Half of long COVID patients improve within three years, study finds

The study, published Nov. 3 in the journal Annals of Internal Medicine, followed nearly 1,020 adults enrolled in the RECOVER Adult Study, a project funded by the US National Institutes of Health that has recruited thousands of Americans who previously tested positive for COVID-19. Researchers scored patients on how they were affected by a range of symptoms, including fatigue, brain fog, shortness of breath and heart palpitations, using a 30-point index called the 2024 LC Research Index (LCRI). Participants were counted as "improved" once they recorded LCRI scores of 10 or less at two consecutive visits, with in-person appointments and symptom surveys every three months.

After two years, 36% of participants had improved, and after three years that figure reached 50%. Scores fell to zero for 26% of participants at three years, meaning all symptoms had cleared at the time of the survey. Men and women improved at similar rates, but adults under 46 were more likely to improve than older participants, and people infected with the Omicron variants, which emerged in 2021, were more likely to improve than those infected with earlier strains.

A previous study grouped participants into five subtypes by their predominant symptoms: loss of smell or taste, chronic cough, brain fog, heart palpitations, and symptoms affecting multiple bodily systems. In the new study, patients in the last three groups were less likely to improve within three years. Roughly 60% of patients whose main symptoms were changes to smell or taste had improved by then, while the multisystem group, whose symptoms affected their cardiac, nervous and gastrointestinal systems, improved at a rate of just 19%.

Dr. Carmen Scheibenbogen, an immunologist at Charité University Medicine Berlin, said the progress of these multisystem patients resembles that of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a poorly understood condition that can be triggered by different infections. "It looks as if at least a major subgroup is suffering from ME-CFS," she said, noting that COVID-19 may have triggered their condition. "This is a disease which is triggered by different infections, but in the end, the disease [itself] is very similar."

Study co-author Harrison Reeder, a biostatistician at Massachusetts General Hospital, said he was careful to avoid describing participants as "recovered," a decision shaped by input from the long COVID community, whose members highlighted that their symptoms can wax and wane, whereas "recovery" implies a permanent resolution. The study did not capture whether individual patients who recorded meaningful improvement later relapsed.

Both researchers said the subtypes would be important to consider when designing potential clinical trials of long COVID treatments. The multisystem subgroup, Reeder said, “might be a group where an effective intervention can make a bigger difference than people who stand to potentially have a higher chance of improvement regardless.” Future work would need to further scientists’ understanding of people affected by long COVID at the level of genes and proteins, both scientists said. “There's a lot of work to do in RECOVER and in the world of long COVID research,” Reeder said. “There's a lot of opportunity.”