Toward a deeper understanding of long COVID

Researchers are gaining a better understanding of the symptoms that can linger after recovering from COVID-19. Georgii / Adobe Stock

For many people, a bout with SARS-CoV-2, the virus that causes COVID-19, doesn’t end when the initial symptoms subside. An array of problems may linger for months or years after infection. They can affect nearly every tissue and organ in the body. Their effects can range from mild to disabling.

These lingering health problems have become known as long COVID, or postacute sequelae of SARS-CoV-2 infection (PASC). The development of therapies for PASC has been challenged by a lack of an agreed-upon definition for the condition. It also hasn’t been clear whether different sets of long COVID symptoms may reflect distinct syndromes that need different treatments.

In 2021, NIH launched the Researching COVID to Enhance Recovery (RECOVER) initiative. RECOVER aims to understand why some people develop long-term symptoms following COVID-19. It’s also testing ways to detect, treat, and prevent the condition.

In a new study, RECOVER scientists collected reports of symptoms from about 8,600 people who had been infected with COVID-19 and about 1,100 uninfected people. The researchers focused on symptoms that were reported by at least 2.5% of the study volunteers. Results were published on May 25, 2023, in JAMA.

The team found that 37 symptoms were substantially more likely to occur in people who had been infected with COVID-19. Of these, 12 in particular best distinguish those with and without long COVID: post-exertional malaise (the worsening of symptoms after physical or mental activity), fatigue, brain fog, dizziness, gut symptoms, heart palpitations, sexual problems, change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements such as muscle twitching or jerking.

Using these 12 symptoms, the researchers developed a score to best differentiate those who have been infected with COVID-19 from those who have not. The team found that long COVID was more common and severe in people infected before Omicron emerged and in those who were unvaccinated at the time of infection. Among those infected during the Omicron era, reinfections were also linked to higher long COVID frequency and severity.

The researchers also identified four clusters of symptoms that often occurred together. Other symptoms commonly reported along with the 12 differentiating ones include dry mouth, weakness, headaches, tremor, muscle and abdominal pain, fever, sweats, chills, and sleep disturbances. The authors note that this approach may evolve over time as researchers gain more insights into the symptoms of long COVID.

“One of the big take-aways from this study is [that] long COVID is not just one syndrome; it’s a syndrome of syndromes,” says senior study author Dr. Andrea Foulkes of the RECOVER Data Resource Core, Harvard Medical School, and Massachusetts General Hospital.

Clinical trials run through RECOVER to address many of the symptoms highlighted in the current study are expected to begin enrolling participants by the end of 2023.

*Editor's Note: This story was modified soon after publication to correct errors and clarify the findings.