A large, prospective US study has identified eight distinct long-COVID trajectories, highlighting the diverse manifestations of the condition and laying the groundwork for future studies to evaluate risk factors and biomarkers that could explain variations in symptoms and identify therapeutic targets.
The study, led by a team at Massachusetts General Hospital, followed 3,659 participants (69% female) from the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Adult Cohort. The National Institutes of Health established RECOVER to address COVID as a global health priority.
Researchers tracked participants from 3 to 15 months after their first COVID infection. Almost all participants (99.6%) were infected with the Omicron variant. The enrollment period spanned October 29, 2021, to June 27, 2023.
Overall, 10.3% of participants met the criteria for long COVID at three months, and 81% of them continued to report persistent or fluctuating symptoms more than a year later.
The findings were published last week in Nature Communications.
14% of participants experienced worsening symptoms over time
Eight symptom trajectories emerged. About 5% of the infected cohort had “persistent, high” symptom burden across the entire 15-month period, while 12% experienced “intermittently high” symptoms. Another 10% showed moderate symptoms that gradually improved, and 9% experienced low-level symptoms that largely resolved by month six.
Notably, 14% followed worsening or delayed-worsening trajectories, including a group whose symptoms remained minimal until spiking at month 15.
The study compared infected participants with an uninfected cohort over the same period. While persistent and improving symptoms were less common among uninfected adults, some worsening patterns appeared in both groups, raising the possibility that not all symptom increases reflect long COVID.
The authors note several study limitations, including reliance on symptom surveys collected every three months (which may not have captured more granular, day-to-day changes), and the inability to capture trajectories beyond 15 months. Still, the large sample size, representative population, detailed symptom questionnaire, standardized long-COVID index, and minimal loss to follow up provide a clearer picture of long COVID’s different trajectories.
In a Mass General Brigham (MGB) press release, corresponding author Bruce Levy, MD, of the MGB Department of Medicine, said, “Our findings will help determine what resources are needed for clinical and public health support of individuals with long COVID and will also inform efforts to understand long COVID’s biological basis.”
