiative’s two-year journey, scientists have made strides to help advance the field of Long COVID research. Among other accomplishments, they have:

• Characterized symptoms of Long COVID and the risk of developing the condition based on different strains of the SARS-CoV-2 virus.
• Explored racial and ethnic disparities seen among Long COVID patients.
• Identified potential risk factors for the condition, such as sleep apnea and diabetes, that may help inform future treatment.
• Evaluated Long COVID symptoms across numerous body systems.
• Identified risks associated with underlying chronic conditions and Long COVID.
• Refined the focus of where researchers may find breakthroughs by discovering 25 common blood tests could not serve as reliable biomarkers for Long COVID.
• Identified SARS-CoV-2 viral antigens in the blood of individuals long after an acute COVID infection, showing viral persistence may be a mechanism behind Long COVID.

RECOVER research and many other outside studies focused on post-COVID conditions have one key finding in common: Long COVID looks different for everyone. Each person’s unique combination of symptoms, known as their “symptom phenotype,” reflects the ever-evolving nature of the disease. Imagine each cluster of Long COVID symptoms as a unique passcode. Each person's passcode may unlock a unique combination of symptoms.

By tracking study participants’ symptoms over time, RECOVER researchers are working to create a more comprehensive understanding of Long COVID. In turn, this research presents an opportunity to explore other post-viral illnesses. One of the most challenging aspects of Long COVID research is the condition’s unpredictability—symptoms can not only come and go but can also change entirely. This not only makes it difficult for scientists researching the virus, but also for patients experiencing the complex condition. Managing symptoms is never easy, and the evolving nature of these symptoms makes receiving appropriate, consistent care even more challenging.

While there is currently no cure for Long COVID, ongoing research efforts like that of RECOVER continue to make progress. Scientists are working hard to transform this progress into effective diagnostic and treatment tools to bring hope to the millions of people impacted.